TNFα is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats

In patients with HIV/AIDS, neuropathic pain is a common neurological complication. Infection with the HIV itself may lead to neuropathic pain, and painful symptoms are enhanced when patients are treated with nucleoside reverse transcriptase inhibitors (NRTIs). The mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. In the current studies, we tested the role of TNF alpha in antiretroviral drug-induced neuropathic pain. We administered 2',3'-dideoxycytidine (ddC, one of the NRTIs) systemically to induce mechanical allodynia. We found that ddC induced overexpression of both mRNA and proteins of GFAP and TNF alpha in the spinal dorsal horn. TNF alpha was colocalized with GFAP in the spinal dorsal horn and with NeuN in the DRG. Knockdown of TNF alpha with siRNA blocked the mechanical allodynia induced by ddC. Intrathecal administration of glial inhibitor or recombinant TNF soluble receptor, reversed mechanical allodynia induced by ddC. These results suggest that TNF alpha is involved in NRTI-induced neuropathic pain. (C) 2011 Elsevier Inc. All rights reserved.