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+). Sigma-1 receptor (σ1R) is a Ca -sensing chaperone known to modulate analgesia induced by opioid drugs. This receptor binds both to TRPV1 and the μ-opioid receptor (MOPr), although the functional repercussions of these physical interactions in peripheral sensitization are unknown.
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