Ž . Regulatory Peptides 103 2002 23–27 www.elsevier.comrlocaterregpep Role of calcitonin gene-related peptide and its antagonist on the evoked discharge frequency of wide dynamic range neurons in the dorsal horn of the spinal cord in rats Yi Yu a,b , Thomas Lundeberg c,d , Long-Chuan Yu a,b,c,d, ) a Department of Physiology, College of Life Sciences, Peking UniÕersity, Beijing 100871, People’s Republic of China b National Laboratory of Biomembrane and Membrane Biotechnology, Peking UniÕersity, Beijing 100871, People’s Republic of China c Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden d Department of Medical Rehabilitation, Karolinska Institutet, 171 77 Stockholm, Sweden Received 19 February 2001; received in revised form 5 September 2001; accepted 17 September 2001 Abstract Ž . The present study was performed to explore the effect of calcitonin gene-related peptide CGRP and its antagonist CGRP8–37 on the Ž . evoked discharge frequency of wide dynamic range WDR neurons in the dorsal horn of the spinal cord in rats. Recording was performed with a multibarrelled glass micropipette and the chemicals were delivered by iontophoresis. The discharge of WDR neurons Ž. was evoked by transdermic electrical stimulation applied on the ipsilateral hindpaw. 1 Iontophoretic application of CGRP at an ejection Ž. current of 100 nA increased the discharge frequency of WDR neurons significantly. 2 Iontophoretic application of CGRP8–37 at an Ž. ejection current of 80 or 160 nA induced significant decreases in the discharge frequency of WDR neurons, but not at 40 nA. 3 Iontophoretic application of CGRP8–37 not only antagonized the CGRP-induced increase in the evoked discharge frequency of WDR neurons but also induced a significant decrease in the evoked discharge frequency of WDR neurons compared to basal levels. The results indicate that CGRP and its receptors play a facilitary role on the transmission andror modulation of nociceptive information in the dorsal horn of the spinal cord in rats. q 2002 Elsevier Science B.V. All rights reserved. Keywords: CGRP8–37; Iontophoresis; Nociceptive information 1. Introduction It has been reported that peripheral noxious stimulation induced the release of calcitonin gene-related peptide Ž . CGRP from primary afferent fibers in the dorsal horn of the spinal cord, suggesting that CGRP is involved in the transmission andror modulation of presumed nociceptive w x information 1,2 . Electrophysiological studies showed that CGRP produced a slow depolarization and prolonged exci- w x tation on dorsal horn cells 3,4 . Studies in our laboratory have demonstrated that intrathecal administration of CGRP8–37, a selective antagonist of CGRP receptors w x 5,6 , induced significant increases in hindpaw withdrawal latency to noxious thermal and mechanical stimulation in ) Corresponding author. Department of Physiology, College of Life Sciences, Peking University, Beijing 100871, People’s Republic of China. Tel.: 86-10-62751867; fax: 86-10-62751526. Ž . E-mail address: yulc@pku.edu.cn L.-C. Yu . rats, thus suggesting an anti-nociceptive role for CGRP8– w x 37 in dorsal horn of the spinal cord 7–10 . Recently, results of our laboratory showed that direct administration of CGRP8–37 on the dorsal surface of the spinal cord inhibited the evoked discharge frequency of wide dynamic Ž . range WDR neurons in the dorsal horn of the spinal cord w x in rats 11 . In order to determinate whether the CGRP and CGRP8–37 act directly on the WDR neurons, the present study was undertaken to investigate the effect of CGRP and CGRP8–37 delivered by iontophoresis on the evoked discharge frequency of WDR neurons in the dorsal horn of rats. 2. Materials and methods 2.1. Animals and surgery All experiments were performed on male Sprague– Ž Dawley rats weighing 250 to 350 g Experimental Animal 0167-0115r02r$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. Ž . PII: S0167-0115 01 00326-3