Substance P and peripheral inflammatory hyperalgesia.

The hyperalgesic effect of substance P (SP) is usually described as presenting short latency. We now report that multiple injections of sub-threshold doses of SP into the foot pad of a hind paw of rats pre-treated with indomethacin induced a long-lasting hyperalgesia, sensitizing the paw to further challenges with small doses of SP, dopamine or prostacyclin. The sensitizing process also occurred after multiple injections of prostacyclin or prostaglandin E2. The sensitizing effect induced by SP, prostaglandin E2 or prostacyclin is inhibited by pre-treatment with the SP antagonist (D-Arg, D-Pro, D-Trp, Leu)-SP. We suggest that SP has an important role as a modulator in peripheral inflammatory pain by sensitizing nociceptors to its own action and to the action of different mediators. This sensitizing process could also be associated with chronic inflammatory pain.