期刊
PAIN
卷 143, 期 3, 页码 252-261出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/j.pain.2009.03.011
关键词
Sigma-1 receptors; Capsaicin; Mechanical allodynia; Hyperalgesia; Pain behavior; Knockout mice
资金
- Formacion de Profesorado Universitario grants (M.E.C.)
- Research Program of the University of Granada
- junta de Andalucia [CTS 109]
- Spanish Ministerio de Educacion y Ciencia (MEC) [SAF 2006-06122]
- FEDER funds
- Laboratorios Dr. Esteve S.A.
- Centro para el Desarrollo Tecnologico Industrial
We evaluated the role of sigma(1) receptors on capsaicin-induced mechanical hypersensitivity and on nociceptive pain induced by punctate mechanical stimuli, using wild-type and sigma(1) receptor knockout (sigma(1)-KO) mice and selective sigma(1) receptor-acting drugs. Mutation in sigma(1)-KO mice was confirmed by PCR analysis of genomic DNA and, at the protein level, by [H-3](+)-pentazocine binding assays. Both wild-type and sigma(1)-KO mice not treated with capsaicin showed similar responses to different intensities of mechanical stimuli (0.05-8 g force), ranging from innocuous to noxious, applied to the hind paw. This indicates that sigma(1) gene inactivation does not modify the perception of punctate mechanical stimuli. The intraplantar (i.pl.) administration of capsaicin induced dose-dependent mechanical allodynia in wild-type mice (markedly reducing both the threshold force necessary to induce paw withdrawal and the latency to paw withdrawal induced by a given force). In contrast, capsaicin was completely unable to induce mechanical hypersensitivity in sigma(1)-KO mice. The high-affinity and selective sigma(1) antagonists BD-1063, BD-1047 and NE-100, administered subcutaneously (s.c.), dose-dependently inhibited mechanical allodynia induced by capsaicin (1 mu g,i.pl.), yielding ED50 (mg/kg) values of 15.80 +/- 0.93, 29.31 +/- 1.65 and 40.74 +/- 7.20, respectively. The effects of the sigma(1) antagonists were reversed by the sigma(1) agonist PRE-084 (32 mg/kg, s.c.). None of the drugs tested modified the responses induced by a painful mechanical punctate stimulus (4 g force) in nonsensitized animals. These results suggest that sigma(1) receptors are essential for capsaicin-induced mechanical hypersensitivity, but are not involved in mechanical nociceptive pain. (C) 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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