Invisibilia: For Some Teens With Debilitating Pain, The Treatment Is More Pain


Some teenagers have a rare and debilitating pain syndrome known as amplified pain. A strange new treatment forces them to suffer more pain in the short term to make the pain go away in the long term.

Invisibilia, the show about the invisible forces that shape human behavior, is back with Season 5. The first episode of the new season looks at pain in our culture through a medical mystery and a bizarre treatment program that offers a counterintuitive treatment approach.

There’s a before, and there’s an after.

In the before, it was a relatively normal night. The kind of night any 14-year-old girl might have.

Devyn ate dinner, watched TV and had small, unremarkable interactions with her family. Then, around 10 o’clock, she decided to turn in.

“I went to bed as I normally would, and then all of a sudden … my hips… they just hurt unimaginably!” Devyn says. “I started crying, and I started shaking.”

It was around midnight, but the pain was so intense she couldn’t stop herself — she cried out so loudly she woke her mother, Sheila. Together, they did everything they could to neutralize the pain — stand up, lie down, hot bath, pain medication. But there was no escape, not for Devyn, and so not for Sheila.

“You go to cancer first, right? It’s like, ‘OK, maybe you have cancer, maybe it’s a tumor?’ ” Sheila says.

When she was calm enough to reason with herself, Sheila decided cancer was improbable but wondered what was going on? The only thing they could think of was that the hip pain was somehow related to the minor knee surgery Devyn had gotten a few months before — she had broken the tip of her distal femur one day during dance practice.

So as usual, Sheila snapped to attention to solve the problem. It was 2016 — surely modern medicine could fix this. (NPR is not using Devyn’s or Sheila’s last name to protect Devyn’s privacy as a minor discussing her medical treatment.)

They started by calling Devyn’s surgeon, but the surgeon had no explanation for the pain. He renewed Devyn’s prescription for Percocet and wrote a new prescription for tramadol. But the pain only got worse, so they lined up more appointments: their pediatrician, a naturopath, a pain specialist, a sports medicine doctor.

Every doctor’s visit was the same. The doctor would ask Devyn about her pain: Where was it, and what was her pain number on a scale from 1 to 10? Then the doctor would order some tests to find the pain’s cause.

But no matter where the doctors looked in Devyn, all they saw was a perfectly normal body.

“You are healthy. Nothing is wrong.” Those are the words the doctors said to Devyn and Sheila over and over again. It made no sense. And it felt, paradoxically, like the more attention they gave to the pain, the bigger the pain grew.

“It spread from my knee down to my entire foot, the whole bottom half of my leg, to my right leg, to my right arm. My entire arm, to my shoulder, to my left hand and then my whole left arm,” says Devyn. “Pain just took over. Sometimes I couldn’t wear pants, I couldn’t wear socks, I couldn’t have the covers on my leg. Sometimes I’d have to turn the fan off, because the fan being on would hurt my leg.”

Of course, Sheila was horrified and frustrated, she had always been able to navigate Devyn’s problems before.

Sheila says she was never a helicopter parent but she was quick to help. She always did whatever she could to make Devyn’s dreams a reality. When Devyn was little, she focused on gymnastics, but at 12, she discovered dance and it was like a revelation. Devyn loved the way she felt when she moved.

Unfortunately once the pain hit, Devyn had to stop dancing. Pain was the focus now, it came to completely dominate both Sheila’s and Devyn’s attention.

“I was constantly thinking … ‘How’s my back feeling? How is my other leg feeling? How is the part that it just spread to feeling? And how am I going to handle it, if it spreads further?’ ” Devyn says.

Devyn withdrew from her public high school because there were days when her body throbbed so badly she could hardly leave her room. In fact, Devyn stopped going out even to short social events with family and friends because if someone bumped her or tried to shake her hand, her pain would flare and she would feel like going home.

Eventually their lives became so unrecognizable that they and the people around them actually began to question their sanity.

“I remember one time when we were sitting in the doctor’s office, and they basically just said to Devyn, ‘You know you need to work really hard on your psychology’ … and I thought, ‘Maybe we’re both crazy!’ ” Sheila says.

But here’s the thing: They weren’t the only ones who were facing this problem.

There are lots of teens like Devyn.

Stuck on the wrong setting

According to rough estimates from pain specialists, there are thousands of teenagers suffering from mysterious pain that grows and grows, jumping at random from one part of their body to the next. It mostly affects girls, though a small number of the cases are in boys. In fact, about 10 years ago, doctors began to use a new term for the problem — amplified pain.

The term acts as a kind of umbrella for a variety of diagnoses (like complex regional pain syndrome), none of which are yet well understood, particularly in children. What is clear is that for most of these kids, the pain can’t be fully explained by an injury or infection. For some kids, their pain seems to emerge after an injury, but it continues and grows long after the injury is healed. And doctors who treat it think the pain comes from an overly sensitized nervous system.

The normal purpose of pain is to act as a warning sign — it tells you to take your hand off the stove. But the doctors who treat children like Devyn think something has happened to make these kids’ brains and nervous systems go haywire and start seeing threats everywhere. For these children, it could be that even normal stimuli — like the breeze from a fan — is amplified and interpreted by the brain as an attack. That could be why Devyn felt pain even though no test found any problem. Her brain was stuck on the wrong setting and couldn’t stop paying attention to the signals it was receiving.

For pain, the go-to move in American medicine has been prescribing painkillers — but that doesn’t typically solve the problem these children have. Now, a small group of doctors across the country have developed an unusual approach that they say is working for some patients.

It doesn’t work for everyone, and the research has a long way to go to prove that it’s effective — but it offers an intriguing alternative treatment, and it starts from a different way of thinking about pain.

Put them in pain to get better

Dr. David Sherry, a pediatric rheumatologist at Children’s Hospital of Philadelphia, has gray hair long enough to gather in a ponytail, a massive number of aggressively playful ties, and a very unconventional, somewhat alarming attitude toward pain.

For Sherry, the way you think about and approach pain is a critical part of the physical sensation you experience. And he believes that since the 1990s, our society has focused way too much attention on aggressively relieving pain.

Sherry says pain used to be more accepted as a normal and predictable part of life. He thinks that the way American medicine now routinely asks patients to rate their pain on a scale of 1 to 10, and treats it like an emergency, has led to more pain in our society: More doctors confronted with kids like Devyn, and more adults complaining of chronic pain. He thinks the more attention you pay to something, the bigger it becomes — because the very act of paying attention to something reinforces connections in the brain.

So to help kids like Devyn, Sherry and a handful of other doctors with this approach want to teach them to stop paying so much attention to pain. Which is why Sherry has concocted an unusual treatment for these kids: “Put them in pain to get them better.”

If you force the kids to push their bodies until they are in tons of pain, over time, their brains can learn to ignore it, according to Sherry’s hypothesis. He has a clinic at Children’s Hospital of Philadelphia where he treats about six kids with amplified pain at a time. He has tracked his patients and says he has seen a lot of success; he published a small study showing that 45 out of 49 patients had remained symptom-free for two years. His approach hasn’t been validated by larger, controlled trials, and in fact, a portion of patients don’t do well; they drop out or don’t benefit in any way.

But many families with these problems have tried and failed at other treatment options. And as unpleasant as it sounds, for them, Sherry’s approach seems worth trying.

From dancer to ‘sick girl’

About eight months after Devyn had woken writhing in pain, she and Sheila still had no solution to Devyn’s problem. They had tried physical therapy, medications, even hypnosis. Then one of the many specialists they went to see suggested Devyn might have amplified pain. She remembers coming home from the doctor and getting on her computer to research this syndrome she had never heard of.

Because of amplified pain, one patient was not able to unclench her right hand.

Cara Tallo/NPR

“The very first video I clicked on, it was a girl, probably around my age, and she could not function at all,” Devyn says. “She had cabinets full of prescription medication, and there was this one part where she was outside and she was in a wheelchair and a mosquito bit her and she cried like she just got stabbed in the leg. That’s how severe her pain was.”

Devyn eventually found an online support group of girls like her with chronic pain, and she found incredible solace in a community of people facing the same set of problems. As the months wore on, she says, she spent more and more time online talking to them.

For her part, Sheila was glad to have a diagnosis and glad that Devyn was finding comfort in a new community. But sometimes, in a dark corner of her mind, she privately worried that her daughter’s identity was being built around being sick.

“You know she’s gone from dancer to performer to sick girl … because right now all her friends are kids with chronic pain,” Sheila says.

What Sheila wanted was a laser focus on getting rid of the pain and back to normal life. And that was when she found out about David Sherry and his program.

So they flew to Philadelphia to meet him, and after a tour of his clinic, they became convinced they should try this approach.

“He’s definitely a little crazy, but anyone who goes into a profession treating this disease has to be a little crazy and out of the box,” says Devyn.

Because of scheduling, Devyn wasn’t able to go to Sherry’s program at CHOP, but she got in to a similar program run by one of his former rheumatology students, Dr. Cara Hoffart, at Children’s Mercy Hospital in Kansas City, Mo.

“Easy, medium, hard”

When Devyn and Sheila sat down for intake with Dr. Emily Fox — one of the doctors at Children’s Mercy Rehabilitation for Amplified Pain Syndromes Program — she was clear right from the start: They were going to put Devyn in as much pain as they possibly could.

“This may be one of the hardest things that you do physically in your life,” she warned Devyn.

Devyn was going to do physical workouts five to six hours a day, so it was absolutely going to hurt. But, Fox explained, they were going to studiously avoid talking about the hurt because, “the focus is not on pain in the program — therapists are going to ask you ‘Are things easy, medium or hard?’ ”

Easy, medium, hard. This bland neutral language was necessary because the whole point of the treatment was to draw attention away from pain. So Devyn, her mother and even the physical therapists charged with putting Devyn in pain should avoid speaking the word “pain” out loud whenever they could.

In addition, pain medication — even medication for apparently unrelated problems, like nausea, shouldn’t be used. Nothing to mask the hurt and difficulty: Devyn had to experience it straight up.

Fox looked at Devyn and Sheila with eyes that were serious and sympathetic but firm. If Devyn followed these rules, nine hours a day, five days a week, for three to six weeks, she said, she thought Devyn’s pain would ease. But it wasn’t going to be easy.

Pain was how Devyn would be cured of her pain.

A focus on function

There are other programs across the country that share some of the same principles with Sherry’s and Hoffart’s approach. Often called intensive interdisciplinary pain treatment programs, they treat chronic pain with a mix of therapies, especially physical therapy and psychotherapy.

