Stefan Lautenbacher

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.

Region-specific encoding of sensory and affective components of pain in the human brain: A positron emission tomography correlation analysis.

Brain imaging with positron emission tomography has identified some of the principal cerebral structures of a central network activated by pain. To discover whether the different cortical and subcortical areas process different components of the multidimensional nature of pain, we performed a regression analysis between noxious heat‐related regional blood flow increases and experimental pain parameters reflecting detection of pain, encoding of pain intensity, as well as pain unpleasantness. The results of our activation study indicate that different functions in pain processing can be attributed to different brain regions; ie, the gating function reflected by the pain threshold appeared to be related to anterior cingulate cortex, the frontal inferior cortex, and the thalamus, the coding of pain intensity to the periventricular gray as well as to the posterior cingulate cortex, and the encoding of pain unpleasantness to the posterior sector of the anterior cingulate cortex. Ann Neurol 1999;45:40–47

Recommendations on terminology and practice of psychophysical DNIC testing

a Department of Neurology, Rambam Health Care Campus, Technion Faculty of Medicine, Haifa, Israel b Department of Diagnostic Sciences, UMDNJ, Newark, NJ, USA c Laboratory of Experimental Pain Research, Aalborg University, Aalborg, Denmark d Hopital Ambroise Pare, Boulogne Billancourt, France e Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School Boston, MA, USA f College of Dentistry, University of Florida, Gainesville, FL, USA g Faculty of Health and Welfare Studies, University of Haifa, Haifa, Israel h Department of Molecular Medicine and Surgery, Karolinska Hospital/Institutet, Stockholm, Sweden i Department of Psychology, Bamberg University, Bamberg, Germany j Department of Surgery and Neurosurgery, Faculty of Medicine, Sherbrooke University, Sherbrooke, QC, Canada k Department of Anesthesiology, Radboud University, Nijmegen, Netherlands

Impairment of pain inhibition in chronic tension-type headache.

&NA; Evidence has been accumulated suggesting that a dysfunction in pain inhibitory systems, i.e. in ‘diffuse noxious inhibitory controls‘ (DNIC)‐like mechanisms, might be—amongst other factors—responsible for the development of anatomically generalized chronic pain like fibromyalgia. The aim of the present study was to look for similar impairments in chronic tension‐type headache (CTTH) as a regionally specific pain syndrome. Twenty‐nine CTTH patients and 25 age‐ and sex‐matched healthy control subjects participated in the study. After baseline assessment of electrical detection and pain thresholds, tonic heat stimuli were concurrently applied by a thermode to the thigh to induce DNIC‐like pain inhibition. Tonic heat stimuli were applied either slightly above (‘pain’ condition) or slightly below (‘heat’ condition) pain threshold. For determination of electrical detection and pain thresholds, electrocutaneous stimuli were administered either to the forearm (extra‐cranial site) or to the temple (cranial site), using a multiple staircase procedure. The increase in the electrical detection and pain thresholds induced by concurrent tonic heat stimulation was significantly smaller in the CTTH patients than in the control subjects. This group difference was present during the ‘pain’ as well as the ‘heat’ condition. Furthermore, the electrical detection and pain thresholds were affected in this group‐specific manner both at the forearm and at the temple. These findings suggest that patients with CTTH suffer from deficient DNIC‐like pain inhibitory mechanisms in a similar manner, as do patients with anatomically generalized chronic pain like fibromyalgia.

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).

Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain.

&NA; Experimental data on age‐related changes in pain perception have so far been contradictory. It has appeared that the type of pain induction method is critical in this context, with sensitivity to heat pain being decreased whereas sensitivity to pressure pain may be even enhanced in the elderly. Furthermore, it has been shown that temporal summation of heat pain is more pronounced in the elderly but it has remained unclear whether age differences in temporal summation are also evident when using other pain induction methods. No studies on age‐related changes in spatial summation of pain have so far been conducted. The aim of the present study was to provide a comprehensive survey on age‐related changes in pain perception, i.e. in somatosensory thresholds (warmth, cold, vibration), pain thresholds (heat, pressure) and spatial and temporal summation of heat and pressure pain. We investigated 20 young (mean age 27.1 years) and 20 elderly (mean age 71.6 years) subjects. Our results confirmed and extended previous findings by showing that somatosensory thresholds for non‐noxious stimuli increase with age whereas pressure pain thresholds decrease and heat pain thresholds show no age‐related changes. Apart from an enhanced temporal summation of heat pain, pain summation was not found to be critically affected by age. The results of the present study provide evidence for stimulus‐specific changes in pain perception in the elderly, with deep tissue (muscle) nociception being affected differently by age than superficial tissue (skin) nociception. Summation mechanisms contribute only moderately to age changes in pain perception.

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.

PAIN PERCEPTION IN PSYCHIATRIC DISORDERS: A REVIEW OF THE LITERATURE

Aberrations of pain experience occur frequently in psychiatric disorders and hence pathological alterations in the basic mechanisms underlying pain experience can be expected. Nevertheless, pain perception, as one of the most important basic mechanisms of pain experience, has rarely been assessed experimentally in psychiatric disorders. The authors review the relevant experimental studies on pain perception in patients with anxiety disorders, schizophrenia, depression, eating disorders and personality disorders and suggest lines for future research. Finally, they point out that the experimental study of pain perception is useful not only in understanding aberrant pain experiences in psychiatric disorders but also in elucidating pathophysiological mechanisms because pain perception is controlled by neurochemical and neurohormonal functions known to be affected by psychiatric disease processes.

Relationship between clinical pain complaints and pain sensitivity in patients with depression and panic disorder.

OBJECTIVE There is evidence that depression and panic disorder are both associated with an increased frequency of clinical pain complaints. A change in pain sensitivity is alleged to be involved in this phenomenon. However, few studies have assessed clinical pain complaints and pain sensitivity in the same group of patients. METHODS Thirteen patients with a major depressive disorder, 13 patients with a panic disorder (diagnoses based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition), and 13 healthy control subjects were investigated. None of the subjects were taking medications. Body maps were used to measure the number of painful sites as well as the intensity and unpleasantness of pain complaints in the previous 6 months. Furthermore, pain thresholds for pressure, cold, and heat were assessed at the forearm or hand. RESULTS Patients with depression and panic disorder had significantly more frequent, more intense, and more unpleasant pain complaints than healthy control subjects. Despite this similarity, patients with depression had significantly higher pain thresholds than patients with panic disorder in two (pressure and cold) of three stimulus modalities and significantly higher pressure pain thresholds than the healthy control subjects. There were no differences between the pain thresholds of patients with panic disorder and healthy control subjects. The correlations between clinical pain measures and pain thresholds were generally weak. CONCLUSIONS These findings suggest that the clinical pain complaints of patients with depression and panic disorder cannot simply be explained by changes in pain sensitivity.