Highly specific σ₂R/TMEM97 ligand alleviates neuropathic pain and inhibits the integrated stress response.

ABSTRACT: The Sigma 2 receptor (σ₂R) was described pharmacologically more than three decades ago, but its molecular identity remained obscure until recently when it was identified as transmembrane protein 97 (TMEM97). We and others have shown that σ₂R/TMEM97 ligands alleviate mechanical hypersensitivity in mouse neuropathic pain models with a time course wherein maximal anti-nociceptive effect is approximately 24 hours following dosing. We sought to understand this unique anti-neuropathic pain effect by addressing two key questions: do these σ₂R/TMEM97 compounds act selectively via the receptor, and what is their downstream mechanism on nociceptive neurons? Using male and female conventional knockout (KO) mice for Tmem97, we find that a new σ₂R/TMEM

SUBMITTER: Yousuf MS 

PROVIDER: S-EPMC10120691 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature