It has been widely accepted that prostaglandins are involved in peripheral mechanisms of hyperalgesia. Several lines of evidence suggest that prostaglandins also contribute to the mechanisms underlying hyperalgesia at the level of the spinal cord. The nociceptive flexor reflex of the hind limb was used to test the hypothesis that products of cyclo-oxygenase contribute to the increased excitability of spinal neurons during hyperalgesia induced by peripheral injection of complete Freund's adjuvant (CFA) into the hind paw. The reflex was evoked by electrical stimulation of the sural nerve at an intensity that activated A- and C-fibers, and muscle potentials were recorded in hamstring muscles in decerebrate, spinalized rats. Intrathecal administration of (S)-ibuprofen (1-100 nmol) dose-dependently attenuated the flexor reflex in CFA treated rats but had no effect in untreated rats. (R)-Ibuprofen had no effect on the reflex in either control or CFA-treated rats at the dose tested (100 nmol). Western blots of lumbar spinal cord extracts showed increased levels of cyclo-oxygenase (COX)-2 protein in the dorsal spinal cord of rats with peripheral inflammation; no change occurred in the level of COX-1. These results indicate that products of COX-2 contribute to the increased excitability of the spinal cord during persistent peripheral inflammation.
Bibliographical noteFunding Information:
These studies were supported by funds from the National Institutes of Health (NS177702, V.S.S.). The authors acknowledge the technical assistance of Kathy Ensrud and Andrew Grande in the generation of the data, and are grateful to Drs D.A. Simone and D.R. Linden for their thoughtful comments during preparation of the manuscript.
- Flexor reflex
- Spinal cord