title: Pathogenesis of HIV-associated sensory neuropathy: evidence from in vivo and in vitro experimental models.
abstract: HIV-associated sensory neuropathy (HIV-SN) is a frequent neurological complication of HIV infection and its treatment with some antiretroviral drugs. We review the pathogenesis of the viral- and drug-induced causes of the neuropathy, and its primary symptom, pain, based on evidence from in vivo and in vitro models of HIV-SN. Viral coat proteins mediate nerve fibre damage and hypernociception through direct and indirect mechanisms. Direct interactions between viral proteins and nerve fibres dominate axonal pathology, while somal pathology is dominated by indirect mechanisms that occur secondary to virus-mediated activation of glia and macrophage infiltration into the dorsal root ganglia. The treatment-induced neuropathy and resulting hypernociception arise primarily from drug-induced mitochondrial dysfunction, but the sequence of events initiated by the mitochondrial dysfunction that leads to the nerve fibre damage and dysfunction are still unclear. Overall, the models that have been developed to study the pathogenesis of HIV-SN, and hypernociception associated with the neuropathy, are reasonable models and have provided useful insights into the pathogenesis of HIV-SN. As new models are developed they may ultimately lead to identification of therapeutic targets for the prevention or treatment of this common neurological complication of HIV infection.
authors.affiliation: Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Johannesburg, South Africa. peter.kamerman@wits.ac.za
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kamerman
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Moss
authors.forename: Juliane
authors.initials: J
authors.lastname: Weber
authors.forename: Victoria C J
authors.initials: VC
authors.lastname: Wallace
authors.forename: Andrew S C
authors.initials: AS
authors.lastname: Rice
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000821:virology*
chemical_list: D044966:Anti-Retroviral Agents