Gp120 in the pathogenesis of human immunodeficiency virus-associated pain.

TitleGp120 in the pathogenesis of human immunodeficiency virus-associated pain.
Publication TypeJournal Article
Year of Publication2014
AuthorsYuan, S-B, Shi, Y, Chen, J, Zhou, X, Li, G, Gelman, B, Lisinicchia, JG, Carlton, SM, Ferguson, MR, Tan, A, Sarna, SK, Tang, S-J
JournalAnn Neurol
Volume75
Issue6
Pagination837-50
Date Published2014 Jun
ISSN1531-8249
KeywordsAdult, Animals, Case-Control Studies, Disease Models, Animal, External, Female, Ganglia, Spinal, HIV Envelope Protein gp120, HIV Infections, Humans, Hyperalgesia, Male, Mice, Mice, Inbred C57BL, Middle Aged, Pain, Pain Threshold, Peripheral Nervous System Diseases, Rats, Rats, Sprague-Dawley, Signal Transduction, Spinal Cord, Viral Load
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.

DOI10.1002/ana.24139
Alternate JournalAnn. Neurol.
PubMed ID24633867
PubMed Central IDPMC4077969
Grant List5R01DK088796 / DK / NIDDK NIH HHS / United States
P30 AI036211 / AI / NIAID NIH HHS / United States
R01 DA027460 / DA / NIDA NIH HHS / United States
R01 DA036165 / DA / NIDA NIH HHS / United States
R01 DK088796 / DK / NIDDK NIH HHS / United States
R01 HL088999 / HL / NHLBI NIH HHS / United States
R01 NS027910 / NS / NINDS NIH HHS / United States
R01 NS079166 / NS / NINDS NIH HHS / United States
R01-DA036165 / DA / NIDA NIH HHS / United States
R01-NS079166 / NS / NINDS NIH HHS / United States
R01DA027460 / DA / NIDA NIH HHS / United States
R01HL088999 / HL / NHLBI NIH HHS / United States
R01NS027910 / NS / NINDS NIH HHS / United States
R24 MH059656 / MH / NIMH NIH HHS / United States
R24 NS045491 / NS / NINDS NIH HHS / United States
R24MH59656 / MH / NIMH NIH HHS / United States
R24NS045491 / NS / NINDS NIH HHS / United States
U01 MH083507 / MH / NIMH NIH HHS / United States
U01MH083507 / MH / NIMH NIH HHS / United States
U24 MH100930 / MH / NIMH NIH HHS / United States
U24MH100930 / MH / NIMH NIH HHS / United States