Pain
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We investigated the involvement of de novo neurosteroid synthesis in the mechanisms underlying the analgesic and antihyperalgesic effects of N-palmitoylethanolamine (PEA) in two models of acute and persistent pain, the formalin test and carrageenan-induced paw edema. The pivotal role of peroxisome proliferator-activated receptor (PPAR)-α in the antinocifensive effect of PEA was confirmed by the lack of this effect in PPAR-α-null mice. ⋯ In agreement with those data, in both pain models, PEA administration in challenged mice specifically restored the expression of two proteins involved in neurosteroidogenensis, the steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage (P450scc) in the ipsilateral horns of spinal cord, without affecting their expression in the contralateral side. These results provide new information about the involvement of de novo neurosteroid synthesis in the modulation of pain behavior by PEA.
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Randomized Controlled Trial Multicenter Study
The CONECSI trial: results of a randomized controlled trial of a multidisciplinary cognitive behavioral program for coping with chronic neuropathic pain after spinal cord injury.
Many people with spinal cord injury (SCI) rate chronic neuropathic pain as one of the most difficult problems to manage. The aim of the CONECSI (COping with NEuropathiC Spinal cord Injury pain) trial was to evaluate a multidisciplinary cognitive behavioral treatment program for persons with chronic neuropathic pain after SCI. The intervention consisted of educational, cognitive, and behavioral elements. ⋯ Significant intervention effects (Time*Group interactions) were found for anxiety and participation in activities, but not for the primary outcomes. Subsequent paired t tests showed significant changes in the intervention group that were not seen in the control group: decrease of pain intensity, pain-related disability, anxiety, and increase of participation in activities. This study implies that a multidisciplinary cognitive behavioral program might have beneficial effects on people with chronic neuropathic SCI pain.
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Randomized Controlled Trial
Treatment of Na(v)1.7-mediated pain in inherited erythromelalgia using a novel sodium channel blocker.
Mutations in the SCN9A gene leading to deficiency of its protein product, Na(v)1.7, cause congenital indifference to pain (CIP). CIP is characterized by the absence of the ability to sense pain associated with noxious stimuli. In contrast, the opposite phenotype to CIP, inherited erythromelalgia (IEM), is a disorder of spontaneous pain caused by missense mutations resulting in gain-of-function in Na(v)1.7 that promote neuronal hyperexcitability. ⋯ The ability to induce pain in IEM patients was significantly attenuated by XEN402 compared with placebo. XEN402 increased the time to maximal pain induction and significantly reduced the amount of pain (42% less) after induction (P=.014). This pilot study showed that XEN402 blocks Na(v)1.7-mediated pain associated with IEM, thereby demonstrating target engagement in humans and underscoring the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept.
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Randomized Controlled Trial
The prevalence and management of low back pain across adulthood: results from a population-based cross-sectional study (the MUSICIAN study).
The aim of the current study was to determine: the prevalence of low back pain (LBP) and associated disability; the frequency of consultation to general practice; whether there were differences in management by age. We conducted a cross-sectional population study in Aberdeen city and Cheshire County, UK. Participants were 15,272 persons aged 25 years and older. ⋯ They were less likely to be prescribed physiotherapy or exercise (OR 0.63, 95% CI 0.46-0.85) or to be referred to a specialist (OR 0.77, 95% CI 0.57-1.04). Older persons were more likely to have previously received exercise therapy for pain, were less likely to be enthusiastic about receiving it now (P<0.0001), and were less likely to think it would result in improved symptoms (P<0.0001). It is important that older persons, who have the highest prevalence of LBP with disability and are most likely to consult, are receiving optimal pharmacological and nonpharmacological management.