Look for centralized pain in rheumatic diseases

LAS VEGAS – Centralized pain or sensitization occurs in most patients with fibromyalgia and can be identified in 20%-30% of patients with other pain states, such as rheumatoid arthritis, lupus, low back pain, and osteoarthritis, according to Dr. Daniel J. Clauw.

This has implications for both diagnosis and treatment of these conditions. However, current paradigms for diagnosis and treatment are antiquated, Dr. Clauw, professor of anesthesiology and medicine, and director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor, said at the annual Perspectives in Rheumatic Diseases conference.

There is no chronic pain state in which the degree of damage or inflammation in the periphery correlates well with the level of pain the patient experiences, and yet, existing diagnostic paradigms – as well as the terms used to describe chronic pain states – imply otherwise, he explained.

In fact, until recently it was typically assumed that when a disparity between peripheral findings and pain existed, the problem was a psychological one, he said.

In reality, there are numerous nonpsychological neurobiologic factors that affect pain sensitivity, and these are operative in many chronic pain states. Thus, it is imperative that the diagnostic and therapeutic paradigms be modified to better identify and treat "central pain," he said.

Centralized pain is pain in which the spinal cord and/or brain play a much bigger role than the peripheral nervous system. In patients with centralized pain, the pain is more associated with pain processing pathways than with "peripheral nociceptive input out at the periphery that you will make better with nonsteroidal anti-inflammatory drugs, opioids, and surgical procedures," Dr. Clauw said.

"The problem is the diseases don’t tell us which pain state someone has," he added.

Certain clinical characteristics can provide clues, however. Among them are multifocal pain, use of neuropathic verbal descriptors of pain, higher current and lifetime history of pain, the presence of multiple other somatic symptoms, and sensitivity to multiple sensory stimuli.

"When someone centralizes their pain, they don’t have just pain any more, they have a lot of other central nervous system symptoms that are also coming from the brain, including fatigue, memory problems, sleep disturbances," he said, noting that when a patient presents with multifocal pain accompanied by these other symptoms, this should be "a blinking neon light that this person has centralized their pain."

Additionally, patients with centralized pain have a wide continuum of pain, may experience exacerbation because of stressors, and may have a generally normal physical examination except for diffuse tenderness and nonspecific neurologic signs. This type of pain is 1.5 to 2 times more common in women than men and has strong genetic underpinnings, so a family history can be helpful in identifying patients with centralized pain, Dr. Clauw noted.

Studies suggest that a number of genes that may be involved in the process, including the gene encoding catecholamine-O-methyltransferase (COMT), certain alleles of which are associated with a threefold increased risk of developing different types of chronic pain conditions, he said.

A number of pharmacologic agents have been studied for central pain; the strongest evidence exists for dual reuptake inhibitors (including tricyclic compounds, selective-norepinephrine reuptake inhibitors, and norepinephrine-selective reuptake inhibitors), and the anticonvulsants gabapentin and pregabalin. Modest evidence exists for tramadol, older less-selective selective-serotonin reuptake inhibitors, gamma-hydroxybutyrate, and low-dose naltrexone. Weak evidence suggests a benefit with cannabinoids (although evidence of benefit is increasing), growth hormone, 5-hydroxytryptamine, tropisetron, S-adenosyl-L-methionine. There is no evidence with respect to opioids, corticosteroids, nonsteroidal antiinflammatory drugs, benzodiazepine and nonbenzodiazepine hypnotics, and guaifenesin.

None of the available pharmacologic agents have anything more than modest efficacy when used as stand-alone therapy, he said, stressing the importance of also using nonpharmacologic therapies in patients with centralized pain.

The nonpharmacologic options are similar for any chronic pain state, Dr. Clauw said, noting that strong evidence exists for education, aerobic exercise, and cognitive-behavior therapy. Modest evidence exists for strength training, hypnotherapy, biofeedback, balneotherapy, yoga, and tai chi. Weak evidence suggests a possible benefit with acupuncture, chiropractic therapy, manual and massage therapy, electrotherapy, and ultrasound. No evidence exists for trigger point injections and flexibility exercise.

Many of the particularly useful nonpharmacologic therapies, including cognitive-behavior therapy or exercise, are rarely used in clinical practice, he noted.

