Gp120 in the pathogenesis of human immunodeficiency virus-associated pain

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

Research output: Contribution to journalArticle

39 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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    Yuan, S. B., Shi, Y., Chen, J., Zhou, X., Li, G., Gelman, B. B., Lisinicchia, J. G., Carlton, S. M., Ferguson, M. R., Tan, A., Sarna, S. K., & Tang, S. J. (2014). Gp120 in the pathogenesis of human immunodeficiency virus-associated pain. Annals of Neurology, 75(6), 837-850. https://doi.org/10.1002/ana.24139