Pain
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Spinal cord stimulation (SCS) is extensively employed in the management of neuropathic pain, but the underlying mechanisms are only partially understood. Recently, we demonstrated that the pain-relieving effect of SCS appears to involve the spinal serotonin system, and the present study aimed at identifying the types of the spinal serotonin receptors involved. Experiments were performed on rats with neuropathy produced by partial ligation of the sciatic nerve. ⋯ The enhancing effect of m-CPBG was abolished by a γ-aminobutyric acid (GABA)(A) or GABA(B) antagonist intrathecally. These results suggest that the activation of 5-HT(2A), 5-HT(3), and 5-HT(4) receptors plays an important role in SCS-induced relief of neuropathic pain. The activation of 5-HT(3) receptors appears to operate via spinal GABAergic interneurons.
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Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperatures and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of bowel hypersensitivity; however, the underlying mechanisms of action are unclear. Here we determined the role of TRPM8 in colonic sensory pathways. ⋯ Icilin also prevented mechanosensory desensitization and sensitization induced by capsaicin and the TRPA1 agonist AITC (40 μmol/L), respectively. TRPM8 is present on a select population of colonic high threshold sensory neurons, which may also co-express TRPV1. TRPM8 couples to TRPV1 and TRPA1 to inhibit their downstream chemosensory and mechanosensory actions.
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Randomized Controlled Trial
Cancer Health Empowerment for Living without Pain (Ca-HELP): effects of a tailored education and coaching intervention on pain and impairment.
We aimed to determine the effectiveness of a lay-administered tailored education and coaching (TEC) intervention (aimed at reducing pain misconceptions and enhancing self-efficacy for communicating with physicians) on cancer pain severity, pain-related impairment, and quality of life. Cancer patients with baseline "worst pain" of ≥4 on a 0-10 scale or at least moderate functional impairment due to pain were randomly assigned to TEC or enhanced usual care (EUC) during a telephone interview conducted in advance of a planned oncology office visit (265 patients randomized to TEC or EUC; 258 completed at least one follow-up). Patients completed questionnaires before and after the visit and were interviewed by telephone at 2, 6, and 12 weeks. ⋯ The improvement in pain-related impairment was not sustained at 6 and 12 weeks. There were no significant intervention by subgroup interactions (P>.10). We conclude that TEC, compared with EUC, resulted in improved pain communication self-efficacy and temporary improvement in pain-related impairment, but no improvement in pain severity.
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Sick leave due to low back pain (LBP-SL) is costly and compromises workforce productivity. The fear-avoidance model asserts that maladaptive pain-related cognitions lead to avoidance and disuse, which can perpetuate ongoing pain. Staying home from work is an avoidant behavior, and hence pain-related psychological features may help explain LBP-SL. ⋯ Administrators and managers were less likely to report LBP-SL (OR=0.44, 95% CI 0.27-0.71), and age had a protective effect in individuals in a married or de facto relationship (OR=0.97, 95% CI 0.95-0.98). In summary, fear of movement, passive coping, frequent manual handling, and severe or radiating pain increase the likelihood of LBP-SL. Gender-specific responses to pain radiation and fear of movement are evident.
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Platinum-based anticancer drugs cause neurotoxicity. In particular, oxaliplatin produces early-developing, painful, and cold-exacerbated paresthesias. However, the mechanism underlying these bothersome and dose-limiting adverse effects is unknown. ⋯ Administration of cisplatin evoked mechanical allodynia, an effect that was reduced in TRPA1-deficient mice. TRPA1 is therefore required for oxaliplatin-evoked mechanical and cold hypersensitivity, and contributes to cisplatin-evoked mechanical allodynia. Channel activation is most likely caused by glutathione-sensitive molecules, including reactive oxygen species and their byproducts, which are generated after tissue exposure to platinum-based drugs from cells surrounding nociceptive nerve terminals.