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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Cholecystokinin (CCK) has been suggested to be both pro-nociceptive and "anti-opioid" by actions on pain-modulatory cells within the rostral ventromedial medulla (RVM). One consequence of activation of RVM CCK₂ receptors may be enhanced spinal nociceptive transmission; but how this might occur, especially in states of pathological pain, is unknown. Here, in vivo microdialysis was used to demonstrate that levels of RVM CCK increased by approximately 2-fold after ligation of L₅/L₆ spinal nerves (SNL). ⋯ Spinal administration of naproxen, a nonselective COX-inhibitor, significantly attenuated RVM CCK-induced hindpaw tactile hypersensitivity. RVM-CCK also resulted in a 2-fold increase in spinal 5-hydroxyindoleacetic acid (5-HIAA), a 5-hydoxytryptophan (5-HT) metabolite, as compared with controls, and mechanical hypersensitivity that was attenuated by spinal application of ondansetron, a 5-HT₃ antagonist. The present studies suggest that chronic nerve injury can result in activation of descending facilitatory mechanisms that may promote hyperalgesia via ultimate release of PGE₂ and 5-HT in the spinal cord.
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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.
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The aim of this study was to test the capacity of the Fear Avoidance Model to explain the relationship between pain and disability in patients with whiplash-associated disorders. Using the method of Baron and Kenny, we assessed the mediating effect of fear of movement on the cross-sectional and longitudinal relationships between pain and disability. Two hundred and five subjects with neck pain due to a motor vehicle accident provided pain intensity (0 to 10 numerical rating scale), fear of movement (Tampa Scale of Kinesiophobia and Pictorial Fear of Activity Scale) and disability (Neck Disability Index) scores within 4 weeks of their accident, after 3 months, and after 6 months. ⋯ Contrary to our initial hypothesis, the proportion of the total effect of pain on disability that was mediated by fear of movement did not substantially change as increasing time elapsed after the accident. The proportion mediated was slightly higher when fear of movement was measured by Tampa Scale of Kinesiophobia as compared with Pictorial Fear of Activity Scale. The findings of this study suggest that the Fear Avoidance Model plays a role in explaining a moderate proportion of the relationship between pain and disability after whiplash injury.
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Randomized Controlled Trial
Cognitive manipulation targeted at decreasing the conditioning pain perception reduces the efficacy of conditioned pain modulation.
Although painfulness of the conditioning stimulus (CS) is required for the activation of conditioned pain modulation (CPM), it is still unclear whether CPM expression depends on the objective physical intensity of the CS or the subjective perception of its pain. Accordingly, we cognitively manipulated the perceived CS pain, rendering the physical aspects of the CPM paradigm untouched. Baseline CPM was measured among 48 young healthy male subjects using the parallel paradigm with contact heat as test pain and hand immersion in hot water as CS. ⋯ Pain inhibition under CPM seems to depend on the perceived level of the CS pain rather than solely its physical intensity. Cognitively decreasing the perceived CS pain attenuates CPM magnitude, although a ceiling effect may limit CPM enhancement after cognitively increased CS pain. These findings emphasize the relevance of cognitive mechanisms in determining endogenous analgesia processes in humans.