Perineural resiniferatoxin selectively inhibits inflammatory hyperalgesia.
Perineural resiniferatoxin selectively inhibits inflammatory hyperalgesia.
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DOI：
10.1186/1744-8069-4-3
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发表时间：
2008-01-16
期刊：
影响因子：
3.3
通讯作者：
Iadarola MJ
中科院分区：
文献类型：
--
作者：
Neubert JK;Mannes AJ;Karai LJ;Jenkins AC;Zawatski L;Abu-Asab M;Iadarola MJ
树脂毒素（RTX）是一种超强效辣椒素类似物，可与瞬时受体电位通道香草素亚家族成员1（TRPV 1）结合。有大量证据支持TRPV1在毒性介导的和炎性痛觉过敏反应中的作用。在这项研究中，我们评估了低，分级，剂量的神经周围RTX作为一种方法，用于区域疼痛控制。我们假设，这种方法可以提供长期的，但可逆的，封锁的一部分伤害性传入纤维周围神经时，在远离背根神经节中的神经元胞体的网站。在神经周围RTX应用于坐骨神经后，我们证明了对炎性伤害感受的显著抑制，其具有剂量和时间依赖性。同时，治疗动物保持正常的本体感觉和运动控制，其他伤害性反应基本不受影响。使用一系列的机械和热痛觉测试，我们发现，最敏感的措施后，神经周围RTX管理是抑制炎性痛觉过敏。恢复研究表明，生理感觉功能可以恢复早在RTX治疗后两周，然而，DRG的免疫组织化学检查显示TRPV1阳性神经元的数量部分但显着减少。我们认为这种方法可以代表一系列慢性疼痛问题的有益治疗，包括对其他疗法无反应的神经性和炎症性疼痛。
Resiniferatoxin (RTX) is an ultrapotent capsaicin analog that binds to the transient receptor potential channel, vanilloid subfamily member 1 (TRPV1). There is a large body of evidence supporting a role for TRPV1 in noxious-mediated and inflammatory hyperalgesic responses. In this study, we evaluated low, graded, doses of perineural RTX as a method for regional pain control. We hypothesized that this approach can provide long-term, but reversible, blockade of a portion of nociceptive afferent fibers within peripheral nerves when given at a site remote from the neuronal perikarya in the dorsal root ganglia. Following perineural RTX application to the sciatic nerve, we demonstrated a significant inhibition of inflammatory nociception that was dose- and time-dependent. At the same time, treated animals maintained normal proprioceptive sensations and motor control, and other nociceptive responses were largely unaffected. Using a range of mechanical and thermal algesic tests, we found that the most sensitive measure following perineural RTX administration was inhibition of inflammatory hyperalgesia. Recovery studies showed that physiologic sensory function could return as early as two weeks post-RTX treatment, however, immunohistochemical examination of the DRG revealed a partial, but significant reduction in the number of the TRPV1-positive neurons. We propose that this method could represent a beneficial treatment for a range of chronic pain problems, including neuropathic and inflammatory pain not responding to other therapies.
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影响因子：
3.3
作者：
FITZGERALD, M;WOOLF, CJ
通讯作者：
WOOLF, CJ
影响因子：
2.9
作者：
IADAROLA, MJ;DOUGLASS, J;NARANJO, JR
通讯作者：
NARANJO, JR
影响因子：
5.7
作者：
MAYS, KS;LIPMAN, JJ;SCHNAPP, M
通讯作者：
SCHNAPP, M
影响因子：
4.8
作者：
Olah, Z;Szabo, T;Iadarola, MJ
通讯作者：
Iadarola, MJ
DOI：
10.1124/jpet.104.079855
发表时间：
2005-04-01
影响因子：
3.5
作者：
Gavva, NR;Tamir, R;Treanor, JJS
通讯作者：
Treanor, JJS