title: Gp120 in the pathogenesis of human immunodeficiency virus-associated pain.
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.
  
  
  CONCLUSIONS
  Our findings suggest that gp120 may critically contribute to the pathogenesis of HIV-associated pain.
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX.
authors.forename: Su-Bo
authors.initials: SB
authors.lastname: Yuan
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Shi
authors.forename: Jinghong
authors.initials: J
authors.lastname: Chen
authors.forename: Xiangfu
authors.initials: X
authors.lastname: Zhou
authors.forename: Guangyu
authors.initials: G
authors.lastname: Li
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.forename: Joshua G
authors.initials: JG
authors.lastname: Lisinicchia
authors.forename: Susan M
authors.initials: SM
authors.lastname: Carlton
authors.forename: Monique R
authors.initials: MR
authors.lastname: Ferguson
authors.forename: Alai
authors.initials: A
authors.lastname: Tan
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Sarna
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Tang
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D006930:Hyperalgesia / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010146:Pain / Q000209:etiology* / Q000378:metabolism* / Q000821:virology; D017288:Pain Threshold; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000821:virology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000473:pathology; D019562:Viral Load
chemical_list: D015699:HIV Envelope Protein gp120