期刊
NEUROPHARMACOLOGY
卷 58, 期 3, 页码 578-584出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2009.12.001
关键词
Diabetic neuropathy; Mechanical hypersensitivity; Rat; Transient receptor potential; ankyrin 1 channel
资金
- Academy of Finland, Helsinki, Finland
- Sigrid Juselius Foundation, Helsinki, Finland
- Orion Pharma, Turku, Finland
Previous results indicate that intaperitoneal administration of a TRPA1 channel antagonist attenuates diabetic hypersensitivity. We studied whether the anti hype rsensitivity effect induced by a TRPA1 channel antagonist in diabetic animals is explained by action on the TRPA1 channel in the skin, the spinal cord, or both. For comparison, we determined the contribution of cutaneous and spinal TRPA1 channels to development of hypersensitivity induced by topical administration of mustard oil in healthy controls. Diabetes mellitus was induced by streptozotocin in the rat. Hypersensitivity was assessed by the monofilament- and paw pressure-induced limb withdrawal response. Intrathecal (i.t.) administration of Chembridge-5861528 (CHEM, a TRPA1 channel antagonist) at doses 2.5-5.0 mu g/rat markedly attenuated diabetic hypersensitivity, whereas 20 mu g of CHEM was needed to produce a weak attenuation of diabetic hypersensitivity with intraplantar (i.pl.) administrations. In controls, i.pl. administration of CHEM (20 mu g) produced a weak anti hype rsensitivity effect at the mustard oil-treated site. I.t. administration of CHEM (10 mu g) in controls produced a strong anti hypersensitivity effect adjacent to the mustard oil-treated area (site of secondary hyperalgesia), while it failed to influence hypersensitivity at the mustard oil-treated area (site of primary hyperalgesia). A reversible antagonism of the rat TRPA1 channel by CHEM was verified using in vitro patch clamp recordings. The results suggest that while cutaneous TRPA1 channels contribute to mechanical hypersensitivity induced by diabetes or topical mustard oil, spinal TRPA1 channels, probably on central terminals of primary afferent nerve fibers, play an important role in maintenance of mechanical hypersensitivity in these conditions. (C) 2009 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据