Central Factors Seen as Key to Chronic Pain

BETHESDA, MD. – When it comes to managing chronic pain, Dr. Daniel J. Clauw said physicians have been looking in the wrong places.

"There is no chronic pain state where degree of damage or inflammation in the periphery correlates well with level of pain. Yet, the diagnostic algorithms or paradigms that everyone uses for treating chronic pain still assume that all pain is nociceptive. What we see in the peripheral tissues is not necessarily what our patients are experiencing," said Dr. Clauw, director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor.

Historically, it has been assumed that when there was a disparity between peripheral findings and pain, psychological factors were at work. But the current view of chronic pain is that while it may originate from peripheral nociceptive input or nerve damage, central neuronal factors – at least some of them genetically determined – are nearly always playing a role in leading to interindividual differences in pain sensitivity, which are in turn closely associated with clinical outcomes.

For instance, population-based studies have shown that 30%-40% of individuals with radiographic evidence of severe damage from osteoarthritis are pain free, while 10% of those with normal radiographs have severe pain (Br. J. Rheumatol. 1997;36:726-8). Psychological factors explain very little of the variance between symptoms and structure (Arthritis Care Res. 1998;11:60-5), suggesting that central mechanisms involved in pain processing are at work, Dr. Clauw said at the workshop, sponsored by the University of Michigan and the National Institutes of Health.

Of course, individuals with osteoarthritis and rheumatoid arthritis will often have evidence of nociceptive input, while those with fibromyalgia have more prominent central factors. But no chronic pain state is solely due to any one of these mechanisms, he said.

"The scientific paradigm shift requires that we rethink everything from diagnostics and treatment approaches – which currently place an unjustified importance on treating peripheral factors," he said.

The new paradigm suggests that, regardless of the specific diagnosis, "central pain states" including fibromyalgia, rheumatoid arthritis, osteoarthritis, lupus, and low back pain all tend to share certain characteristics that can be better assessed by asking questions than by physical examination.

Showing patients a body diagram and asking them to label all the areas where they have pain is a simple assessment tool for multifocal pain. Also, ask about previous pain and other somatic symptoms such as fatigue, memory difficulty, mood disorders, and sleep disturbances, all common in the context of central pain but not with pain that is solely peripheral.

Is the pain triggered or exacerbated by stressors, such as psychological stress, infections, or physical trauma? Was there a salient stressor in the patient’s early life, such as an auto accident or the death of a loved one? All are common among patients with central pain, said Dr. Clauw, professor of anesthesiology and medicine (rheumatology) at the university.

Because these patients tend to have global sensory processing problems, asking about hypersensitivity to bright lights, odors, or noises will also help confirm the "central" diagnosis. Take a family history of pain as well, as there are strong familial and genetic linkages among the chronic pain syndromes, at least among women (Psychol. Med. 2009;39:497-505).

Physical examination is likely to be normal except for diffuse tenderness and nonspecific neurologic signs (Arthritis Rheum. 2009;60:2839-44). "This is why, historically, patients with fibromyalgia haven’t been believed," Dr. Clauw commented.

As for treatment, it is becoming increasingly clear that peripherally-acting pharmacologic agents such as opioids, corticosteroids, and nonsteroidal anti-inflammatory drugs simply do not work in central pain states.

Far more effective for fibromyalgia – and most likely other central pain states as well – are dual reuptake inhibitors such as tricyclic compounds (amitriptyline, cyclobenzaprine), serotonin-norepinephrine reuptake inhibitors (milnacipran, duloxetine), gamma hydroxybutyrate, and gabapentin. There is also modest evidence supporting the use of tramadol, selective serotonin reuptake inhibitors, and dopamine agonists (JAMA 2004;292:2388-95).

Nonpharmacologic therapies are also beneficial, including cognitive-behavioral therapy, exercise, and sleep hygiene (Best Pract. Res. Clin. Rheumatol. 2003;17:685-701).

Despite an abundance of emerging data to support the new way of thinking about chronic pain, Dr. Clauw said he thinks that shifting to a new management strategy could be difficult. "It takes a long time for people trained in one way of thinking to think differently. This isn’t just a new drug or a new device. This is a major paradigm shift."

Dr. Clauw disclosed that he is a consultant for Pfizer, Forest, Eli Lilly, Pierre Fabre Laboratories, Cypress Biosciences, Wyeth, UCB, AstraZeneca, Merck, Johnson & Johnson, Nuvo, and Jazz. He said he has also received research support from Pfizer, Cypress, and Forest.

