A minimal stress model for the assessment of electroacupuncture analgesia in rats under halothane Yeong-Ray Wen a,b , Geng-Chang Yeh a , Bai-Chuang Shyu c , Qing-Dong Ling d , Kuo-Ching Wang b , Ta-Liang Chen a , Wei-Zen Sun e, * a Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan b Department of Anesthesiology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan c Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan d Cell Biology and Anatomy Lab., Cathay Medical Research Institute, Cathay General Hospital, Taipei, Taiwan e Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan Received 30 April 2006; received in revised form 14 November 2006 Available online 10 January 2007 Abstract The use of anesthetics in acupuncture analgesia is controversial. We evaluate a steady-state light anesthesia model to test whether minimal stress manipulation and reliable measurement of analgesia could be simultaneously achieved during electroacupuncture (EA) in animals. A series of experiments were performed. Firstly, EA compliance and tail-flick latencies (TFL) were compared in rats under 0.1%, 0.3%, 0.5%, 0.7%, or 1.1% halothane for 120 min. Under 0.5% halothane, TFL were then measured in groups receiving EA at inten- sity of 3, 10 or 20 volt (V), 1 or 2 mg/kg morphine, 20 V EA plus naloxone, or control. Subsequently, the effect of EA on formalin- induced hyperalgesia was tested and c-fos expression in the spinal dorsal horn was analyzed. Rats exhibited profound irritable behaviors and highly variable TFL under 0.1% or 0.3% halothane, as well as a time-depen- dent increase of TFL under 0.7% or 1.1% halothane. TFL remained constant at 0.5% halothane, and needle insertion and elec- trical stimulation were well tolerated. Under 0.5% halothane, EA increased TFL and suppressed formalin-induced hyperalgesia in an intensity-dependent and naloxone-reversible manner. EA of 20 V prolonged TFL by 74%, suppressed formalin-induced hyper- algesia by 32.6% and decreased c-fos expression by 29.7% at the superficial and deep dorsal horn with statistically significant difference. In conclusion, 0.5% halothane provides a steady-state anesthetic level which enables the humane application of EA stimulus with the least interference on analgesic assessment. This condition serves as a minimal stress EA model in animals devoid of stress- induced analgesia while maintaining physiological and biochemical response in the experiment. Ó 2006 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. Keywords: Electroacupuncture; Model; Halothane; c-Fos; Formalin 1. Introduction Although acupuncture is commonly accepted as a treatment of choice for many pain conditions, the mech- anism underlying acupuncture analgesia is still under debate. Many outcome studies in human are classified as ‘‘less convincing scientific data’’ for not including sham needling to exclude the potential placebo effect (NIH Consensus Statement, 1997; Linde et al., 2005). Application of acupuncture to conscious animal is even more complicated because needle insertion per se is 1090-3801/$32 Ó 2006 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejpain.2006.11.003 * Corresponding author. Tel.: +886 2 23562157; fax: +886 2 23415736. E-mail address: wzsun@ntu.edu.tw (W.-Z. Sun). www.EuropeanJournalPain.com European Journal of Pain 11 (2007) 733–742