Pain Sensitivity In Fibromyalgia Research Articles

Pressure-Induced Referred Pain as a Biomarker of Pain Sensitivity in Fibromyalgia

Fibromyalgia (FM) syndrome is characterized by widespread pain, fatigue, and generalized increased pain sensitivity. Appropriate and simple pain models are methods employed to assess pain mechanisms that can potentially lead to improved treatments. Pressure pain thresholds (PPTs) or mapping the referred pain area produced by pressure stimulation at suprathreshold intensities are used to assess pain mechanisms. The optimal suprathreshold stimulation intensity to elicit referred pain with minimal discomfort for patients with FM has yet to be determined. The aim of this study was to compare the area and intensity of pressure-induced referred pain in patients with FM as elicited by systematic increases in PPTs, compared with controls. Observational, crossed-section study. Research laboratory. Twenty-six patients with FM and 26 healthy controls, age- and gender-matched, were included. Suprathreshold stimulation was applied to the infraspinatus muscle of the dominant side at 4 different intensities (PPT +20%, +30%, +40%, and +50%), after which referred pain was evaluated by measuring the area of pain in pixels using a digital body chart and its intensity on a Visual Analog Scale. Factors related to anxiety condition, pain catastrophizing, depression, and quality of life were recorded. The referred pain areas were larger in the FM group compared with healthy individuals at 120% (P = 0.024), 130% (P = 0.001), 140% (P = 0.001), and 150% (P = 0.001) PPT, however, within the FM group no differences were found between the intensity of suprathreshold stimulation and the size of the referred pain areas (P = 0.135) or pain intensity (P > 0.05). There was a positive correlation between the size of referred pain areas and pain catastrophizing in the FM group (r = 0.457, P = 0.032). This study presents some limitations, among which is the variability found in the referred pain areas. These findings show that referred pain induced by applying a suprathreshold pressure of 120% PPT can be a useful biomarker to assess sensitized pain mechanisms in patients suffering from FM. Referred pain, pain sensitivity, fibromyalgia, central sensitization, suprathreshold, pressure pain threshold, biomarker, facilitated pain mechanisms.

Automated Nociceptive Withdrawal Reflex Measurements Reveal Normal Reflex Thresholds and Augmented Pain Ratings in Patients with Fibromyalgia.

The nociceptive withdrawal reflex (NWR) is used to probe spinal cord excitability in chronic pain states. Here, we used an automated and unbiased procedure for determining the NWR threshold and compared the reflex thresholds and corresponding pain ratings in a well-characterized cohort of fibromyalgia (n = 29) and matched healthy controls (n = 21). Surface electrical stimuli were delivered to the foot in a stepwise incremental and decremental manner. The surface electromyographic activity was recorded from the ipsilateral tibialis anterior muscle. Fibromyalgia patients reported significantly higher scores for psychological distress and pain-related disability and a significantly lower score for perceived state of health compared to the matched controls. The subjective pain ratings were significantly higher in patients. The NWR thresholds were similar to the controls. In the patients, but not in controls, the NWR thresholds and subjective pain ratings were significantly correlated. Our results showed an increased subjective pain sensitivity in fibromyalgia, but we found no evidence for spinal sensitization based on the reflex measures.