BETHESDA, MD. – When it comes to managing chronic pain, Dr. Daniel J. Clauw said physicians have been looking in the wrong places.

"There is no chronic pain state where degree of damage or inflammation in the periphery correlates well with level of pain. Yet, the diagnostic algorithms or paradigms that everyone uses for treating chronic pain still assume that all pain is nociceptive. What we see in the peripheral tissues is not necessarily what our patients are experiencing," said Dr. Clauw, director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor.

Historically, it has been assumed that when there was a disparity between peripheral findings and pain, psychological factors were at work. But the current view of chronic pain is that while it may originate from peripheral nociceptive input or nerve damage, central neuronal factors – at least some of them genetically determined – are nearly always playing a role in leading to interindividual differences in pain sensitivity, which are in turn closely associated with clinical outcomes.

For instance, population-based studies have shown that 30%-40% of individuals with radiographic evidence of severe damage from osteoarthritis are pain free, while 10% of those with normal radiographs have severe pain (Br. J. Rheumatol. 1997;36:726-8). Psychological factors explain very little of the variance between symptoms and structure (Arthritis Care Res. 1998;11:60-5), suggesting that central mechanisms involved in pain processing are at work, Dr. Clauw said at the workshop, sponsored by the University of Michigan and the National Institutes of Health.

Of course, individuals with osteoarthritis and rheumatoid arthritis will often have evidence of nociceptive input, while those with fibromyalgia have more prominent central factors. But no chronic pain state is solely due to any one of these mechanisms, he said.

"The scientific paradigm shift requires that we rethink everything from diagnostics and treatment approaches – which currently place an unjustified importance on treating peripheral factors," he said.

The new paradigm suggests that, regardless of the specific diagnosis, "central pain states" including fibromyalgia, rheumatoid arthritis, osteoarthritis, lupus, and low back pain all tend to share certain characteristics that can be better assessed by asking questions than by physical examination.

Showing patients a body diagram and asking them to label all the areas where they have pain is a simple assessment tool for multifocal pain. Also, ask about previous pain and other somatic symptoms such as fatigue, memory difficulty, mood disorders, and sleep disturbances, all common in the context of central pain but not with pain that is solely peripheral.

Is the pain triggered or exacerbated by stressors, such as psychological stress, infections, or physical trauma? Was there a salient stressor in the patient’s early life, such as an auto accident or the death of a loved one? All are common among patients with central pain, said Dr. Clauw, professor of anesthesiology and medicine (rheumatology) at the university.

Because these patients tend to have global sensory processing problems, asking about hypersensitivity to bright lights, odors, or noises will also help confirm the "central" diagnosis. Take a family history of pain as well, as there are strong familial and genetic linkages among the chronic pain syndromes, at least among women (Psychol. Med. 2009;39:497-505).

Physical examination is likely to be normal except for diffuse tenderness and nonspecific neurologic signs (Arthritis Rheum. 2009;60:2839-44). "This is why, historically, patients with fibromyalgia haven’t been believed," Dr. Clauw commented.

As for treatment, it is becoming increasingly clear that peripherally-acting pharmacologic agents such as opioids, corticosteroids, and nonsteroidal anti-inflammatory drugs simply do not work in central pain states.

Far more effective for fibromyalgia – and most likely other central pain states as well – are dual reuptake inhibitors such as tricyclic compounds (amitriptyline, cyclobenzaprine), serotonin-norepinephrine reuptake inhibitors (milnacipran, duloxetine), gamma hydroxybutyrate, and gabapentin. There is also modest evidence supporting the use of tramadol, selective serotonin reuptake inhibitors, and dopamine agonists (JAMA 2004;292:2388-95).

Nonpharmacologic therapies are also beneficial, including cognitive-behavioral therapy, exercise, and sleep hygiene (Best Pract. Res. Clin. Rheumatol. 2003;17:685-701).

Despite an abundance of emerging data to support the new way of thinking about chronic pain, Dr. Clauw said he thinks that shifting to a new management strategy could be difficult. "It takes a long time for people trained in one way of thinking to think differently. This isn’t just a new drug or a new device. This is a major paradigm shift."

Dr. Clauw disclosed that he is a consultant for Pfizer, Forest, Eli Lilly, Pierre Fabre Laboratories, Cypress Biosciences, Wyeth, UCB, AstraZeneca, Merck, Johnson & Johnson, Nuvo, and Jazz. He said he has also received research support from Pfizer, Cypress, and Forest.