They’re all intended to help patients learn to cope better with pain and re-engage with the activities that are meaningful to them. The approach has been shown to be effective for some chronic pain complaints among adults and has shown some positive results for children with pain syndromes in small studies.

One similar program at Boston Children’s Hospital is run by Dr. Christine Greco, a pediatric pain specialist, and Deirdre Logan, a psychologist. They also treat kids with chronic pain, using a combination of therapies, including intensive physical therapy, which is typically painful for patients. But they say causing kids to experience pain is not the focus.

“Really the focus is on getting kids functional again,” says Greco. They measure success not in terms of lessened pain, but in terms of kids getting back to activities they want to do.

Before the patients get started in the program, the therapists make sure the participants don’t have an underlying injury that could be worsened by treatment. Then, Logan says, the therapists get the families ready for the pain their child is about to suffer, explaining that there’s a “difference between hurt and harm.”

“We try to tell families that is very real pain that they’re experiencing. But it is not any longer a signal of ongoing tissue damage,” say Logan.

Sherry and Hoffart agree that restoring function is the top priority, but the intensity of their programs and restrictions on pain medications can make the treatment feel even more daunting.

Day after day

Days at the Children’s Mercy pain program begin at 7:30 a.m. with an hour of exercise in the hospital pool. One day during Devyn’s treatment, the physical therapist led Devyn and two other girls through a routine.

The air in the pool room was hot, making the girls excruciatingly uncomfortable. Because of their amplified pain, the girls’ skin is so sensitive that even a cool breeze could feel like someone was holding fire to their body.

At Children’s Mercy Amplified Pain Syndrome Program, patients start most days with an hour of intense therapy in the hospital pool.

Cara Tallo/NPR

After some laps, the physical therapist brought out a stopwatch and told them to get out of the pool and jump back in as fast as they could.

So that is what they did. They jumped in the pool, then turned back to the edge and pulled the full weight of their body up by their arms. Then they did it again, and again.

It went on for five minutes, each of the girls struggling to do the task over and over. One of the girls had lost the use of one side of her body — which sometimes happens with amplified pain — so it was especially hard for her. She was mostly using her good arm; she still tried to throw her other elbow over the edge of the pool to help, only it kept on slipping.

After swimming, Devyn moved into a full day of exercise. Her first activity was to perform a series of jumps with her arms stretched overhead.

Devyn started fine, but about 30 seconds in, she began to have an asthma attack. Her breathing got more and more labored, until she was gasping, struggling to get the air she needed.

She told the physical therapist that she probably should get her inhaler, but since inhalers are medicine, the therapist directed Devyn to simply walk around the gym and calm herself down.

Later, when Devyn got a nosebleed, the therapist signaled her to continue with her workout. Again, she did not want Devyn to linger over the problem, to give more attention to pain.

So Devyn did push on. And through it all, her attitude never seemed to waiver from a cheerful can-do.

Boring the brain

As far as Hoffart can tell, there are very few other pain programs in the U.S. besides Children’s Mercy that refuse to bridge pain with medications. But, her view is that meds are sabotaging in cases of amplified pain.

In the amplified pain treatment program at Children’s Mercy, patients spend hours a day doing uncomfortable exercises with the idea that they can gradually retrain their nervous systems to be less sensitive to pain.

Cara Tallo/NPR

“I am asking a teenager to do an incredibly complex, challenging, hard treatment approach, and most of my patients will tell you this is their last resort,” she says. “And if they still are holding out that maybe some medication is going to save them or fix this, it’s really hard to give your all to something that sounds so hard and challenging. And so you kind of have to be all in.”

In a sense, what the program is trying to do, Hoffart says, is to slowly, laboriously retrain the brain. That’s why the children have to be in so much pain for so long. Because of their past behaviors, Hoffart says, she thinks their brains have been trained in the wrong way.

She gives the example of walking, which for these kids can actually be a painful activity. And if you quit walking because of the pain?

“Your nerves just heard from you that walking is dangerous because you stopped. So next time you start walking, they’ll remember that… you actually just empowered them to send more pain signals,” she says.

The alternative she wants for her patients: Keep walking even though it hurts.

“If you keep walking, your nerves are essentially getting the message of, ‘Well she’s still walking [so] this must not be dangerous. Why are we firing?’ and then, as I tell my kids, they’ll get bored and stop firing,” she says.

So that’s what they’re trying to do: Bore the brain into submission. That’s also why they avoid the word “pain.” When a kid is asked about their pain, Hoffart says one way to think about what happens is that the brain must take an inventory — run through the body checking —and that refreshes all the nerve connections. Again, she speculates, that is the problem with paying too much attention to something.

But boring the brain is a big job, so they can’t just work with the kids. They need the whole world around the kid to change, too. So they also have therapy for the parents.

Enabling or supporting

Dustin Wallace, the program’s lead psychologist, has a very clear message for the parents: Once they go home, avoid the topic of pain with their kids but also with their adult friends and family outside their home. He bases this advice on his belief that attention moves through networks of people, infecting everyone and changing how they act.

“The people that are in your lives are often in your kids’ lives. They’re parents of your kids’ friends, they’re your kids’ relatives, they’re in your town or network. And so you don’t want them to see your kid through this lens, because it will color their behavior,” Wallace explains.

Sheila takes Wallace’s words to heart when it comes to Devyn: “I think as a parent you always teeter on the edge of ‘Am I enabling?’ or ‘Am I supporting?’ ” she says.

But while the program is premised on the idea that there are problems associated with the increasing amount of attention our society pays to pain, the answer, Wallace says, isn’t to reinstate the pure grin-and-bear-it approach of decades ago before pain became more widely treated.

Wallace believes that when you’re unable to name and think about your emotions and don’t have the tools to diffuse them, whatever stress you experience is directed at and absorbed by the body. That’s an important part of the problem with these girls, Wallace says: They’re not in touch with their feelings; they just plaster on what the program calls an “I’m fine” face.

So, Wallace says, one way to understand what’s happening to them is that their nervous systems go haywire because they don’t have the sophisticated emotional skills they need to manage in an increasingly stressful world.

“What the world expects today of everybody, but in particular coming down to our kids, is so much greater, so much faster, so much more all-day-long, that they are facing far more stress, more hours of the day,” he says.

So in the treatment, when the kids are going through their exercises, before and after many of the activities, their trainers ask them for a word that describes how they are feeling. They also complete worksheets and diary entries so they can learn to better articulate their inner thoughts. They’re taught breathing exercises, and the program gives the patients both individual and group therapy.

At the Children’s Mercy amplified pain program, patients track their progress on a board. When their physical therapist determines that they have completed each activity to their fullest potential, a “maxed” label is placed on the board as a celebration of their accomplishment.

Cara Tallo/NPR

Wallace says kids should have the ability to explore and manage the thoughts and emotions that they need to struggle with, but should also know when — especially in the case of pain — it’s going to serve them better to release those feelings and move on.

Graduation

After three weeks of treatment, it was the last day for Devyn, and everyone gathered in the gym so Fox could hand her a certificate of completion.

Just before she left, Fox asked Devyn her official pain score so she could put the closing number on her chart — and Devyn answered “6.” In other words, Devyn was still in a lot of pain.

But that was apparently normal. Fox told Devyn that if she kept up all her exercises and kept on pushing through, the pain should dramatically diminish within a year. So that was the hope as Devyn and Sheila waved goodbye and loaded themselves into the car to drive away.

And about a month after the program ended, Devyn reported her pain had gone down a lot. Devyn says that some days it’s at a zero. Not every day, but sometimes.

For both Devyn and Sheila, it was an incredible relief. Devyn even went back to dancing.

Why Do Some People Develop Chronic, Treatment-Resistant Pain and Not Others?


In their landmark 1965 article, Melzack and Wall[9] wrote “it is possible for central nervous system activities subserving attention, emotion, and memories of previous experience to exert control over the sensory input.” But they acknowledged “the manner in which the appropriate central activities are triggered into action presents a problem.” Fifty-three years later, Borsook et al.[1] have gone a long way to solving this problem.

The question of why some people and not others develop chronic pain that seems refractory to treatment has challenged pain researchers and clinicians since chronic pain was first delineated. Although it is possible to believe that these people just have not had the “right” treatment, this is unlikely as no treatment has proven universally effective in relieving chronic pain. For example, in the case of chronic low back pain, the most common and globally disabling form of chronic pain,[17] treatments typically achieve only small pain reductions that are not much greater than those for placebos and well short of what patients usually seek.[8] The effects of analgesic agents and antiepileptics for different types of chronic pain are also quite limited, helping a small proportion of patients only.[12,13]

As is common in apparently inexplicable conditions, especially when no obvious physical cause has been identified, various psychological “explanations” have been proffered. In the case of chronic pain, these have included concepts such as “pain-prone personality”,[4] “masked depression,”[7] and “compensation neurosis.”[10] As Merskey[11] pointed out, these sorts of explanations for what have been described as “medically unexplained symptoms” have not been helpful in advancing our understanding or treatment of patients with chronic pain, and none of these labels have stood up to rigorous investigation.[2,16]

More recent psychological and social explanations for chronic pain have focussed less on causation and psychopathology and more on the influence of normal psychological processes that may influence the experience and impact of pain through mechanisms such as modulation and mediation.[3,15,18] Although these lines of study have more robust theoretical and empirical bases than the earlier attempts to use abnormal psychology constructs to explain the development and persistence of chronic pain, they have been relatively silent on the possible roles of biological contributors to chronic pain and how they may relate to the influence of psychological constructs such as learning, attention, perception, memory, and emotions. But there are notable exceptions, as can be seen in the work of researchers such as Flor[6,14] and Davis[5] and their colleagues. Nevertheless, if we are to solve the challenge posed by Melzack and Wall,[9] we also need to make sense of the burgeoning literature on the biological contributors to chronic pain as well. In this edition of PAIN, Borsook et al.[1] have tried to do just that.