1010 MORNING BRIGHT LIGHT TREATMENT IMPROVES FUNCTION AND REDUCES PAIN SENSITIVITY IN FIBROMYALGIA

Fibromyalgia is characterized by chronic widespread pain, mood and sleep disturbance, cognitive dysfunction, and affects over 20 million Americans. Pharmacological treatments (antidepressants, antiepileptics, opioids) often have small treatment effects and adverse side-effects. Exercise therapy requires significant patient motivation, and psychotherapy requires specialized personnel. Here we report on a pilot study in which we tested a home-based morning and evening bright light treatment in patients with fibromyalgia and examined changes in function and pain sensitivity. Ten adults (22–59 years) meeting ACR 2010 diagnostic criteria for fibromyalgia participated in a 15-day protocol. Each subject slept at home on their usual sleep schedule for 1 week before an overnight session. During the overnight session, baseline function (Fibromyalgia Impact Questionnaire, FIQ), pain sensitivity (heat threshold and tolerance), and circadian timing (dim light melatonin onset, DLMO) were assessed. The next morning subjects were randomized to either 6 days of a self-administered home morning or evening light treatment (light boxes, 1 hour per day). Afterwards, function, pain sensitivity and circadian timing were reassessed. On average, subjects completed 84% of the scheduled light treatments. No side effects were reported. Both morning and evening light treatments led to improvements in function and pain sensitivity. However, only morning light treatment led to a clinically meaningful improvement in function (>14% reduction in FIQ) and heat pain threshold (p<0.05). Phase advances in circadian timing were associated with an increase in pain tolerance (r=0.67, p<0.05). Morning bright light treatment should be further explored as a potentially feasible, acceptable and effective adjunctive treatment for fibromyalgia. The improvement in function was similar to that seen after psychotherapy, and about half of the improvement seen after months of exercise training. Phase advances in circadian timing may be one mechanism by which morning bright light improves function and pain sensitivity in fibromyalgia. Fogarty Sleep Research Pilot Grant, Rush University Medical Center.

40. The association between childhood abuse and pain sensitivity in fibromyalgia

Fibromyalgia, the second most common widespread pain disorder in America, is commonly associated with a history of abuse. Discerning the relationship between fibromyalgia pain and abuse may inform investigations of its pathology and diagnostics. We aimed to test the hypothesis that childhood, but not adult abuse, would be related to fibromyalgia pain. Women with fibromyalgia ( n = 119, age 47. ± 11) were assessed by history and physical, Pain Catastrophization Scale (PCS), Brief Pain Inventory (BPI), and dolorimetric evaluation. Those with a history of childhood abuse (26.0%) had lower pain pressure threshold (PPT) ( t (112) = −2.15, p = 0.03) and more tender points below a 4 kg threshold ( t (79.7) = 2.06, p = 0.04). Childhood physical, but not emotional, abuse was associated with lower PPT ( p t (111) = −2.39, p = .02). Abuse in adulthood only (17.6%) was not associated with objective measures, but was associated with greater self-reported pain relief with anti-inflammatory drugs (NSAIDs) than other medications alone ( p = 0.02) on BPI. No difference in age, pain severity (BPI) or self-reported NSAID use (BPI) was seen by abuse profile. In conclusion, we show evidence that childhood abuse may be associated with increased pain sensitivity in adult women with fibromyalgia. Though differences between groups were small and may not directly impact clinical practice, this provides a foundation for understanding pain behavior and response, and differentiating potential epigenetic, inflammatory and biological underpinnings of child and adult abuse.

The role of cardiovascular activity in fibromyalgia and conditioned pain modulation

Fibromyalgia (FM) is a chronic widespread pain condition of unknown origin. Reduced endogenous pain inhibition could be related to high pain sensitivity in FM. Associations between conditioned pain modulation (CPM) and cardiovascular responses to pain have been observed in healthy subjects (HS). Because reduced cardiovascular reactivity to various stressors has been reported in FM patients, we investigated relationships between CPM and cardiovascular response to the cold pressor test (CPT) in 22 FM patients and 25 HS. CPM was evaluated by comparing pain intensity produced by a 120-second heat test stimulus (HTS) before and after a CPT (2minutes, 12°C). The CPT, used to activate CPM, produced greater pain intensity in FM patients. Patients with FM had higher heart rates than HS at baseline and during CPT. Higher heart rate was related with higher pain intensity during the CPT. Blood pressure increments during CPT were weaker in the FM group. CPM was less effective in FM patients than in HS. Importantly, systolic blood pressure responses during CPT were positively related to CPM effectiveness, suggesting that reduced blood pressure response during the conditioning stimulus could be involved in CPM dysfunction in the FM group. Higher heart rate could be implicated in the greater sensitivity to cold pain in FM. Patients with FM have reduced blood pressure response to a painful CPT. Reduced cardiovascular reactivity to pain could have important involvement in diminished endogenous pain inhibition efficacy and FM pathophysiology.

