title: Is endogenous opioid system involved in non-opioid analgesics tolerance?
abstract: Recent investigations using metamizol and lysine-acetylsalicylate have shown that these non-opioid analgesics produce central anti-nociceptive effects probably through neural substrates that also support the analgesic effects of opiates. The aim of this study was to examine whether a clinically relevant approach, e.g. systemic administration of analgine, ketorolac and xefocam causes tolerance to them, and cross-tolerance to morphine. The experiments were carried out on experimental and control rats with saline by the model of tail-flick reflex to the stimulation of focusing light. Latency increase of this reflex indicates the degree of antinociception. This study of non-opioid analgesic effects on the latency of tail-flick reflex in rats has shown that systemic injections of analgine, ketorolac and xefocam result in significant antinociception as compared with the control group of rats with saline. Repeated administrations of these drugs revealed tolerance to them and cross-tolerance to morphine. Intraperitoneal injections of naloxone did not significantly decrease the morphine analgesic effect in analgine- and ketorolac-tolerant rats, whereas in saline-treated animals morphine analgesic effect was reverted. Taken together the present and previous findings support the notion that the contribution of the CNS, particularly of downstream pain-control structures, to the analgesic effects of NSAIDs involves endogenous opioidergic mechanisms. Thus, obtained data support the suggestion about a close relation between non-opioid tolerance and endogenous opioid system.
authors.affiliation: Department of Neurophysiology, Beritashvili Institute of Physiology, Tbilisi, Georgia.
authors.forename: N
authors.initials: N
authors.lastname: Tsiklauri
authors.forename: G
authors.initials: G
authors.lastname: Gurtskaia
authors.forename: M
authors.initials: M
authors.lastname: Tsagareli
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D004361:Drug Tolerance; D009020:Morphine / Q000008:administration & dosage; D018847:Opioid Peptides / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects
chemical_list: D018712:Analgesics, Non-Narcotic; D018847:Opioid Peptides; D009020:Morphine