In their comprehensive review, Borsook et al.[1] set out to consider the broad landscape of contributions and interactions of biological, social, and psychological factors towards the evolution of treatment-resistant chronic pain. Not surprisingly, given the size of the task, in the end, they have focused more heavily on the biological factors rather than social and psychological ones, and they acknowledge there is still work to be performed to clarify all the potential mechanisms that produce or exacerbate persistent pain. But, from what is known, they consider how differences in the relative contribution of factors such as stress, age, genetics (and epigenetics), environmental characteristics, and immune responsivity may produce different risk profiles for disease development, pain severity, and chronicity. Admittedly, the complexity of the topic necessitates careful reading, but the authors provide some assistance to the general reader using terms such as “stickiness” as a soubriquet for capturing the effect of the multiple influences on the persistence of pain, which may lead to pain and maladaptive coping becoming rigidly fixed or “stuck,” and intractable.

The review incorporates methods from other fields, such as Network Biology, which may be used to model or simulate a complex multifactorial entity like pain, and also covers the familiar constructs and processes that have been widely reported in the pain research literature, such as homeostasis, resilience, allostasis, drug-induced hyperalgesia, synaptic plasticity, endogenous regulation, centralization, and sensitization. To the authors’ credit, this article cogently describes where each of these constructs and processes may fit into the picture of pain chronification and treatment resistance. In this regard, the authors have made a major contribution to our field. Importantly, the authors conclude by articulating a research agenda aimed at extending the knowledge summarised here, as well as potential therapeutic opportunities. These include the development of more neurobiologically informed pain therapies—both pharmacological and psychological—that might offer, singly or in combination, the prospect of reversing pain stickiness and unlocking fixed pain behaviours to facilitate resilience and a return to homeostasis. It may have taken us 50 years to get here, but it also reminds us, if we had not realized already, the foresight of Melzack and Wall.

Origins of Pain


Researchers identify pathway that drives sustained pain following injury

painful shoulder

Researchers have identified the nerve-signaling pathway behind the deep, sustained pain that sets in following injury.

A toddler puts her hand on a hot stove and swiftly withdraws it. Alas, it’s too late—the child’s finger has sustained a minor burn. To soothe the pain, she puts the burned finger in her mouth.

Withdrawing one’s hand to avoid injury and soothing the pain of that injury are two distinct evolutionary responses, but their molecular origins and signaling pathways have eluded scientists thus far.

Now research led by investigators at Harvard Medical School, published Dec. 10 in Natureidentifies the nerve-signaling pathway behind the deep, sustained pain that sets in immediately following injury. The findings also shed light on the different pathways that drive reflexive withdrawal to avoid injury and the subsequent pain-coping responses.

Clinical observations of patients with neurological damage together with past research have outlined the distinct brain regions that differentiate between the reflexive withdrawal from a skin prick, for example, and the long-lasting pain arising from tissue injury caused by the pinprick.

The new study, however, is the first one to map out how these responses arise outside the brain.

The findings, based on experiments in mice, put into question the validity of current experimental approaches for assessing the efficacy of candidate pain-relief compounds. Most current methods rely on measuring the initial, reflexive response that serves to avert tissue injury, rather than on measuring the lasting pain that arises from actual tissue damage, the researchers said. As a result, they said, some drug compounds that might have been successful in assuaging the sustained pain—the lasting sensation of pain that immediately follows injury—could have been dismissed as ineffective because they were assessed against the wrong outcome.

“The ongoing opioid crisis has created an acute and pressing need to develop new pain treatments, and our findings suggest that a more tailored approach to assessing pain response would be to focus on sustained pain response rather than reflexive protective withdrawal,” said study senior author Qiufu Ma, professor of neurobiology in the Blavatnik Institute at Harvard Medical School and a researcher at Dana-Farber Cancer Institute.

“All these years, researchers may have been measuring the wrong response,” Ma added. “Indeed, our results could explain, at least in part, the poor translation of candidate treatments from preclinical studies into effective pain therapies.”

Previous work by Ma and colleagues, as well as others, points to the existence of two sets of peripheral neurons—the nerve cells located outside the brain and spinal cord. One set of peripheral nerve cells send and receive signals exclusively to and from the superficial layers of the skin. As a first-line of defense against external threats, these peripheral nerve cells are geared toward preventing injury by triggering reflexive withdrawal—think pulling your hand after a pinprick or to avoid the hot tip of a flame. Another set of neurons are dispersed throughout the body and thought to drive the lasting pain that sets in after initial injury and induces pain-coping behaviors such as pressing a banged finger or licking a cut in the skin to sooth the damaged area.

Yet the existence of these neurons could not fully explain how the pain signal travels throughout the body and to the brain. So, Ma and colleagues proposed the existence of another critical player in this relay.

The team focused on a set of neurons called Tac1 emanating from the so-called dorsal horn, a cluster of nerves located at the lower end of the spinal cord that transmit signals between the brain and the rest of the body. The precise function of Tac1 had remained poorly understood so Ma and colleagues wanted to know whether and how these neurons were involved in the sensation of sustained pain.

In a series of experiments, the team assessed pain response in two groups of mice—one with intact Tac1 neurons and another with chemically disabled Tac1 neurons.

Mice with inactivated Tac1 neurons had normal withdrawal reflexes when exposed to a painful stimulus. They showed no notable differences in their withdrawal from pricking or exposure to heat and cold. However, when the researchers injected the animals with burn-inducing mustard oil, they did not engage in the typical paw licking that animals perform immediately following injury. By contrast, mice with intact Tac1 neurons engaged in vigorous and prolonged paw licking to assuage the pain.

Similarly, mice with disabled Tac1 neurons showed no pain-coping responses when their hind paws were pinched—something that induces sustained pain in humans. These animals did not engage in any paw licking as a result of the pinch. Such loss of sensitivity to a specific type of pain mimics the loss of sensation seen in people with strokes or tumors in a particular area of the brain’s pain-processing center—the thalamus—that renders them incapable of sensing lasting pain.

These observations confirm that Tac1 neurons are critical for pain-coping behaviors stemming from sustained irritation or injury but that they play no role in reflexive-defensive reactions to external threats.

Next, researchers wanted to know whether Tac1 neurons shared a common connection with another class of neurons, called Trpv1, present throughout the body and already known to drive the sensation of lasting pain induced by injury. Mice that had functional Tac1 but nonfunctioning Trpv1 neurons responded weakly to pinch-induced pain, showing minimal paw licking. The finding suggests that pain-sensing Trvp1 neurons connect to Tac1 neurons in the dorsal horn of the spinal cord to transmit their signals.

“We believe that Tac1 neurons act as a relay station that dispatches pain signals from the tissue, through Trpv1 nerve fibers all the way to the brain,” Ma said.

Taken together, the results of the study affirm the presence of two lines of defense in response to injury, each controlled by separate nerve-signaling pathways. The rapid withdrawal reflex is nature’s first line of defense, an escape attempt designed to avoid injury. By contrast, the secondary, pain coping response helps reduce suffering and avert widespread tissue damage as a result of the injury.

“We believe it’s an evolutionary mechanism conserved across multiple species to maximize survival,” Ma said.

Where pain lives


Fixing chronic back pain is possible only when patients understand how much it is produced by the brain, not the spine,

For patient after patient seeking to cure chronic back pain, the experience is years of frustration. Whether they strive to treat their aching muscles, bones and ligaments through physical therapy, massage or rounds of surgery, relief is often elusive – if the pain has not been made even worse. Now a new working hypothesis explains why: persistent back pain with no obvious mechanical source does not always result from tissue damage. Instead, that pain is generated by the central nervous system (CNS) and lives within the brain itself.

I caught my first whiff of this news about eight years ago, when I was starting the research for a book about the back-pain industry. My interest was both personal and professional: I’d been dealing with a cranky lower back and hip for a couple of decades, and things were only getting worse. Over the years, I had tried most of what is called ‘conservative treatment’ such as physical therapy and injections. To date, it had been a deeply unsatisfying journey.

Like most people, I was convinced that the problem was structural: something had gone wrong with my skeleton, and a surgeon could make it right. When a neuroscientist I was interviewing riffed on the classic lyric from My Fair Lady, intoning: ‘The reign of pain is mostly in the brain,’ I was not amused. I assumed that he meant that my pain was, somehow, not real. It was real, I assured him, pointing to the precise location, which was a full yard south of my cranium.

Like practically everyone I knew with back pain, I wanted to have a spinal MRI, the imaging test that employs a 10-ft-wide donut-shaped magnet and radio waves to look at bones and soft tissues inside the body. When the radiologist’s note identified ‘degenerative disc disease’, a couple of herniated discs, and several bone spurs, I got the idea that my spine was on the verge of disintegrating, and needed the immediate attention of a spine surgeon, whom I hoped could shore up what was left of it.

Months would pass before I understood that multiple studies, dating back to the early 1990s, evaluating the usefulness of spinal imaging, had shown that people who did not have even a hint of lower-back pain exhibited the same nasty artefacts as those who were incapacitated. Imaging could help rule outcertain conditions, including spinal tumours, infection, fractures and a condition called cauda equina syndrome, in which case the patient loses control of the bowel or bladder, but those diagnoses were very rare. In general, the correlation between symptoms and imaging was poor, and yet tens of thousands of spinal MRIs were ordered every year in the United States, the United Kingdom and Australia.

Very often, the next stop was surgery.  For certain conditions, such as a recently herniated disc that is pressing on a spinal nerve root, resulting in leg pain or numbness coupled with progressive weakness, or foot drop, a nerve decompression can relieve the pain. The problem is that all surgeries carry risks, and substantial time and effort is required for rehabilitation. After a year, studies show, the outcomes of patients who opt for surgery and those who don’t are approximately the same.

More invasive surgeries carry greater risks. Lumbar spinal fusion – surgery meant to permanently anchor two or more vertebrae together, eliminating any movement between them – is recognised as particularly hazardous. Even when the vertebral bones fuse properly, patients often do not get relief from the pain that sent them to the operating room. Beyond that, fusion surgery often results in ‘adjacent segment deterioration’, requiring a revision procedure.

In the US, about 80,000 spine procedures fail each year , and one in five patients returns for another operation. Typically, second, third and fourth attempts have an even lower chance of success, and patients continue to require painkillers over the long term. Even the procedures that surgeons deem successful, because the bones fuse and look perfect on a scan, are often unhelpful to patients. In one study, two years after spinal fusion, patients’ pain had barely been reduced by half, and most patients continued to use painkillers. Given such unimpressive outcomes, the cost of treating back pain is unacceptably high. Spine surgery costs a fortune, but otherapproaches, including epidural steroid injections, physical therapy and chiropractic treatment, are also expensive.

