The effect of maximal exercise on temporal summation of second pain (windup) in patients with fibromyalgia syndrome

Exercise activates endogenous opioid and adrenergic systems, but attenuation of experimental pain by exercise has not been shown consistently. In this study, effects of exercise on temporal summation of late pain responses to stimulation of unmyelinated (C) nociceptors were assessed. When a preheated thermode was applied repetitively to glabrous skin of the hand in a series of brief contacts at rates of 0.2 to 0.5 Hz, the perceived intensity of late thermal sensations increased after successive contacts. This summation of pain sensations provides information regarding the status of central opioid and N-methyl-D-aspartate receptor systems. For normal subjects, temporal summation of late pain sensations was substantially attenuated when testing began 1.5 or 10 minutes after exercise. Individuals diagnosed with fibromyalgia syndrome (FMS) report generalized chronic pain that is increased after exercise. Therefore, we hypothesized that strenuous exercise would increase summation of late pain sensations in this cohort. Patients with FMS and control subjects exerted to similarly high metabolic rates, as shown by physiologic monitoring. Ratings of late pain sensations increased for patients with FMS after exercise, an effect opposite to a decrease in ratings for age/sex-matched control subjects. In contrast to this result for experimentally induced pain, clinical pain ratings were not substantially altered after strenuous exercise by patients with FMS.     

Enhanced temporal summation of second pain and its central modulation in fibromyalgia patients

We have previously shown that fibromyalgia (FMS) patients have enhanced temporal summation (windup) and prolonged decay of heat-induced second pain in comparison to control subjects, consistent with central sensitization. It has been hypothesized that sensory abnormalities of FMS patients are related to deficient pain modulatory mechanisms. Therefore, we conducted several analyses to further characterize enhanced windup in FMS patients and to determine whether it can be centrally modulated by placebo, naloxone, or fentanyl. Pre-drug baseline ratings of FMS and normal control (NC) groups were compared with determine whether FMS had higher pain sensitivity in response to several types of thermal tests used to predominantly activate A-delta heat, C heat, or cold nociceptors. Our results confirmed and extended our earlier study in showing that FMS patients had larger magnitudes of heat tap as well as cold tap-induced windup when compared with age- and sex-matched NC subjects. The groups differed less in their ratings of sensory tests that rely predominantly on A-delta-nociceptive afferent input. Heat and cold-induced windup were attenuated by saline placebo injections and by fentanyl (0.75 and 1.5 microg/kg). However, naloxone injection had the same magnitudes of effect on first or second pain as that produced by placebo injection. Hypoalgesic effects of saline placebo and fentanyl on windup were at least as large in FMS as compared to NC subjects and therefore do not support the hypothesis that pain modulatory mechanisms are deficient in FMS. To the extent that temporal summation of second pain (windup) contributes to processes underlying hyperalgesia and persistent pain states, these results indirectly suggest that these processes can be centrally modulated in FMS patients by endogenous and exogenous analgesic manipulations.     

Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients

Central mechanisms related to referred muscle pain and temporal summation of muscular nociceptive activity are facilitated in fibromyalgia syndrome (FMS) patients. The present study assessed the effects of an NMDA-antagonist (ketamine) on these central mechanisms. FMS patients received either i.v. placebo or ketamine (0.3 mg/kg, Ketalar((R))50% decrease in pain intensity at rest by active drug on two consecutive VAS assessments). Fifteen out of 17 ketamine-responders were included in the second part of the study. Before and after ketamine or placebo, experimental local and referred pain was induced by intramuscular (i.m.) infusion of hypertonic saline (0.7 ml, 5%) into the tibialis anterior (TA) muscle. The saline-induced pain intensity was assessed on an electronic VAS, and the distribution of pain drawn by the subject. In addition, the pain threshold (PT) to i.m. electrical stimulation was determined for single stimulus and five repeated (2 Hz, temporal summation) stimuli. The pressure PT of the TA muscle was determined, and the pressure PT and pressure pain tolerance threshold were determined at three bilaterally located tenderpoints (knee, epicondyle, and mid upper trapezius). VAS scores of pain at rest were progressively reduced during ketamine infusion compared with placebo infusion. Pain intensity (area under the VAS curve) to the post-drug infusion of hypertonic saline was reduced by ketamine (-18. 4+/-0.3% of pre-drug VAS area) compared with placebo (29.9+/-18.8%, P<0.02). Local and referred pain areas were reduced by ketamine (-12. 0+/-14.6% of pre-drug pain areas) compared with placebo (126.3+/-83. 2%, P<0.03). Ketamine had no significant effect on the PT to single i.m. electrical stimulation. However, the span between the PT to single and repeated i.m. stimuli was significantly decreased by the ketamine (-42.3+/-15.0% of pre-drug PT) compared with placebo (50. 5+/-49.2%, P<0.03) indicating a predominant effect on temporal summation. Mean pressure pain tolerance from the three paired tenderpoints was increased by ketamine (16.6+/-6.2% of pre-drug thresholds) compared with placebo (-2.3+/-4.9%, P<0.009). The pressure PT at the TA muscle was increased after ketamine (42.4+/-9. 2% of pre-drug PT) compared with placebo (7.0+/-6.6%, P<0.011). The present study showed that mechanisms involved in referred pain, temporal summation, muscular hyperalgesia, and muscle pain at rest were attenuated by the NMDA-antagonist in FMS patients. It suggested a link between central hyperexcitability and the mechanisms for facilitated referred pain and temporal summation in a sub-group of the fibromyalgia syndrome patients. Whether this is specific for FMS patients or a general phenomena in painful musculoskeletal disorders is not known.     

Temporal summation of second pain and its maintenance are useful for characterizing widespread central sensitization of fibromyalgia patients.

Temporal summation of second pain (TSSP) results from repetitive stimulation of peripheral C-fibers (>0.33 Hz) and is thought to reflect summation mechanisms of dorsal horn neurons (ie, windup). Both TSSP and windup result in short term enhancement of C fiber-evoked responses that decay rapidly after the end of stimulation. However, very low stimulus frequencies (0.17 to 0.08 Hz) can maintain this enhancement after TSSP and windup have occurred. This maintained enhancement is termed TSSP-maintenance (TSSP-M) and is indicative of central sensitization. TSSP-M may be especially relevant for chronic pain conditions such as fibromyalgia (FM) and may play an important role in its pathogenesis. Whereas TSSP-M of heat induced pain is well-characterized in human subjects at spinal cord levels related to the upper body, TSSP-M at spinal levels related to the lower body has not been previously studied. The present study was designed to evoke TSSP-M at the upper and lower extremities of normal controls (NC) and FM patients and thus characterize their spatial distribution of central sensitization. Twenty-three NC and 26 FM patients were enrolled in this study. TSSP-M testing consisted of repetitive heat pain stimulation at the thenar eminences of the hands or feet. The subjects rated the pain intensity of repetitive heat stimuli as well as 15- and 30-second pain aftersensations. The experiments demonstrated significant TSSP-M for both NC and FM patients. In contrast to NC, TSSP-M ratings of heat stimuli were increased in FM patients and their TSSP-aftersensations (TSSP-AS) were prolonged. There was, however, no statistical difference between TSSP-M ratings or TSSP-AS at the hands or feet in either NC or FM patients. These findings demonstrate that central sensitization of FM patients is widespread and similar along the spinal neuroaxis. PERSPECTIVE: The pain of FM seems to be accompanied by generalized central sensitization, involving the length of the spinal neuroaxis. Thus, widespread central sensitization appears to be a hallmark of FM and may be useful for the clinical case definition of this prevalent pain syndrome. In addition, measures of widespread central sensitization, like TSSP-M could also be used to assess treatment responses of FM patients.     

