Opioid-induced latent sensitization in a model of non-inflammatory viscerosomatic hypersensitivity.
Exposure to opioids can induce a state of "latent sensitization" characterized by long-lasting enhanced responses to subsequent cutaneous injury. Here, we explored the possibility that prior treatment with morphine could induce a state of latent sensitization to visceral pain conditions. Following butyrate enemas to induce non-inflammatory visceral pain, acute morphine administration produced dose-related inhibition of referred viscerosomatic hypersensitivity. Treatment with morphine for a period of six days resulted in a persistent hyperalgesia that resolved many days after termination of drug administration. In morphine pre-exposed rats, butyrate-induced referred hypersensitivity was enhanced and extended in duration. No differences were observed in the morphine dose-response curve in suppression of acute nociception (i.e., the hot-plate assay) when morphine pre-exposed rats were compared to naïve rats indicating that opioid antinociceptive tolerance was not present. However, the morphine dose-response curve to suppress evoked viscerosomatic hypersensitivity was displaced to the right by approximately 4-fold in morphine pre-exposed rats. Induction of viscerosomatic hypersensitivity resulted in an increased labeling of CGRP-, but not substance P-positive cells in the lumbar dorsal root ganglia; increased labeling was not affected by prior exposure to morphine. The data indicate that a period of morphine exposure can induce a state of "latent sensitization" to subsequent visceral pain characterized by extended duration of hypersensitivity. This condition likely reflects enhanced visceral "pain" intensity as a consequence of persistent pronociceptive adaptive changes.
Lian
Bo
B
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA.
Vera-Portocarrero
Louis
L
King
Tamara
T
Ossipov
Michael H
MH
Porreca
Frank
F
D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002087:Butyrates; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology; D008297:Male; D009020:Morphine / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D002087:Butyrates; D009020:Morphine; D015740:Calcitonin Gene-Related Peptide