Pain
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A critical component in development of opioid analgesics is assessment of their abuse liability (AL). Standardization of approaches and measures used in assessing AL have the potential to facilitate comparisons across studies, research laboratories, and drugs. The goal of this report is to provide consensus recommendations regarding core outcome measures for assessing the abuse potential of opioid medications in humans in a controlled laboratory setting. ⋯ A brief historical perspective on AL testing is provided, and those measures that can be considered primary and secondary outcomes and possible additional outcomes in AL assessment are then discussed. These outcome measures include the following: subjective effects (some of which comprise the primary outcome measures, including drug liking; physiological responses; drug self-administration behavior; and cognitive and psychomotor performance. Before presenting recommendations for standardized approaches and measures to be used in AL assessments, the appropriateness of using these measures in clinical trials with patients in pain is discussed.
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A connection between pain and depression has long been recognized in the clinical setting; however, its mechanism remains unclear. This study showed that mechanical hyperalgesia induced by unilateral temporomandibular joint (TMJ) inflammation was exacerbated in Wistar-Kyoto (WKY) rats with genetically predisposed depressive behavior. Reciprocally, TMJ inflammation enhanced depressive behavior such that a lower nociceptive threshold correlated with a higher score of depressive behavior in the same WKY rats. ⋯ Intracisternal administration of 6-chloromelatonin (250 μg, twice daily for 7 days) concurrently attenuated mechanical hyperalgesia and depressive behavior in WKY rats as well as downregulated the NR1 expression in the ipsilateral Sp5C. In patch-clamp recordings, melatonin dose-dependently decreased NMDA-induced currents in spinal cord dorsal horn substantia gelatinosa neurons. These results demonstrate a reciprocal relationship between TMJ inflammation-induced mechanical hyperalgesia and depressive behavior and suggest that the central melatoninergic system, through modulation of the NMDA receptor expression and activity, may play a role in the mechanisms of the comorbidity between pain and depression.
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Whether self-reported lifetime civilian and war-related potential traumatic events are associated with widespread pain (WP) and if so, whether the association is attributable to posttraumatic stress disorder (PTSD) and depression has not been studied in a representative sample of the general population. In a randomly selected sample of the German general population, persons aged 60-85 years answered validated self-rating instruments: Regional Pain Scale, trauma list of the Composite International Diagnostic Interview, Posttraumatic Diagnostic Scale, and Patient Health Questionnaire 2. Participants with WP were compared with participants with no or local or regional pain (controls). ⋯ The significant association between some potential traumatic events and WP was completely abrogated after adjusting for demographic variables and PTSD. In the final model, PTSD (odds ratio 3.43, 95% confidence interval 1.88-6.26) and lifetime employment status as a worker (odds ratio 1.55, 95% confidence interval 1.04-2.31) predicted WP. Prospective studies are necessary to understand the temporal association of PTSD and WP.
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Randomized Controlled Trial
Brain networks predicting placebo analgesia in a clinical trial for chronic back pain.
A fundamental question for placebo research is whether such responses are a predisposition, quantifiable by brain characteristics. We examine this issue in chronic back pain (CBP) patients who participated in a double-blind brain imaging (functional magnetic resonance imaging) clinical trial. We recently reported that when the 30 CBP participants were treated, for 2 weeks, with topical analgesic or no drug patches, pain and brain activity decreased independently of treatment type and thus were attributed to placebo responses. ⋯ Additionally, by means of frequency domain contrasts, we observe that at baseline, left dorsolateral prefrontal cortex high-frequency oscillations also predicted treatment outcomes and identified an additional set of functional connections distinguishing treatment outcomes. Combining medial and lateral prefrontal functional connections, we observe a statistically higher accuracy (0.9) for predicting posttreatment groups. These findings indicate that placebo response can be identified a priori at least in CBP, and that neuronal population interactions between prefrontal cognitive and pain processing regions predetermine the probability of placebo response in the clinical setting.
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The aim of this study was to establish the somatosensory profiles of patients with cervical radiculopathy and patients with nonspecific neck-arm pain associated with heightened nerve mechanosensitivity (NSNAP). Sensory profiles were compared to healthy control (HC) subjects and a positive control group comprising patients with fibromyalgia (FM). Quantitative sensory testing (QST) of thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimulation was performed in the maximal pain area, the corresponding dermatome and foot of 23 patients with painful C6 or C7 cervical radiculopathy, 8 patients with NSNAP in a C6/7 dermatomal pain distribution, 31 HC and 22 patients with FM. ⋯ Both neck-arm pain groups demonstrated increased cold sensitivity in their maximal pain area (P<.03) and the foot (P<.009), and this was also the dominant sensory characteristic in patients with NSNAP. Both neck-arm pain groups differed from patients with FM, the latter characterised by a widespread gain of function in most nociceptive parameters (thermal, pressure, mechanical pain sensitivity P<.027). Despite commonalities in pain characteristics between the 2 neck-arm pain groups, distinct sensory profiles were demonstrated for each group.