Repetition-induced activity-related summation of pain in patients with fibromyalgia

This study compared individuals with fibromyalgia (FM) and individuals with chronic low back pain (CLBP) on repetition-induced summation of activity-related pain (RISP). Fear of movement, pain catastrophizing and depression were examined as potential mediators of group differences. The sample consisted of 50 women with FM and 50 women with CLBP who were matched on age, pain severity and pain duration. Participants were asked to lift a series of 18 weighted canisters. In one trial, participants were asked to rate their pain after each lift. In a second trial, participants estimated the weight of each of the canisters. An index of repetition-induced summation of pain was derived as the change in pain ratings across repeated lifts. Analyses revealed that women with FM obtained higher scores on the index of RISP than women with CLBP. The heightened sensitivity to RISP in individuals with FM was not due to generalized hyperalgesia or a greater work output. Consistent with previous research, fear of movement was positively correlated with RISP. Pain disability was also associated with greater RISP, but not pain catastrophizing or depression. Discussion addresses the processes by which individuals with FM might have increased RISP responses. The findings of this study point to possible neurophysiological mechanisms that could help explain the high levels of pain-related disability seen in individuals with FM.     

Diffuse noxious inhibitory controls (DNIC) attenuate temporal summation of second pain in normal males but not in normal females or fibromyalgia patients

Diffuse noxious inhibitory control (DNIC) is part of a central pain modulatory system that relies on spinal and supraspinal mechanisms. Previous studies have shown that fibromyalgia (FMS) patients are lacking DNIC effects on experimental pain, compared to normal control (NC) subjects. Because DNIC has a greater effect on second pain than on first pain, we hypothesized that wind-up (WU) of second pain should be attenuated by a strong conditioning stimulus. Thus, we compared DNIC's effect on WU in three groups of subjects: 11 NC males, 22 NC females, and 11 FMS females. To separately assess the contributions of distraction related mechanisms to inhibition of second pain, we designed the experiment in such a way that directed the subjects' attention to either the test or conditioning stimulus. Repeated heat taps to the thenar surface of the right hand were used as test stimuli to generate WU of second pain. Immersion of the left hand into a hot water bath was the conditioning stimulus. As previous experiments have shown, DNIC requires a strong conditioning stimulus for pain attenuation, which may be at least partly dependent on a distraction effect. DNIC significantly inhibited thermal WU pain in normal male subjects, but adding distraction to the DNIC effect did not increase the extent of this inhibition. In contrast, neither DNIC nor DNIC plus distraction attenuated thermal WU pain in female NCs. DNIC plus distraction but not DNIC alone produced significant inhibition of thermal WU pain in female FMS patients. Our results indicate that DNIC effects on experimental WU of second pain are gender specific, with women generally lacking this pain-inhibitory mechanism.     

Cutaneous C-fiber pain abnormalities of fibromyalgia patients are specifically related to temporal summation

Temporal summation of "second pain" (TSSP) is considered to be the result of C-fiber-evoked responses of dorsal horn neurons, termed 'windup'. TSSP is dependent on stimulus frequency (> or=0.33Hz) and is relevant for central sensitization and chronic pain. We have previously shown that compared to normal controls (NC), fibromyalgia (FM) subjects show abnormal TSSP, requiring lower stimulus intensities/frequencies to achieve similar TSSP. However, it is unknown whether abnormal TSSP in FM is influenced by peripheral sensitization of C-fiber nociceptors and/or bias in pain ratings. Thus, we evaluated 14 FM subjects and 19 NC with pain threshold tests to selective C-fiber stimulation, 30s heat stimuli, and repetitive brief (1.5s) heat pulses at 0.33Hz using a contact heat stimulator (CHEPS). The intensity of heat pulses was varied to achieve maximal TSSP ratings of 45+/-10 (numerical pain scale 0-100) in both FM and NC groups. We found that NC and FM subjects had similar pain thresholds to C-fiber stimulation and yet FM subjects required lower heat pulse temperatures to generate the same magnitudes of TSSP (p<.05). This combination of findings does not support peripheral sensitization and suggests central TSSP abnormalities in FM subjects. In a second experiment, all aspects of individually adjusted TSSP heat pulses were kept the same except that the baseline temperature (BT) between heat pulses was surreptitiously alternated between 35 degrees C and 40 degrees C. These changes of BT resulted in significantly greater TSSP ratings of FM subjects compared to NC subjects, both at 35 degrees C and at 40 degrees C, but did not change their response to the first heat pulse of a stimulus train. These findings provide strong support for alterations of central pain sensitivity and not peripheral sensitization or rating bias as responsible for TSSP differences between NC and FM subjects.     

