The mechanism of the local hyperalgesic action of prostaglandin E2 has been studied using rat paw oedema. Prostaglandin E2 is a metabotropic transmitter, activating adenylate cyclase, either directly or through the release of a stimulatory protein factor. This activation of adenylate-cyclase is blocked, locally, by opiates. Hyperalgesia results from the alteration of the cAMP/Ca2+ balance after chemical or mechanical initiation of generator potentials at the nociceptor.