Peripheral nerve exposure to HIV viral envelope protein gp120 induces neuropathic pain and spinal gliosis

Painful sensory neuropathy is a common and debilitating consequence of huma n immunodeficiency virus (HIV). The underlying causes of neuropathic pain a re most likely not due to direct infection of the nervous system by active virus. The goal of this study was to determine whether epineural exposure t o the HIV-1 envelope protein gp120 could lead to chronic painful peripheral neuropathy. Two doses of gp120 or BSA control were transiently delivered e pineurally via oxidized cellulose wrapped around the rat sciatic nerve. Ani mals were assessed for neuropathic pain behaviors at several intervals from 1-30 days following nerve surgery. Allodynia and hyperalgesia were observe d within 1-3 days following gp120 and sustained throughout the testing peri od. The gp120-exposed sciatic nerve exhibited early but transient pathology , notably axonal swelling and increased tumor necrosis factor alpha (TNF-al pha) within the nerve trunk. In contrast, intense astrocytic and microglial activation was observed in the spinal cord, and this gliosis persisted for at least 30 days following epineural gp120, in parallel with neuropathic p ain behaviors. These findings demonstrate that limited peripheral nerve exp osure to HIV protein can induce persistent painful sensory neuropathy that may be sustained and magnified by long-term spinal neuropathology. (C) 2001 Elsevier Science B.V. All rights reserved.