Effective connectivity among brain regions associated with slow temporal summation of C-fiber-evoked pain in fibromyalgia patients and healthy controls

Temporal summation of "second pain" (TSSP) or "windup" results from the summation of C-fiber-evoked responses of dorsal-horn neurons. This phenomenon is dependent on stimulus frequency (≥.33 Hz) and relevant to central sensitization and chronic pain. Our previous neuroimaging studies characterized brain regions associated with TSSP in normal control (NC) and fibromyalgia (FM) groups. During an fMRI scan, subjects received sensitivity-adjusted repetitive heat pulses at .33 on the right foot. FM subjects required significantly lower stimulus intensities than NC to achieve similar TSSP and no significant group differences in the pain-related brain activity were detected. In our current study, we asked whether the effective connectivity among a set of TSSP-related brain regions identified in our previous work differs amongst FM and NC groups. Structural equation modeling was used to characterize the effective connectivity amongst a priori selected brain areas, including the thalamus, S1, S2, posterior insula, and the anterior midcingulate cortex (aMCC) within the left and right hemispheres. This analysis confirmed our a priori models of effective connectivity among these regions mainly confirmed those hypothesized, yet some unpredicted connections were additionally identified (thalamus to aMCC and aMCC to S1). While the models of effective connectivity were not identical in the FM and NC groups, they were very similar. Additionally, the TSSP related effective connectivity of right and left hemisphere regions was very similar. These results provide evidence for significant overlap of the fundamental brain mechanisms that process sensory and affective information related to TSSP in NC and FM groups. PERSPECTIVE: Models of effective connectivity involving pain-related processes were estimated with fMRI data from chronic pain and healthy populations. Models were estimated in both hemispheres, and although similar, fibromyalgia was associated with unique models of pain-related processes. Group differences involved the left hemisphere and S1, S2, and posterior insula.     

Brain activity associated with slow temporal summation of C‐fiber evoked pain in fibromyalgia patients and healthy controls

Temporal summation of “second pain” (TSSP) is the result of C‐fiber‐evoked responses of dorsal‐horn neurons, termed “windup”. This phenomenon is dependent on stimulus frequency (≥0.33Hz) and relevant for central sensitization as well as chronic pain. Whereas, our previous functional magnetic resonance imaging (fMRI) study characterized neural correlates of TSSP in 11 healthy volunteers, the present study was designed to compare brain responses associated with TSSP across these healthy participants and 13 fibromyalgia (FM) patients. Volume‐of‐interest analysis was used to assess TSSP‐related brain activation. All participants underwent fMRI‐scanning during repetitive heat pulses at 0.33Hz and 0.17Hz to the right foot. Stimulus intensities were adjusted to each individual's heat sensitivity to achieve comparable TSSP‐ratings of moderate pain in all subjects. Experimental pain ratings showed robust TSSP during 0.33Hz but not 0.17Hz stimuli. When stimulus strength was adjusted to induce equivalent levels of TSSP, no differences in activation of pain‐related brain regions occurred across NC and FM groups. Subsequently, the fMRI‐data of both groups were combined to increase the power of our statistical comparisons. fMRI‐statistical maps identified several brain regions with stimulus and frequency dependent activation consistent with TSSP, including ipsilateral and contralateral thalamus, medial thalamus, S1, bilateral S2, mid‐ and posterior insula, rostral and mid‐anterior cingulate cortex. However, the stimulus temperatures necessary to evoke equivalent levels of TSSP and corresponding brain activity were less in FM patients. These results suggest that enhanced neural mechanisms of TSSP in FM are reflected at all pain related brain areas, including posterior thalamus, and are not the result of selective enhancement at cortical levels.     