Age-of-onset of menopause is associated with enhanced painful and non-painful sensitivity in fibromyalgia

Fibromyalgia (FM) is a chronic pain condition characterized by high prevalence in women. In particular, estrogen deficit has been considered as a potentially promoting factor of FM symptoms. This study was aimed to examine the relationship between age-of-onset of menopause and pain sensitivity in FM. For this purpose, pain sensitivity was assessed in 74 FM and 32 pain-free control women. All participants were postmenopausal and underwent a detailed semi-structured clinical interview, including data about menopause transition, previous history of hysterectomy or ovariectomy, and menses time. Participants were divided into two groups depending on age-of-onset of menopause: early menopause [≤49 years] vs. late menopause [>49 years]. Pain and non-pain thresholds were assessed by using cold, heat, mechanical, and electrical stimulation. FM women showed higher overall pain sensitivity as compared with healthy subjects. FM women with early age-of-onset of menopause displayed greater pain and non-pain sensitivity than FM women with late age-of-onset of menopause, whereas no differences were observed in healthy women due to age-of-onset of menopause. These results suggest that an early transition to menopause (shortening the time of exposure to estrogens) may influence pain hypersensitivity and could be related to aggravation of FM symptoms.

Pain sensitivity in fibromyalgia is associated with catechol‐O‐methyltransferase (COMT) gene

Recent evidence suggests that genetic factors might contribute to individual differences in pain sensitivity, risk for developing clinical pain conditions and efficacy of pain treatments. The purpose of the present study was to investigate the relationship of three common haplotypes of COMT gene affecting the metabolism of catecholamines on pain sensitivity in patients with fibromyalgia (FM). One hundred and thirteen FM patients and 65 age-matched healthy volunteers participated in the study. We genotyped four single-nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4818 and rs4680 or Val158Met) and identified haplotypes previously designated as low (LPS), average (APS) and high pain sensitivity (HPS). Thermal, pressure and touch thresholds were also examined using a quantitative sensory testing protocol. The frequency of genetic variations associated with low COMT enzyme activity was significantly higher in FM patients than in healthy volunteers. FM patients were more sensitive to experimental pain than healthy volunteers and, in particular, FM individuals with the met/met genotype (Val158Met SNP) or the HPS-APS haplotypes showing higher sensitivity to thermal and pressure pain stimuli than patients carrying the LPS haplotype or val alleles (Val158Met SNP). No differences due to genotype or haplotypes were found on non-painful touch thresholds. According with previous research, our findings revealed that haplotypes of the COMT gene and genotypes of the Val158Met polymorphism play a key role on pain sensitivity in FM patients.

(306/691): Family aggregation of pain sensitivity in fibromyalgia (FM)

The aim of this study was to examine pain sensitivity and blood serum levels of serotonin in female patients with FM (probands), sex-matched healthy controls, and siblings of probands and controls. Participants included (a) 16 probands with FM; (b) 5 male and 11 female proband siblings; (c) 23 female, pain-free, control individuals; and (d) 8 male and 15 control siblings. All participants underwent assessment of pain thresholds for (a) dolorimeter pressure at 5 bilateral tender points, (b) thermal heat stimulation (Medoc TSA-2001) of left forearm (double random staircase procedure); and (c) ischemic stimulation of left arm (modified submaximal effort tourniquet test).

