Articles: chronic-pain.
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This article examines an explanation circulating within a U. S. multidisciplinary pediatric pain clinic that links the neurobiology of functional pain disorders to desirable personal attributes such as smartness and creativity. ⋯ Within this narrative logic, diagnostic explanations reveal not only causal pathways but also predictive claims about recovery. By considering what is at stake when personal attributes are marshaled within a neurobiological diagnostic register that also lays out the patient's role in healing, this article complicates psychosomatic accounts of 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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A major unmet clinical need exists for long-acting neurotherapeutics to alleviate chronic pain in patients unresponsive to available nonaddictive analgesics. Herein, a new strategy is described for the development of potent and specific inhibitors of the neuronal exocytosis of transmitters and pain mediators that exhibit unique antinociceptive activity. This entailed recombinant production in Escherichia coli of two serotypes of botulinum neurotoxin (BoNT) (BoNT(A) and BoNT(E) ), which are proteins that are known to block the release of transmitters by targeting and entering nerve endings, where their proteases cleave and inactivate a protein, synaptosomal protein of M(r) 25 000 (SNAP-25), that is essential for Ca(2+) -regulated exocytosis. ⋯ As this enzyme lasted for more than 1 month (as compared with 5 days for BoNT(E) alone), such a dramatic extension in the lifetime of this BoNT(E) protease is attributable to a stabilizing influence of the BoNT(A) mutant. Most importantly, injecting this novel biotherapeutic into the foot pads of rats resulted in extended amelioration of inflammatory pain. Thus, a new generation of biotherapeutics has been created with the potential to give long-term relief of pain.
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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.