Pain
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Heat pain and its modulation by capsaicin varies among subjects in experimental and clinical settings. A plausible cause is a genetic component, of which TRPV1 ion channels, by their response to both heat and capsaicin, are primary candidates. However, TRPA1 channels can heterodimerize with TRPV1 channels and carry genetic variants reported to modulate heat pain sensitivity. ⋯ Of note, TRPA1 variants were more important for correct phenotype group association than TRPV1 variants. This indicates a role of the TRPA1 and TRPV1 next-generation sequencing-based genetic pattern in the modulation of the individual response to heat-related pain phenotypes. When considering earlier evidence that topical capsaicin can induce neuropathy-like quantitative sensory testing patterns in healthy subjects, implications for future analgesic treatments with transient receptor potential inhibitors arise.
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Quantitative sensory testing after macroreplantation: evidence for a specific somatosensory profile.
A comprehensive functional recovery is one of the criteria for successful replantation of an amputated limb. Functionality of a replanted limb is strongly dependent on its regained sensibility. In previous studies concerning the sensibility of replanted limbs, only a few somatosensory submodalities were examined in small samples. ⋯ This distinct profile of impaired somatosensation shares some features of the somatosensory profile of neuropathic pain syndromes. Patients' limbs that were replanted many years before the present quantitative sensory testing showed more sensory deficits than patients with more recent replantations. This knowledge might be helpful in the development of more specific and more successful rehabilitation programs with replanted patients and improves the behavioral function of the replanted limb.
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Little is known about the burden and impact of orofacial pain in deprived areas, and whether it mediates the relationship between socioeconomic position and impacts on daily life. We analysed data from a representative sample of 2168 adults, aged 16 to 65 years, from the East London Oral Health Inequality study. Participants completed a validated questionnaire on demographics, socioeconomic position (area deprivation), orofacial pain (by anatomical site) in the past month, and impacts related to oral conditions on daily life. ⋯ Orofacial pain did not mediate the relationship between area deprivation and impacts on daily life. Our study demonstrated a substantial burden and impact of orofacial pain in a socially deprived and culturally diverse area of the United Kingdom. To address this burden, interventions that lie within the remit of health services are needed to improve access to dental care for adults with orofacial pain.
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Activation of innate immune mechanisms within the dorsal root ganglion and spinal dorsal horn has been shown to play a key role in the development of neuropathic pain including paclitaxel-related chemotherapy-induced peripheral neuropathy (CIPN). Here, we tested whether similar mechanisms are generalizable to oxaliplatin-induced CIPN. After a single intraperitoneal injection of 3 mg/kg oxaliplatin, mechanical withdrawal threshold and the expression of C-C chemokine ligand 2 (CCL2) and its receptor, CCR2, in the dorsal root ganglion were measured by behavioral testing and immunohistochemical staining, respectively. ⋯ Cotreatment with intrathecal anti-CCL2 antibodies prevented the development of oxaliplatin-induced mechanical hyperresponsiveness, and transiently reversed established hyperalgesia when given 1 week after chemotherapy. This is the first study to demonstrate CCL2/CCR2 signaling in a model of oxaliplatin-related CIPN; and it further shows that blocking of this signal can attenuate the development of oxaliplatin-induced mechanical hyperalgesia. Activation of innate immune mechanisms may therefore be a generalized basis for CIPN irrespective of the specific class of agent.
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Sickle cell disease (SCD) is a chronic inflammatory disorder accompanied by chronic pain. In addition to ongoing pain and hyperalgesia, vaso-occlusive crises-induced pain can be chronic or episodic. Because analgesics typically used to treat pain are not very effective in SCD, opioids, including morphine, are a primary treatment for managing pain in SCD but are associated with many serious side effects, including constipation, tolerance, addiction, and respiratory depression. ⋯ Our results show that intraperitoneal administration of MCC22 produced exceptionally potent dose-dependent antihyperalgesia as compared to morphine, dramatically decreased evoked responses of nociceptive dorsal horn neurons, and decreased expression of proinflammatory cytokines in the spinal cord. Moreover, tolerance did not develop to its analgesic effects after repeated administration. In view of the extraordinary potency of MCC22 without tolerance, MCC22 and similar compounds may vastly improve the management of pain associated with SCD.