Original Article DOI 10.3349/ymj.2010.51.1.82 pISSN: 0513-5796, eISSN: 1976-2437 Yonsei Med J 51(1): 82-87, 2010 Effect of Sildenafil on Neuropathic Pain and Hemodynamics in Rats Lan Ji Huang,2 Myung Ha Yoon,1,2 Jeong Il Choi,1 Woong Mo Kim,1 Hyung Gon Lee,1 and Yeo Ok Kim1 1Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju; 2The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea. Purpose: The inhibition of phosphodiesterase 5 produces an antinociception through the increase of cyclic guanosine monophosphate (cGMP), and increasing cGMP levels enhance the release of γ -aminobutyric acid (GABA). Furthermore, this phosphodiesterase 5 plays a pivotal role in the regulation of the vasodilatation associated to cGMP. In this work, we examined the contribution of GABA receptors to the effect of sildenafil, a phosphodiesterase 5 inhibitor, in a neuropathic pain rat, and assessed the hemodynamic effect of sildenafil in normal rats. Materials and Methods: Neuropathic pain was induced by ligation of L5/6 spinal nerves in Sprague- Dawley male rats. After observing the effect of intravenous sildenafil on neuropathic pain, GABAA receptor antagonist (bicuculline) and GABAB receptor antagonist (saclofen) were administered prior to delivery of sildenafil to determine the role of GABA receptors in the activity of sildenafil. For hemodynamic measurements, catheters were inserted into the tail artery. Mean arterial pressure (MAP) and heart rate (HR) were measured over 60 min following administration of sildenafil. Results: Intravenous sildenafil dose-dependently increased the withdrawal threshold to the von Frey filament application in the ligated paw. Intravenous bicuculline and saclofen reversed the antinociception of sildenafil. Intravenous sildenafil increased the magnitude of MAP reduction at the maximal dosage, but it did not affect HR response. Conclusion: These results suggest that sildenafil is active in causing neuropathic pain. Both GABAA and GABAB receptors are involved in the antinociceptive effect of sildenafil. Additionally, intravenous sildenafil reduces MAP without affecting HR. Key Words: Antinociception, GABA receptor, hemodynamics, neuropathic pain, sildenafil, Sprague-Dawley rat Received: February 18, 2009 Revised: April 13, 2009 Accepted: May 9, 2009 Corresponding author: Dr. Myung Ha Yoon, Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, 8 Hak-dong, Dong-gu, Gwangju 501-757, Korea. Tel: 82-62-220-6893, Fax: 82-62-232-6294 E-mail: mhyoon@chonnam.ac.kr ∙The authors have no financial conflicts of interest. © Copyright: Yonsei University College of Medicine 2010 INTRODUCTION Neuropathic pain refers to pain due to injury or diseases of the peripheral or central nervous system.1-3 It is associated with severe, chronic sensory disturbances characterized by spontaneous pain, increased responsiveness to painful stimuli (hyperalgesia), and pain perceived in response to normally innocuous stimuli (allodynia).4,5 Prevalent symptoms in human patients include cold hyperalgesia, mechanical allodynia, and, less commonly, heat hyperalgesia. Chronic neuro- pathic pain remains a significant clinical problem and is often resistant to conven- tional analgesics, therefore, multimodal therapeutic options have been proposed.1-3 Guanylyl cyclase catalyzes the formation of cyclic guanosine monophosphate (cGMP) from GTP, leading to the synthesis of cGMP, whereas cGMP-specific phosphodiesterase catalyzes the hydrolysis of cGMP to GMP.2 Accordingly, intra- cellular cGMP concentrations are regulated by the action of guanylyl cyclase and the rate of degradation by cGMP-specific phosphodiesterase.6,7 82 Yonsei Med J http://www.eymj.org Volume 51 Number 1 January 2010