title: Cyclooxygenase inhibition and the spinal release of prostaglandin E2 and amino acids evoked by paw formalin injection: a microdialysis study in unanesthetized rats.
abstract: Injection of formalin into the hind paw evokes a biphasic flinching of the injured paw. Pharmacological characterization of this behavior has implicated the spinal release of excitatory amino acids (EAAs) and cyclooxygenase (COX) products. To address this hypothesis, we examined the effect of paw formalin injection on release of EAAs and prostaglandin E2-like immunoreactivity (PGE2-LI) from the spinal cord in unanesthetized rats using a dialysis probe placed in the lumbar subarachnoid space. To assess the contribution of spinal COX products, the effects of S(+)- and R(-)-ibuprofen (active and inactive COX inhibitors) were examined. Paw formalin injection evoked a biphasic spinal release of PGE2-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 paw had no effect on behavior, PGE2-LI, or EAA release. Intraperitoneal administration of 10 mg/kg, but not 1 mg/kg, S(+)-ibuprofen reduced paw flinching, blocked the elevated levels of PGE2-LI, and suppressed Glu and Asp release to 50% of control. Intrathecal delivery of 10 micrograms, but not 1 microgram, S(+)-ibuprofen also suppressed formalin-induced behavior, PGE2-LI, Glu, and Asp release. R(-)-ibuprofen showed no effect on formalin-induced behaviors or spinal release. These data demonstrate that paw formalin injection produces spinal release of PGE2-LI corresponding to the biphasic behavioral response and that the evoked release is blocked by antinociceptive doses of COX inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesiology, University of California at San Diego, La Jolla 92093, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Malmberg
authors.forename: T L
authors.initials: TL
authors.lastname: Yaksh
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005557:Formaldehyde; D018698:Glutamic Acid / Q000378:metabolism*; D006614:Hindlimb; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D017551:Microdialysis / Q000379:methods; D010146:Pain / Q000503:physiopathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000596:Amino Acids; D005557:Formaldehyde; D001224:Aspartic Acid; D018698:Glutamic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007052:Ibuprofen