Comment on: Increased pain sensitivity in fibromyalgia: effects of stimulus type and mode of presentation, Petzke et al., Pain 105 (2003) 403?413, and the related editorial: Hyperalgesia versus response bias in fibromyalgia, Fillingim, Pain, 105 (2003) 385?386

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Increased pain sensitivity in fibromyalgia: effects of stimulus type and mode of presentation

Fibromyalgia (FM) is defined in part by sensitivity to blunt pressure. Pressure pain sensitivity in FM is evaluated typically by the use of ‘ascending’ testing methods such as tender point counts or dolorimetry, which can be influenced by response bias of both the subject and examiner. Methods that present stimuli in a random, unpredictable fashion might minimize the influence of these factors. In this study, we compared the results of ascending and random assessments of both pressure and thermal pain sensitivities in 43 FM patients and 28 age- and gender-matched controls. Even though FM is defined on the basis of pressure sensitivity, this group was also more sensitive to heat stimuli, presented in either ascending or random paradigms. In both the patient and control groups, the pain ratings to painful sensations evoked by both thermal and pressure stimuli were significantly greater in the random, compared with the ascending method. The number of subjects classified as ‘expectant’ because they rated pain higher in ascending than random paradigms was similar for FM and control groups. Both patients and controls exhibited a similar degree of sensitization to pressure and thermal stimuli. The increased sensitivity to both pressure and thermal stimuli for threshold and suprathreshold stimuli in FM patients is consistent with central augmentation of pain processing.

Evoked pain measures in fibromyalgia.

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.

Is fibromyalgia a neurologic disease?

Fibromyalgia (FM) is characterized by abnormal pain sensitivity in response to diverse stimuli as well as persistent widespread pain and other symptoms such as fatigue and sleep disturbance. Progress has been made in identifying factors that contribute to the etiopathogenesis of abnormal pain sensitivity, but there is no single model of pathophysiology or treatment of FM that has gained wide acceptance among health care professionals. We review the literature on the etiopathogenesis of abnormal pain sensitivity in FM and describe an explanatory model that serves as a source of testable hypotheses in our laboratory. This model posits that interactions of exogenous (e.g., environmental stressors) and endogenous (e.g., neuroendocrine dysfunction) abnormalities in genetically predisposed individuals lead to a final common pathway, i.e., alterations in central nervous system function and neuropeptide production that underlie central sensitization and abnormal pain sensitivity. This model also suggests that efforts to develop and evaluate treatments for FM should focus on interventions with direct or indirect effects on central functions that influence pain sensitivity.

Psychosocial and health status variables independently predict health care seeking in fibromyalgia.

To determine whether variables derived from the self-regulatory model of health and illness behavior accurately predict status as a patient or nonpatient with fibromyalgia (FM). Subjects were 79 patients who met American College of Rheumatology (ACR) criteria for FM and 39 community residents who met ACR criteria for FM but had not sought medical care for their symptoms (nonpatients). Subjects were administered 14 measures that produced 6 domains of variables: background demographics and pain duration; psychiatric morbidity; and personality, environmental, cognitive, and health status factors. These domains were entered in 4 different hierarchical logistic regression analyses to predict status as patient or nonpatient. The full regression model was statistically significant (P < 0.0001) and correctly identified 90.7% of the subjects with a sensitivity of 92.4% and a specificity of 87.2%. The best individual predictors of group status were self-reports of self-efficacy, negative affect, recent stressful events, and perceived pain. Relative to nonpatients, patients reported higher levels of negative affect and perceived pain and a greater number of recent stressful experiences, as well as lower levels of self-efficacy. Consistent with the self-regulatory model of health and illness behavior, psychosocial and health status variables predict health care-seeking behavior in persons with FM independently of background demographics and psychiatric morbidity. These variables may influence the severity of symptoms experienced by persons with this disorder as well as their health care-seeking behavior, but they are not necessary to produce abnormal pain sensitivity in FM.

Use of neuroimaging to understand abnormal pain sensitivity in fibromyalgia.

This paper examines the use of neuroimaging to measure change in regional cerebral blood flow (rCBF) produced by pain in patients with fibromyalgia and in healthy individuals. Fibromyalgia patients differ from healthy persons in rCBF distribution in several brain structures involved in pain processing and pain modulation both at rest and during experimental pain induction. These abnormalities may contribute to abnormal pain sensitivity as well as the maladaptive pain behaviors that characterize many patients with fibromyalgia. We anticipate that future neuroimaging studies will enhance our understanding of abnormal pain sensitivity and of pain management interventions aimed at altering central nervous system function in patients with fibromyalgia.