Gp120 in the pathogenesis of human immunodeficiency virus-associated pain

Su Bo Yuan, Yuqiang Shi, Jinghong Chen, Xiangfu Zhou, Guangyu Li, Benjamin Gelman, Joshua G. Lisinicchia, Susan M Carlton, Monique R. Ferguson, Alai Tan, Sushil Sarna, Shao-Jun Tang

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Objective Chronic pain is a common neurological comorbidity of human immunodeficiency virus (HIV)-1 infection, but the etiological cause remains elusive. The objective of this study was to identify the HIV-1 causal factor that critically contributes to the pathogenesis of HIV-associated pain. Methods We first compared the levels of HIV-1 proteins in postmortem tissues of the spinal cord dorsal horn (SDH) from HIV-1/acquired immunodeficiency syndrome patients who developed chronic pain (pain-positive HIV-1 patients) and HIV-1 patients who did not develop chronic pain (pain-negative HIV-1 patients). Then we used the HIV-1 protein that was specifically increased in the pain-positive patients to generate mouse models. Finally, we performed comparative analyses on the pathological changes in the models and the HIV-1 patients. Results We found that HIV-1 gp120 was significantly higher in pain-positive HIV-1 patients (vs pain-negative HIV-1 patients). This finding suggested that gp120 was a potential causal factor of the HIV-associated pain. To test this hypothesis, we used a mouse model generated by intrathecal injection of gp120 and compared the pathologies of the model and the pain-positive human HIV-1 patients. The results showed that the mouse model and pain-positive human HIV-1 patients developed extensive similarities in their pathological phenotypes, including pain behaviors, peripheral neuropathy, glial reactivation, synapse degeneration, and aberrant activation of pain-related signaling pathways in the SDH. Interpretation Our findings suggest that gp120 may critically contribute to the pathogenesis of HIV-associated pain. Ann Neurol 2014;75:837-850

Original languageEnglish (US)
Pages (from-to)837-850
Number of pages14
JournalAnnals of Neurology
Volume75
Issue number6
DOIs
StatePublished - Jun 2014

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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