Including direct medical expenses and indirect expenses such as lost earnings, spine care costs the US about $100 billion a year. In the UK, that tab is about £10.6 billion (c$13.6 billion). In Australia, it’s A$1.2 billion (c$950 million). Many of these costs derive from the loss of productivity, as people take time off from work. Others result from the devastation wrought by addiction to prescription opioids. In Australia, between 1992 and 2012, prescription opioid dispensing increased 15-fold, and the cost to the Australian government increased more than 32-fold.

Pain falls into four basic categories. There’s nociceptive pain, the normally short-lived kind you feel when you accidentally slam your finger in the car door. There’s inflammatory pain, a response to damage or infection, resulting in a rush of small proteins called inflammatory cytokines to the site of the casualty. That pain has a habit of spreading, to affect everything in the vicinity. Beyond that, there’s neuropathic pain, known as ‘radiculopathy’. It results, usually, from an insult to a nerve, culminating in burning, tingling or shock-like sensations that travel the length of the affected nerve (sciatic pain is a good example).

‘As pain becomes more centralised, it becomes increasingly more difficult and less relevant to identify the initial source’

When any of those three types of pain sticks around long after the inciting injury has healed – or in the absence of any noxious stimulus – the patient can be said to be suffering from ‘central sensitisation’. Central sensitisation is a condition in which even mild injury can lead to a hyperactive and persistent response from the central nervous system.

The CNS includes the dorsal root ganglia, containing the cell bodies of sensory neurons that allow information to travel from the peripheral sites to the spinal cord and the brain. The peripheral nervous system (PNS) consists of the nerves beyond the brain and the spinal cord, serving all parts of the body that the CNS does not, comprising roughly 40 miles of nerve fibres, if they were laid out, end to end.

‘As pain becomes more centralised,’ wrote Clifford Woolf, a neurologist and neurobiologist at Harvard Medical School, ‘it becomes increasingly more difficult and less relevant to identify the initial source.’

More than three centuries ago, the French philosopher, mathematician and natural scientist René Descartes advanced the heretical idea that pain was not a punishment from God, nor a test or trial to be endured, for which prayer was the only intervention. Instead, he said, pain existed as a mechanical response to physical damage. His work Treatise of Man would not be published until after he died (some say because he feared persecution by Christian authorities, for whom the threat of pain was a useful recruitment tool). But when the volume finally emerged, Descartes posited the existence of ‘hollow tubules’ that allowed messages he described as ‘animal spirits’ to travel on a dedicated somatosensory pathway, from the afflicted site to the brain. The intensity of pain, Descartes believed, rose with the severity of tissue damage. In the absence of such damage – a shattered bone, a wound, a burn – pain ought not to exist.

But of course, it did.

In the mid-1960s, two scientists, the Canadian psychologist Ronald Melzack and the British neurobiologist Patrick Wall, both then working at the Massachusetts Institute of Technology, set out to answer the question of how pain could persist in the absence of an injury. It was mostly guesswork. It would be years before neuroimaging would allow them to view the structure of a living human brain.

In their landmark article ‘Pain Mechanisms: A New Theory’ (1965), published in the journal Science, they considered the pathophysiology of chronic pain, based on post-mortem studies, surgical notes, neurofeedback and patients’ reports of their experiences. Ultimately, the two scientists described the ‘gate control theory of pain’, hypothesising that nerve cells in the spinal cord acted as gates, flipping open to allow pain messages to pass through, or closing to prevent such messages from reaching the brain. At times, the scientists posited, the gates became stuck in the open position, allowing pain messages to flow unabated. It was that last little bit – the notion that messages would travel unceasingly, from the PNS to the CNS – that sparked Clifford Woolf’s interest in how pain was generated, and how it could be silenced.

In 1983, Woolf was a young anaesthesiologist with a PhD in neurobiology. As a post-doc, he had worked in Wall’s laboratory, which by that time had moved to University College London. There he observed post-mortem cellular and molecular changes in brain tissue in subjects who had suffered from chronic pain when they were alive.

Instead of responding to externally generated discomfort, under siege the brain itself begins to generate the pain

Later, he had access to high-powered neuroimaging in the form of functional magnetic resonance imaging, or fMRI. This neuroimaging could measure changes in the brain’s blood flow, volume, oxygen or glucose mechanism, allowing Woolf to see how the brain responded to pain in a living subject. Woolf thus began to explore the many ways in which neurons in different brain regions communicate; how they form a greater number of synapses, linking regions that are not normally hot-wired to work in concert; and how those neural changes lead to the perception of pain. He saw that the regions of the brain that responded to acute, experimental pain were different from the regions that were involved in chronic pain. Over the next three decades, Woolf explored the relationship between specific gene phenotypes and chronic pain, looking for potential targets for drug therapy. It would be slow-going, in part because pharmaceutical companies were profitably selling opioid analgesics. When, in the mid-2000s, the efficacy and safety of opioids began to be questioned, Woolf’s work took on new vigour.

By then, the neuroscientist A Vania Apkarian, a professor of physiology, anaesthesiology and physical medicine at Northwestern University’s Feinberg School of Medicine in Chicago, was well into his own study of what happens to specific regions of the brain under the onslaught of chronic pain. For two decades, in his provocatively named Pain and Passions Lab, where his group works with both rodents and humans, Apkarian’s focus has been on pain’s cognitive consequences.

‘When we started this research in 1999,’ Apkarian said, ‘very few people believed that pain was more than nerves sending a signal into one part of the brain.’ With grants from the National Institutes of Neurological Disorders and Stroke – part of the National Institutes of Health (NIH), Apkarian demonstrated that instead of simply responding to externally generated discomfort, under siege the brain itself would begin to generate the pain. ‘The official definition of chronic pain,’ Apkarian wrote in the journal Pain Management, ‘is that it persists past the completion of injury-related healing processes.’

Brain activity in subjects with chronic pain was different from the nociception (perception of harm) evident in patients with experimentally induced pain, for instance, a hot poker placed on a sensitive part of the arm. While nociceptive-provoked pain activated primarily sensory regions – the ones that would cause you to yank your arm out of harm’s way – Apkarian’s group observed that chronic pain activated the prefrontal cortex and the limbic regions of the brain. The prefrontal cortex dictates higher-level thinking, including goal-setting and decision-making, while the limbic regions, including the hippocampus and the nucleus accumbens, govern memory, motivation and pleasure.

In a revelation that set the international media abuzz, Apkarian’s group found that the anatomy of the human brain in patients who suffered from chronic pain was abnormal. In those who had suffered for five years, both the hippocampus and the prefrontal cortex were structurally transformed, sacrificing 5 to 11 per cent of their grey matter density. That was important because the prefrontal cortex, in concert with the hippocampus, dictates how optimistic or depressed patients feel about their prospects, how well they can cope and make decisions about treatment. There’s still a great deal of work to do in this area but, wrote Apkarian, ‘the concept is that the continued, unrelenting pain impacts limbic structures in the brain that in turn entrain the cortex to reflect both the suffering and coping strategies that develop in chronic-pain patients.’

The brain of a person with lower-back pain looks different from that of a person with a repetitive-stress injury

Subsequently, more than 50 studies, most from other investigators, have documented regional decreases in grey matter density, volume or thickness. Beyond that, the neuronal network of the remaining grey matter is rearranged, in patterns that are specific to chronic-pain conditions. That means, for instance, that the brain of a person with lower-back pain will look different from that of a person with a repetitive-stress injury. It’s still unknown, Apkarian adds, ‘the extent to which the observed brain reorganisation is a causal response to the condition or a predisposing factor’.

At least one other aspect of brain activity is transformed in people with chronic pain. The nucleus accumbens’ role is to monitor the brain’s reward circuit, thus governing feelings of pleasure and motivation. According to the scientists at Stanford University who studied the nucleus accumbens in mice, the brain structure is involved in ‘computing the behavioural strategies that prompt us to seek out or avoid things that can affect our survival ’.

In chronic-pain patients, Apkarian’s researchers observed, the nucleus accumbens and the medial prefrontal cortex (which, once again, mediates decision-making) become unusually chatty.

This much-enhanced level of communication between the two regions represents a profound reorganisation of neuronal connections. It’s possible that this chattiness might correspond with chronic-pain patients’ reluctance to follow self-care protocols such as exercise. The heightened communication might also drive a tendency to select interventions that seem ‘easy’, but often are not, and in hindsight might be damaging. It’s easy to see why that would be. In the absence of any sense that hard work will be rewarded, or that things will get better, it’s difficult to summon the energy to follow through.

There’s much debate about what sparks the complex neurobiological sequence that results in central sensitisation and, puzzlingly, why this occurs in some people but not in others. Both environmental and hereditary factors are likely involved, Woolf has found. His lab at Boston Children’s Hospital is focused on identifying human genes with a link to ‘dramatic familial pain phenotypes’ – extreme pain disorders that run in families – and could offer insight into more typical chronic-pain conditions.

Woolf’s lab has identified a haplotype (an inherited DNA variation) that matches up with high sensitivity to pain from sciatica, osteoarthritis and lumbar disc degeneration. ‘It is becoming clearer,’ observed Woolf and his co-authors in a paper in the Journal of Pain in 2016, ‘that the development of chronic low back pain may occur because of a combination of genetically based susceptibility factors as well as local pathological risk factors.’ In other words, whether your intervertebral disc is going to rupture has much to do with your physiology and physical condition. But how much it’s going to bother you, and for how long, is likely to be a matter of genetic predisposition. Woolf’s group is currently working on a process that allows them to genetically reprogram skin cells to turn into pain-sensing nerve cells, which can be studied in a petri dish. Woolf hopes that once the nerve cells are established, they will be valuable for pre-screening patients to see who has the physical and biochemical traits that make it likely they will develop chronic pain.

Scientists suspect that shared genetic background is the reason that pain hypersensitivity often runs in families

Scientists now recognise that there are gene variations that ‘wire’ certain people for suffering, and variations that leave others unscathed. The enzyme catechol-O-methyltransferase (COMT) is essential to the production of several stress-related neurotransmitters, including dopamine, norepinephrine and epinephrine, each of which is involved in modulating mood and cognition. One variant of COMT produces a slower-acting enzyme that leaves a flood of dopamine intact within the synapse, a condition that is associated with a very high level of stress. People who inherit that slow-acting COMT variant can be especially emotional and pain-sensitive. Intriguingly, unless they choose more even-keeled partners, it’s likely that their progeny will share their tendency towards pain sensitivity.

