Toxicon 51 (2008) 102–111 Inhibitory effect of crotoxin on the pain-evoked discharge of neurons in thalamic parafascicular nucleus in rats $ Qi Zhu a,d , Dian-Chen Wu a,b , Xi-Ping Zhou b , Shan Gong a,d , Bo-Chao Cheng a,b , Zheng-Hong Qin c,d , Paul F. Reid e , Qi-Zhang Yin a,d , Xing-Hong Jiang a,d,Ã a Department of Neurobiology, School of Medicine, Soochow University, Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou 215123, PR China b Department of Physiology, School of Medicine, Soochow University, Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou 215123, PR China c Department of Pharmacology, School of Medicine, Soochow University, Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou 215123, PR China d Laboratory of Aging and Nervous Diseases, School of Medicine, Soochow University, Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou 215123, PR China e Celtic Biotech Ltd., Dublin, Ireland Received 11 May 2007; received in revised form 22 August 2007; accepted 27 August 2007 Available online 2 September 2007 Abstract Crotoxin (Cro), the principal neurotoxic component of Crotalus durissus terrificus, has been previously reported to have a behavioral analgesic effect in rats and mice. The present study investigated electrophysiologically the effect of Cro on pain-evoked unit discharge of neurons in thalamic parafascicular nucleus (Pf) and underlying mechanisms of its effect. The electrical discharge of Pf neurons was recorded with the microelectrode technique in rats. Intracerebroventricular (icv) injection of Cro at 0.25, 0.45 and 0.65 mg/kg resulted in a dose-dependent inhibitory effect on the pain-evoked discharge of Pf neurons. The discharge frequency and the discharge duration significantly (Po0.05) decreased after Cro administration. This inhibitory effect was significantly (Po0.05) attenuated after pretreatment with para-chlorophenylalanine (pCPA), or electrolytic lesion of dorsal raphe (DR) nucleus. In contrast, icv injection of atropine (muscarinic receptor antagonist, 5 mg) or naloxone (opioid receptor antagonist, 4 mg) had no effect on Cro-induced inhibition of discharge of Pf neurons. The results suggested that Cro has an analgesic effect, which is mediated, at least partially, by the central serotonergic system. r 2007 Elsevier Ltd. All rights reserved. Keywords: Crotoxin; Analgesia; Thalamic parafascicular nucleus; Unit discharge; Serotonin; pCPA; Dorsal raphe nucleus; Atropine; Naloxone ARTICLE IN PRESS www.elsevier.com/locate/toxicon 0041-0101/$ - see front matter r 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.toxicon.2007.08.009 $ Ethical statement: On behalf of, and having obtained permission from all the authors, Xing-Hong Jiang declares that: (a) the material has not been published in whole or in part elsewhere; (b) the paper is not currently being considered for publication elsewhere; (c) all authors have been personally and actively involved in substantive work leading to the report, and will hold themselves jointly and individually responsible for its content; and (d) all experimental procedures in this study were reviewed and approved by the Animal Care and Use Committee of Soochow University. Xing-Hong Jiang testifies to the accuracy of the above on behalf of all the authors. Ã Corresponding author. Department of Neurobiology, School of Medicine, Soochow University, Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou 215123, PR China. Tel.: +86 512 65880126; fax: +86 512 65880397. E-mail address: jiangxinghong@suda.edu.cn (X.-H. Jiang).