SOMATOSENSORY SYSTEMS, PAIN NEUROREPORT 0959-4965 & Lippincott Williams & Wilkins Vol 12 No 1 22 January 2001 175 Decrease in spinal CGRP and substance P is not related to neuropathic pain in a rat model Heung Sik Na, CA Hee Jin Kim, Backil Sung, Seung Keun Back, Do Young Kim, Joon Seon Kim and Seung Kil Hong Neuroscience Research Institute and Department of Physiology, Korea University College of Medicine, 126-1 Anam-dong 5 Ga, Sungbuk-gu, Seoul, 136-705, Korea CA Corresponding Author Received 9 October 2000; accepted 9 November 2000 We tested the hypothesis that the decrease in spinal levels of SP and CGRP after peripheral nerve injury is related to neuropathic pain. We compared two groups of rats, both of which were subjected to unilateral transection of the inferior and superior caudal trunks between the S1 and S2 spinal nerves. One group exhibited well-developed neuropathic signs after the nerve injury, whereas the other group showed poorly developed signs despite the same nerve injury. The decrease in immunoreactivity of CGRP and SP in the S1 dorsal horn (injured segment) was not signi®cantly different between the two groups. These results suggest that the decrease in spinal levels of CGRP and SP after peripheral nerve injury is not related to neuropathic pain. NeuroReport 11:175±178 & 2001 Lippincott Williams & Wilkins. Key words: Allodynia; Calcitonin gene-related peptide; Neuropathic pain; Peripheral nerve injury; Peripheral neuropathy; Substance P INTRODUCTION Peripheral nerve injury often leads to chronic neuropathic pain signs [1±3]. Although numerous efforts have been made to elucidate how neuropathic pains are generated, the current understanding of the mechanisms of neuro- pathic pain is far from being complete [4±6]. Calcitonin gene-related peptide (CGRP) and substance P (SP), excitatory neurotransmitters localized in primary afferents, play a key role in nociceptive signaling [7,8]. Peripheral nerve injury resulting in neuropathic pain, how- ever, decreases the levels of spinal CGRP and SP [9±11]. At present, the correlation between the decrease in spinal CGRP and SP, and the generation of neuropathic pain is uncertain. In this study, using a rat model of peripheral neuropathy, we assessed whether the decrease in spinal CGRP and SP following peripheral nerve injury is speci®c for neuropathic pain. To this aim, we compared two groups of rats with respect to the changes in spinal CGRP and SP; one group exhibited well-developed neuropathic signs after the nerve injury, whereas the other group showed poorly-developed signs despite the same nerve injury. Here we report results that the reduction of these neuropeptides is not related to the generation of neuro- pathic pain. Preliminary data for this study have been presented in abstract form [12]. MATERIALS AND METHODS Young adult male rats (Sprague±Dawley, 150±200 g, n  56 rats) were used in this study. Under en¯urane anesthesia (0.5±2%) the left inferior and superior caudal trunks were transected at the level between the S1 and S2 spinal nerves [13]. The behavioral tests for mechanical, cold and warm allodynia were conducted 1 day prior to the nerve injury and 1, 7 and 14 day(s) postoperatively. As described previously [14,15], mechanical allodynia of the tail was measured by the tail withdrawal frequency evoked by the application of a von Frey hair (19.6 mN, 2.0 g). To test for cold and warm allodynia, the tail was immersed in cold (48C) and warm (408C) water, respectively, and the latency of tail withdrawal response was measured with a cut-off time of 15 s. After the behavioral tests for 2 weeks, we compared two groups of rats with respect to the spinal levels of CGRP and SP; one group showed well-developed neuropathic signs (NP() group), and the other group showed poorly- developed signs (NP() group). The rats were perfused with 4% paraformaldehyde in 0.1 M phosphate buffer (PB) containing 0.1% picric acid. The S1 spinal segment (injured level) excised was post®xed for 6±8 h in the same ®xative and placed overnight in 0.1 M PB (pH 7.4) containing 30% sucrose at 48C. The excised segment was sectioned at 14 ìm on a freezing microtome. Sections were reacted with