Research on this topic is still sparse, but scientists suspect that this shared genetic background, rather than any identifiable pathology, is the reason that pain hypersensitivity often runs in families, and it’s common to hear stories of multiple family members who suffer from similar chronic back-pain conditions. Woolf’s lab found that the gene GCH1 controls the production of the chemical BH4, a precursor of serotonin. Those without the protective variety of BH4 feel a great deal of pain, but about 15 per cent of the population carry the ‘bulletproof’ version of the GCH1 gene, which leaves them remarkably impervious to pain. At least one study has shown that patients with this pain-busting biology recover much more successfully from spine surgery than their ultrasensitive brethren.

An excellent article on Mosaic, a digital magazine produced by the Wellcome Trust in the UK, quotes professor Irene Tracey, head of the Nuffield Department of Clinical Neurosciences at the University of Oxford. The most significant change in evaluating chronic pain, observes Tracey, is the understanding that chronic pain is a different animal from nociceptive pain. ‘We always thought of it as acute pain that just goes on and on – and if chronic pain is just a continuation of acute pain, let’s fix the thing that caused the acute, and the chronic should go away,’ she said. ‘That has spectacularly failed. Now we think of chronic pain as a shift to another place, with different mechanisms, such as changes in genetic expression, chemical release, neurophysiology and wiring. We’ve got all these completely new ways of thinking about chronic pain. That’s the paradigm shift in the pain field.’

One explanation for the phenomenon of central sensitisation is that when an injury has afflicted some aspect of the peripheral nervous system, neurons in the central nervous system can also become agitated. This bumped-up signal-to-noise ratio can result in increased activation of calcium channels, the molecular pores that govern the flow of calcium ions across the cell membrane. This boosts the number of chemical messages travelling between nerve cells. Certain vulnerable neurons can also get a dose of NMDA (N-methyl-D-aspartate), opening more calcium channels, and sending even more messages whirling around the CNS. One class of drug now being evaluated in laboratory studies, an NMDA antagonist, could one day be useful in treating central sensitisation by blocking the excess ‘chatter’ that flies between overwhelmed neurons.

A final hypothesis suggests that central sensitisation reflects a type of neurobiological learning disorder: essentially, the brain is misinterpreting pain messages, which are never dismissed, but continue to travel endlessly from PNS to CNS, leaving the brain unable to set a new course. Some researchers have remarked that central sensitisation can be understood as a form of classical conditioning: just as the Russian physiologist Ivan Pavlov conditioned his dogs to salivate when a bell was paired with food, and then to salivate when the bell alone was heard, the body that has learned to experience pain in response to insult or injury continues to experience it in response to inconsequential stimuli.

Recent research has revealed what many patients know all too well: chronic back pain is often accompanied by other types of pain, including headaches, other musculoskeletal disorders, temporomandibular joint disorders, fibromyalgia, irritable bowel syndrome and chronic fatigue syndrome. People who develop central sensitisation can also find light, noise or smells unusually disturbing, or display hypervigilance. Anxiety, stress and depression are problems for an estimated 30 to 45 per cent of patients with chronic back pain, and an even higher percentage of back-pain patients who experienced early childhood adversity.

If you wish to get past the terror, you are going to have to follow pain deep into its lair

One would think that opioid analgesics would be helpful in calming an agitated and dysregulated nervous system, but this premise has been debunked. In fact, to the contrary, long-term use of opioid analgesics, especially high-dose extended release drugs such as OxyContin and methadone, have been associated with the development of a particular type of central sensitisation called ‘opioid-induced hyperalgesia’, resulting in abnormal sensitivity to pain.

Despite Apkarian and Woolf’s decades-long efforts, it is likely to be years before physicians can use targeted compounds to treat the neurobiological mechanisms that lead to central sensitisation. ‘A huge clinical challenge remains to identify these mechanisms from the individual pain patient phenotype and to then target the molecular mechanism with a specific treatment,’ Woolf says.

It’s easy to see why progress has been slow: to make money in medicine, the common wisdom holds that it’s necessary to incise, prescribe, implant or inject. Pain science, dealing with complex neurological function, doesn’t readily allow for those kinds of interventions.

Historically, NIH has dedicated only 1 per cent of its research budget to pain science-related investigations. And until recently, painkiller manufacturers saw no reason to invest in very speculative research, thus unwisely diluting their shareholders’ earnings. But with opioid treatment on the skids, and profits sinking, finding new therapeutic targets is suddenly very attractive.

Drug targets are still on the horizon. But many pain psychologists and rehab specialists believe that central sensitisation can be successfully treated with a combination of cognitive behavioural therapy (CBT) and graded, non-pain-contingent exercise. The good news is that several labs have now shown that, after a patient’s pain has been properly treated, three months of CBT can substantially reverse pain-induced changes in grey matter.

While researching my book Crooked: Outwitting the Back Pain Industry and Getting on the Road to Recovery (2017), I listened to hundreds of back-pain patients explain their chronic pain: they spoke of degenerative disc disease, herniated discs, pinched nerves, sciatica, spondylolisthesis, scoliosis and spinal stenosis. But I never encountered a single patient who described his or her struggle in terms of central sensitisation, or had heard of terms commonly used in behavioural psychology, such as ‘guarding’ (walking with an attention-getting limp) or ‘fear-avoidant behaviour’ (eschewing activities that might tax back muscles, thereby making them progressively weaker) or ‘pain catastrophising’ (ruminating over how severe the condition is likely to become, ruining any hope of a productive future).

As a practice, CBT provides graded exposure to feared stimuli. That means if you’re afraid of spiders or flying, you dull your terror by facing down the arachnid or the take-off and landing, safely and repetitively. With back-pain patients, the fear of pain might seem life-threatening. This idea is often implanted by healthcare practitioners who caution patients, unnecessarily, to ‘be careful,’ and to ‘spare their backs’. The job is to let patients know that, in the case of chronic back pain, hurt does not typically mean harm; that in fact, if you wish to get past the terror, you are going to have to follow pain deep into its lair.

Depending on the kind of chronic-pain rehab programme you enter, you might find yourself hauling around a plastic milk-crate filled with steel bricks, or engaging in water aerobics, or doing reps with free weights, or pushing an industrial sled (a heavy aluminium rectangle equipped with sliders on its base and sturdy handles on either end) or playing a game of beach volleyball, all under the close but generally unsympathetic supervision of someone who understands how bodies work and has seen it all before. The grimacing, the groaning, the odd body mechanics – all of them must go. Strengthening must follow. And when it does, the patient is rewarded with a sense of mastery over his or her own body, and no longer feels like a helpless victim.

People Mistakenly Think These Animals Feel No Pain or Emotions


common fish owner mistakes

Story at-a-glance

  • Fish are still widely regarded as ornamental and throwaway pets, but they are deserving of ethical treatment, veterinary care, enrichment and stimulation
  • There is a large gap between people’s perception of fish intelligence and the scientific reality, which is that fish have perception and cognitive abilities that rival, or exceed, that of other vertebrates
  • Common fish owner mistakes include overfeeding, overcrowding and mismatching fish species

Aquatic animals, including fish, are the most popular pets in the U.S. if you calculate popularity based on the number of owned pets.1 Sadly, many spend their days silently circling mundane fish bowls that are undersized or improperly prepared.

Many also start out unhealthy and disease-prone because of overbreeding and selective breeding to create a certain aesthetic feature like long fins, bubble eyes or a round belly.2

Despite advances in many areas of animal welfare, fish are still widely regarded as ornamental and throwaway pets. But these creatures are far more complex than many people realize and are deserving not only of basic ethical treatment but also far more, including veterinary care, enrichment and stimulation.

Would You Seek Veterinary Care for Your Fish?

A commentary published in Clinician’s Brief brought up some important points about the ramifications of viewing ornamental fish as just that — mere “decorations” for your office or child’s bedroom.3 For starters, many fish owners do not seek veterinary care for their fish because they don’t know it’s available — or that they should.

In fact, when asked about fish conditions, some veterinarians, lacking in appropriate treatment options or know-how, may refer clients to pet stores, who may in turn give out inaccurate information in response.

As a result, “concern for the welfare of pet fish may not extend past their perceived economic value.” As noted by Clinician’s Brief, more research is needed into ornamental fish and there should be more education available for retailers, hobbyists and even veterinarians in the realm of fish medicine. In addition:4

“Pharmaceutical companies have not kept pace with advances for fish as for other companion species, and a proliferation of inexpensive over-the-counter treatments, how-to articles and general misinformation leads to sick fish often being treated (or mistreated) with chemicals and even invasive home surgeries without a proper diagnosis.

Protracted and unnecessary suffering often results. Prejudices and misconceptions may suggest that fish-welfare issues are grossly underreported.”

Why It’s Important to Consider the Needs of Your Fish

Many are surprised to learn that fish have “needs” beyond water and daily food, and that’s precisely the point. The fact that fish can feel pain, show emotions and “talk” using a wide range of communicatory methods is not widely known, though it should be — especially by those who choose to have fish as pets.

As reported in the journal Animal Cognition, there is a large gap between people’s perception of fish intelligence and the scientific reality, which is that fish have perception and cognitive abilities that rival, or exceed, that of other vertebrates.5 Fish, for instance:6

  • Perform multiple complex tasks simultaneously (a trait that was once believed to exist only among humans)
  • Recall the location of objects using “feature cues” (which humans figure out how to do around age 6)
  • Have excellent long-term memories
  • “Cooperate with one another and show signs of Machiavellian intelligence such as cooperation and reconciliation”
  • Use tools

Culum Brown, Ph.D., associate professor at Macquarie University in Australia, who authored the Animal Cognition review, said in an interview with the Huffington Post:7

The big issue here is that people don’t treat fish the same way as they do other animals. It’s complicated, but it boils down to the fact that most people just don’t understand them and can’t relate to them. If you don’t have that connection, you are less likely to feel any empathy …

Fish are similar to humans in so many ways. This is the message we need to get across … My mission in life is to make people think about fish as something other than food.”

10 Common Fish Owner Mistakes

Many fish owners do strive to take good care of their pets, but misinformation may lead to sick or stressed-out animals. Here are some top mistakes, compiled by PetMD, that many fish owners make:8

1.Overfeeding

This may lead to excess waste, which in turn can interfere with water quality. A general guide is to feed fish the amount of food they consume in three minutes. Remove any excess with a net.

Scavengers like crabs can also help to clean up uneaten food. Be aware that not all fish feed the same way; some fish do better with two smaller feedings a day while others like to nibble plants.