BETHESDA, MD. – When it comes to managing chronic pain, Dr. Daniel J. Clauw said physicians have been looking in the wrong places.

"There is no chronic pain state where degree of damage or inflammation in the periphery correlates well with level of pain. Yet, the diagnostic algorithms or paradigms that everyone uses for treating chronic pain still assume that all pain is nociceptive. What we see in the peripheral tissues is not necessarily what our patients are experiencing," said Dr. Clauw, director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor.

Historically, it has been assumed that when there was a disparity between peripheral findings and pain, psychological factors were at work. But the current view of chronic pain is that while it may originate from peripheral nociceptive input or nerve damage, central neuronal factors – at least some of them genetically determined – are nearly always playing a role in leading to interindividual differences in pain sensitivity, which are in turn closely associated with clinical outcomes.

For instance, population-based studies have shown that 30%-40% of individuals with radiographic evidence of severe damage from osteoarthritis are pain free, while 10% of those with normal radiographs have severe pain (Br. J. Rheumatol. 1997;36:726-8). Psychological factors explain very little of the variance between symptoms and structure (Arthritis Care Res. 1998;11:60-5), suggesting that central mechanisms involved in pain processing are at work, Dr. Clauw said at the workshop, sponsored by the University of Michigan and the National Institutes of Health.

Of course, individuals with osteoarthritis and rheumatoid arthritis will often have evidence of nociceptive input, while those with fibromyalgia have more prominent central factors. But no chronic pain state is solely due to any one of these mechanisms, he said.

"The scientific paradigm shift requires that we rethink everything from diagnostics and treatment approaches – which currently place an unjustified importance on treating peripheral factors," he said.

The new paradigm suggests that, regardless of the specific diagnosis, "central pain states" including fibromyalgia, rheumatoid arthritis, osteoarthritis, lupus, and low back pain all tend to share certain characteristics that can be better assessed by asking questions than by physical examination.

Showing patients a body diagram and asking them to label all the areas where they have pain is a simple assessment tool for multifocal pain. Also, ask about previous pain and other somatic symptoms such as fatigue, memory difficulty, mood disorders, and sleep disturbances, all common in the context of central pain but not with pain that is solely peripheral.

Is the pain triggered or exacerbated by stressors, such as psychological stress, infections, or physical trauma? Was there a salient stressor in the patient’s early life, such as an auto accident or the death of a loved one? All are common among patients with central pain, said Dr. Clauw, professor of anesthesiology and medicine (rheumatology) at the university.

Because these patients tend to have global sensory processing problems, asking about hypersensitivity to bright lights, odors, or noises will also help confirm the "central" diagnosis. Take a family history of pain as well, as there are strong familial and genetic linkages among the chronic pain syndromes, at least among women (Psychol. Med. 2009;39:497-505).

Physical examination is likely to be normal except for diffuse tenderness and nonspecific neurologic signs (Arthritis Rheum. 2009;60:2839-44). "This is why, historically, patients with fibromyalgia haven’t been believed," Dr. Clauw commented.

As for treatment, it is becoming increasingly clear that peripherally-acting pharmacologic agents such as opioids, corticosteroids, and nonsteroidal anti-inflammatory drugs simply do not work in central pain states.

Far more effective for fibromyalgia – and most likely other central pain states as well – are dual reuptake inhibitors such as tricyclic compounds (amitriptyline, cyclobenzaprine), serotonin-norepinephrine reuptake inhibitors (milnacipran, duloxetine), gamma hydroxybutyrate, and gabapentin. There is also modest evidence supporting the use of tramadol, selective serotonin reuptake inhibitors, and dopamine agonists (JAMA 2004;292:2388-95).

Nonpharmacologic therapies are also beneficial, including cognitive-behavioral therapy, exercise, and sleep hygiene (Best Pract. Res. Clin. Rheumatol. 2003;17:685-701).

Despite an abundance of emerging data to support the new way of thinking about chronic pain, Dr. Clauw said he thinks that shifting to a new management strategy could be difficult. "It takes a long time for people trained in one way of thinking to think differently. This isn’t just a new drug or a new device. This is a major paradigm shift."

Dr. Clauw disclosed that he is a consultant for Pfizer, Forest, Eli Lilly, Pierre Fabre Laboratories, Cypress Biosciences, Wyeth, UCB, AstraZeneca, Merck, Johnson & Johnson, Nuvo, and Jazz. He said he has also received research support from Pfizer, Cypress, and Forest.