Streptozotocin-induced early thermal hyperalgesia is independent of glycemic state of rats: role of transient receptor potential vanilloid 1(TRPV1) and inflammatory mediators.
Streptozotocin-induced early thermal hyperalgesia is independent of glycemic state of rats: role of transient receptor potential vanilloid 1(TRPV1) and inflammatory mediators.
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DOI：
10.1186/1744-8069-7-52
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发表时间：
2011-07-27
期刊：
影响因子：
3.3
通讯作者：
Premkumar LS
中科院分区：
文献类型：
--
作者：
Bishnoi M;Bosgraaf CA;Abooj M;Zhong L;Premkumar LS
链脲佐菌素（STZ）是诱发糖尿病和研究糖尿病引起的并发症（包括糖尿病周围神经病变（DPN））的常用工具。以前，我们已经报道，STZ诱导通过瞬时受体电位香草酸1（TRPV 1）通道在感觉神经元中的表达和功能，导致热痛觉过敏，甚至在非糖尿病STZ治疗的小鼠神经元的直接影响。在本研究中，我们研究了TRPV 1在STZ诱导的大鼠痛敏中在脊髓中枢感觉神经末梢的表达和功能的作用。我们发现，一部分STZ治疗的大鼠血糖正常，但仍表现出热痛觉过敏和机械异常性疼痛。免疫组化数据显示，STZ治疗，无论动物的血糖状态，引起小胶质细胞激活和增加的TRPV 1在脊髓背角的表达。此外，无论血糖状态如何，脊髓组织中的促炎介质（IL-1β、IL-6和TNF-α）水平均显著升高。辣椒素刺激释放降钙素基因相关肽（CGRP）显着较高的STZ治疗的动物脊髓。鞘内注射一种有效的TRPV 1激动剂树脂毒素（RTX）可显著减弱STZ诱导的热痛觉过敏，但对机械性异常性疼痛无影响。RTX治疗还阻止了脊髓组织中TRPV 1介导的神经肽释放的增加。从这些结果中，可以得出结论，TRPV 1是启动和维持炎性热痛觉过敏的组成部分，这可以通过鞘内注射RTX来缓解。此外，结果表明，脊髓中TRPV 1的表达增强和炎症诱导的致敏可能在STZ诱导的神经病变中的中枢致敏中起作用。
Streptozotocin (STZ) is used as a common tool to induce diabetes and to study diabetes-induced complications including diabetic peripheral neuropathy (DPN). Previously, we have reported that STZ induces a direct effect on neurons through expression and function of the Transient receptor potential vanilloid 1 (TRPV1) channel in sensory neurons resulting in thermal hyperalgesia, even in non-diabetic STZ-treated mice. In the present study, we investigated the role of expression and function of TRPV1 in the central sensory nerve terminals in the spinal cord in STZ-induced hyperalgesia in rats. We found that a proportion of STZ-treated rats were normoglycemic but still exhibited thermal hyperalgesia and mechanical allodynia. Immunohistochemical data show that STZ treatment, irrespective of glycemic state of the animal, caused microglial activation and increased expression of TRPV1 in spinal dorsal horn. Further, there was a significant increase in the levels of pro-inflammatory mediators (IL-1β, IL-6 and TNF-α) in spinal cord tissue, irrespective of the glycemic state. Capsaicin-stimulated release of calcitonin gene related peptide (CGRP) was significantly higher in the spinal cord of STZ-treated animals. Intrathecal administration of resiniferatoxin (RTX), a potent TRPV1 agonist, significantly attenuated STZ-induced thermal hyperalgesia, but not mechanical allodynia. RTX treatment also prevented the increase in TRPV1-mediated neuropeptide release in the spinal cord tissue. From these results, it is concluded that TRPV1 is an integral component of initiating and maintaining inflammatory thermal hyperalgesia, which can be alleviated by intrathecal administration of RTX. Further, the results suggest that enhanced expression and inflammation-induced sensitization of TRPV1 at the spinal cord may play a role in central sensitization in STZ-induced neuropathy.
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DOI：
10.1523/jneurosci.3795-08.2008
发表时间：
2008-12-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Binshtok AM;Wang H;Zimmermann K;Amaya F;Vardeh D;Shi L;Brenner GJ;Ji RR;Bean BP;Woolf CJ;Samad TA
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Samad TA
DOI：
10.1515/bchm3.1995.376.3.179
发表时间：
1995-03-01
期刊：
BIOLOGICAL CHEMISTRY HOPPE-SEYLER
影响因子：
--
作者：
KRONCKE, KD;FEHSEL, K;KOLBBACHOFEN, V
通讯作者：
KOLBBACHOFEN, V
影响因子：
7.7
作者：
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Zochodne, DW
影响因子：
4.8
作者：
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DOI：
10.1016/1056-8719(94)90087-6
发表时间：
1994-12-01
影响因子：
1.9
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ESCHALIER, A