Some fish scavenge for their food while others hunt, for instance. Consider the use of puzzle feeders and sinking feeders, or live prey, if applicable to your fish species.

2.New Tank Syndrome

Before adding fish to a new tank, bacteria must build up to process the nitrogen compounds in fish waste. Certain additives can be found to assist in this process, as can adding sand or gravel from an established healthy tank.

You should have water samples tested by an aquarium store to be sure you’ve got the right balance.

3.Mismatching Fish Species

Fish have different personalities and not all get along well together. It’s very important to be aware of whether the fish species you choose are known for being aggressive.

Aggressive fish can bully or fight more passive fish, even to the point of death or starvation (in which a fish is too frightened to come out of hiding to eat).

4.Overcrowding

In general, fish need 1 gallon of water per inch of fish. Aggressive fish need double that amount, and be sure to take into account rocks and decorations, which, though important, take up valuable swimming space.

5.Vacation Care

If you leave for vacation, your fish need to be cared for while you’re away, just like other pets. In addition to carefully letting a pet sitter know how much food to feed, be sure to prepare the sitter for what to do in the event of tank issues and how to check water temperature.

6.Temperature Control

You’ll need to install a thermometer to monitor water temperature, which should generally be between 68 and 76 degrees F, depending on the species of fish. Be aware that drafts and sun can change the temperature of the tank, and smaller tanks are more vulnerable to rapid temperature shifts than larger tanks. Be vigilant in monitoring water temperature.

7.Overlooking Disease

If your fish is showing signs of disease, via appearance or changes in habits, transfer him to a quarantine tank and seek veterinary care.

Oftentimes, a new fish added to the tank may be a source of disease. Before new animals are added to an existing tank, a quarantine period of 21 to 28 days is recommended. To help relieve stress during the quarantine, a hiding spot (such as PVC pipe or stacked rocks) should be provided and water quality and temperature should be maintained.

8.Neglect

Successfully caring for an aquarium takes daily care and regular maintenance. Make a point to mark maintenance needs on your calendar or use tools like automatic feeders or water-quality probes to help you stay on track. You can even track the water quality of your aquarium right on your computer via wireless monitoring devices.

9.Being Impatient

Building a healthy and beautiful aquarium doesn’t happen overnight. It takes time to research and build the correct mix of fish, plants and ornamental objects, as well as learn how to monitor water quality and conduct maintenance. Acting impulsively may lead to choices that could harm your fish.

10.Using Tap Water

The water from your tap is treated with chlorine that can harm fish. Water for your tank must be treated with chlorine-removing tablets. Also be sure to avoid using soap in your aquarium. Most cleansing can be done with hot water and a small amount of bleach that’s thoroughly rinsed off.

Finally, provide non-toxic items for your fish to explore — plants, rocks, structures, ceramic objects and more — and change them regularly to provide new stimulation. Then, enjoy getting to know each of your fish. Many enjoy interacting with their owners and can learn to recognize you and even perform tricks.

If you decide ornamental fish sound like pets you may be interested in keeping make sure to only purchase captive-bred fish; leave wild fish in the ocean, where they belong.

Source:mercola.com

Why Some People Don’t Feel Pain.


Scientists are learning more and more about people who do not feel pain. Currently, they have identified several genetic indicators for people who do not experience any sensations typically associated with physical pain. One such mutation occurs in the PRDM12 gene. It leads to a malformation of nerve cells, which are the transmitters of physical sensations to the brain. A different genetic mutation, located on the SCN9A gene, inhibits the proper formation of the sodium channels used by neurons to communicate and conduct pain.

Interestingly, scientists have found that, just because there’s no pain sensation, the body may have a way of reacting regardless. In one study published in Nature Communications, scientists used mice with these genetic mutations and exposed them to extreme hot and cold conditions. The mice showed no physical response, but scientists were able to identify high levels of enkephalins, a natural opioid produced by the body. The researchers posited that if people with such genetic mutations did not experience a release of opioids, maybe they would feel pain. The team administered naloxone, a medication typically used to treat opioid overdose, to a woman with the PRDM12 genetic condition. The subject did indeed report a feeling of pain-the first time she had ever felt such a sensation.

Read More:

Transcriptional regulator PRDM12 is essential for human pain perception (Nature)
“Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal”
Why do we experience physical pain? (Gizmodo)
“There’s no doubt about it: Pain sucks. We all hate it – and some people go to immense lengths to try and get rid of chronic pain. And yet, it’s a constant part of human experience. But why do people feel physical pain? How does it even work? And does everybody feel pain the same way?”

Ketamine for Depression Treatment


The experimental drug esketamine (also known as ketamine) has been placed on the fast track for U.S. Food and Drug Administration approval for treating major depression, according to Janssen Pharmaceutical.

Ketamine — perhaps best known as a street drug — is listed by the World Health Organization as an important anesthetic and has been used off-label for pain, anxiety, depression and post-traumatic stress disorder, CNN reported.

In 1970, the drug received FDA approval for use in people and was used on American soldiers in Vietnam as an analgesic and sedative. However, doctors became reluctant to use it because it caused minor hallucinogenic side effects.

If the new use gets the go-ahead from the FDA, it would be the first new treatment for major depression approved in about half a century, according to CNN.

Try a Massage to Reduce Your Pain


Pain is the reason behind about 80 percent of physician visits in the U.S. Not only does pain, especially persistent and chronic pain, take a physical toll but it also interferes with patients’ social, mental, emotional and spiritual sides.

Benefit of Massage Therapy

Story at-a-glance

  • Massage therapy relieves pain better than getting no treatment at all
  • When compared to other pain treatments like acupuncture and physical therapy, massage therapy still proved beneficial and had few side effects
  • In addition to relieving pain, massage therapy also improved anxiety and health-related quality of life

A person struggling with pain may find it difficult to carry out daily activities and engage in social activities. Psychological health and quality of life also often suffer. Unfortunately, medication is the go-to pain treatment in the U.S.

As a result, we now have an epidemic of opioid overuse and misuse, with people quickly becoming hooked on the drugs, often after taking them for chronic pain, like back pain. Deaths from overdosing on opioid painkillers now far surpass those from illicit street drugs.

The point is, if you’re struggling with chronic pain, it makes sense to exhaust all other options before moving on to prescription drugs. And one option that’s definitely worth trying due to its effectiveness and excellent safety record is massage.

Massage Helps Relieve Pain

A systematic review and meta-analysis, published in the journal Pain Medicine, included 60 high-quality and seven low-quality studies that looked into the use of massage for various types of pain, including muscle and bone pain, headaches, deep internal pain, fibromyalgia pain and spinal cord pain.1

The review revealed that massage therapy relieves pain better than getting no treatment at all. When compared to other pain treatments like acupuncture and physical therapy, massage therapy still proved beneficial and had few side effects.

In addition to relieving pain, massage therapy also improved anxiety and health-related quality of life. It’s unknown how massage, which involves the manipulation of soft tissue, alleviates pain, but it’s likely that multiple mechanisms are at play. These include factors that are:

  • Biomechanical
  • Physiological
  • Neurological
  • Psychological

Massage is far from a new form of pain relief and was described by Hippocrates as an effective therapy for sports or war injuries.2 As noted in Pain Medicine in a call to action for massage therapy for pain, this age-old practice is desperately needed in our “pill for every ill” mentality:3

“ … [T]he ‘pill for every ill’ mentality of many Americans, including those investors in pharmaceutical stocks, has generated significant health and social issues for this country.

This issue is exemplified by the major public health crisis of chronic pain in America and has been highlighted recently by its most prominent symptom — opioid misuse and addiction.”

Massage Might Work By Reducing Local Inflammation and Providing Stress Relief

The benefits of massage therapy for pain relief are established enough that it’s commonly used during physical therapy and rehabilitation from injury. In one study, researchers took muscle biopsies from study participants who had received massage therapy or no treatment for exercise-induced muscle damage.

It turned out that massage therapy reduced inflammation and promoted mitochondrial biogenesis in the skeletal muscle.4

In addition, a review published in the journal Complementary Therapies in Clinical Practice revealed that moderate pressure massage reduced depression, anxiety, heart rate and cortisol levels and altered EEG patterns to indicate a relaxation response.5 According to the study:

Moderate pressure massage has also led to increased vagal activity and decreased cortisol levels.

Functional magnetic resonance imaging data have suggested that moderate pressure massage was represented in several brain regions including the amygdala, the hypothalamus and the anterior cingulate cortex, all areas involved in stress and emotion regulation.”

Frequency and Dosage Matter for Certain Types of Pain

Some people experience immense relief from massage, anecdotally speaking, while others do not. The difference might come down to the dose. Researchers from the Group Health Research Institute in Seattle looked into the optimal massage dose for people with chronic neck pain.

Study participants received 30-minute massages two or three times a week, or 60-minute massages one, two or three times weekly (with a comparison group that received no massages).6

Compared with the no-massage group, those who got massages three times a week were nearly five times more likely to report a significant improvement in function and more than twice as likely to report a significant decrease in pain.

The best pain-relief results were obtained by those who received 60-minute massages two or three times a week. It appears that longer massages worked best for neck pain, as did multiple treatments a week, especially during the first four weeks.

If you try massage therapy and find you’re not getting relief, you therefore may benefit from altering the dose and frequency. There are other variables that impact massage effectiveness as well, such as the technique used and the skill level of the massage therapist.

When choosing a massage therapist, ask your holistic health care provider to recommend a certified massage therapist who is experienced in the type of pain relief you’re seeking.

More Than 80 Percent of Hospitals Now Offer Massage Therapy

A survey by the American Hospital Association (AHA) found that 82 percent of hospitals offering complementary and alternative therapies include massage therapy as an option.

Among them, more than 70 percent offer massage therapy for pain management and relief.7 The practice has a positive reputation among those who have tried it. According to the American Massage Therapy Association (AMTA):8

“In a recent consumer survey commissioned by AMTA, 91 percent of respondents agreed that massage can be effective in reducing pain, and nearly half of those polled (47 percent) have had a massage specifically for the purpose of relieving pain.”

