title: Chronic forced swim stress inhibits ultra-low dose morphine-induced hyperalgesia in rats.
abstract: Ultra-low doses of morphine (UL-morphine) induce hyperalgesia, which is assumed to be mediated by stimulatory G proteins (G(alphas)) signaling pathway. G(alphas) pathway inhibition and chronic stress both attenuate development of tolerance to analgesic effect of morphine. This study evaluated the effect of chronic stress on UL-morphine-induced hyperalgesia to find out if chronic stress interacts with the G(alphas) signaling pathway. Repeated daily forced swim stress was applied to induce chronic stress. UL-morphine (1 microg/kg, intraperitoneal)-induced hyperalgesia was assessed using the tail-flick test on day 6, in male rats that during days 1-5 received different treatments of swim stress, dexamethasone, swim stress following adrenalectomy (ADX) or swim stress after sham operation. Chronic stress by itself induced hyperalgesia in control and sham-operated rats but inhibited UL-morphine-induced hyperalgesia. In ADX animals, chronic stress did not produce hyperalgesia and could not inhibit UL-morphine-induced hyperalgesia. Chronic dexamethasone produced hyperalgesia but did not change the UL-morphine-induced hyperalgesia. Inhibition of UL-morphine hyperalgesia by chronic stress suggests that chronic stress interacts with the G(alphas) signaling pathway, which is responsible for UL-morphine-induced hyperalgesia. The absence of this effect in the ADX-rats or after repetitive dexamethasone administration demonstrates that hypothalamic-pituitary-adrenal (HPA) axis activation is necessary for controlling UL-morphine-induced hyperalgesia. Finally, the interaction of stress with the G(alphas) signaling pathway may provide an explanation for the inhibitory effect of stress on development of tolerance to the analgesic effect of morphine.
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Fereidoni
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
authors.forename: Saeed
authors.initials: S
authors.lastname: Semnanian
authors.forename: Abolhasan
authors.initials: A
authors.lastname: Ahmadiani
mesh_terms: D000315:Adrenalectomy; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D004361:Drug Tolerance; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects*; D010913:Pituitary-Adrenal System / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013315:Stress, Psychological / Q000503:physiopathology*; D013550:Swimming
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D003907:Dexamethasone; D019205:GTP-Binding Protein alpha Subunits, Gs; D003345:Corticosterone