sc-236 and Neuralgia

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.

Topics: Animals; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Ibuprofen; Isoenzymes; Ligation; Lumbar Vertebrae; Male; Membrane Proteins; Microdialysis; Neuralgia; Physical Stimulation; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Nerves; Sulfonamides; Touch