A neuron-to-astrocyte Wnt5a signal governs astrogliosis during HIV-associated pain pathogenesis

Xin Liu, Chilman Bae, Benjamin B. Gelman, Jin Mo Chung, Shao-Jun Tang

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic pain is the most common neurological disorder of HIV patients. Multiple neuropathologies were identified in the pain pathway. Among them is the prominent astrocytic reaction (also know an astrogliosis). However, the pathogenic role and mechanism of the astrogliosis are unclear. Here, we show that the astrogliosis is crucial for the pain development induced by a key neurotoxic HIV protein gp120 and that a neuron-to-astrocyte Wnt5a signal controls the astrogliosis. Ablation of astrogliosis blocked the development of gp120-induced mechanical hyperalgesia, and concomitantly the expression of neural circuit polarization in the spinal dorsal horn. We demonstrated that conditional knockout of either Wnt5a in neurons or its receptor ROR2 in astrocytes abolished not only gp120-induced astrogliosis but also hyperalgesia and neural circuit polarization. Furthermore, we found that the astrogliosis promoted expression of hyperalgesia and NCP via IL-1β regulated by a Wnt5a-ROR2-MMP2 axis. Our results shed light on the role and mechanism of astrogliosis in the pathogenesis of HIV-associated pain.

Original languageEnglish (US)
Pages (from-to)4108-4123
Number of pages16
JournalBrain
Volume145
Issue number11
DOIs
StatePublished - Nov 1 2022
Externally publishedYes

Keywords

  • HIV-1 gp120
  • Wnt
  • astrocyte
  • neural circuit
  • pain

ASJC Scopus subject areas

  • Clinical Neurology

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