Localization of the central antinociceptive effects of diclofenac in the rat.

The ethacrynic acid-induced writhing response (WR) in the rat was studied after microinjections of diclofenac 0.1 ng-1 microgram/0.5 microliter (0.32 pmol to 3.2 nmol) into several brain regions involved in control of nociceptive behavior. The WR was inhibited after injections into the periaqueductal grey matter (PAG), ventromedial thalamus (VM), medial preoptic area (MPA) and the nucleus raphe magnus (NRM). Morphine 50 ng/0.5 microliter (0.16 nmol) was used as a positive control and vehicle injections were performed as negative reference. After diclofenac, there was a dose-dependent reduction of the WR with a threshold dose of approximately 1-10 ng in all brain areas studied except the nucleus reticularis paragigantocellularis interna (NRPGi). Naloxone 50 ng/0.5 microliter (0.15 nmol) administered into the same site 30 min after diclofenac injection, antagonized the diclofenac-induced inhibition of the WR almost completely in PAG and VM. Previous results demonstrate a central, naloxone-reversible component in the analgetic action of diclofenac. A qualitatively similar, centrally induced inhibition of the WR may be elicited after injections into PAG, VM and NRM. Thus, in addition to its peripheral mechanism of action, the non-steroidal anti-inflammatory drug, diclofenac, has a central mechanism of action which directly or indirectly involves a central opioid component.