The Effects of Intrathecal Cyclooxygenase-1, Cyclooxygenase-2, or Nonselective Inhibitors on Pain Behavior and Spinal Fos-Like Immunoreactivity

Abstract

Prostaglandins are synthesized by cyclooxygenase (COX) and are thought to play an important role in nociceptive transmission in the spinal cord. Fos expression is an indicator of spinal neuron activation. We examined the role of intrathecal selective and nonspecific COX inhibitors on spinal C-Fos expression. To evaluate the relative contribution of COX-1 and COX-2 in nociceptive transmission in the spinal cord, we assessed the effects of the selective COX-1 inhibitor SC 560, the selective COX-2 inhibitor celecoxib, and the nonselective COX inhibitor ketorolac on formalin-evoked behavior and spinal c-Fos-like immunoreactivity (FLI). Rats received each of the drugs (30, 60, or 90 microg) intrathecally before the subcutaneous administration of formalin (5%, 50 microL) to the plantar surface of a hindpaw. The control group received vehicle intrathecally before the administration of formalin. Phase 1 flinching behavior decreased in rats given celecoxib or ketorolac 90 mug. Phase 2 flinching behavior decreased in rats given all doses of ketorolac or celecoxib 90 microg (P < 0.05). The FLI was significantly reduced in rats given celecoxib or ketorolac 90 microg for laminae I-II (P < 0.05). By contrast, for laminae V-VI, only the ketorolac 60 or 90 microg treatment group demonstrated a larger decrease in FLI (P < 0.05). The FLI expression in laminae V-VI had a significant correlation with phase 2 flinching behavior (P < 0.05). A dual inhibitor of COX-1 and COX-2 suppressed both responses of formalin-evoked behaviors and FLI expression of whole laminae in the lumbar spinal cord. FLI expression of laminae I-II alone may not be a good indicator of the ability to produce anti-hypersensitivity; however, the FLI of laminae V-VI correlates with phase 2 responses.