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

Xuexing Zheng, Handong Ouyang, Shue Liu, Marina Mata, David J. Fink, Shuanglin Hao

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1668-1676
Number of pages9
JournalBrain, Behavior, and Immunity
Volume25
Issue number8
DOIs
StatePublished - Nov 1 2011

Fingerprint

Reverse Transcriptase Inhibitors
Neuralgia
Nucleosides
Hyperalgesia
Zalcitabine
Tumor Necrosis Factor Receptors
Diagnosis-Related Groups
Neuroglia
Small Interfering RNA
HIV Infections
Acquired Immunodeficiency Syndrome
HIV
Messenger RNA
Pharmaceutical Preparations
Proteins

Keywords

  • DdC
  • HIV
  • Neuropathic pain
  • TNFα

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems

Cite this

TNFα is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats. / Zheng, Xuexing; Ouyang, Handong; Liu, Shue; Mata, Marina; Fink, David J.; Hao, Shuanglin.

In: Brain, Behavior, and Immunity, Vol. 25, No. 8, 01.11.2011, p. 1668-1676.

Research output: Contribution to journalArticle

Zheng, Xuexing ; Ouyang, Handong ; Liu, Shue ; Mata, Marina ; Fink, David J. ; Hao, Shuanglin. / TNFα is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats. In: Brain, Behavior, and Immunity. 2011 ; Vol. 25, No. 8. pp. 1668-1676.
@article{4660dbe3e4b14c8f868af56ca6dd4b76,
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.",
keywords = "DdC, HIV, Neuropathic pain, TNFα",
author = "Xuexing Zheng and Handong Ouyang and Shue Liu and Marina Mata and Fink, {David J.} and Shuanglin Hao",
year = "2011",
month = "11",
day = "1",
doi = "10.1016/j.bbi.2011.06.010",
language = "English",
volume = "25",
pages = "1668--1676",
journal = "Brain, Behavior, and Immunity",
issn = "0889-1591",
publisher = "Academic Press Inc.",
number = "8",

}

TY - JOUR

T1 - TNFα is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats

AU - Zheng, Xuexing

AU - Ouyang, Handong

AU - Liu, Shue

AU - Mata, Marina

AU - Fink, David J.

AU - Hao, Shuanglin

PY - 2011/11/1

Y1 - 2011/11/1

N2 - 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.

AB - 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.

KW - DdC

KW - HIV

KW - Neuropathic pain

KW - TNFα

UR - http://www.scopus.com/inward/record.url?scp=80053896545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053896545&partnerID=8YFLogxK

U2 - 10.1016/j.bbi.2011.06.010

DO - 10.1016/j.bbi.2011.06.010

M3 - Article

C2 - 21741472

AN - SCOPUS:80053896545

VL - 25

SP - 1668

EP - 1676

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

SN - 0889-1591

IS - 8

ER -