Involvement of adrenomedullin in the attenuation of acute morphine-induced analgesia in rats.
Adrenomedullin (AM) is a member of calcitonin gene-related peptide (CGRP) family and a pain-related peptide. We have shown that chronic administration of morphine (20 μg) upregulates AM activity contributing to morphine tolerance. The present study investigated if AM is involved in acute morphine-induced analgesia. Single intrathecal (i.t.) injection of morphine at a dose of 5 μg increased the tail-flick latency (TFL). This analgesic effect was potentiated by the co-administration of the AM receptor antagonist AM22-52 (5 and 10 nmol). Exposure of sensory ganglion culture to morphine increased AM content in the ganglia in concentration (0.33-10 μM)- and time (10-240 min)-dependent manners. However, treatment with morphine (3.3 μM) for 30-240 min did not alter AM mRNA levels in the cultured ganglia. Furthermore, exposure of ganglion cultures to morphine (3.3 μM) for 30-240, but not 10 min induced an increase in AM content in the culture medium. These results reveal that a single morphine treatment potentiates post-translational change and the release of AM in sensory ganglia masking morphine-induced analgesia. Thus, targeting AM and its receptors should be considered as a novel approach to improve the analgesic potency of opiates during their acute use.
College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University, Fuzhou, Fujian 350108, China.
Dongmei
D
Wang
College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University, Fuzhou, Fujian 350108, China.
Yuanhui
Y
Huo
Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Québec H4H 1R3, Canada.
Rémi
R
Quirion
College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University, Fuzhou, Fujian 350108, China. Electronic address: yhong@fjnu.edu.cn.
Yanguo
Y
Hong
D053607:Adrenomedullin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D058265:Receptors, Adrenomedullin / Q000037:antagonists & inhibitors / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism
D000701:Analgesics, Opioid; D010446:Peptide Fragments; D058265:Receptors, Adrenomedullin; C104782:adrenomedullin (22-52); D053607:Adrenomedullin; D009020:Morphine