The Sigma‐1 Receptor Curtails Endogenous Opioid Analgesia During Sensitization of TRPV1 Nociceptors

Peripheral sensitization contributes to pathological pain. While prostaglandin E2 (PGE2) and nerve growth factor (NGF) sensitize peptidergic C‐nociceptors (TRPV1+), glial cell line‐derived neurotrophic factor (GDNF) sensitizes non‐peptidergic C‐neurons (IB4+). The sigma‐1 receptor (sigma‐1R) is a Ca2+‐sensing chaperone known to modulate opoid analgesia. This receptor binds both to TRPV1 and the μ opioid receptor, although the functional repercussions of these physical interactions in peripheral sensitization are unknown.