CYCLOOXYGENASE INHIBITION AND THE SPINAL RELEASE OF PROSTAGLANDIN E(2) AND AMINO-ACIDS EVOKED BY PAW FORMALIN INJECTION - A MICRODIALYSIS STUDY IN UNANESTHETIZED RATS

Injection of formalin into the hind paw evokes a biphasic flinching of the injured paw, Pharmacological characterization of this behavior ha s implicated the spinal release of excitatory amino acids (EAAs) and c yclooxygenase (COX) products, To address this hypothesis, we examined the effect of paw formalin injection on release of EAAs and prostaglan din E(2)-like immunoreactivity (PGE(2)-LI) from the spinal cord in una nesthetized rats using a dialysis probe placed in the lumbar subarachn oid space, To assess the contribution of spinal COX products, the effe cts of S(+)- and R(-)-ibuprofen (active and inactive COX inhibitors) w ere examined. Paw formalin injection evoked a biphasic spinal release of PGE(2)-LI with an increase above resting concentrations of 110% in the 0-10 min sample, and of 83% in the 20-30 min sample, Significantly increased release of glutamate (Glu; 110%) and aspartate (Asp; 112%) was only observed in the 0-10 min sample, Saline injection into the pa w had no effect on behavior, PGE(2)-LI, or EAA release, Intraperitonea l administration of 10 mg/kg, but not 1 mg/kg, S(+)-ibuprofen reduced paw flinching, blocked the elevated levels of PGE(2)-LI, and suppresse d Glu and Asp release to 50% of control, Intrathecal delivery of 10 mu g, but not 1 mu g, S(+)-ibuprofen also suppressed formalin-induced be havior, PGE(2)-LI, Glu, and Asp release. R(-)-ibuprofen showed no effe ct on formalin-induced behaviors or spinal release. These data demonst rate that paw formalin injection produces spinal release of PGE(2)-LI corresponding to the biphasic behavioral response and that the evoked release is blocked by antinociceptive doses of COX inhibitors, The sup pressant effect of COX inhibition on EAA release indicates that prosta glandins may be involved in facilitation of afferent-evoked EAA releas e in the spinal dorsal horn.