The molecular and pharmacological mechanisms of HIV-related neuropathic pain

Research output: Contribution to journalReview article

42 Scopus citations

Abstract

Infection of the nervous system with the human immunodeficiency virus (HIV-1) can lead to cognitive, motor and sensory disorders. HIV-related sensory neuropathy (HIV-SN) mainly contains the HIV infection-related distal sensory polyneuropathy (DSP) and antiretroviral toxic neuropathies (ATN). The main pathological features that characterize DSP and ATN include retrograde ("dying back") axonal degeneration of long axons in distal regions of legs or arms, loss of unmyelinated fibers, and variable degree of macrophage infiltration in peripheral nerves and dorsal root ganglia (DRG). One of the most common complaints of HIV-DSP is pain. Unfortunately, many conventional agents utilized as pharmacologic therapy for neuropathic pain are not effective for providing satisfactory analgesia in painful HIV-related distal sensory polyneuropathy, because the molecular mechanisms of the painful HIV-SDP are not clear in detail. The HIV envelope glycoprotein, gp120, appears to contribute to this painful neuropathy. Recently, preclinical studies have shown that glia activation in the spinal cord and DRG has become an attractive target for attenuating chronic pain. Cytokines/chemokines have been implicated in a variety of painful neurological diseases and in animal models of HIV-related neuropathic pain. Mitochondria injured by ATN and/or gp120 may be also involved in the development of HIV-neuropathic pain. This review discusses the neurochemical and pharmacological mechanisms of HIV-related neuropathic pain based on the recent advance in the preclinical studies, providing insights into novel pharmacological targets for future therapy.

Original languageEnglish (US)
Pages (from-to)499-512
Number of pages14
JournalCurrent Neuropharmacology
Volume11
Issue number5
DOIs
StatePublished - Sep 1 2013

Keywords

  • DRG
  • Gp120
  • HIV
  • Neuropathic pain
  • NRTI
  • Spinal cord

ASJC Scopus subject areas

  • Clinical Neurology
  • Pharmacology (medical)
  • Pharmacology
  • Neurology
  • Psychiatry and Mental health

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