AMTA notes that massage has a beneficial impact on pain just by the virtue of human touch, and may be especially effective for relieving low back pain, migraine pain and pain from carpal tunnel syndrome. AMTA points out several proven benefits of massage for pain relief:

  • Massage therapy may alleviate the perception of pain and anxiety in cancer patients
  • Massage therapy may reduce post-traumatic headaches better than cold packs
  • Massage received in a hospital after heart bypass surgery reduces pain and muscle spasms
  • Massage stimulates your brain to produce endorphins. According to AMTA, “Massage therapy benefits that are applicable to sufferers of any kind of pain include the stimulation of endorphin production in the brain and the encouragement of patient confidence in improving their condition.”

Stronger massage stimulates blood circulation to improve the supply of oxygen and nutrients to body tissues and helps your lymphatic system to flush away waste products. It also eases tense and knotted muscles and stiff joints, improving mobility, and flexibility. Massage is said to increase activity of the vagus nerve, 1 of 10 cranial nerves, that affects the secretion of food-absorption hormones, heart rate, and respiration.

19 Non-Drug Solutions for Pain Relief

Massage is only one non-drug option for pain relief. Below are 19 more that may be very effective in helping you become pain-free. I do understand there are times when pain is so severe that a prescription drug may be necessary. Even in those instances, the options that follow may be used in addition to such drugs, and may allow you to at least reduce your dosage. If you are in pain that is bearable, please try these first, before resorting to prescription painkillers of any kind.

1.Eliminate or radically reduce most grains and sugars from your diet: Avoiding grains and sugars will lower your insulin and leptin levels and decrease insulin and leptin resistance, which is one of the most important reasons why inflammatory prostaglandins are produced. That is why stopping sugar and sweets is so important to controlling your pain and other types of chronic illnesses.

2.Take a high-quality, animal-based omega-3 fat: My personal favorite is krill oil. Omega-3 fats are precursors to mediators of inflammation called prostaglandins. (In fact, that is how anti-inflammatory painkillers work, by manipulating prostaglandins.)

3.Optimize your production of vitamin D by getting regular, appropriate sun exposure, which will work through a variety of different mechanisms to reduce your pain.

4.Emotional Freedom Techniques (EFT) is a drug-free approach for pain management of all kinds. EFT borrows from the principles of acupuncture in that it helps you balance out your subtle energy system. It helps resolve underlying, often subconscious, and negative emotions that may be exacerbating your physical pain.

By stimulating (tapping) well-established acupuncture points with your fingertips, you rebalance your energy system, which tends to dissipate pain.

5.K-Laser Class 4 Laser Therapy: If you suffer pain from an injury, arthritis, or other inflammation-based pain, I’d strongly encourage you to try out K-Laser therapy. It can be an excellent choice for many painful conditions, including acute injuries.

By addressing the underlying cause of the pain, you will no longer need to rely on painkillers. K-Laser is a class 4 infrared laser therapy treatment that helps reduce pain, reduce inflammation, and enhance tissue healing — both in hard and soft tissues, including muscles, ligaments, or even bones.

The infrared wavelengths used in the K-Laser allow for targeting specific areas of your body and can penetrate deeply into the body to reach areas such as your spine and hip.

6.Chiropractic: Many studies have confirmed that chiropractic management is much safer and less expensive than allopathic medical treatments, especially when used for pain such as low back pain.

Qualified chiropractic, osteopathic, and naturopathic physicians are reliable, as they have received extensive training in the management of musculoskeletal disorders during their course of graduate healthcare training, which lasts between four to six years. These health experts have comprehensive training in musculoskeletal management.

7.Acupuncture can also effectively treat many kinds of pain. Research has discovered a “clear and robust” effect ofacupuncture in the treatment of back, neck and shoulder pain, osteoarthritis, and headaches.

8. Physical therapy has been shown to be as good as surgery for painful conditions such as torn cartilage and arthritis.

9.Astaxanthin is one of the most effective fat-soluble antioxidants known. It has very potent anti-inflammatory properties and in many cases works far more effectively than anti-inflammatory drugs. Higher doses are typically required and you may need 8 milligrams (mg) or more per day to achieve this benefit.

10.Ginger: This herb has potent anti-inflammatory activity and offers pain relief and stomach-settling properties. Fresh ginger works well steeped in boiling water as a tea or grated into vegetable juice.

11.Curcumin: In a study of osteoarthritis patients, those who added 200 mg of curcumin a day to their treatment plan had reduced pain and increased mobility. A past study also found that a turmeric extract composed of curcuminoids blocked inflammatory pathways, effectively preventing the overproduction of a protein that triggers swelling and pain.9

12.Boswellia: Also known as boswellin or “Indian frankincense,” this herb contains specific active anti-inflammatory ingredients. This is one of my personal favorites as I have seen it work well with many rheumatoid arthritis patients.

13.Bromelain: This enzyme, found in pineapples, is a natural anti-inflammatory. It can be taken in supplement form but eating fresh pineapple, including some of the bromelain-rich stem, may also be helpful.

14.Cetyl Myristoleate (CMO): This oil, found in fish and dairy butter, acts as a “joint lubricant” and an anti-inflammatory. I have used this for myself to relieve ganglion cysts and a mildly annoying carpal tunnel syndrome that pops up when I type too much on non-ergonomic keyboards. I used a topical preparation for this.

15.Evening Primrose, Black Currant and Borage Oils: These contain the essential fatty acid gamma-linolenic acid (GLA), which is useful for treating arthritic pain.

16.Cayenne Cream: Also called capsaicin cream, this spice comes from dried hot peppers. It alleviates pain by depleting the body’s supply of substance P, a chemical component of nerve cells that transmits pain signals to your brain.

17.Medical cannabis has a long history as a natural analgesic. Its medicinal qualities are due to high amounts (up to 20 percent) of cannabidiol (CBD), medicinal terpenes and flavonoids.

Varieties of cannabis exist that are very low in tetrahydrocannabinol (THC) — the psychoactive component of marijuana that makes you feel “stoned” — and high in medicinal CBD. The Journal of Pain (JOP),10 a publication by the American Pain Society (APS), has a long list of studies on the pain-relieving effects of cannabis.

18.Methods such as yoga, Foundation Training, acupuncture, exercise, meditation, hot and cold packs, and mind-body techniques can also result in astonishing pain relief without any drugs.

19.Grounding, or walking barefoot on the earth, may also provide a certain measure of pain relief by combating inflammation.

Pain, physical function improves after bariatric surgery for severe obesity


A large proportion of patients with severe obesity who underwent either Roux-en-Y gastric bypass or laparoscopic adjustable gastric banding experienced improvements in pain, physical function and walk time during the first 3 years after surgery, according to data published in JAMA.

“Although evidence of improvements in pain and physical function following bariatric surgery is increasing, the variability and durability of improvement have not been well described — with most studies limited by small sample size and follow-up of 1 year or less by the study of obsolete surgical procedures,” Wendy C. King, PhD, of University of Pittsburgh, and colleagues wrote.

To assess changes in pain and physical function over 3 years after bariatric surgery, and to identify factors linked to improvement, King and colleagues conducted the Longitudinal Assessment of Bariatric Surgery-2 study. This was an observational cohort study evaluating 2,458 adults who underwent bariatric surgery between March 2006 and April 2009 at 10 U.S. hospitals.

Patients were evaluated before surgery and annually for 3 years after surgery, with clinically meaningful improvements in bodily pain, physical function and walk time serving as the primary endpoints. Improvement in the Western Ontario McMaster Osteoarthritis Index served as the key secondary endpoint.

Of the 2,221 patients who completed baseline and follow-up evaluations, 78.5% were women, median age was 47 years (range, 37–55 years), median BMI was 45.9, 70.4% underwent Roux-en-Y gastric bypass, 25% underwent laparoscopic adjustable gastric banding, and less than 5% underwent another procedure.

At 1 year, 57.6% (95% CI, 55.3-59.9) experienced improvements in pain, 76.5% (95% CI, 74.6-78.5) experienced improvements in physical function and 59.5% (95% CI, 56.4-62.7) experienced improvements in walk time. Of the 633 patients with baseline severe knee pain or disability, 77.1% (95% CI, 73.5-80.7) experienced joint-specific improvements, and of the 500 patients with baseline severe hip pain or disability, 79.2% (95% CI, 75.3-83.1) experienced improvements. Most patients with a mobility deficit at baseline experienced remission at year 1 (55.6%; 95% CI, 52-59.3).

Between years 1 and 3, improvement rates for pain dropped to 48.6% (95% CI, 46-51.1) and improvement rates for physical function dropped to 70.2% (95% CI, 67.8-72.5), whereas improvement rates for walk time, knee pain and function, and hip pain and function did not decrease (all P .05)

Factors associated with improvements included younger age, male sex, higher income, lower BMI, fewer depressive symptoms before surgery, no diabetes and no venous edema with ulcerations after surgery, and presurgery-to-postsurgery reductions in weight and depressive symptoms.

“The findings from this study reinforce shorter-term results from studies that have reported significant improvements in SF-36 bodily pain and physical function scores, WOMAC scores, walking capacity … resting heart rate, or other measures of pain and function in the first 3 to 12 months following RYGB or LAGB,” the researchers concluded. – by Adam Leitenberger

Palliative care prescribing: pain


NICE guidelines

In 2012 NICE published guidelines on the use of opioids in palliative care. Selected points are listed below. Please see the link for more details.

Starting treatment
•when starting treatment, offer patients with advanced and progressive disease regular oral modified-release (MR) or oral immediate-release morphine (depending on patient preference), with oral immediate-release morphine for breakthrough pain
•if no comorbidities use 20-30mg of MR a day with 5mg morphine for breakthrough pain. For example, 15mg modified-release morphine tablets twice a day with 5mg of oral morphine solution as required
•oral modified-release morphine should be used in preference to transdermal patches
•laxatives should be prescribed for all patients initiating strong opioids
•patients should be advised that nausea is often transient. If it persists then an antiemetic should be offered
•drowsiness is usually transient – if it does not settle then adjustment of the dose should be considered

SIGN guidelines

SIGN issued guidance on the control of pain in adults with cancer in 2008. Selected points
•the breakthrough dose of morphine is one-sixth the daily dose of morphine
•all patients who receive opioids should be prescribed a laxative
•opioids should be used with caution in patients with chronic kidney disease. Alfentanil, buprenorphine and fentanyl are preferred
•metastatic bone pain may respond to NSAIDs, bisphosphonates or radiotherapy

Other points

When increasing the dose of opioids the next dose should be increased by 30-50%.

Opioid side-effects

Usually transient

Usually persistent

Nausea
Drowsiness Constipation

Conversion between opioids

From

To

Conversion factor

Oral codeine Oral morphine Divide by 10
Oral tramadol Oral morphine Divide by 10*

Oxycodone generally causes less sedation, vomiting and pruritis than morphine but more constipation.

