TY - JOUR
T1 - Opioid-induced latent sensitization in a model of non-inflammatory viscerosomatic hypersensitivity
AU - Lian, Bo
AU - Vera-Portocarrero, Louis
AU - King, Tamara
AU - Ossipov, Michael H.
AU - Porreca, Frank
PY - 2010/10/28
Y1 - 2010/10/28
N2 - 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.
AB - 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.
KW - IBS
KW - Opioid-induced latent sensitization
UR - http://www.scopus.com/inward/record.url?scp=77957358303&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957358303&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2010.08.032
DO - 10.1016/j.brainres.2010.08.032
M3 - Article
C2 - 20727859
AN - SCOPUS:77957358303
VL - 1358
SP - 64
EP - 70
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -