Inhibitory effects of tachykinin receptor antagonists on thermally induced inflammatory reactions in a rat model

Recent studies have proposed that activation of the sensory nervous system after thermal injury induces the release of vasoactive neuropeptides, including tachykinins which contribute to the local inflammatory reaction as well as to the nociceptive transmission at the spinal cord level. Effects of the tachykinins substance P and neurokinin A are mediated by the neurokinin 1 and 2 (NK1, NK2) receptors. The aim of the present study was to investigate the modulatory role of NK1 and NK2 antagonists on edema formation, and on hindpaw withdrawal latency to experimentally asses nociception. Thermal injury was inflicted on the anaesthetized rat by dipping the right hindpaw into hot water at 60 degrees C for 20 s. The amount of edema formation was calculated by measuring the hindpaw volume with a plethysmograph before and during 420 min after scalding. In other studies scalding was inflicted under brief anesthesia, and hindpaw withdrawal latencies (HWL) to mechanical stimulation were recorded before injury and at 180 min after. The effect on edemic reactions of rats treated locally with NK1 and NK2 receptor antagonist were studied, as well as the effect of the same compounds on HWL after intrathecal injection. Scalding induced a progressive edema formation which was reduced significantly in rats treated with local injection of 100 nmol of NK1 and NK2 antagonists 45 min after the injury. The thermally induced inflammation was followed by significant decrease of the latency of hindpaw withdrawal response to mechanical stimulation. Intrathecal injection of 30 nmol of the same drugs 180 min after scalding was followed by significant increase in HWL. The results indicate that SP and NKA contribute to the inflammatory reactions after thermal injury and that the tachykinin receptor antagonists possess the ability to reduce both the local edemic reaction as well as the nociceptive transmission at the spinal cord level.