From

To

Conversion factor

Oral morphine Oral oxycodone Divide by 1.5-2**

The current BNF gives the following conversion factors for transdermal perparations
•a transdermal fentanyl 12 microgram patch equates to approximately 30 mg oral morphine daily
•a transdermal buprenorphine 10 microgram patch equates to approximately 24 mg oral morphine daily.

From

To

Conversion factor

Oral morphine Subcutaneous diamorphine Divide by 3
Oral oxycodone Subcutaneous diamorphine Divide by 1.5

*this has previously been stated as 5 but the current version of the BNF states a conversion of 10

**historically a conversion factor of 2 has been used (i.e. oral oxycodone is twice as strong as oral morphine). The current BNF however uses a conversion rate of 1.5

Palliative care prescribing: pain

NICE guidelines

In 2012 NICE published guidelines on the use of opioids in palliative care. Selected points are listed below. Please see the link for more details.

Starting treatment
•when starting treatment, offer patients with advanced and progressive disease regular oral modified-release (MR) or oral immediate-release morphine (depending on patient preference), with oral immediate-release morphine for breakthrough pain
•if no comorbidities use 20-30mg of MR a day with 5mg morphine for breakthrough pain. For example, 15mg modified-release morphine tablets twice a day with 5mg of oral morphine solution as required
•oral modified-release morphine should be used in preference to transdermal patches
•laxatives should be prescribed for all patients initiating strong opioids
•patients should be advised that nausea is often transient. If it persists then an antiemetic should be offered
•drowsiness is usually transient – if it does not settle then adjustment of the dose should be considered

SIGN guidelines

SIGN issued guidance on the control of pain in adults with cancer in 2008. Selected points
•the breakthrough dose of morphine is one-sixth the daily dose of morphine
•all patients who receive opioids should be prescribed a laxative
•opioids should be used with caution in patients with chronic kidney disease. Alfentanil, buprenorphine and fentanyl are preferred
•metastatic bone pain may respond to NSAIDs, bisphosphonates or radiotherapy

Other points

When increasing the dose of opioids the next dose should be increased by 30-50%.

Opioid side-effects

Usually transient

Usually persistent

Nausea
Drowsiness Constipation

Conversion between opioids

From

To

Conversion factor

Oral codeine Oral morphine Divide by 10
Oral tramadol Oral morphine Divide by 10*

Oxycodone generally causes less sedation, vomiting and pruritis than morphine but more constipation.

From

To

Conversion factor

Oral morphine Oral oxycodone Divide by 1.5-2**

The current BNF gives the following conversion factors for transdermal perparations
•a transdermal fentanyl 12 microgram patch equates to approximately 30 mg oral morphine daily
•a transdermal buprenorphine 10 microgram patch equates to approximately 24 mg oral morphine daily.

From

To

Conversion factor

Oral morphine Subcutaneous diamorphine Divide by 3
Oral oxycodone Subcutaneous diamorphine Divide by 1.5

*this has previously been stated as 5 but the current version of the BNF states a conversion of 10

**historically a conversion factor of 2 has been used (i.e. oral oxycodone is twice as strong as oral morphine). The current BNF however uses a conversion rate of 1.5

Palliative care prescribing: pain

NICE guidelines

In 2012 NICE published guidelines on the use of opioids in palliative care. Selected points are listed below. Please see the link for more details.

Starting treatment
•when starting treatment, offer patients with advanced and progressive disease regular oral modified-release (MR) or oral immediate-release morphine (depending on patient preference), with oral immediate-release morphine for breakthrough pain
•if no comorbidities use 20-30mg of MR a day with 5mg morphine for breakthrough pain. For example, 15mg modified-release morphine tablets twice a day with 5mg of oral morphine solution as required
•oral modified-release morphine should be used in preference to transdermal patches
•laxatives should be prescribed for all patients initiating strong opioids
•patients should be advised that nausea is often transient. If it persists then an antiemetic should be offered
•drowsiness is usually transient – if it does not settle then adjustment of the dose should be considered

SIGN guidelines

SIGN issued guidance on the control of pain in adults with cancer in 2008. Selected points
•the breakthrough dose of morphine is one-sixth the daily dose of morphine
•all patients who receive opioids should be prescribed a laxative
•opioids should be used with caution in patients with chronic kidney disease. Alfentanil, buprenorphine and fentanyl are preferred
•metastatic bone pain may respond to NSAIDs, bisphosphonates or radiotherapy

Other points

When increasing the dose of opioids the next dose should be increased by 30-50%.

Opioid side-effects

Usually transient

Usually persistent

Nausea
Drowsiness Constipation

Conversion between opioids

From

To

Conversion factor

Oral codeine Oral morphine Divide by 10
Oral tramadol Oral morphine Divide by 10*

Oxycodone generally causes less sedation, vomiting and pruritis than morphine but more constipation.

From

To

Conversion factor

Oral morphine Oral oxycodone Divide by 1.5-2**

The current BNF gives the following conversion factors for transdermal perparations
•a transdermal fentanyl 12 microgram patch equates to approximately 30 mg oral morphine daily
•a transdermal buprenorphine 10 microgram patch equates to approximately 24 mg oral morphine daily.

From

To

Conversion factor

Oral morphine Subcutaneous diamorphine Divide by 3
Oral oxycodone Subcutaneous diamorphine Divide by 1.5

*this has previously been stated as 5 but the current version of the BNF states a conversion of 10

**historically a conversion factor of 2 has been used (i.e. oral oxycodone is twice as strong as oral morphine). The current BNF however uses a conversion rate of 1.5

Palliative care prescribing: pain

NICE guidelines

In 2012 NICE published guidelines on the use of opioids in palliative care. Selected points are listed below. Please see the link for more details.

Starting treatment
•when starting treatment, offer patients with advanced and progressive disease regular oral modified-release (MR) or oral immediate-release morphine (depending on patient preference), with oral immediate-release morphine for breakthrough pain
•if no comorbidities use 20-30mg of MR a day with 5mg morphine for breakthrough pain. For example, 15mg modified-release morphine tablets twice a day with 5mg of oral morphine solution as required
•oral modified-release morphine should be used in preference to transdermal patches
•laxatives should be prescribed for all patients initiating strong opioids
•patients should be advised that nausea is often transient. If it persists then an antiemetic should be offered
•drowsiness is usually transient – if it does not settle then adjustment of the dose should be considered

SIGN guidelines

SIGN issued guidance on the control of pain in adults with cancer in 2008. Selected points
•the breakthrough dose of morphine is one-sixth the daily dose of morphine
•all patients who receive opioids should be prescribed a laxative
•opioids should be used with caution in patients with chronic kidney disease. Alfentanil, buprenorphine and fentanyl are preferred
•metastatic bone pain may respond to NSAIDs, bisphosphonates or radiotherapy

Other points

When increasing the dose of opioids the next dose should be increased by 30-50%.

Opioid side-effects

Usually transient

Usually persistent

Nausea
Drowsiness Constipation

Conversion between opioids

From

To

Conversion factor

Oral codeine Oral morphine Divide by 10
Oral tramadol Oral morphine Divide by 10*

Oxycodone generally causes less sedation, vomiting and pruritis than morphine but more constipation.

From

To

Conversion factor

Oral morphine Oral oxycodone Divide by 1.5-2**

The current BNF gives the following conversion factors for transdermal perparations
•a transdermal fentanyl 12 microgram patch equates to approximately 30 mg oral morphine daily
•a transdermal buprenorphine 10 microgram patch equates to approximately 24 mg oral morphine daily.

From

To

Conversion factor

Oral morphine Subcutaneous diamorphine Divide by 3
Oral oxycodone Subcutaneous diamorphine Divide by 1.5

*this has previously been stated as 5 but the current version of the BNF states a conversion of 10

**historically a conversion factor of 2 has been used (i.e. oral oxycodone is twice as strong as oral morphine). The current BNF however uses a conversion rate of 1.5

Palliative care prescribing: pain

NICE guidelines

In 2012 NICE published guidelines on the use of opioids in palliative care. Selected points are listed below. Please see the link for more details.

Starting treatment
•when starting treatment, offer patients with advanced and progressive disease regular oral modified-release (MR) or oral immediate-release morphine (depending on patient preference), with oral immediate-release morphine for breakthrough pain
•if no comorbidities use 20-30mg of MR a day with 5mg morphine for breakthrough pain. For example, 15mg modified-release morphine tablets twice a day with 5mg of oral morphine solution as required
•oral modified-release morphine should be used in preference to transdermal patches
•laxatives should be prescribed for all patients initiating strong opioids
•patients should be advised that nausea is often transient. If it persists then an antiemetic should be offered
•drowsiness is usually transient – if it does not settle then adjustment of the dose should be considered

SIGN guidelines

SIGN issued guidance on the control of pain in adults with cancer in 2008. Selected points
•the breakthrough dose of morphine is one-sixth the daily dose of morphine
•all patients who receive opioids should be prescribed a laxative
•opioids should be used with caution in patients with chronic kidney disease. Alfentanil, buprenorphine and fentanyl are preferred
•metastatic bone pain may respond to NSAIDs, bisphosphonates or radiotherapy

Other points

When increasing the dose of opioids the next dose should be increased by 30-50%.

Opioid side-effects

Usually transient

Usually persistent

Nausea
Drowsiness Constipation

Conversion between opioids

From

To

Conversion factor

Oral codeine Oral morphine Divide by 10
Oral tramadol Oral morphine Divide by 10*

Oxycodone generally causes less sedation, vomiting and pruritis than morphine but more constipation.

From

To

Conversion factor

Oral morphine Oral oxycodone Divide by 1.5-2**

The current BNF gives the following conversion factors for transdermal perparations
•a transdermal fentanyl 12 microgram patch equates to approximately 30 mg oral morphine daily
•a transdermal buprenorphine 10 microgram patch equates to approximately 24 mg oral morphine daily.

From

To

Conversion factor

Oral morphine Subcutaneous diamorphine Divide by 3
Oral oxycodone Subcutaneous diamorphine Divide by 1.5

*this has previously been stated as 5 but the current version of the BNF states a conversion of 10

**historically a conversion factor of 2 has been used (i.e. oral oxycodone is twice as strong as oral morphine). The current BNF however uses a conversion rate of 1.5