Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
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Antimicrotubulin chemotherapeutic agents, including plant-derived vincaalkaloids such as vincristine, can cause peripheral neuropathic pain. Exogenously activated heme oxygenase 1 (HO-1) is a potential therapy for chemotherapy-induced neuroinflammation. In this study, we investigated a role for Nrf2/HO-1/CO in mediating vincristine-induced neuroinflammation by inhibiting connexin 43 (Cx43) production in the spinal cord following the intrathecal application of the HO-1 inducer protoporphyrin IX cobalt chloride (CoPP) or inhibitor protoporphyrin IX zinc (ZnPP), and we analyzed the underlying mechanisms by which levo-corydalmine (l-CDL, a tetrahydroprotoberberine) attenuates vincristine-induced pain. ⋯ Furthermore, l-CDL had no effect on Cx43 following the silencing of the HO-1 gene. Taken together, our findings reveal a novel mechanism by which Nrf2/HO-1/CO mediates Cx43 expression in vincristine-induced neuropathic pain. In addition, the present findings suggest that l-CDL likely protects against nerve damage and attenuates vincristine-induced neuroinflammation by upregulating Nrf2/HO-1/CO to inhibit Cx43 expression.
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Despite high mortality rates due to opioid overdose and excessive alcohol consumption, medications for the treatment of alcohol and opioid use disorder have not been widely used in the USA. This paper provides an overview of the literature on the availability of alcohol and opioid used disorder medications in the specialty substance use disorder treatment system, other treatment settings and systems, and among providers with a federal waiver to prescribe buprenorphine. We also present the most current data on the availability of alcohol and opioid use disorder medications in the USA. ⋯ Availability of buprenorphine-waivered providers has increased significantly since 2002. However, geographic disparities in access to buprenorphine remain. Some of the most promising strategies to increase availability of alcohol and opioid use disorder medications include the following: incorporating substance use disorder training in healthcare education programs, educating the substance use disorder workforce about the benefits of medication treatment, reducing stigma surrounding the use of medications, implementing medications in primary care settings, implementing integrated care models, revising regulations on methadone and buprenorphine, improving health insurance coverage of medications, and developing novel medications for the treatment of substance use disorder.