An approach known as the ExPRESS approach to chronic pain can help improve outcomes by addressing the various factors involved in centralized pain. ExPRESS stands for exercise, psychiatric comorbidity, regaining function, education, sleep hygiene, and stress management, he said.

The approach was proposed by Afton L. Hassett, Psy.D., and Richard N. Gevirtz, Ph.D., in a 2009 study (Rheum. Dis. Clin. North Am. 2009;35:393-407), which stresses the importance of providing comprehensive care for patients with chronic pain by addressing each of these interrelated factors.

It doesn’t matter where the pain is coming from. Long-term pain increases stress levels, decreases sleep and exercise, and can lead to social isolation – all things that can make pain worse. Thus, a change in the "volume control" of the central nervous system isn’t necessarily to blame when a patient experiences worsening over time, rather it may be the accumulation of these other factors, he said at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"Unless and until you treat these patients with exercise, education, and cognitive-behavioral therapy ... you’re not going to make chronic pain patients better, and you’re certainly not going to make centralized pain patients better unless you aggressively use [these tools]," he said.

Dr. Clauw has been a consultant for Merck, UCB, Cypress Biosciences, Eli Lilly, Jazz Pharmaceuticals, Pierre Fabre Pharmaceuticals, Pfizer, Nuvo Research, and Forest Laboratories, and has received grant support from Nuvo Research and Forest Laboratories.

LAS VEGAS – Centralized pain or sensitization occurs in most patients with fibromyalgia and can be identified in 20%-30% of patients with other pain states, such as rheumatoid arthritis, lupus, low back pain, and osteoarthritis, according to Dr. Daniel J. Clauw.

This has implications for both diagnosis and treatment of these conditions. However, current paradigms for diagnosis and treatment are antiquated, Dr. Clauw, professor of anesthesiology and medicine, and director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor, said at the annual Perspectives in Rheumatic Diseases conference.

There is no chronic pain state in which the degree of damage or inflammation in the periphery correlates well with the level of pain the patient experiences, and yet, existing diagnostic paradigms – as well as the terms used to describe chronic pain states – imply otherwise, he explained.

In fact, until recently it was typically assumed that when a disparity between peripheral findings and pain existed, the problem was a psychological one, he said.

In reality, there are numerous nonpsychological neurobiologic factors that affect pain sensitivity, and these are operative in many chronic pain states. Thus, it is imperative that the diagnostic and therapeutic paradigms be modified to better identify and treat "central pain," he said.

Centralized pain is pain in which the spinal cord and/or brain play a much bigger role than the peripheral nervous system. In patients with centralized pain, the pain is more associated with pain processing pathways than with "peripheral nociceptive input out at the periphery that you will make better with nonsteroidal anti-inflammatory drugs, opioids, and surgical procedures," Dr. Clauw said.

"The problem is the diseases don’t tell us which pain state someone has," he added.

Certain clinical characteristics can provide clues, however. Among them are multifocal pain, use of neuropathic verbal descriptors of pain, higher current and lifetime history of pain, the presence of multiple other somatic symptoms, and sensitivity to multiple sensory stimuli.

"When someone centralizes their pain, they don’t have just pain any more, they have a lot of other central nervous system symptoms that are also coming from the brain, including fatigue, memory problems, sleep disturbances," he said, noting that when a patient presents with multifocal pain accompanied by these other symptoms, this should be "a blinking neon light that this person has centralized their pain."

Additionally, patients with centralized pain have a wide continuum of pain, may experience exacerbation because of stressors, and may have a generally normal physical examination except for diffuse tenderness and nonspecific neurologic signs. This type of pain is 1.5 to 2 times more common in women than men and has strong genetic underpinnings, so a family history can be helpful in identifying patients with centralized pain, Dr. Clauw noted.

Studies suggest that a number of genes that may be involved in the process, including the gene encoding catecholamine-O-methyltransferase (COMT), certain alleles of which are associated with a threefold increased risk of developing different types of chronic pain conditions, he said.

