Fibromyalgia: Giesecke T

Petzke F, Giesecke T. · No affiliation provided · Schmerz. · Pubmed #15997479 No free full text.

This publication has no abstract.

Gracely RH, Grant MA, Giesecke T. · Department of Medicine, University of Michigan Health System, Ann Arbor VAMC, Ann Arbor, MI 48109-0483, USA. · Best Pract Res Clin Rheumatol. · Pubmed #12849714 No free full text.

Abstract: Fibromyalgia is defined by widespread pain and tenderness at a minimum of 11 of 18 defined tender points. Current evidence indicates that tender points are not unique to fibromyalgia and are simply regions in the body where all people are more tender. Tenderness (i.e. sensitivity to pressure) is widespread in fibromyalgia rather than being confined to tender points, and patients are also more sensitive to heat, cold and electrical stimulation. Using the number of painful tender points as a measure of tenderness is clinically expedient but is theoretically vulnerable to bias and is influenced by subjective distress. Other means of assessing tenderness (e.g. pressure dolorimeter devices, or more elaborate psychophysical methods) demonstrate the same increased pain sensitivity in fibromyalgia that is noted with tender point assessments, but these measures are relatively independent of biasing factors or distress. Fibromyalgia is one of only a few syndromes defined by the presence of both spontaneous (i.e. clinical) and evoked (i.e. experimental) pain. While the issues associated with the evaluation of spontaneous pain are shared with all chronic pain syndromes, the issues associated with the evaluation of evoked pain sensitivity are specific to fibromyalgia and related musculoskeletal disorders. This chapter focuses on the evaluation of altered pain sensitivity in fibromyalgia. It describes current measurement methodology, briefly reviews studies of sensitivity to experimentally evoked painful and non-painful sensations, analyses the factors assessed by different measurement methodologies, and concludes with recommendations for future diagnostic criteria and measurement methods.

Jensen KB, Kosek E, Petzke F, Carville S, Fransson P, Marcus H, Williams SC, Choy E, Giesecke T, Mainguy Y, Gracely R, Ingvar M. · Stockholm Brain Institute, Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden. · Pain. · Pubmed #19410366 No free full text.

Abstract: Over the years, many have viewed Fibromyalgia syndrome (FMS) as a so-called "functional disorder" and patients have experienced a concomitant lack of interest and legitimacy from the medical profession. The symptoms have not been explained by peripheral mechanisms alone nor by specific central nervous system mechanisms. In this study, we objectively evaluated the cerebral response to individually calibrated pain provocations of a pain-free body region (thumbnail). The study comprised 16 female FMS patients and 16 individually age-matched controls. Brain activity was measured using functional magnetic resonance imaging (fMRI) during individually calibrated painful pressures representing 50 mm on a visual analogue scale (VAS) ranging from 0 to 100 mm. Patients exhibited higher sensitivity to pain provocation than controls as they required less pressure to evoke equal pain magnitudes (U(A)=48, p<.002). Despite lower pressures applied in patients at VAS 50 mm, the fMRI-analysis revealed no difference in activity in brain regions relating to attention and affect or regions with sensory projections from the stimulated body area. However, in the primary link in the descending pain regulating system (the rostral anterior cingulate cortex) the patients failed to respond to pain provocation. The attenuated response to pain in this brain region is the first demonstration of a specific brain region where the impairment of pain inhibition in FMS patients is expressed. These results validate previous reports of dysfunctional endogenous pain inhibition in FMS and advance the understanding of the central pathophysiologic mechanisms, providing a new direction for the development of successful treatments in FMS.

Harris RE, Gracely RH, McLean SA, Williams DA, Giesecke T, Petzke F, Sen A, Clauw DJ. · Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, Michigan 48106, USA. · J Pain. · Pubmed #16814691 No free full text.

