In the present study we have investigated the effects of galanin and/or oxytocin on carrageenan-induced hyperalgesia, the relationship between oxytocin and galanin-containing nerve fibers in the spinal cord and the influence of galanin on oxytocin secretion. Galanin (1 microgram) given intrathecally (i.t.) decreased significantly the mechanical nociceptive threshold of the carrageenan-treated hindpaw, with no significant effect on thermal nociception. The decrease in the mechanonociceptive threshold exerted by galanin was modulated by oxytocin (1 microgram, i.t.) administered simultaneously. There was a close relationship between galanin- and oxytocin-immunoreactive fibers in the dorsal horn of the thoracic spinal cord, although there was no evidence for colocalization. Galanin 0.1 and 1 microgram given intracerebroventricularly or intraperitoneally significantly decreased the oxytocin level in plasma 60 min after injection. Taken together, these data indicate that galanin may contribute to mechanical hyperalgesia by inhibiting the release of oxytocin from nerve terminals in the spinal cord and that oxytocin may be a potential analgesic agent.