The journal of pain : official journal of the American Pain Society
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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.
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Omega-3 and omega-6 fatty acids are biosynthetic precursors of endocannabinoids with antinociceptive, anxiolytic, and neurogenic properties. We recently reported that targeted dietary manipulation-increasing omega-3 fatty acids while reducing omega-6 linoleic acid (the H3-L6 intervention)-reduced headache pain and psychological distress among chronic headache patients. It is not yet known whether these clinical improvements were due to changes in endocannabinoids and related mediators derived from omega-3 and omega-6 fatty acids. We therefore used data from this trial (N = 55) to investigate 1) whether the H3-L6 intervention altered omega-3- and omega-6-derived endocannabinoids in plasma and 2) whether diet-induced changes in these bioactive lipids were associated with clinical improvements. The H3-L6 intervention significantly increased the omega-3 docosahexaenoic acid derivatives 2-docosahexaenoylglycerol (+65%, P < .001) and docosahexaenoylethanolamine (+99%, P < .001) and reduced the omega-6 arachidonic acid derivative 2-arachidonoylglycerol (-25%, P = .001). Diet-induced changes in these endocannabinoid derivatives of omega-3 docosahexaenoic acid, but not omega-6 arachidonic acid, correlated with reductions in physical pain and psychological distress. These findings demonstrate that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids in humans and suggest that 2-docosahexaenoylglycerol and docosahexaenoylethanolamine could have physical and/or psychological pain modulating properties.
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Although high levels of negative affect and cognitions have been associated with greater pain sensitivity in chronic pain conditions, the neural mechanisms mediating the hyperalgesic effect of psychological factors in patients with pain disorders are largely unknown. In this cross-sectional study, we hypothesized that 1) catastrophizing modulates brain responses to pain anticipation and 2) anticipatory brain activity mediates the hyperalgesic effect of different levels of catastrophizing in fibromyalgia (FM) patients. Using functional magnetic resonance imaging, we scanned the brains of 31 FM patients exposed to visual cues anticipating the onset of moderately intense deep-tissue pain stimuli. Our results indicated the existence of a negative association between catastrophizing and pain-anticipatory brain activity, including in the right lateral prefrontal cortex. A bootstrapped mediation analysis revealed that pain-anticipatory activity in the lateral prefrontal cortex mediates the association between catastrophizing and pain sensitivity. These findings highlight the role of the lateral prefrontal cortex in the pathophysiology of FM-related hyperalgesia and suggest that deficits in the recruitment of pain-inhibitory brain circuitry during pain-anticipatory periods may play an important contributory role in the association between various degrees of widespread hyperalgesia in FM and levels of catastrophizing, a well-validated measure of negative cognitions and psychological distress. ⋯ This article highlights the presence of alterations in pain-anticipatory brain activity in FM. These findings provide the rationale for the development of psychological or neurofeedback-based techniques aimed at modifying patients' negative affect and cognitions toward pain.