Anti-nociception induced by systemic or PAG-microinjected lysine-acetylsalicylate in rats. Effects on tail-flick related activity of medullary off- and on-cells.
Previous experiments using metamizol have shown that this non-steroidal anti-inflammatory drug (NSAID) produces a central anti-nociceptive effect probably through neural substrates that also support the analgesic effects of opiates, such as the periaqueductal grey matter (PAG) and the off- and on-cells of the rostral ventromedial medulla (RVM). Off- and on-cells have been postulated to respectively inhibit and facilitate nociceptive transmission, since the heat-elicited tail flick reflex (TF) occurs only after off-cells have decreased (pause), and on-cells, have increased (burst) their activity. The aim of the present study was to examine whether the effect of metamizol upon TF and off- and on-cells responses could be generalized to other NSAIDs such as, in this case, lysine-acetylsalicylate (LASA). Fifty-nine off- and on-cells of the RVM were recorded in lightly anaesthetized rats. Systemic administration (200 and 300 mg/kg) or PAG microinjection (30, 50 and 100 micrograms) of LASA caused retardation of the heat-elicited off-cell pause, on-cell burst and the corresponding TF. Neuronal responses and TF retained their mutual time relationship but shifted simultaneously toward longer latencies. This anti-nociceptive effect of LASA was dose-dependent, present 5 min after administration and reached a maximum in 30 min for both administration methods. These data confirm that analgesics typically defined as peripherally-acting, such as metamizol and LASA in this study, may also have an anti-nociceptive effect by acting directly upon PAG, and suggest that this central effect involves the RVM off- and on-cells.
Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.
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D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004177:Dipyrone / Q000494:pharmacology; D007275:Injections, Intravenous; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000166:cytology* / Q000502:physiology*; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects; D010487:Periaqueductal Gray / Q000033:anatomy & histology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004177:Dipyrone; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate