Effect of Intrathecal COX Inhibitors on Inflammatory Pain and c-Fos Expression in Central Nervous System Induced by Formalin Injection in Rat / 대한마취과학회지

ABSTRACT

BACKGROUND: Prostaglandins (PGs) play important roles in the transmission of nociceptive information in the spinal cord. PGs are produced by cyclooxygenase (COX). Two forms of COX have been identified COX-1 and COX-2. c-Fos is a marker of neuronal activity related to the stimulation of primary sensory neuron. We investigated the effect of intrathecal non-selective COX inhibitor, selective COX-1 or COX-2 inhibitors on the inflammatory pain and c-Fos expression in the brain. METHODS: A PE (polyethylene) intrathecal catheter was installed in male Sprague-Dawley rats (250-300 g). Control, nonselective COX inhibitor, COX-1 inhibitor, and COX-2 inhibitor groups (n = 8, each) received intrathecal dimethylsulfoxide (DMSO) solution, ketorolac 50microgram, SC-560 50microgram, or celecoxib 50microgram respectively 7 min before formalin injection. For formalin test, rats received 50microliter of 5% formalin in the right hindpaw subcutaneously. Pain-related behavior was quantified by counting the incidence of flinching for 60 minutes. c-Fos expression in the thalamus, hypothalamus, and amygdala was examined by immunohistochemistry. RESULTS: Nonselective COX inhibitor and COX-2 inhibitor groups showed less frequent phase 2 flinching than the control (P < 0.05). But there was no significant differences in the expression of FLI in the thalamus, hypothalamus, and amygdala between control and experimental groups. And the expression of FLI was not correlated with flinching behavior. CONCLUSIONS: These result represented that COX-2 would play important roles in the transmission of pain induced by formalin test and that FLI in thalamus, hypothalamus, and amygdala could not be a good parameter for evaluating central sensitization.