A number of pharmacologic agents have been studied for central pain; the strongest evidence exists for dual reuptake inhibitors (including tricyclic compounds, selective-norepinephrine reuptake inhibitors, and norepinephrine-selective reuptake inhibitors), and the anticonvulsants gabapentin and pregabalin. Modest evidence exists for tramadol, older less-selective selective-serotonin reuptake inhibitors, gamma-hydroxybutyrate, and low-dose naltrexone. Weak evidence suggests a benefit with cannabinoids (although evidence of benefit is increasing), growth hormone, 5-hydroxytryptamine, tropisetron, S-adenosyl-L-methionine. There is no evidence with respect to opioids, corticosteroids, nonsteroidal antiinflammatory drugs, benzodiazepine and nonbenzodiazepine hypnotics, and guaifenesin.

None of the available pharmacologic agents have anything more than modest efficacy when used as stand-alone therapy, he said, stressing the importance of also using nonpharmacologic therapies in patients with centralized pain.

The nonpharmacologic options are similar for any chronic pain state, Dr. Clauw said, noting that strong evidence exists for education, aerobic exercise, and cognitive-behavior therapy. Modest evidence exists for strength training, hypnotherapy, biofeedback, balneotherapy, yoga, and tai chi. Weak evidence suggests a possible benefit with acupuncture, chiropractic therapy, manual and massage therapy, electrotherapy, and ultrasound. No evidence exists for trigger point injections and flexibility exercise.

Many of the particularly useful nonpharmacologic therapies, including cognitive-behavior therapy or exercise, are rarely used in clinical practice, he noted.

An approach known as the ExPRESS approach to chronic pain can help improve outcomes by addressing the various factors involved in centralized pain. ExPRESS stands for exercise, psychiatric comorbidity, regaining function, education, sleep hygiene, and stress management, he said.

The approach was proposed by Afton L. Hassett, Psy.D., and Richard N. Gevirtz, Ph.D., in a 2009 study (Rheum. Dis. Clin. North Am. 2009;35:393-407), which stresses the importance of providing comprehensive care for patients with chronic pain by addressing each of these interrelated factors.

It doesn’t matter where the pain is coming from. Long-term pain increases stress levels, decreases sleep and exercise, and can lead to social isolation – all things that can make pain worse. Thus, a change in the "volume control" of the central nervous system isn’t necessarily to blame when a patient experiences worsening over time, rather it may be the accumulation of these other factors, he said at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"Unless and until you treat these patients with exercise, education, and cognitive-behavioral therapy ... you’re not going to make chronic pain patients better, and you’re certainly not going to make centralized pain patients better unless you aggressively use [these tools]," he said.

Dr. Clauw has been a consultant for Merck, UCB, Cypress Biosciences, Eli Lilly, Jazz Pharmaceuticals, Pierre Fabre Pharmaceuticals, Pfizer, Nuvo Research, and Forest Laboratories, and has received grant support from Nuvo Research and Forest Laboratories.

LAS VEGAS – Centralized pain or sensitization occurs in most patients with fibromyalgia and can be identified in 20%-30% of patients with other pain states, such as rheumatoid arthritis, lupus, low back pain, and osteoarthritis, according to Dr. Daniel J. Clauw.

This has implications for both diagnosis and treatment of these conditions. However, current paradigms for diagnosis and treatment are antiquated, Dr. Clauw, professor of anesthesiology and medicine, and director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor, said at the annual Perspectives in Rheumatic Diseases conference.

There is no chronic pain state in which the degree of damage or inflammation in the periphery correlates well with the level of pain the patient experiences, and yet, existing diagnostic paradigms – as well as the terms used to describe chronic pain states – imply otherwise, he explained.

In fact, until recently it was typically assumed that when a disparity between peripheral findings and pain existed, the problem was a psychological one, he said.

In reality, there are numerous nonpsychological neurobiologic factors that affect pain sensitivity, and these are operative in many chronic pain states. Thus, it is imperative that the diagnostic and therapeutic paradigms be modified to better identify and treat "central pain," he said.

Centralized pain is pain in which the spinal cord and/or brain play a much bigger role than the peripheral nervous system. In patients with centralized pain, the pain is more associated with pain processing pathways than with "peripheral nociceptive input out at the periphery that you will make better with nonsteroidal anti-inflammatory drugs, opioids, and surgical procedures," Dr. Clauw said.