Abstract: Evoked pain measures such as tender point count and dolorimetry are often used to determine tenderness in studies of fibromyalgia (FM). However, these measures frequently do not improve in clinical trials and are known to be influenced by factors other than pain such as distress and expectancy. The purpose of this investigation was to determine whether evoked pain paradigms that present pressure stimuli in a random fashion (eg, Multiple Random Staircase [MRS]) would track with clinical pain improvement in patients with FM better than traditional measures. Sixty-five subjects enrolled in a randomized clinical trial of acupuncture were observed longitudinally. Clinical pain was measured on a 101-point numerical rating scale (NRS) and the Short Form McGill Pain Questionnaire (SF-MPQ), whereas evoked pressure sensitivity was assessed via manual tender point count, dolorimetry, and MRS methods. Improvements in clinical pain and evoked pain were assessed irrespective of group assignment. Improvement was seen in clinical pain during the course of the trial as measured by both NRS (P = .032) and SF-MPQ (P = .001). The MRS was the only evoked pain measure to improve correspondingly with treatment (MRS, P = .001; tender point count and dolorimeter, P > .05). MRS change scores were correlated with changes in NRS pain ratings (P = .003); however, this association was not stronger than tender point or dolorimetry correlations with clinical pain improvement (P > .05). Pain sensitivity as assessed by random paradigms was associated with improvements in clinical FM pain. Sophisticated pain testing paradigms might be responsive to change in clinical trials. PERSPECTIVE: Trials in fibromyalgia often use both clinical and experimental methods of pain assessment; however, these two outcomes are often poorly correlated. We explore the relationship between changes in clinical and experimental pain within FM patients. Pressure pain testing that applies stimuli in a random order is associated with improvements in clinical pain, but this association was not stronger than other experimental techniques.

Geisser ME, Gracely RH, Giesecke T, Petzke FW, Williams DA, Clauw DJ. · Chronic Pain and Fatigue Research Center, Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA. · Eur J Pain. · Pubmed #16546424 No free full text.

Abstract: Evoked or experimental pain is often used as a model for the study of clinical pain, yet there are little data regarding the relationship between the two. In addition, there are few data regarding the types of stimuli and stimulus intensities that are most closely related to clinical pain. In this study, 36 subjects with fibromyalgia (FM), chronic fatigue syndrome (CFS), or both syndromes were administered measures of clinical pain and underwent a dolorimetry evaluation. Subjects also underwent experimental pain testing utilizing heat and pressure stimulation. Stimulation levels evoking low, moderate and high sensory intensity, and comparable levels of unpleasantness, were determined for both types of stimuli using random staircase methods. Clinical pain was assessed using visual analogue ratings and the short form of the McGill Pain Questionnaire (MPQ). Ratings of heat pain sensation were not significantly associated with clinical pain ratings, with the exception of unpleasantness ratings at high stimulus intensities. Pain threshold and tolerance as assessed by dolorimetry were significantly associated with average measures of clinical pain. Both intensity and unpleasantness ratings of pressure delivered using random staircase methods were significantly associated with clinical pain at low, moderate and high levels, and the strength of the association was greater at increasingly noxious stimulus intensities. These findings suggest that random pressure stimulation as an experimental pain model in these populations more closely reflects the clinical pain for these conditions. These findings merit consideration when designing experimental studies of clinical pain associated with FM and CFS.

Giesecke T, Gracely RH, Williams DA, Geisser ME, Petzke FW, Clauw DJ. · University of Michigan, Ann Arbor, USA. · Arthritis Rheum. · Pubmed #15880832 links to  free full text

Abstract: OBJECTIVE: Individuals with chronic pain frequently display comorbid depression, but the impact of symptoms of depression on pain processing is not completely understood. This study evaluated the effect of symptoms of depression and/or clinically diagnosed major depressive disorder (MDD) on pain processing in patients with fibromyalgia (FM). METHODS: Results of quantitative sensory testing and neural responses to equally painful pressure stimuli (measured by functional magnetic resonance imaging [fMRI]) were compared with the levels of symptoms of depression and comorbid MDD among patients with FM. RESULTS: Neither the level of symptoms of depression nor the presence of comorbid MDD was associated with the results of sensory testing or the magnitude of neuronal activation in brain areas associated with the sensory dimension of pain (primary and secondary somatosensory cortices). However, symptoms of depression and the presence of MDD were associated with the magnitude of pain-evoked neuronal activations in brain regions associated with affective pain processing (the amygdalae and contralateral anterior insula). Clinical pain intensity was associated with measures of both the sensory dimension of pain (results of sensory testing) and the affective dimension of pain (activations in the insula bilaterally, contralateral anterior cingulate cortex, and prefrontal cortex). CONCLUSION: In patients with FM, neither the extent of depression nor the presence of comorbid major depression modulates the sensory-discriminative aspects of pain processing (i.e., localizing pain and reporting its level of intensity), as measured by sensory testing or fMRI. However, depression is associated with the magnitude of neuronal activation in brain regions that process the affective-motivational dimension of pain. These data suggest that there are parallel, somewhat independent neural pain-processing networks for sensory and affective pain elements. The implication for treatment is that addressing an individual's depression (e.g., by prescribing an antidepressant medication that has no analgesic properties) will not necessarily have an impact on the sensory dimension of pain.

