INTRATHECAL ADMINISTRATION OF PROSTAGLANDIN E(2) CAUSES SENSITIZATIONOF THE PRIMARY AFFERENT NEURON VIA THE SPINAL RELEASE OF GLUTAMATE

Objective and Design: The present investigation was aimed at assessing the involvement of primary sensory neurons in the hyperalgesia induce d by the intrathecal injection of PGE(2), as well as whether the hyper algesic effect was due to the spinal release of glutamate. Material: M ale Wistar rats were used. Methods: Hyperalgesia was measured using th e rat paw pressure test. Results: Intrathecal PGE(2) (2.5-50 ng/rat) a dministration caused a dose-dependent hyperalgesia in both paws. Ipsil ateral intraplantar injections of morphine (0.5-8 mu g/paw) or SNAP (S -nitroso-N-acetyl-D,L-penicillamine, 50-200) mu g/paw) dose-dependentl y antagonized spinally-induced PGE(2) hyperalgesia (ANOVA, p < 0.001). Their antinociceptive effects were confirmed to be peripheral by abol ition following pretreatment of the paws with L-NMMA (N-G-monomethyl-L -arginine monoacetate), 50 mu g/paw or with methylene blue (500 mu g/p aw). The spinally-induced PGE(2) hyperalgesia was antagonized by intra thecal injections (9 mu g) of AP5 (2-amino-5-phosphonopentanoate/2-ami no-5 a selective NMDA receptor antagonist. Conclusions: Intrathecal ad ministration of PGE(2) seems to cause hyperalgesia by spinal sensitiza tion of the primary afferent neuron through the release of glutamate.