Advanced continuous-contact heat pulse design for efficient temporal summation of second pain (windup).

Temporal summation of second pain or windup (WU(SP)) can be reliably evoked in normal human subjects by repetitive heat pulses to the skin at frequencies of 0.33 Hz or more. This phenomenon is dependent on activation of peripheral C-nociceptors and central N-methyl-D-aspartate receptors, resulting in windup of C-fiber-evoked discharges of dorsal horn neurons. Several investigations of heat pain summation have used Peltier devices for intermittent-contact heat pulses to the skin. This method returns the skin to an adapting temperature between each stimulus and can result in distinct first and second pain sensations. An alternative method of temporal summation consists of continuous-contact heat stimuli by computerized Peltier thermodes that can provide rapid heat pulses. Previously used continuous-contact heat pulse trains, however, seemed to lack characteristics that result in efficient WU(SP). The present study sought to obtain psychophysical evidence that reliable WU(SP) can be elicited with an advanced pulse design by using a computerized heat-foil/Peltier thermode. WU(SP) was elicited by repetitive thermal stimulation of the hands at frequencies of 0.33 Hz but not 0.25 and 0.17 Hz. WU(SP) stimuli were either adjusted to resemble the heat transfer characteristics of intermittent-contact stimulus trains, or they remained unadjusted. The estimated transmission velocity of impulses giving rise to second pain and WU(SP) was characteristic of C fibers. More pronounced second pain and efficient WU(SP) could be elicited with adjusted than with unadjusted heat pulse trains. Thus, specifically designed continuous-contact heat pulses can be used to elicit distinct second pain and robust WU(SP), thereby providing an efficient psychophysical test of this phenomenon. PERSPECTIVE: Temporal summation testing is rapidly becoming a relevant psychophysical tool for the study of chronic pain disorders. The results of this study will allow more efficient use of currently available constant-contact thermodes for clinical and research applications.     

Predictors of clinical pain intensity in patients with fibromyalgia syndrome

Central changes in pain processing have been previously reported in patients with fibromyalgia syndrome. These changes include decreased thresholds to mechanical and thermal stimuli (allodynia) and central sensitization, both of which are fundamental to the generation of clinical pain. Therefore, psychophysical measures of central pain processing may be useful predictors of clinical pain intensity of fibromyalgia syndrome patients. Previous studies of fibromyalgia syndrome patients have shown statistically significant correlations of psychophysical test results with clinical pain intensity. The tests used to characterize this important relationship were dependent on spinal cord pain mechanisms and included temporal summation of pain or wind-up and wind-up after-sensations. Particularly, the magnitude of wind-up after-sensations appeared to be one of the best predictors for clinical pain intensity of fibromyalgia syndrome patients (27%). Furthermore, the combination of tender point count, negative affect, and wind-up aftersensations accounted for approximately 50% of the variance in clinical pain intensity of fibromyalgia syndrome patients. Therefore, wind-up after-sensations, tender point count, and negative affect not only seem to represent relevant pain mechanisms but also strongly emphasize their importance for fibromyalgia syndrome pain.     

Temporal summation of pain from mechanical stimulation of muscle tissue in normal controls and subjects with fibromyalgia syndrome

Individuals diagnosed with fibromyalgia syndrome (FMS) report chronic pain that is frequently worsened by physical activity and improved by rest. Palpation of muscle and tendinous structures suggests that nociceptors in deep tissues are abnormally sensitive in FMS, but methods of controlled mechanical stimulation of muscles are needed to better characterize the sensitivity of deep tissues. Accordingly, force-controlled mechanical stimulation was applied to the flexor digitorum muscle of the forearm in a series of brief contacts (15 stimuli, each of 1s duration, at 3 or 5s interstimulus intervals). Repetitive stimulation was utilized to determine whether temporal summation of deep muscular pain would occur for normal subjects and would be enhanced for FMS subjects. Moderate temporal summation of deep pain was observed for normal controls (NC), and temporal summation was greatly exaggerated for FMS subjects. Temporal summation for FMS subjects occurred at substantially lower forces and at a lower frequency of stimulation. Furthermore, painful after-sensations were greater in amplitude and more prolonged for FMS subjects. These observations complement a previous demonstration that temporal summation of pain and after-sensations elicited by thermal stimulation of the skin are moderately enhanced for FMS subjects. Abnormal input from muscle nociceptors appears to underlie production of central sensitization in FMS that generalizes to input from cutaneous nociceptors.     

