The journal of pain : official journal of the American Pain Society
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Allergic contact dermatitis (ACD) is a common condition that can significantly affect the quality of life. Contact with allergens results in delayed hypersensitivity reactions involving T lymphocytes, with associated skin inflammation and spontaneous itch and nociceptive sensations. However, psychophysical studies of these sensations are lacking. In the present study, we sensitized 8 healthy volunteers to squaric acid dibutyl ester (SADBE). Two weeks later, 1 volar forearm was challenged with SADBE, and the other with acetone vehicle control. Subsequently, participants rated the maximal perceived intensity of spontaneous itch, pricking/stinging, and burning every 6 to 12 hours for 1 week, using the generalized Labeled Magnitude Scale. In the laboratory, they judged stimulus-evoked sensations within and outside the chemically treated area. The SADBE- but not the acetone-treated skin resulted in 1) localized inflammation, with spontaneous itch and nociceptive sensations peaking at 24 to 48 hours after challenge, 2) alloknesis, hyperknesis, and hyperalgesia to mechanical stimuli that were reduced or eliminated by anesthetic cooling of the SADBE-treated area and restored on rewarming, suggesting that sensations and dysesthesias are dependent on ongoing peripheral neural activity, and 3) enhanced itch to intradermal injection of histamine, BAM8-22, or β-alanine. This experimental model of T-cell-mediated inflammation may prove useful in evaluating potential treatments of itch from ACD. ⋯ In a model of allergic contact dermatitis, experimentally applied in humans, psychophysical measurements were obtained of persistent, spontaneous itch and enhanced stimulus-evoked itch and pain sensations. These sensory measurements will be useful in the identification of the neural mechanisms underlying inflammatory itch and pain.
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Fibromyalgia syndrome (FMS) is characterized by widespread chronic pain, fatigue, sleep disorders, and cognitive-emotional disturbance. Patients with FMS exhibit increased sensitivity to experimental pain and pain-related cues, as well as deficits in emotional regulation. The present study investigated the spatiotemporal patterns of brain activations for observed pain in 19 patients with FMS and 18 age-matched, healthy control individuals using event-related potential analysis. Patients with FMS attributed greater pain and unpleasantness to pain pictures, relative to healthy control participants. An augmented late positive potential (LPP) component (>500 milliseconds) was found in patients viewing both pain and nonpain pictures, and this amplitude difference in the LPP covaried with perceived unpleasantness of pictures. Mid-latency potentials (250-450 milliseconds) demonstrated similar amplitude increases of positive potentials in the FMS patient group. By contrast, the short-latency positive potential (140 milliseconds) was reduced in patients with FMS relative to healthy control participants. Results suggest amplitude increases to mid- to long-latency cortical activations in patients with FMS, which are known to reflect emotional control and motivational salience of stimuli. ⋯ Patients with FMS demonstrate increased activations associated with pain and nonpain pictures. The findings suggest that even innocuous, everyday visual stimuli with somatic connotations may challenge the emotional state of patients with FMS. Our study points toward the importance of cognitive-emotional therapeutic approaches for the treatment of FMS.
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Review Meta Analysis
Assay Sensitivity of Pain Intensity Versus Pain Relief in Acute Pain Clinical Trials: ACTTION Systematic Review and Meta-Analysis.
The magnitude of the effect size of an analgesic intervention can be influenced by several factors, including research design. A key design component is the choice of the primary endpoint. The purpose of this meta-analysis was to compare the assay sensitivity of 2 efficacy paradigms: pain intensity (calculated using summed pain intensity difference [SPID]) and pain relief (calculated using total pain relief [TOTPAR]). A systematic review of the literature was performed to identify acute pain studies that calculated both SPIDs and TOTPARs within the same study. Studies were included in this review if they were randomized, double-blind, placebo-controlled investigations involving medications for postsurgical acute pain and if enough data were provided to calculate TOTPAR and SPID standardized effect sizes. Based on a meta-analysis of 45 studies, the mean standardized effect size for TOTPAR (1.13) was .11 higher than that for SPID (1.02; P = .01). Mixed-effects meta-regression analyses found no significant associations between the TOTPAR - SPID difference in standardized effect size and trial design characteristics. Results from this review suggest that for acute pain studies, utilizing TOTPAR to assess pain relief may be more sensitive to treatment effects than utilizing SPID to assess pain intensity. ⋯ The results of this meta-analysis suggest that TOTPAR may be more sensitive to treatment effects than SPIDs are in analgesic trials examining acute pain. We found that standardized effect sizes were higher for TOTPAR compared to SPIDs.