Gracely RH, Geisser ME, Giesecke T, Grant MA, Petzke F, Williams DA, Clauw DJ. · Department of Internal Medicine, Division of Rheumatology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, MI 48106, USA. · Brain. · Pubmed #14960499 links to  free full text

Abstract: Pain catastrophizing, or characterizations of pain as awful, horrible and unbearable, is increasingly being recognized as an important factor in the experience of pain. The purpose of this investigation was to examine the association between catastrophizing, as measured by the Coping Strategies Questionnaire Catastrophizing Subscale, and brain responses to blunt pressure assessed by functional MRI among 29 subjects with fibromyalgia. Since catastrophizing has been suggested to augment pain perception through enhanced attention to painful stimuli, and heightened emotional responses to pain, we hypothesized that catastrophizing would be positively associated with activation in structures believed to be involved in these aspects of pain processing. As catastrophizing is also strongly associated with depression, the influence of depressive symptomatology was statistically removed. Residual scores of catastrophizing controlling for depressive symptomatology were significantly associated with increased activity in the ipsilateral claustrum (r = 0.51, P < 0.05), cerebellum (r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.47, P < 0.05), and parietal cortex (r = 0.41, P < 0.05), and in the contralateral dorsal anterior cingulate gyrus (ACC; r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.41, P < 0.05), medial frontal cortex (r = 0.40, P < 0.05) and lentiform nuclei (r = 0.40, P < 0.05). Analysis of subjects classified as high or low catastrophizers, based on a median split of residual catastrophizing scores, showed that both groups displayed significant increases in ipsilateral secondary somatosensory cortex (SII), although the magnitude of activation was twice as large among high catastrophizers. Both groups also had significant activations in contralateral insula, SII, primary somatosensory cortex (SI), inferior parietal lobule and thalamus. High catastrophizers displayed unique activation in the contralateral anterior ACC, and the contralateral and ipsilateral lentiform. Both groups also displayed significant ipsilateral activation in SI, anterior and posterior cerebellum, posterior cingulate gyrus, and superior and inferior frontal gyrus. These findings suggest that pain catastrophizing, independent of the influence of depression, is significantly associated with increased activity in brain areas related to anticipation of pain (medial frontal cortex, cerebellum), attention to pain (dorsal ACC, dorsolateral prefrontal cortex), emotional aspects of pain (claustrum, closely connected to amygdala) and motor control. These results support the hypothesis that catastrophizing influences pain perception through altering attention and anticipation, and heightening emotional responses to pain. Activation associated with catastrophizing in motor areas of the brain may reflect expressive responses to pain that are associated with greater pain catastrophizing.

Giesecke T, Gracely RH, Grant MA, Nachemson A, Petzke F, Williams DA, Clauw DJ. · University of Michigan, Ann Arbor, MI 48106, USA. · Arthritis Rheum. · Pubmed #14872506 links to  free full text

