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 HIVrelated
neuropathic pain. Mitochondria injured by ATN and/or gp120 may be also involved in the development of HIVneuropathic
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