Pain
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Even though psychological interventions are well established in the treatment of pediatric chronic pain, there is a clear need for further development, especially with severely disabled patients. However, optimizing effectiveness in psychological treatments for pain requires clarification of the mechanisms of action. Studies addressing change processes are scarce, however, particularly in relation to pediatric chronic pain. ⋯ Results illustrated that pain impairment beliefs and pain reactivity were the only variables that significantly mediated the differential effects of treatment on outcomes at follow-up. Also, these 2 mediators were shown to independently predict effects in outcome variables at follow-up while controlling for earlier effects in outcome, but only for the ACT condition. Although tentative, the pattern of results suggests that variables consistent with psychological flexibility mediate the effects of ACT-based interventions to improve functioning in patients with chronic debilitating pain.
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This study investigated the effects of pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K)γ in the pruriceptive, inflammatory, and nociceptive responses induced by trypsin in mice. The animals were orally treated with the selective PI3Kγ inhibitor AS605240 (0.3-30 mg/kg) 30 minutes beforehand. In separate groups, AS605240 was given by intrathecal (i.t.) or intracerebroventricular (i.c.v.) routes. ⋯ In contrast, the oral administration of AS605240 did not significantly modify capsaicin-evoked nociception, although this inhibitor was effective when dosed by i.c.v. route. Noteworthy, AS605240 (1mg/kg) was able to prevent c-Fos and phospho-Akt immunopositivity at the spinal cord of trypsin-injected mice, either into the back of the neck or the paws. To conclude, PI3Kγ inhibition might well represent a valuable alternative for treating inflammatory and painful conditions, as well as pruritus.
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The role of muscarinic receptor subtype-1 (M1) in chronic pain is unclear. In an attempt to gain an understanding of its role, we have tested xanomeline, an M1/M4-preferring agonist, together with nonselective (scopolamine and pirenzepine), and selective (MT-7 and MT-3) muscarinic receptor (M1 and M4, respectively) antagonists in a number of inflammatory and neuropathic pain models. Xanomeline potently and effectively reversed tactile allodynia and heat hyperalgesia associated with established neuropathic and inflammatory pain in both rat and mouse models. ⋯ The highly selective M1 receptor toxin, MT-7, almost completely abolished the analgesic response to xanomeline when administered supraspinally. However, the highly selective M4 receptor toxin, MT-3, only marginally reversed the analgesia when given supraspinally, and had no effect when given spinally. In conclusion, the data presented show that the nonselective muscarinic agonist xanomeline is analgesic in models of persistent pain and suggest that the activation of supraspinal M1 receptors, and to a lesser extent supraspinal M4 receptors, contributes to that analgesia.
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Comparative Study
Engagement of descending inhibition from the rostral ventromedial medulla protects against chronic neuropathic pain.
A puzzling observation is why peripheral nerve injury results in chronic pain in some, but not all, patients. We explored potential mechanisms that may prevent the expression of chronic pain. Sprague Dawley (SD) or Holtzman (HZ) rats showed no differences in baseline sensory thresholds or responses to inflammatory stimuli. ⋯ Thus, expression of nerve injury-induced pain may ultimately depend on descending modulation. Engagement of descending inhibition protects in the transition from acute to chronic pain. These unexpected findings might provide a mechanistic explanation for medications that engage descending inhibition or mimic its consequences.
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Review Meta Analysis
The population prevalence of foot and ankle pain in middle and old age: a systematic review.
A systematic review and meta-analysis of population-based epidemiological studies was undertaken to determine the prevalence of foot and ankle pain in middle and old age. Searches were conducted in the following electronic databases from inception to October 2010: PubMed, EMBASE, AMED, CINAHL, Cochrane, PEDro, and SportDiscus. Full-text English language articles were included if they used population sample frames, cross-sectional design or analysis, and reported prevalence estimates for foot and/or ankle pain in adults aged 45 years and over. ⋯ Narrative synthesis of evidence from existing studies suggested preponderance in females, an age-related increase in prevalence in women but not men, that the toes/forefoot were the most common anatomical sites of pain, and that moderate disability in an aspect of daily life was reported by two-thirds of cases. This review provides estimates of the community burden of foot and ankle pain in middle and old age. By outlining the scale of this clinical problem, these findings can be used to inform health care planning and provision.