title: TNFα is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats.
abstract: 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 TNFα 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 TNFα in the spinal dorsal horn. TNFα was colocalized with GFAP in the spinal dorsal horn and with NeuN in the DRG. Knockdown of TNFα 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 TNFα is involved in NRTI-induced neuropathic pain.
authors: Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
authors: Xuexing
authors: X
authors: Zheng
authors: Handong
authors: H
authors: Ouyang
authors: Shue
authors: S
authors: Liu
authors: Marina
authors: M
authors: Mata
authors: David J
authors: DJ
authors: Fink
authors: Shuanglin
authors: S
authors: Hao
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D034961:Antigens, Nuclear / Q000096:biosynthesis; D015153:Blotting, Western; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009437:Neuralgia / Q000139:chemically induced* / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology; D010812:Physical Stimulation; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018894:Reverse Transcriptase Inhibitors; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D016047:Zalcitabine / Q000494:pharmacology
chemical_list: D000700:Analgesics; D034961:Antigens, Nuclear; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C546339:Rbfox3 protein, rat; D018894:Reverse Transcriptase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016047:Zalcitabine; D010431:Pentoxifylline