Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society.

Neuropathic pain (NeP), generated by disorders of the peripheral and central nervous system, can be particularly severe and disabling. Prevalence estimates indicate that 2% to 3% of the population in the developed world suffer from NeP, which suggests that up to one million Canadians have this disabling condition. Evidence-based guidelines for the pharmacological management of NeP are therefore urgently needed. Randomized, controlled trials, systematic reviews and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting. Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one methodologically sound, randomized, controlled trial showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment are based on degree of evidence of analgesic efficacy, safety, ease of use and cost-effectiveness. Analgesic agents recommended for first-line treatments are certain antidepressants (tricyclics) and anticonvulsants (gabapentin and pregabalin). Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine. Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain. Recommended fourth-line treatments include cannabinoids, methadone and anticonvulsants with lesser evidence of efficacy, such as lamotrigine, topiramate and valproic acid. Treatment must be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Further studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes, and treatment of pediatric and central NeP.

An upper body musculoskeletal assessment instrument for patients with work-related musculoskeletal disorders: a pilot study.

OBJECTIVES: To examine the reliability and validity of a new outcome measure, the Upper Body Musculoskeletal Assessment (UBMA). DESIGN: Twenty subjects physician-diagnosed as having work-related musculoskeletal disorders (WRMD) and ten healthy subjects were assessed using the UBMA on three separate occasions. All subjects with WRMD attributed their injury to equipment use on their job. RESULTS: The WRMD group had significantly higher UBMA scores on the side of equipment use than on the other side (p <0.01), whereas the healthy group had similar scores on both sides (p> 0.05). UBMA scores for the WRMD group were significantly greater on both sides of the body than scores for the healthy group (p<0.01). Only one test occasion was required to produce excellent reliability coefficients (ICCs>0.88). Although group reliability was excellent, changes of 24% for patients with WRMD and 44% for healthy subjects would be required for confidence that UBMA scores for individual patients on the side of equipment use had changed from baseline. CONCLUSIONS: Although testing on one occasion produced reliable UBMA scores, healthy subjects could be distinguished from patients with WRMD, and the side of equipment use could be distinguished from the other side in patients with WRMD, prediction of individual UBMA scores was poor. In its present form, the UBMA is useful for making decisions about groups but not about individual patients. Modifications of the current UBMA are required to reduce measurement error.

Sex differences in musculoskeletal pain.

Epidemiologic, clinical, and experimental evidence points to sex differences in musculoskeletal pain. Adult women more often have musculoskeletal problems than do men. Discrepant findings regarding the presence of such differences during childhood and adolescence continue. Biologic and psychosocial factors might account for these differences. The authors review evidence showing that mechanically induced pressure is more likely to show sex differences than other noxious stimuli and to discriminate between individuals suffering from musculoskeletal pain and matched controls. The authors suggest that a state of increased pain sensitivity, with a peripheral or central origin, predisposes individuals to chronic muscle pain conditions, and that there are sex differences in the operation of these mechanisms; women are vulnerable to the development and maintenance of musculoskeletal pain conditions.

The role of psychosocial factors in temporomandibular disorders.

The temporomandibular disorders (TMDs) comprise a constellation of symptoms affecting the joints and muscles involved in jaw movement. Patients complain of orofacial pain, limited jaw opening, and clicking or popping sounds. Although pain is generally the defining characteristic of TMD, patients often report marked degrees of stress and interference in daily life. This article reviews recent studies on epidemiology, sex differences, pediatric TMD, classification systems, comparisons to other chronic pain disorders of uncertain etiology, psychological assessment, depression, central modulation and hypervigilance, sleep disturbances, stress, and the management of TMD by conservative physical interventions and cognitive behavioral therapy. Both the assessment and the management of TMD requires a multidisciplinary perspective with strong emphasis on psychosocial variables.

Somesthesis.

In this review we focus on the perceptual and psychophysical aspects of somesthesis, although some information on neurophysiological aspects will be included as well; we look primarily at studies that have appeared since 1988. In the section on touch, we cover peripheral sensory mechanisms and several topics related to spatial and temporal pattern perception, specifically measures of spatial sensitivity, texture perception with particular emphasis on perceived roughness, complex spatial-temporal patterns, and the use of touch as a possible channel of communication. Other topics under this section include the effects of attention on processing tactile stimuli, cortical mechanisms, and the effects of aging on sensitivity. We also deal with thermal sensitivity and some aspects of haptics and kinesthesis. In the section on pain, we review work on the gate-control theory, sensory fibers, and higher neural organization. In addition, studies on central neurochemical effects and psychophysics of pain are examined.

Possible deficiencies of pain modulation in fibromyalgia.

OBJECTIVE: To examine possible deficiencies in endogenous pain modulating mechanisms in fibromyalgia patients compared with matched pain-free control subjects. DESIGN/SUBJECTS/METHODOLOGY: Pain reduction was investigated in 25 female patients with fibromyalgia and 26 age-matched healthy women using the diffuse noxious inhibitory controls (DNIC) paradigm. Tonic thermal stimuli at painful and nonpainful intensities, tailored to individual heat pain thresholds, were employed to induce pain inhibition. The anticipated effect was assessed by measuring the electrical pain threshold and detection threshold, using a double staircase method. Only nontender control points were stimulated (thermode on the foot, electrodes on the inner forearm). RESULTS: The patients with fibromyalgia had significantly lower heat pain thresholds than the healthy subjects, but similar electrical detection and pain thresholds. The repeatedly applied electrical stimuli resulted in a degree of perceptual adaptation that was similar between the two groups. However, concurrent tonic thermal stimuli, at both painful and nonpainful levels, significantly increased the electrical pain threshold in the healthy subjects but not in the fibromyalgia patients. The electrical detection threshold was not affected in either group. CONCLUSIONS: Pain modulation, produced by a concurrent tonic stimulus in healthy persons, was not seen in the fibromyalgia group. The patients either had deficient pain modulation or were unable to tolerate a tonic stimulus intense enough to engage a modulatory process. It remains to be established whether the pain reduction found in the healthy subjects was the conventional DNIC effect, another effect (e.g., distraction), or a combination of both.

The cortisol response to psychological stress in temporomandibular dysfunction.

The salivary cortisol response to psychological stress and its relationship to psychological variables was examined in 36 female temporomandibular dysfunction (TMD) sufferers and 39 female control participants. Saliva samples were taken at baseline, after completion of a modified version of the Trier Social Stress Test, and after rest. Participants also completed a battery of measures, including Visual Analog Scales for measuring pain intensity and disability and a number of established psychological scales. The TMD group showed a significantly higher cortisol response to experimental stress than the control group. Closer examination of the data revealed that the TMD group was heterogeneous and composed of a group that hypersecreted cortisol in response to stress (Hi-SC TMD group) and another group whose cortisol response was not significantly different from the control group (Lo-SC TMD group). The Lo-SC TMD group showed significant negative relationships between cortisol response and self-reported symptoms of both anxiety and depression, plus significantly more use of the Praying or Hoping coping strategy on the Coping Strategies Questionnaire. A dual relationship between TMD symptoms and the stress response is proposed. First, a biological predisposition to TMD is suggested by the stress response in the Hi-SC TMD group. Second, both psychological and biological variables appear to be important factors in those TMD patients who respond to stress with low cortisol secretion.

Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification.

The hypervigilance model of pain perception states that chronic pain patients have a heightened sensitivity to pain (e.g. low threshold and tolerance) because of increased attention to external stimulation and a preoccupation with pain sensations. This study tested the hypothesis that individuals with fibromyalgia, a chronic pain disorder of undetermined origin, have a generalized hypervigilant pattern of responding that extends beyond the pain domain. Twenty fibromyalgia out-patients, 20 rheumatoid arthritis (RA) patients, and 20 normal controls served as subjects. The RA and normal control subjects were age and sex matched to the fibromyalgia patients. Subjects were tested for pain tolerance, pain threshold, and noise tolerance and were asked to complete a number of questionnaires that assessed hypervigilance. As predicted, the responses of the fibromyalgia patients to both the pain and auditory stimuli were consistent with the generalized hypervigilance hypothesis. These patients had significantly lower threshold and tolerance values than the RA patients, who in turn, had lower values than the normal control subjects. The results of the psychological questionnaires revealed that the fibromyalgia and RA patients preferred lower levels of external stimulation than the control subjects. The outcome of this study supports the generalized hypervigilance hypothesis, suggesting that fibromyalgia patients have a perceptual style of amplification. The implications of these findings for understanding the role of biological, cognitive, and perceptual factors in pain disorders are discussed.

The reliability of examination for tenderness in patients with myofascial pain, chronic fibromyalgia and controls.

