Spinal Prostaglandins Facilitate Exaggerated A- and C-fiber-mediated Reflex Responses and Are Critical to the Development of Allodynia Early after L5-L6 Spinal Nerve Ligation

Abstract

Spinal prostaglandins are important in the early pathogenesis of spinal nerve ligation (SNL)-induced allodynia. This study examined the effect of SNL on the expression of cyclooxygenase (COX)-1, COX-2, and prostaglandin E2 receptors in the rat lumbar spinal cord, and the temporal and pharmacologic relation of these changes to the exaggerated A- and C-fiber-mediated reflex responses and allodynia, 24 h after injury. Male Sprague-Dawley rats, fitted with intrathecal catheters, underwent SNL or sham surgery. Paw withdrawal threshold, electromyographic analysis of the biceps femoris flexor reflex, and immunoblotting of the spinal cord were used. Both allodynia (paw withdrawal threshold of < or = 4 g) and exaggerated A- and C-fiber-mediated reflex responses (i.e., decrease in activation threshold, increase in evoked activity, including windup; P < 0.05) were evident 24 h after SNL but not sham surgery. Allodynic animals exhibited significant increases in prostaglandin E2 receptor (subtypes 1-3) and COX-1 (but not COX-2) expression in the ipsilateral lumbar dorsal horn. The corresponding ventral horns and contralateral dorsal horn were unchanged from sham controls. Exaggerated A- and C-fiber-mediated reflex responses were significantly attenuated by intrathecal SC-560 or SC-51322, but not SC-236, given 24 h after SNL. These results provide further evidence that spinal prostaglandins, derived primarily from COX-1, are critical in the exaggeration of A- and C-fiber input and allodynia, 24 h after SNL.