Effects of the N-methyl-D-aspartate receptor antagonist dextromethorphan on temporal summation of pain are similar in fibromyalgia patients and normal control subjects.

Temporal summation of second pain at least partly reflects temporal summation of dorsal horn neuronal responses, and both have been termed windup (WU), a form of nociception-dependent central sensitization. Animal and human experiments have shown that both forms of WU depend on N-methyl-D-aspartate (NMDA) and substance P receptor systems. WU of second pain (WU(SP)) in patients with fibromyalgia (FM) is enhanced compared with normal control (NC) subjects and is followed by exaggerated WU(SP) aftersensations and prolonged WU(SP) maintenance at low stimulus frequencies. Because the enhanced WU(SP) of FM patients could be related to abnormal endogenous modulation of NDMA receptors, we tested the effects of the NMDA receptor antagonist dextromethorphan (DEX) on WU(SP) in FM and NC subjects in a double-blind, placebo-controlled, crossover study. WU(SP) was elicited by trains of 0.7-second duration thermal pulses applied to the glabrous surface of the hands or by 1-second mechanical stimuli to the adductor pollicis muscle of the hands at a frequency of 0.33 Hz. In comparison to baseline and placebo conditions, single oral doses of DEX 60 and 90 mg reduced thermal and mechanical WU(SP) in NC and FM subjects, with DEX 90 mg being most effective. These effects did not differ for male and female NC subjects. FM subjects required less thermal and mechanical stimulus intensity than NC to achieve maximal WU(SP), but the extent of WU(SP) reduction by DEX did not statistically differ between NC and FM subjects for all study conditions. Thus, central pain processing of FM subjects is not different from NC in at least one important aspect, namely their NMDA receptor system responsiveness to pharmacologic inhibition by DEX. PERSPECTIVE: Results of this study demonstrate that FM patients show abnormal WU(SP) during thermal and mechanical stimulation compared with NC. Because oral doses of the NMDA receptor antagonist DEX attenuated thermal and mechanical WU(SP) similarly in FM patients and NC, other mechanisms than WU(SP) need to be considered for the widespread pain of FM patients. These mechanisms might include tonic nociceptive input from peripheral tissues and/or enhanced descending facilitation.     

Prevalence of fear of pain and activity in patients with fibromyalgia syndrome

Patients with fibromyalgia syndrome (FMS) report pain, fatigue, emotional distress, activity avoidance, and disability. The role of fear of pain and activity in FMS patients has received only limited attention. FMS patients (N = 233) underwent examinations by a physician, physical therapist, and psychologist and completed measures of fear of pain and activity, disability, depressive mood, impact, and pain. Patients with high levels of fear of pain and activity (38.6%) reported greater disability (t = 4.02, P < .001), depressed mood (t = -4.14, P < .001), pain severity (t = -2.71, P < .01), and lower treadmill performance (t = -2.39, P < .05) than patients with low fear. Patients classified on the Multidimensional Pain Inventory as Dysfunctional reported greater fear than Interpersonally Distressed patients and Adaptive Copers (F = 8.13, P < .001). Only 50% of Dysfunctional patients, however, met the criterion of high fear, whereas 23.4% of Adaptive Copers met this criterion. Demographic factors, perceived disability, and Multidimensional Pain Inventory subgroup significantly predicted fear of pain and activity, accounting for 21.2% of the variance. Fear of pain and activity is prevalent among FMS patients. Treatment should address patient fears, because it might reduce disability and rates of nonadherence and attrition from outcome studies. PERSPECTIVE: Fear of movement is a significant concern for chronic pain sufferers because these behaviors maintain pain and increase disability. This study examined the role of fear in FMS, including associations between fear of pain/movement, pain severity, depressed mood, physical performance, and disability in FMS subgroups.     