Abstract: OBJECTIVE: For many individuals with chronic low back pain (CLBP), there is no identifiable cause. In other idiopathic chronic pain conditions, sensory testing and functional magnetic resonance imaging (fMRI) have identified the occurrence of generalized increased pain sensitivity, hyperalgesia, and altered brain processing, suggesting central augmentation of pain processing in such conditions. We compared the results of both of these methods as applied to patients with idiopathic CLBP (n = 11), patients with widespread pain (fibromyalgia; n = 16), and healthy control subjects (n = 11). METHODS: Patients with CLBP had low back pain persisting for at least 12 months that was unexplained by MRI/radiographic changes. Experimental pain testing was performed at a neutral site (thumbnail) to assess the pressure-pain threshold in all subjects. For fMRI studies, stimuli of equal pressure (2 kg) and of equal subjective pain intensity (slightly intense pain) were applied to this same site. RESULTS: Despite low numbers of tender points in the CLBP group, experimental pain testing revealed hyperalgesia in this group as well as in the fibromyalgia group; the pressure required to produce slightly intense pain was significantly higher in the controls (5.6 kg) than in the patients with CLBP (3.9 kg) (P = 0.03) or the patients with fibromyalgia (3.5 kg) (P = 0.006). When equal amounts of pressure were applied to the 3 groups, fMRI detected 5 common regions of neuronal activation in pain-related cortical areas in the CLBP and fibromyalgia groups (in the contralateral primary and secondary [S2] somatosensory cortices, inferior parietal lobule, cerebellum, and ipsilateral S2). This same stimulus resulted in only a single activation in controls (in the contralateral S2 somatosensory cortex). When subjects in the 3 groups received stimuli that evoked subjectively equal pain, fMRI revealed common neuronal activations in all 3 groups. CONCLUSION: At equal levels of pressure, patients with CLBP or fibromyalgia experienced significantly more pain and showed more extensive, common patterns of neuronal activation in pain-related cortical areas. When stimuli that elicited equally painful responses were applied (requiring significantly lower pressure in both patient groups as compared with the control group), neuronal activations were similar among the 3 groups. These findings are consistent with the occurrence of augmented central pain processing in patients with idiopathic CLBP.

Giesecke T, Williams DA, Harris RE, Cupps TR, Tian X, Tian TX, Gracely RH, Clauw DJ. · University of Michigan, Ann Arbor, USA. · Arthritis Rheum. · Pubmed #14558098 links to  free full text

Abstract: OBJECTIVE: Although the American College of Rheumatology (ACR) criteria for fibromyalgia are used to identify individuals with both widespread pain and tenderness, individuals who meet these criteria are not a homogeneous group. Patients differ in their accompanying clinical symptoms, as well as in the relative contributions of biologic, psychological, and cognitive factors to their symptom expression. Therefore, it seems useful to identify subsets of fibromyalgia patients on the basis of which of these factors are present. Previous attempts at identifying subsets have been based solely on psychological and cognitive features. In this study, we attempt to identify patient subsets by incorporating these features as well as the degree of hyperalgesia/tenderness, which is a key neurobiologic feature of this illness. METHODS: Ninety-seven individuals meeting the ACR criteria for fibromyalgia finished the same battery of self-report and evoked-pain testing. Analyzed variables were obtained from several domains, consisting of 1) mood (evaluated by the Center for Epidemiologic Studies Depression Scale [for depression] and the State-Trait Personality Inventory [for symptoms of trait-related anxiety]), 2) cognition (by the catastrophizing and control of pain subscales of the Coping Strategies Questionnaire), and 3) hyperalgesia/tenderness (by dolorimetry and random pressure-pain applied at suprathreshold values). Cluster analytic procedures were used to distinguish subgroups of fibromyalgia patients based on these domains. RESULTS: Three clusters best fit the data. Multivariate analysis of variance (ANOVA) confirmed that each variable was differentiated by the cluster solution (Wilks' lambda [degrees of freedom 6,89] = 0.123, P < 0.0001), with univariate ANOVAs also indicating significant differences (all P < 0.05). One subgroup of patients (n = 50) was characterized by moderate mood ratings, moderate levels of catastrophizing and perceived control over pain, and low levels of tenderness. A second subgroup (n = 31) displayed significantly elevated values on the mood assessments, the highest values on the catastrophizing subscale, the lowest values for perceived control over pain, and high levels of tenderness. The third group (n = 16) had normal mood ratings, very low levels of catastrophizing, and the highest level of perceived control over pain, but these subjects showed extreme tenderness on evoked-pain testing. CONCLUSION: These data help support the clinical impression that there are distinct subgroups of patients with fibromyalgia. There appears to be a group of fibromyalgia patients who exhibit extreme tenderness but lack any associated psychological/cognitive factors, an intermediate group who display moderate tenderness and have normal mood, and a group in whom mood and cognitive factors may be significantly influencing the symptom report.