title: Antinociceptive effects of amiloride and benzamil in neuropathic pain model rats.
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.
authors: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea.
authors: Seongtae
authors: S
authors: Jeong
authors: Seong Heon
authors: SH
authors: Lee
authors: Yeo Ok
authors: YO
authors: Kim
authors: Myung Ha
authors: MH
authors: Yoon
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D062565:Acid Sensing Ion Channels; D000700:Analgesics; D012333:RNA, Messenger; C013407:benzamil; D000584:Amiloride
keywords: Acid Sensing Ion Channels; Amiloride; Benzamil; Spinal Cord Dorsal Horn; Spinal Nerve Ligation
references: Pain. 1992 Sep;50(3):355-363
references: 1333581
references: Pharmacol Biochem Behav. 2010 Jul;96(1):108-13
references: 20434481
references: Pain. 1996 Dec;68(2-3):293-9
references: 9121817
references: Pain. 2007 Dec 15;133(1-3):150-60
references: 17467171
references: Mol Biol Rep. 2010 Oct;37(7):3233-8
references: 19885742
references: J Neurosci. 1992 Feb;12(2):430-9
references: 1311030
references: J Neurosci. 2008 Feb 6;28(6):1498-508
references: 18256271
references: J Neurophysiol. 2008 Jun;99(6):3151-6
references: 18417624
references: Neuroscience. 2009 Apr 21;160(1):156-64
references: 19248819
references: Physiol Behav. 1976 Dec;17(6):1031-6
references: 14677603
references: Curr Pain Headache Rep. 2007 Jun;11(3):208-14
references: 17504648
references: J Biol Chem. 2007 Jun 15;282(24):17325-9
references: 17430882
references: J Biol Chem. 2004 Oct 15;279(42):43716-24
references: 15302881
references: J Biol Chem. 2004 Nov 5;279(45):46962-8
references: 15317815
references: J Neurosci Methods. 1994 Jul;53(1):55-63
references: 7990513
references: Curr Pharm Des. 2009;15(15):1750-66
references: 19442188
references: Anesthesiology. 2010 Sep;113(3):647-54
references: 20693874
references: Eur J Pharmacol. 2008 Jun 10;587(1-3):104-11
references: 18486127
references: J Pain. 2009 Mar;10(3):336-42
references: 19185546
references: Nat Neurosci. 2007 Aug;10(8):943-5
references: 17632507
references: Brain. 2004 Feb;127(Pt 2):294-303
references: 14662515
references: Pain. 1983 Jun;16(2):109-110
references: 6877845
references: Brain Res. 2002 Oct 4;951(2):336-40
references: 12270514
references: Neuron. 2010 Oct 6;68(1):61-72
references: 20920791
references: Eur J Pharmacol. 2009 Jan 28;603(1-3):56-61
references: 19109946
references: J Neurosci. 2007 Oct 10;27(41):11139-48
references: 17928456
references: J Clin Invest. 2002 Oct;110(8):1185-90
references: 12393854
references: Pain. 2007 May;129(1-2):102-12
references: 17134831
references: Neurology. 2008 Apr 29;70(18):1630-5
references: 18003941
references: Future Med Chem. 2010 May;2(5):803-42
references: 21426204
references: Pharmacology. 2010;85(5):295-300
references: 20453553
references: Trends Neurosci. 2003 Sep;26(9):477-83
references: 12948658
references: Eur J Pain. 2011 Apr;15(4):335-43
references: 20888277
references: Mol Pain. 2010 Dec 08;6:88
references: 21143836
references: J Pain. 2010 Mar;11(3):210-8
references: 20015700
references: Physiol Rev. 2002 Jul;82(3):735-67
references: 12087134
references: Pain. 2008 Feb;134(3):245-253
references: 17531389
references: EMBO J. 2008 Nov 19;27(22):3047-55
references: 18923424
references: Br J Pharmacol. 2008 Mar;153 Suppl 2:S1-209
references: 18347570