Morphine acts in vitro to directly prime nociceptors

Mol Pain. 2024 Jan-Dec:20:17448069241260348. doi: 10.1177/17448069241260348.

Abstract

Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked prolongation of prostaglandin E2 (PGE2)-induced mechanical hyperalgesia, in vivo. In vitro, priming in nociceptors is characterized by a leftward shift in the concentration dependence for PGE2-induced nociceptor sensitization. In the present in vitro study we tested the hypothesis that a mu-opioid receptor (MOR) agonist opioid analgesic, morphine, can produce priming by its direct action on nociceptors. We report that treatment of nociceptors with morphine, in vitro, produces a leftward shift in the concentration dependence for PGE2-induced nociceptor sensitization. Our findings support the suggestion that opioids act directly on nociceptors to induce priming.

Keywords: Morphine; nociceptor; opioid-induced hyperalgesic priming; patch-clamp electrophysiology; prostaglandin E2; rheobase; sensitization.

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Animals
  • Dinoprostone* / metabolism
  • Dinoprostone* / pharmacology
  • Dose-Response Relationship, Drug
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy
  • Male
  • Morphine* / pharmacology
  • Nociceptors* / drug effects
  • Nociceptors* / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / metabolism

Substances

  • Morphine
  • Dinoprostone
  • Receptors, Opioid, mu
  • Analgesics, Opioid