The journal of pain : official journal of the American Pain Society
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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.
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Randomized Controlled Trial
A More Pessimistic Life Orientation Is Associated With Experimental Inducibility of a Neuropathy-like Pain Pattern in Healthy Individuals.
The clinical pattern of neuropathic pain, diagnosed using the quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain), could be partly mimicked in healthy volunteers after topical capsaicin application. However, similar to clinical neuropathic pain that develops in only a subgroup of patients who have a neurologic lesion, this attempt to mimick a neuropathic pain pattern succeeded only in a small fraction (18%) of healthy individuals. In the present assessment, we pursued the hypothesis that the inducible subgroup differed from the other healthy participants with respect to their psychological phenotype. Therefore, in an observational study, participants were assessed using a comprehensive set of psychological variables comprising general psychological and pain-related cognitive-emotional mechanisms. The sum scores of the questionnaires were significantly linearly correlated with each other. Principal component analysis indicated that a major source of variance (46%) could be attributed to dispositional optimism examined via the Life Orientation Test (LOT). The LOT score significantly differed between the groups of participants, either those in whom a neuropathy-like pattern of pain assessed via QST could be partly (50-60% of the 11 QST parameters) induced (n = 20) or not (n = 90; P = .0375). It emerged again as the main selection criterion in a classification and regression tree predicting a participant's group assignment (inducible neuropathy-like QST pattern versus noninducible neuropathy-like QST pattern) at a cross-validated accuracy of 95.5 ± 2.1%. Thus, the few participants in a random sample of healthy volunteers who, after topical capsaicin application, partly resemble (to a degree of about 60%) the clinical pattern of neuropathic pain in the QST test battery, are preselectable on the basis of psychological factors, with a particular emphasis on pessimistic life attitudes. ⋯ In a small fraction of 18% of healthy volunteers, topical capsaicin application resulted in a neuropathy-like pattern in 50 to 60% of the components of a clinical test battery. These individuals displayed a more pessimistic life attitude as assessed by means of the LOT.
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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.