Spatial summation of heat pain within and across dermatomes in fibromyalgia patients and pain-free subjects

The mechanisms of spatial summation of pain (SSP) include pain coding dependent on impulse frequency and the number of recruited central neurons. However, SSP may also be influenced by pain inhibitory mechanisms, such as diffuse noxious inhibitory controls. Abnormal interactions between pain inhibitory mechanisms and SSP may be relevant for chronic pain conditions such as fibromyalgia (FM) and may help explain why widespread pain is characteristic for this chronic pain syndrome. The present study was designed to determine the difference of thermal SSP in the upper extremities between FM and normal control (NC) subjects, particularly within and across dermatomes of the hand. Fourteen NC and 19 FM subjects were enrolled in this study. SSP testing sessions involved immersion of each individual fingertip as well as stepwise immersion of the fingers, hands, and forearms in a hot water bath (46 degrees Celsius) for 5s and 20s. In addition, immersion of several fingertips across dermatome C(7)-C(8) was compared to progressive immersion of the index finger (dermatome C(7)). These experiments demonstrated significant spatial summation of heat-induced pain in both FM and NC subjects. SSP was most extensive within the fingers, and became negligible as the stimulus area increased above the hand. Furthermore, SSP was more pronounced within one dermatome such as that of the index finger than across several dermatomes of the hand. These results were similar for both FM and NC subjects. Thus, mechanisms of SSP, including possible inhibitory factors that limit this relevant pain mechanism, appear to be similar for both FM and NC subjects.     

Spatial summation of mechanically evoked muscle pain and painful aftersensations in normal subjects and fibromyalgia patients

Impulse frequency and number of recruited central neurons are relevant for pain encoding and temporal as well as spatial summation of pain (SSP). Whereas SSP of heat-induced pain is well characterized, mechanical SSP (MSSP) has been less studied. MSSP may be relevant for chronic pain conditions like fibromyalgia (FM) and play an important role in the pathogenesis of this chronic pain syndrome. Our study was designed to determine MSSP in 12 normal controls (NC) and 11 FM subjects. MSSP testing consisted of 5 s suprathreshold pressure-pain stimulations of forearm muscles by up to three identical probes (separated by 4 or 8 cm). The stimulated areas ranged between 0.79 and 2.37 cm2. The subjects rated the pain intensity of mechanical stimuli as well as pain aftersensations. Although MSSP increased monotonically in NC and FM subjects, pressure pain and pressure pain aftersensations were greater in FM subjects and highly associated with clinical pain intensity (r2=.44-.64), suggesting that spatial and temporal summation factors may contribute to overall clinical pain. However, despite higher experimental pain ratings, the magnitude of MSSP was not statistically different between NC and FM subjects. Furthermore, muscle stimuli elicited more MSSP when separated by 8 cm than 4 cm and this finding was not different between NC and FM subjects. Thus, mechanisms of MSSP were similar for both FM and NC subjects. The important role of MSSP for pain encoding suggests that decreasing pain in some muscle areas by local anesthetics or other means may improve overall clinical pain of FM patients.     

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

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.     

Myofascial pain syndrome and fibromyalgia

Myofascial pain syndrome and fibromyalgia represent two of the most common musculoskeletal disorders seen in clinical practice. Although evidence is not conclusive, these two syndromes appear to be distinct pathophysiologically. Trigger points represent a hallmark of myofascial pain whereas fibromyalgia is characterized by diffuse pain complaints. Characterization of the pain with fibromyalgia has been reproducible across patients and mapped out by the American College of Rheumatology. Both conditions require multidisciplinary therapy when not responsive to specific treatment plans. Both conditions benefit greatly from maintaining a regular physical therapy program. Cognitive and behavioral therapies as well as relaxation and coping strategies are effective modalities for many patients. Selective medications and nerve blocks in myofascial pain can help make patients more functional.