title: Dexamethasone mimics the inhibitory effect of chronic pain on the development of tolerance to morphine analgesia and compensates for morphine induced changes in G proteins gene expression.
abstract: It is previously reported that the HPA axis plays role in the inhibitory effect of pain on tolerance development to analgesic effect of opioids. The present study was designed to investigate whether the chronic co-administration of dexamethasone as a glucocorticoid is also able to prevent or reverse analgesic tolerance to morphine and to compare the expression of G(alphai/o) and G(beta) subunits of G proteins in the context of chronic dexamethasone, development of morphine tolerance and their combination. Analgesic tolerance to morphine was induced by chronic intraperitoneally (i.p.) administration of morphine 20 mg/kg to male Wistar rats weighing 200-240 g within 4 consecutive days and analgesia was assessed using tail-flick test. Chronic dexamethasone was applied using 4 daily i.p. injections. Lumbar spinal tissues were assayed for the expression of G(alphai/o) and G(beta) proteins using "semiquantitative PCR" normalized to beta-actin gene expression. Results showed that chronic administration of dexamethasone could reduce and reverse the development of tolerance in rats that received chronic i.p. injections of morphine. Chronic administration of dexamethasone significantly increased the expression of G(alphai/o), while chronic administration of morphine did not change its expression. The expression of G(beta), however, was increased after the chronic administration of morphine, but did not change after the administration of chronic dexamethasone. None of these increases were observed when morphine and dexamethasone were co-administered. We conclude that the development of tolerance to analgesic effect of morphine could be prevented and reversed by dexamethasone co-administration. The increase in G(alphai/o) genes expression produced by chronic dexamethasone may facilitate the opioid signaling pathway and compensate for morphine-induced tolerance.
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modarres Univ., Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
authors.forename: Bahram
authors.initials: B
authors.lastname: Kazemi
authors.forename: Abolhassan
authors.initials: A
authors.lastname: Ahmadiani
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Motamedi
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001522:Behavior, Animal; D003907:Dexamethasone / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004361:Drug Tolerance / Q000502:physiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D000893:Anti-Inflammatory Agents; D012333:RNA, Messenger; D009020:Morphine; D003907:Dexamethasone; D019204:GTP-Binding Proteins