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Randomized Controlled Trial
Effects of Milnacipran on Clinical Pain and Hyperalgesia of Patients With Fibromyalgia: Results of a 6-Week Randomized Controlled Trial.
Milnacipran is a serotonin-norepinephrine reuptake inhibitor that was approved by the U.S. Food and Drug Administration as effective therapy for fibromyalgia (FM) symptoms. However, its analgesic mechanism of action is not well understood. We hypothesized that improvement of mechanical and heat hyperalgesia would be a critical component of overall milnacipran efficacy in FM. We used a novel quantitative sensory testing protocol for assessment of mechanical and heat pain sensitivity that can be used for testing of peripheral and central pain mechanisms and their impact on clinical pain over time. We applied tonic mechanical and heat pain stimuli to 46 patients with FM during a randomized controlled trial with either 50 mg milnacipran (n = 23) or placebo (n = 23) twice daily over 6 weeks. During this trial, mean clinical pain (standard deviation) was evaluated daily, and mechanical and heat pain sensitivity every 2 weeks. At study entry, clinical pain was 5.0 (1.8) and 5.5 (1.8) visual analog scale units for patients with FM randomized to placebo and milnacipran, respectively (P > .05). Over 6 weeks, clinical pain of patients with FM significantly declined by 15%, but this improvement was not statistically different between milnacipran and placebo. However, repeated measures of mechanical and heat pain sensitivity reliably predicted up to 80% of the variance in clinical FM pain at every time point. Clinical pain and mechanical/heat pain sensitivity of patients with FM steadily declined during this trial, but the effects of milnacipran were not found to be superior to placebo. Repeated measures of mechanical/heat hyperalgesia reliably predicted large amounts of the variance in clinical pain across all participants, indicating their relevance for FM pain. ⋯ Although clinical pain and hyperalgesia decreased during this 6-week trial, the efficacy of milnacipran was not superior to placebo. The high correlations between clinical pain and hyperalgesia ratings at every time point seem to emphasize the relevant contributions of mechanical and heat hyperalgesia to clinical FM pain.
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This study investigated the cross-cultural factor stability and internal consistency of the Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R), a measure of the quality of postoperative pain management used internationally. We conducted exploratory factor analysis (EFA) of APS-POQ-R data from 2 point prevalence studies comprising 268 and 311 surveys of Danish and Australian medical-surgical patients, respectively. Parallel analysis indicated 4- and 3-factor solutions for Danish and Australian patients, respectively, which accounted for 58.1% and 52.9% of variance. Internal consistency was unsatisfactory among both Danish (Cronbach α = .54) and Australian (Cronbach α = .63) cohorts. There was a high degree of between-group similarity in item-factor loadings of variables coded as "pain experience," but not "pain management." This finding reflected cross-cultural differences in ratings of treatment satisfaction. For Danish patients, satisfaction was associated with the degree of pain severity and activity interference, whereas for Australian patients, satisfaction was associated with their perceived ability to participate in treatment. To facilitate further cross-cultural comparison, we compared our findings with past research conducted in the United States and Iceland. EFA supported the construct validity of the APS-POQ-R as a measure of "pain experience" but indicated that items measuring "pain management" may vary cross-culturally. Findings highlighted the need for further validation of the APS-POQ-R internationally. ⋯ This study revealed the APS-POQ-R as a valid measure of postoperative pain experience for Danish and Australian patients. Measures of patients' perception of pain management were not robust to group differences in treatment expectations and demonstrated cross-cultural instability. Results highlighted the difficulties in establishing stable cross-cultural, cross-population subscales for the APS-POQ-R.