J Korean Med Sci.  2013 Aug;28(8):1238-1243. 10.3346/jkms.2013.28.8.1238.

Antinociceptive Effects of Amiloride and Benzamil in Neuropathic Pain Model Rats

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea. mhyoon@jnu.ac.kr
  • 2Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea.
  • 3Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea.

Abstract

Amiloride and benzamil showed antinocicepitve effects in several pain models through the inhibition of acid sensing ion channels (ASICs). However, their role in neuropathic pain has not been investigated. In this study, we investigated the effect of the intrathecal amiloride and benzamil in neuropathic pain model, and also examined the role of ASICs on modulation of neuropathic pain. Neuropathic pain was induced by L4-5 spinal nerve ligation in male Sprague-Dawley rats weighing 100-120 g, and intrathecal catheterization was performed for drug administration. The effects of amiloride and benzamil were measured by the paw-withdrawal threshold to a mechanical stimulus using the up and down method. The expression of ASICs in the spinal cord dorsal horn was also analyzed by RT-PCR. Intrathecal amiloride and benzamil significantly increased the paw withdrawal threshold in spinal nerve-ligated rats (87%+/-12% and 76%+/-14%, P=0.007 and 0.012 vs vehicle, respectively). Spinal nerve ligation increased the expression of ASIC3 in the spinal cord dorsal horn (P=0.01), and this increase was inhibited by both amiloride and benzamil (P<0.001 in both). In conclusion, intrathecal amiloride and benzamil display antinociceptive effects in the rat spinal nerve ligation model suggesting they may present an alternative pharmacological tool in the management of neuropathic pain at the spinal level.

Keyword

Amiloride; Benzamil; Acid Sensing Ion Channels; Spinal Nerve Ligation; Spinal Cord Dorsal Horn
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