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.