Gary B. Rollman

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.

Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification.

&NA; 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.

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

&NA; 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. The pattern of hyperresponsiveness appears to involve both peripheral factors (e.g., sensitization of muscle nociceptors) and central ones (e.g., hypervigilance or a lack of nociceptive inhibition).

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.

Sex differences in responsiveness to painful and non-painful stimuli are dependent upon the stimulation method

&NA; Sex differences in thermo‐ and electrocutaneous responsiveness to painful and non‐painful stimuli were investigated in 20 women and 20 men. Heat pain, warmth, and cold thresholds were assessed on the hand and foot with a Peltier thermode system. In addition, subjects used magnitude estimation to judge the sensation intensity evoked by temperatures ranging from 38°C to 48°C applied to the forearm. To measure detection, pain, and tolerance thresholds of electrocutaneous sensitivity, electrical pulses were administered to the hand. Magnitude estimates of sensation intensity were assessed for stimuli ranging from 0.5 mA to 4.0 mA. There were no sex differences in heat pain, warmth and cold thresholds. There were significant sex differences in electrical detection, pain and tolerance thresholds, with lower thresholds in women. Correspondingly, magnitude estimates were similar in women and men when using thermal stimuli while women judged stimuli from 2.5 mA on as more intense than men when using electrical stimuli. Despite these discrepancies, the measures for pain responsiveness from the two stimulation methods correlated significantly. In contrast, no significant correlations between the methods were found when considering the responsiveness to non‐painful stimuli. The findings help to clarify controversies in the pain literature about sex differences. Results affirming and denying such differences could be obtained within a single sample, with stimulation method as the critical variable.

Signal detection theory measurement of pain: a review and critique.

Pain is a subjective experience. Therefore, attempts to measure its extent face the same difficulties which have long plagued experimenters hoping to scale other human sensations, but they are compounded further by complex emotional reactions and cognitive interpretations [ 411. Nonetheless, the need for improved methods of pain control mandates continued research on pain and its possible modulation by chemical, surgical, physiologic(al, or psychological procedures. Laboratory studies with normal rather than clinical subjecks allow parametric variations in the level of an experimentally induced pain, rather than reliance upon some unknown endogenous one. It is possible, as well, that some of the emotional variability associated with a pain of internti origin is thus eliminated, leading to more stable estimates of the magnitude of the pain sensation itself. The ability to vary the level of a potentially nociceptive stimulus has raised the hope that psychophysical procedures 1393, well-developed for studies of vision, audition, and the other senses, might also increase our understanding of human suffering. Although some notable advances have been made in the scaling of intense discomfort [1,26,34,51], many pain investigations have concentrated on the traditional “‘threshold” as the dependent variable, sometimes attempting to distinguish sep te thresholds for sensation, mild pain, strong pain, and maximal tolerance. The threshold appears, at first, to be easy to measure an easy to in”%3 pret. Its value can be obtained by noting the level of some uncomfor stimulus such as radiant heat or electric shock ntecessary to elicit a report of pain. In those instances where no manipulation is involved, thresholds hw been compared across groups (e.g. the variables of age, sex, race, or &l-ok group). In other instances, where the nature of a adecluate control is still

Signal detection theory pain measures: Empirical validation studies and adaptation-level effects

&NA; Proponents of the use of signal detection theory (SDT) in the assessment of pain modulation have generally looked for changes in d′ to indicate a reduction of sensory function, and a change in criterion to indicate a modification of the subjects response bias or attitudinal predisposition. In the first experiment, both assumptions failed to receive empirical verification. Discrimination d′ was equivalent before and after two strong levels of electrical current were reduced. The criterion parameter appeared to shift in a more conservative direction after the stimulus diminution. These results are used to question the validity of both detection and discrimination indices in the measurement of pain. An alternative means for describing the experimental results revealed a striking adaptation‐level effect with implications for the assessment of both experimentally induced and endogenous pain. The outcome of a second experiment reinforced the adaptation‐level theory interpretation of the results and provided additional evidence concerning the difficulties in evaluating SDT parameters in studies of potential analgesics.

Menstrual cycle modulation of tender points

Abstract Changes in pain sensitivity throughout the menstrual cycle were assessed in 36 normally menstruating women and 30 users of oral contraceptives. Pain sensitivity was measured with palpation of rheumatological tender points and with pressure dolorimetry. The number of tender points identified by palpation was greater in the follicular (postmenstrual) phase of the cycle as compared to the luteal (intermenstrual) phase in normally cycling women but not in users of oral contraceptives. These findings are related to previously described physiological and psychological features of the menstrual cycle, with particular emphasis on the role of hormonal events in modulating pain perception, particularly in musculoskeletal disorders such as fibromyalgia.

Simultaneous detection and recognition of chromatic flashes

Studies of simultaneous detection and recognition were performed to test alternative models of the detection process, signal detection theory and low-threshold theory. Sensitivity in a detection experiment was independent of whether the type of signal (red or green light flash) was known in advance, because only one type of s trial was possible, or was unknown because either stimulus could occur. When a recognition judgment was added to either a binary or rating-scale detection response, Ss were able to report the nature of the stimulus at better than chance levels even when they indicated that the stimulus was not detected. Since such performance occurred when Ss used detection responses likely to have been given only in the nondetect state, the data lead to the rejection of low-threshold theory.

The detectability, discriminability, and perceived magnitude of painful electrical shock

Thresholds for sensation, pain, and tolerance were obtained from 20 male and 20 female observers who received trains of electrical pulses applied to the volar forearm. Also determined were estimates of sensory magnitude for a series of stimuli that spanned the pain sensitivity range (PSR) between pain threshold and tolerance, as well as Weber fractions for the discrimination of stimuli at the midpoint of the PSR. There were great individual differences in all dependent variables. Females had significantly lower values for all thresholds but did not differ from males in the growth of sensory magnitude or in discriminatory capacity. Power functions, with a median exponent of 1.74 and a mean of 2.39, fit the scaling data well. The results are analyzed for a suggested negative correlation between exponent and stimulus range. The presence of such an effect indicates that electrocutaneous stimulation provides a powerful technique for the analysis of individual differences and the evaluation of psychophysical theories.