Pain
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Randomized Controlled Trial Multicenter Study
The efficacy of a glial inhibitor, minocycline, for preventing persistent pain after lumbar discectomy: a randomized, double-blind, controlled study.
Minocycline strongly inhibits microglial activation, which contributes to central sensitization, a major mechanism underlying chronic pain development. We hypothesized that the perioperative administration of minocycline might decrease persistent pain after lumbar discectomy. We randomly assigned 100 patients undergoing scheduled lumbar discectomy to placebo and minocycline groups. ⋯ The incidence and intensity of neuropathic pain and functional scores did not differ between the minocycline and placebo groups. Exploratory analysis suggested that minocycline might be effective in a subgroup of patients with predominantly deep spontaneous pain at baseline. Perioperative minocycline administration for 8 days does not improve persistent pain after lumbar discectomy.
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Randomized Controlled Trial
Oxycodone alters temporal summation but not conditioned pain modulation: preclinical findings and possible relations to mechanisms of opioid analgesia.
Opioid analgesia is mediated primarily by modulating (inhibiting and enhancing) pain mechanisms at the spinal and supraspinal levels. Advanced psychophysical paradigms of temporal summation (TS) and conditioned pain modulation (CPM) likely represent pain mechanisms at both levels. Therefore, the study of opioid effects on TS and CPM can shed light on their analgesic mechanisms in humans. ⋯ In contrast, no significant effects of either oxycodone (F=0.871, P=.458) or placebo (F=2.086, P=.106) on the magnitude of CPM were found. These results suggest that under the current experimental conditions, oxycodone exerted spinal, rather than supraspinal, analgesic effects. Furthermore, compared with CPM, TS seems more suitable for studying the mechanisms of opioid analgesia in humans.
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Inflammatory processes in the sensory ganglia contribute to many forms of chronic pain. We previously showed that local inflammation of the lumbar sensory ganglia rapidly leads to prolonged mechanical pain behaviors and high levels of spontaneous bursting activity in myelinated cells. Abnormal spontaneous activity of sensory neurons occurs early in many preclinical pain models and initiates many other pathological changes, but its molecular basis is not well understood. ⋯ In vivo knockdown of NaV1.6 locally in the lumbar DRG at the time of DRG inflammation completely blocked development of pain behaviors and abnormal spontaneous activity, while having only minor effects on unmyelinated C cells. Current research on isoform-specific sodium channel blockers for chronic pain is largely focused on NaV1.8 because it is present primarily in unmyelinated C fiber nociceptors, or on NaV1.7 because lack of this channel causes congenital indifference to pain. However, the results suggest that NaV1.6 may be a useful therapeutic target for chronic pain and that some pain conditions may be mediated primarily by myelinated A fiber sensory neurons.
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Individual vulnerability factors influencing the function of the hypothalamic-pituitary-adrenal axis may contribute to the risk of the development of persistent musculoskeletal pain after traumatic stress exposure. The objective of the study was to evaluate the association between polymorphisms in the gene encoding FK506 binding protein 51, FKBP5, a glucocorticoid receptor co-chaperone, and musculoskeletal pain severity 6 weeks after 2 common trauma exposures. The study included data from 2 prospective emergency department-based cohorts: a discovery cohort (n=949) of European Americans experiencing motor vehicle collision and a replication cohort of adult European American women experiencing sexual assault (n=53). ⋯ The association of rs3800373, rs9380526, rs9394314, rs2817032, and rs2817040 with neck pain and/or overall pain 6 weeks after trauma was replicated in the sexual assault cohort, showing the same direction of the effect in each case. The results of this study indicate that genetic variants in FKBP5 influence the severity of musculoskeletal pain symptoms experienced during the weeks after motor vehicle collision and sexual assault. These results suggest that glucocorticoid pathways influence the development of persistent posttraumatic pain, and that such pathways may be a target of pharmacologic interventions aimed at improving recovery after trauma.
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Multicenter Study
Intraoral somatosensory abnormalities in patients with atypical odontalgia--a controlled multicenter quantitative sensory testing study.
Intraoral somatosensory sensitivity in patients with atypical odontalgia (AO) has not been investigated systematically according to the most recent guidelines. The aims of this study were to examine intraoral somatosensory disturbances in AO patients using healthy subjects as reference, and to evaluate the percent agreement between intraoral quantitative sensory testing (QST) and qualitative sensory testing (QualST). Forty-seven AO patients and 69 healthy control subjects were included at Universities of Washington, Malmö, and Aarhus. ⋯ The most frequent LossGain code was L0G2 (no somatosensory loss with gain of mechanical somatosensory function) (31.9% of AO patients). Percent agreement between corresponding QST and QualST measures of thermal and mechanical sensitivity ranged between 55.6% and 70.4% in AO patients and between 71.1% and 92.1% in control subjects. In conclusion, intraoral somatosensory abnormalities were commonly detected in AO patients, and agreement between quantitative and qualitative sensory testing was good to excellent.