"The problem is the diseases don’t tell us which pain state someone has," he added.

Certain clinical characteristics can provide clues, however. Among them are multifocal pain, use of neuropathic verbal descriptors of pain, higher current and lifetime history of pain, the presence of multiple other somatic symptoms, and sensitivity to multiple sensory stimuli.

"When someone centralizes their pain, they don’t have just pain any more, they have a lot of other central nervous system symptoms that are also coming from the brain, including fatigue, memory problems, sleep disturbances," he said, noting that when a patient presents with multifocal pain accompanied by these other symptoms, this should be "a blinking neon light that this person has centralized their pain."

Additionally, patients with centralized pain have a wide continuum of pain, may experience exacerbation because of stressors, and may have a generally normal physical examination except for diffuse tenderness and nonspecific neurologic signs. This type of pain is 1.5 to 2 times more common in women than men and has strong genetic underpinnings, so a family history can be helpful in identifying patients with centralized pain, Dr. Clauw noted.

Studies suggest that a number of genes that may be involved in the process, including the gene encoding catecholamine-O-methyltransferase (COMT), certain alleles of which are associated with a threefold increased risk of developing different types of chronic pain conditions, he said.

A number of pharmacologic agents have been studied for central pain; the strongest evidence exists for dual reuptake inhibitors (including tricyclic compounds, selective-norepinephrine reuptake inhibitors, and norepinephrine-selective reuptake inhibitors), and the anticonvulsants gabapentin and pregabalin. Modest evidence exists for tramadol, older less-selective selective-serotonin reuptake inhibitors, gamma-hydroxybutyrate, and low-dose naltrexone. Weak evidence suggests a benefit with cannabinoids (although evidence of benefit is increasing), growth hormone, 5-hydroxytryptamine, tropisetron, S-adenosyl-L-methionine. There is no evidence with respect to opioids, corticosteroids, nonsteroidal antiinflammatory drugs, benzodiazepine and nonbenzodiazepine hypnotics, and guaifenesin.

None of the available pharmacologic agents have anything more than modest efficacy when used as stand-alone therapy, he said, stressing the importance of also using nonpharmacologic therapies in patients with centralized pain.

The nonpharmacologic options are similar for any chronic pain state, Dr. Clauw said, noting that strong evidence exists for education, aerobic exercise, and cognitive-behavior therapy. Modest evidence exists for strength training, hypnotherapy, biofeedback, balneotherapy, yoga, and tai chi. Weak evidence suggests a possible benefit with acupuncture, chiropractic therapy, manual and massage therapy, electrotherapy, and ultrasound. No evidence exists for trigger point injections and flexibility exercise.

Many of the particularly useful nonpharmacologic therapies, including cognitive-behavior therapy or exercise, are rarely used in clinical practice, he noted.

An approach known as the ExPRESS approach to chronic pain can help improve outcomes by addressing the various factors involved in centralized pain. ExPRESS stands for exercise, psychiatric comorbidity, regaining function, education, sleep hygiene, and stress management, he said.

The approach was proposed by Afton L. Hassett, Psy.D., and Richard N. Gevirtz, Ph.D., in a 2009 study (Rheum. Dis. Clin. North Am. 2009;35:393-407), which stresses the importance of providing comprehensive care for patients with chronic pain by addressing each of these interrelated factors.

It doesn’t matter where the pain is coming from. Long-term pain increases stress levels, decreases sleep and exercise, and can lead to social isolation – all things that can make pain worse. Thus, a change in the "volume control" of the central nervous system isn’t necessarily to blame when a patient experiences worsening over time, rather it may be the accumulation of these other factors, he said at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"Unless and until you treat these patients with exercise, education, and cognitive-behavioral therapy ... you’re not going to make chronic pain patients better, and you’re certainly not going to make centralized pain patients better unless you aggressively use [these tools]," he said.

Dr. Clauw has been a consultant for Merck, UCB, Cypress Biosciences, Eli Lilly, Jazz Pharmaceuticals, Pierre Fabre Pharmaceuticals, Pfizer, Nuvo Research, and Forest Laboratories, and has received grant support from Nuvo Research and Forest Laboratories.