Mol Pain
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The evolution of therapeutics for and management of human immunodeficiency virus-1 (HIV-1) infection has shifted it from predominately manifesting as a severe, acute disease with high mortality to a chronic, controlled infection with a near typical life expectancy. However, despite extensive use of highly active antiretroviral therapy, the prevalence of chronic widespread pain in people with HIV remains high even in those with a low viral load and high CD4 count. Chronic widespread pain is a common comorbidity of HIV infection and is associated with decreased quality of life and a high rate of disability. ⋯ The specific mechanisms underlying these three broad categories that contribute to chronic widespread pain are not well understood, hindering the development and application of pharmacological and nonpharmacological approaches to mitigate chronic widespread pain. The consequent insufficiencies in clinical approaches to alleviation of chronic pain in people with HIV contribute to an overreliance on opioids and alarming rise in active addiction and overdose. This article reviews the current understanding of the pathogenesis of chronic widespread pain in people with HIV and identifies potential biomarkers and therapeutic targets to mitigate it.
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Neuropathic pain can be generated by chronic compression of dorsal root ganglion (CCD). Stimulation of primary motor cortex can disrupt the nociceptive sensory signal at dorsal root ganglion level and reduce pain behaviors. But the mechanism behind it is still implicit. ⋯ In vivo extracellular recording of the ventral posterolateral thalamus, viral expression in the primary motor cortex, and protein kinase C gamma expression in dorsal root ganglion were investigated. So, optical cortico-thalamic inhibition by motor cortex stimulation can improve neuropathic pain behaviors in CCD animal, and knocking down of protein kinase C gamma plays a conducive role in the process. This study provides feasibility for in vivo optogenetic stimulation on primary motor cortex of dorsal root ganglion-initiated neuropathic pain.