Spinal nerve injury activates prostaglandin synthesis in the spinal cord that contributes to early maintenance of tactile allodynia

Abstract

To determine if spinal prostaglandins (PG) contribute to tactile allodynia, male, Sprague-Dawley rats were fitted with either intrathecal (i.t.) microdialysis or drug delivery catheters 3 days before tight ligation of the left lumber 5/6 spinal nerves. Paw withdrawal thresholds (PWT) were determined using von Frey filaments. Ligated rats developed tactile allodynia within 24h, as evidenced by a decrease in PWT in the affected hindpaw (<4 g vs. >15 g control). Sham-operated controls were unchanged from baseline (>15 g). Allodynia was also characterized by a significant increase in the evoked release of PGE(2). Thus, brushing the plantar surface of the affected hindpaw with a cotton-tipped applicator, 5 days postligation, increased the [PGE(2)](dialysate) to 199+/-34% of the prestimulus control period. In contrast, brushing had no detectable effect on release before surgery or in sham-operated animals. Basal release (no brushing) was similar before and after surgery (sham-operated and ligated rats). In a separate group of rats and beginning 2 days after ligation, the acute i.t. injection of S(+)-ibuprofen, SC-51322, SC-236, or SC-560 significantly reversed allodynia (maximum effect=69+/-9, 66+/-6, 57+/-4, 20+/-5%, respectively). R(-)-ibuprofen or vehicle were without effect. The results of this study suggest that: (a). spinal PG synthesis and allodynia-like behaviour are triggered by normally innocuous brushing after spinal nerve ligation; (b). pharmacological disruption of this cascade significantly reverses allodynia; (c). COX-2 is the relevant isozyme; and (d). the PG effect is mediated by spinal EP receptors.