OBJECTIVE: To establish the reliability with which tenderness could be evaluated in patients with chronic myalgias, using dolorimetry and palpation. METHODS: Three blinded examiners using pressure dolorimetry and digital palpation compared 19 paired tender points and 8 paired control points in 4 matched groups of 6 patients with fibromyalgia (FM), myofascial pain, pain controls, and healthy controls. RESULTS: Good interrater and test-retest reliability were found for dolorimetry scores. There were significant differences in tenderness ratings by dolorimetry between the diagnostic groups, with the patients with FM and myofascial pain having the greatest tenderness, the normals having the least tenderness, and the pain controls having tenderness levels midway between the patients with FM or myofascial pain and the normals. In all patients, control points had higher pain thresholds than tender points. One-third of patients with localized pain complaints demonstrated a significant relationship between region of clinical pain complaint and measured tenderness thresholds by dolorimetry. In ratings of tenderness by digital palpation, there was very good intrarater reliability over 26 of 27 paired points, and good interrater reliability at 75% of the points. One-half of patients with localized pain complaints demonstrated a significant relationship between region of clinical pain complaint and number of tender points by palpation. CONCLUSION: Both dolorimetry and palpation are sufficiently reliable to discriminate control patients from patients with myofascial pain and FM, but may not discriminate patients with myofascial pain from those with FM. Neither method appears to correlate well with the location of the clinical pain complaint, regardless of diagnosis.

Multi-method assessment of experimental and clinical pain in patients with fibromyalgia.

Experimental measures of responsiveness to painful and non-painful stimuli as well as measures of typical and present clinical pain were assessed in 26 female patients with fibromyalgia and in an equal number of age-matched healthy women. Pressure pain thresholds, determined by means of a dolorimeter, were lower in the patients compared to the control subjects both at a tender point (trapezius) and at a non-tender control point (inner forearm). The same was true for the heat pain thresholds, measured using a contact thermode. In contrast, the pain thresholds for electrocutaneous stimuli were decreased only at the tender point. The detection thresholds for non-painful stimuli (warmth, cold and electrical stimuli) seemed to be less affected in the fibromyalgia patients, with only the detection threshold for cold being lower at both sites. Tender points were more sensitive than control points for mechanical pressure. The reverse was found for the other modalities which were tested. Although the 3 experimental pain thresholds showed patterns of either generalized or site-specific pain hyperresponsiveness, the between-methods correlations were not very high. While the correlations between the experimental pain thresholds and the various measures of clinical pain (Localized Pain Rating, McGill Pain Questionnaire) in the patients were generally low, there were significant negative correlations between pressure pain thresholds at the two sites and the level of present pain assessed by the Localized Pain Rating. We conclude that a pattern of pain hyperresponsiveness, generalized across the site of noxious stimulation and across the physical nature of the stressor, is associated with fibromyalgia.(ABSTRACT TRUNCATED AT 250 WORDS)

Are there psychologic predictors of treatment outcome in temporomandibular joint pain and dysfunction?

This study explores the relationship between diverse psychologic factors and treatment outcome in temporomandibular joint pain and dysfunction (TMJPD). During assessment, 178 patients with TMJPD were given a pressure pain threshold and tolerance task and completed the Basic Personality Inventory, the Illness Behavior Questionnaire, the Multidimensional Health Locus of Control, the Perceived Stress Scale, and the Ways of Coping Checklist. Subjects also answered questions pertaining to TMJPD symptomatology, including chronicity and severity. After conservative treatment with simple jaw exercises and ultrasound, patients were contacted again at 5 months to complete a follow-up questionnaire package similar to the initial questionnaire battery. Percent reduction in average pain intensity and perceived TMJPD severity were used as outcome criteria. The data were analyzed with discriminant function analyses. One hundred patients responded to the follow-up questionnaire. Patients who reported more than a 50% reduction in average pain intensity tended to be less inclined to accept responsibility for their problems and were slightly better able to distance themselves from their problems than the less improved groups. Those who reported more than a 50% reduction in TMJPD severity indicated that the condition was not associated with an identifiable onset event and that the condition had become moderately worse between onset and first seeking help.

Perceived locus and intensity of electrocutaneous stimulation.

Two experiments investigated perceived locus and intensity for electrocutaneous stimulation. In Experiment 1, 21 subjects reported the perceived locus for various combinations of four electrode sites, two current directions, two pulse characteristics (single versus multiple), and two sensation levels (detection versus pain). In Experiment 2, 16 subjects reported the perceived locus and intensity for a wide range of current levels and two polarity conditions. The main results were 1) sensations were likely to be perceived under the cathode at detection levels, but under both electrodes at intense levels; 2) the "cathode" localization was gradually supplanted by "both" ("anode" and "cathode") localization with increasing current; 3) subjective intensity under the cathode was greater than that under the anode; 4) the effects of cathode position on perceived locus were found for only some pairs of electrodes. These results challenge the simple hypothesis that electrical stimulation of the skin through paired electrodes is perceived under the cathode.

