Kirsten Ambrose

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

&NA; 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.

Large candidate gene association study reveals genetic risk factors and therapeutic targets for fibromyalgia.

OBJECTIVE Fibromyalgia (FM) represents a complex disorder that is characterized by widespread pain and tenderness and is frequently accompanied by additional somatic and cognitive/affective symptoms. Genetic risk factors are known to contribute to the etiology of the syndrome. The aim of this study was to examine >350 genes for association with FM, using a large-scale candidate gene approach. METHODS The study group comprised 496 patients with FM (cases) and 348 individuals with no chronic pain (controls). Genotyping was performed using a dedicated gene array chip, the Pain Research Panel, which assays variants characterizing >350 genes known to be involved in the biologic pathways relevant to nociception, inflammation, and mood. Association testing was performed using logistic regression. RESULTS Significant differences in allele frequencies between cases and controls were observed for 3 genes: GABRB3 (rs4906902; P = 3.65 × 10(-6)), TAAR1 (rs8192619; P = 1.11 × 10(-5)), and GBP1 (rs7911; P = 1.06 × 10(-4)). These 3 genes and 7 other genes with suggestive evidence for association were examined in a second, independent cohort of patients with FM and control subjects who were genotyped using the Perlegen 600K platform. Evidence of association in the replication cohort was observed for TAAR1, RGS4, CNR1, and GRIA4. CONCLUSION Variation in these 4 replicated genes may serve as a basis for development of new diagnostic approaches, and the products of these genes may contribute to the pathophysiology of FM and represent potential targets for therapeutic action.

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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Reply to Clark's letter

traditional thresholds are pure measures of sensory experience uninfluenced by the subject’s attitude is patently false; the threshold is an unresolvable conglomerate of physiological and psychological variables. Finally, it is important to realize that, since the data collection procedures for the method of constant stimuli and for SDT are identical (stimuli of different intensities are presented randomly), the data collected by Petzke and colleagues can and should be analyzed by the SDT procedure. This will make it possible to determine to what extent the lower pain thresholds in patients with FM are due to neurosensory augmentation and how much to a lower criterion for reporting pain.