A Wnt5a signaling pathway in the pathogenesis of HIV-1 gp120-induced pain

Su Bo Yuan, Guangchen Ji, Bei Li, Tommy Andersson, Volker Neugebauer, Shao-Jun Tang

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Pathological pain is one of the most common neurological complications in patients with HIV-1/AIDS. However, the pathogenic process is unclear. Our recent studies show that Wnt5a is upregulated in the spinal cord dorsal horn (SDH) of the patients with HIV who develop pain and that HIV-1 gp120, a potential causal factor of the HIV-associated pain, rapidly upregulates Wnt5a in the mouse SDH. Using a mouse model, we show here that a specific Wnt5a antagonist, Box-5, attenuated gp120-induced mechanical allodynia. Conversely, a Wnt5a agonist, Foxy5, facilitated the allodynia. To elucidate the molecular mechanism by which Wnt5a regulates gp120-induced allodynia, we tested the role of the JNK/TNF-α pathway. We observed that the JNK-specific inhibitor SP600125 blocked either gp120- or Foxy5-induced allodynia. Similarly, the TNF-α-specific antagonist Enbrel also reversed either gp120- or Foxy5-induced allodynia. These data suggest that JNK and TNF-α mediate the biological effects of Wnt5a in regulating gp120-induced allodynia. To investigate the cellular mechanism, we performed extracellular single-unit recording from SDH neurons in anesthetized mice. Both Box-5 and SP600125 negated gp120-induced potentiation of SDH neuron spiking evoked by mechanical stimulation of the hind paw. Furthermore, while Foxy5 potentiated spike frequency of SDH neurons, either SP600125 or Enbrel blocked the potentiation. The data indicate that Wnt5a potentiates the activity of SDH neurons through the JNK-TNF-α pathway. Collectively, our findings suggest that Wnt5a regulates the pathogenesis of gp120-induced pain, likely by sensitizing painprocessing SDH neurons through JNK/TNF-α signaling.

Original languageEnglish (US)
Pages (from-to)1311-1319
Number of pages9
JournalPain
Volume156
Issue number7
DOIs
StatePublished - Jul 1 2015

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Keywords

  • Gp120
  • HIV-1
  • Neuroinflammation
  • Pain
  • Wnt

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine
  • Neurology
  • Pharmacology

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