Ž . Brain Research 859 2000 358–360 www.elsevier.comrlocaterbres Short communication Antinociceptive effects of calcitonin gene-related peptide injected into periaqueductal grey of rats with mononeuropathy Shi-Lian Xu a , Thomas Lundeberg b , Long-Chuan Yu a,b, ) a Department of Physiology, College of Life Sciences, Peking UniÕersity, Beijing 100871, China b Department of Physiology and Pharmacology, and Department of Medical Rehabilitation, Karolinska Institutet, 171 77 Stockholm, Sweden Accepted 23 November 1999 Abstract Ž . Ž . Intra-periaqueductal grey PAG injection of calcitonin gene-related peptide CGRP induced dose-dependent increases in hindpaw Ž . withdrawal latency HWL to thermal and mechanical stimulation in rats with mononeuropathy. CGRP-induced increases in HWLs were blocked by intra-PAG injection of the CGRP antagonist CGRP8-37. The results demonstrated that CGRP and CGRP receptors in PAG play an important role in antinociception in rats with mononeuropathy. q 2000 Elsevier Science B.V. All rights reserved. Ž . Ž . Keywords: Calcitonin gene-related peptide CGRP ; CGRP8-37; Hindpaw withdrawal latency; Periaqueductal grey PAG ; Sciatic nerve ligation Ž . Periaqueductal grey PAG is one of the most important structures of the endogenous analgesic system in the brain w x 5,7 . Many neurotransmitters and neuropeptides exist andror co-exist in PAG, including calcitonin gene-related Ž . w x peptide CGRP 10 . CGRP is involved in the modulation w x of nociception 3,4,9,11,12 . The present study was per- formed to investigate the effect of intra-PAG injection of CGRP on neurogenic pain in rats. All experiments were performed on freely moving male Sprague–Dawley rats weighing 200–300 g. Rats were housed in cages with free access to food and water, and maintained in a room temperature with a 12-h lightrdark cycle. All experiments were conducted according to the guidelines of The Animal Ethical Committee of Karolinska Institutet and every effort was made to minimize animal Ž . suffering. The hindpaw withdrawal latency HWL to nox- Ž . ious heat stimulation was assessed by the hot-plate 528C and the HWL to mechanical stimulation was assess by Ž . w x Randall Selitto Test Ugo Basile, Type 7200, Italy 11,12 . The average values obtained before intra-PAG injection were regarded as the basal HWL. The HWL recorded during subsequent experiments was expressed as percent- ) Corresponding author. Department of Physiology, College of Life Sciences, Peking University, Beijing 100871, China. Fax: q 86-10- 62751526; e-mail: yulc@pku.edu.cn age changes of the basal level for each rat. Each rat was tested with both types of stimulation. The rat mononeu- ropathy model was made by left common sciatic nerve w x loose ligation 2,11 . The animals were anaesthetized by intraperitoneal Ž . pentobarbital 45 mgrkg and were mounted on a stereo- taxic instrument. A stainless steel guide cannula of 0.8 mm Ž o.d. was directed to PAG AP s 5.5, L s 0.5, H s 4.0 mm . from the surface of the skull according to Paxinos and wx Watson 8 , and the guide cannula was fixed to the skull by dental acrylic. On the experimental day, a stainless steel needle with 0.4 mm diameter was directly inserted into the guide cannula, with 1 mm beyond the tip of the latter. One microliter of solution was thereafter infused into PAG over 1 min. Solutions for intra-PAG injection were prepared Ž. with sterilized saline, each with a volume of 1 ml: 1 Ž 0.003, 0.03 or 0.3 nmol of CGRP hCGRP, Peninsula .Ž. Labs, Europe LIT ; 2 0.003, 0.03 or 0.3 nmol of CGRP8- Ž . 37 hCGRP8-37, Peninsula Labs . Data from nociceptive tests were presented as mean " S.E.M. The difference Ž . between groups the difference between two curves was Ž . determined by a two-way analysis of variance ANOVA , F is the F value getting from ANOVA to compare leftrleft left HWLs of two groups. Rats with mononeuropathy received intra-PAG injection Ž . Ž . of 0.003 n s 8 , 0.03 n s 9 or 0.3 nmol of CGRP Ž . Ž . n s 9 , or 1 ml of 0.9% saline as a control n s 8. Compared to the control group, the HWL increased signifi- 0006-8993r00r$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. Ž . PII: S0006-8993 99 02407-5