The effect of spinal and systemic administration of indomethacin on zymosan-induced edema, mechanical hyperalgesia, and thermal hyperalgesia

Pretreatment with intraperitoneal (IP) indomethacin was used to determine w hether indomethacin preferentially affected the development of edema and hy peralgesia to thermal and mechanical stimuli produced by injection of zymos an in the ispsilateral hindpaw of the rat. Indomethacin also was delivered intrathecally (IT) either 30 minutes before or 4 hours after intraplantar z ymosan to determine whether spinal prostaglandin production was important f or the induction and/or maintenance of hyperalgesia. Zymosan alone produced a robust edema, a monophasic mechanical hyperalgesia, and a biphasic therm al hyperalgesia in the ipsilateral hindpaw. Systemic administration of indo methacin reduced zymosan-induced edema and increased thermal and mechanical response thresholds in the zymosan-injected paw. Systemic indomethacin did not affect thermal withdrawal response thresholds in the uninjected contra lateral hindpaw of zymosan-treated rats, but significantly increased mechan ical withdrawal thresholds of the uninjected contralateral paw of zymosan-t reated rats. IT administration of indomethacin before the induction of hype ralgesia attenuated the development of zymosan-induced mechanical hyperalge sia, but did not affect the development of either zymosan-induced edema or thermal hyperalgesia. Once hyperalgesia was established, IT indomethacin al so attenuated the mechanical hyperalgesia whereas it had no effect on therm al hyperalgesia or edema. These data suggest that peripheral, but not spina l prostaglandins contribute to the edema and development of thermal hyperal gesia produced by zymosan. In contrast, spinal prostaglandins contribute to the development and maintenance of mechanical hyperalgesia.