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BioMed Research International
Volume 2013, Article ID 529871, 6 pages
http://dx.doi.org/10.1155/2013/529871
Research Article

Effects of Repeated Central Administration of Endothelin Type A Receptor Antagonist on the Development of Neuropathic Pain in Rats

1Department of Anaesthesiology, The University of Hong Kong, Queen Mary Hospital, Room 424, 4/F, Block K, 102 Pokfulam, Pokfulam, Hong Kong
2Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, Queen Mary Hospital, Room 424, 4/F, Block K, 102 Pokfulam, Pokfulam, Hong Kong
3Department of Anaesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
4Department of Anatomy, The University of Hong Kong, 1/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong
5Research Center of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, 2/F, William MW Mong Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong

Received 9 April 2013; Revised 13 June 2013; Accepted 26 July 2013

Academic Editor: Lap Ho

Copyright © 2013 Lydia W. Tai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Endothelin-1 (ET-1) predominates in the endothelin family effectively in vascular tone control, mitogenesis, and neuromodulation. Its receptors are widespread in the central nervous system (CNS) associated with endogenous pain control, suggesting an important role of ET-1 in central pain processing. This study aimed to evaluate the effect of central ET-1 on the development of neuropathic pain behaviour by repeated intrathecal administration of endothelin type A receptor (ETAR) antagonist (BQ-123) in a sciatic nerve ligation (SNL) animal model. BQ-123 was administered intrathecally to rats at dosages 15 μg, 20 μg, 25 μg, and 30 μg, daily for 3 days. Mechanical allodynia was assessed daily 30 minutes before/after injection, 1 hour after injection of BQ-123 from post-SNL day 4 to day 6, and once on day 7 (without BQ-123 administration) before rats were sacrificed. Increasing trends of mechanical threshold were observed, and they reached significance at all dosages on post-SNL day 7 ( at dosage 15 μg and at dosages 20 μg, 25 μg, and 30 μg) in comparison to control group. BQ-123 at dosage 30 μg showed the most stable and significant mechanical threshold rise. Repeated central administration of BQ-123 alleviated mechanical allodynia after SNL. Our results provide insight into the therapeutic strategies, including timing, against neuropathic pain development with ETAR antagonist.