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Journal of Neuroscience, Vol 15, 2768-2776, Copyright © 1995 by Society for Neuroscience
Cyclooxygenase inhibition and the spinal release of prostaglandin E2 and amino acids evoked by paw formalin injection: a microdialysis study in unanesthetized rats
AB Malmberg and TL Yaksh
Department of Anesthesiology, University of California at San Diego, La Jolla 92093, USA.
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)
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