TRPV4 mediates pain-related behavior induced by mild hypertonic stimuli in the presence of inflammatory mediator
TRPV4 mediates pain-related behavior induced by mild hypertonic stimuli in the presence of inflammatory mediator
复制标题
DOI：
10.1016/j.pain.2005.07.016
复制
发表时间：
2005-11-01
期刊：
影响因子：
7.4
通讯作者：
Levine, JD
中科院分区：
文献类型：
--
作者：
Alessandri-Haber, N;Joseph, E;Levine, JD
配体门控离子通道TRPV 4在初级传入伤害感受神经元中作为低渗刺激的换能器起作用，并促成炎性和神经病理性疼痛。高渗盐水还刺激初级传入伤害感受器，并且注射轻度高渗盐水（2-5%）被广泛用作人类疼痛的实验模型。因此，我们测试了TRPV 4是否参与高渗刺激的转导。在大鼠后爪皮内注射2%（607 mOsm）或10%（3250 mOsm）的生理盐水溶液诱导了浓度依赖性的疼痛相关行为，退缩。用前列腺素E-2（PGE（2））致敏后，2%生理盐水引起的退缩次数增加了7倍，但10%生理盐水引起的退缩次数没有增加。脊髓给药TRPV 4的反义寡核苷酸引起2%盐水诱导的退缩次数减少46%，但10%盐水诱导的退缩没有变化。类似地，在TRPV 4（-/-）敲除小鼠中，仅由2%盐水引起的伤害性行为减少。TRPV 4介导的伤害性行为由高和低渗刺激诱导依赖于Src酪氨酸激酶。我们认为TRPV 4是初级传入神经的一个转导子，介导渗透压的小幅增加或降低引起的伤害性行为。渗透压的这种变化可能有助于炎症和神经病理状态下的疼痛。(c)2005年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
The ligand-gated ion channel, TRPV4, functions as a transducer of hypotonic stimuli in primary afferent nociceptive neurons and contributes to inflammatory and neuropathic pain. Hypertonic saline also stimulates primary afferent nociceptors and the injection of mild hypertonic saline (2-5%) is widely used as an experimental model of pain in humans. Therefore, we tested whether TRPV4 participates in the transduction of hypertonic stimuli. Intradermal injection of 2% (607 mOsm) or 10% (3250 mOsm) saline solution in the hind paw of rats induced a concentration-dependent pain-related behavior, flinching. Sensitization with prostaglandin E-2 (PGE(2)) caused a 7-fold increase in the number of flinches induced by 2% saline but failed to increase those caused by 10% saline. Spinal administration of antisense oligodeoxynucleotides to TRPV4 caused a 46% decrease in the number of flinches induced by 2% saline, but there was no change in flinching induced by 10% saline. Similarly, only the nociceptive behavior caused by 2% saline was reduced in TRPV4(-/-) knockout mice. The TRPV4-mediated nociceptive behaviors induced by hyper- and hypotonic stimuli were dependent on Src tyrosine kinase. We suggest TRPV4 is a transducer in primary afferents that mediates nociceptive behavior induced by small increases or decreases in osmolarity. Such changes in osmolarity might contribute to pain in inflammatory and neuropathic states. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.