Improvements in pain responsiveness in patients with fibrositis after successful treatment with amitriptyline.

Thirty-six patients with fibrositis received low dose amitriptyline and placebo in a randomized double blind crossover study lasting 10 weeks. Amitriptyline was associated with significant changes on the outcome measures of pain, tender point sensitivity and patient assessment of well being. Clinically significant improvements for pain and tender point sensitivity and a statistically significant improvement in generalized pain responsiveness were found between patients who reported subjective improvement on amitriptyline and those who felt no change.

Measurement of pain in fibromyalgia in the clinic and laboratory.

Fibromyalgia involves constant aching pain throughout the body and acute pain at widely distributed tender points. This review emphasizes the different aspects of the pain experience which are assessed by verbal questionnaires, analysis of descriptive adjectives, numerical and verbal category scales and visual analogue scales. There is a need for studies which utilize ratio scale techniques to measure the different components of the pain experience and which explore a wider range of behavioral and functional measures. Laboratory data on responsiveness at tender and nontender points, examined with respect to adaptation level and hypervigilance theories, suggest that patients with fibromyalgia are overly reactive to external events which other groups, both pain free and pain suffering, find innocuous.

Pain perception and personality measures as discriminators in the classification of fibrositis.

Twenty patients with fibrositis were compared to age and sex matched groups of patients with rheumatoid arthritis (RA) and normal controls regarding personality variables measured by the Basic Personality Inventory (BPI) and responsiveness to experimentally induced pain. The group with fibrositis scored significantly higher than the normal group on 4 of the BPI scales and had lower pain threshold and tolerance than the normal group. The group with RA was found to be significantly different from the normal group on hypochondriasis and pain tolerance. Using only pain and personality measures, a statistical discriminant function that was developed resulted in a 72% classification accuracy for the 3 groups studied and 85% accuracy when only the 2 clinical groups were considered.

Stress analgesia: effects of PCPA, yohimbine, and naloxone.

Evidence suggests that morphine analgesia depends on the integrity of monoaminergic transmitter systems. Some forms of stress analgesia seem to be related to morphine analgesia, while others are not. To assess whether opioid and non-opioid stress analgesia differ in their reliance on monoamine systems, the effects of parachlorophenylalanine (PCPA) and yohimbine on analgesia produced by prolonged intermittent and brief continuous footshock were examined on the hotplate test. The interaction of adrenergic and endorphinergic activity with serotonergic mechanisms following these stressors was also investigated by testing the effects of yohimbine and naloxone on rats with prior PCPA treatment. Yohimbine alone significantly reduced baseline hotplate latencies, while PCPA and naloxone did not. The two stressors differed in the effects produced by both naloxone and PCPA. Naloxone significantly reversed stress analgesia in the prolonged stress condition, but not the brief stress condition. PCPA significantly enhanced the antinociceptive effect of brief continuous shock, while leaving the response to prolonged intermittent shock unaffected. In contrast, yohimbine blocked the analgesic effects of prolonged stress. For the brief stress condition, naloxone reversed the elevated thresholds elicited in PCPA treated rats. Naloxone also reversed stress analgesia for PCPA treated rats exposed to prolonged intermittent stress. Yohimbine lowered the responses of PCPA treated rats subjected to brief continuous shock. These results support an interactive model of stress analgesia dependent upon serotonergic, adrenergic, and endorphinergic transmitter systems.

Naloxone hyperalgesia and stress-induced analgesia in rats.

Since past studies concerning the effects of naloxone on nociception have yielded inconclusive findings, the variables of pain test, baseline sensitivity, and stress condition were examined. Within a pure-bred strain of rats, consistent individual differences did not occur. All three measures of pain responsiveness demonstrated hyperalgesic effects of naloxone, but they differed in their capacity to reflect the effects of analgesia produced by continuous or intermittent electrical shock. By some measures, naloxone reversed the stress-induced analgesia due to intermittent shock; it did not influence the analgesia produced by continuous stress. The data support a model of pain inhibition involving both opioid and non-opioid systems and suggest that the hyperalgesic effects of naloxone can sometimes give rise to erroneous conclusions concerning apparent naloxone-reversability of putative analgesic procedures.