Dipyrone is one of the most commonly used non-opioid analgesic and antipyretic drug. Its anti-nociceptive and hypothermic effects have long been suspected to be centrally mediated. The involvement of the most recently discovered opioid peptide, nociceptin/orphanin FQ (N/OFQ), and its receptor (NOP) in pain transmission is controversial. It appears to be pro-nociceptive when administered supra-spinally, but exerts anti-nociceptive effects when injected spinally or systemically.

Investigation of the role of the N/OFQ system in paracetamol-induced anti-nociception and hypothermia led us to determine its role in the anti-nociceptive and hypothermic effects of dipyrone.

Hot-plate and tail-flick tests were used to assess nociception, and a rectal thermometer was used to measure rectal temperature in mice.

Mice injected with dipyrone (150, 300, 600 mg/kg, i.p.) displayed dose-related anti-nociception and hypothermia. The NOP receptor antagonist JTC-801 (3 mg/kg, i.p.), at a dose that exerted no effect when used alone, alleviated dipyrone-induced anti-nociception but did not reverse dipyrone-induced hypothermia.

We conclude that NOP receptors participate in the anti-nociceptive, but not in the hypothermic, effects of dipyrone.