Prolonged analgesic response of cornea to topical resiniferatoxin, a potent TRPV1 agonist.
Prolonged analgesic response of cornea to topical resiniferatoxin, a potent TRPV1 agonist.
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DOI：
10.1016/j.pain.2010.03.024
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发表时间：
2010-06
期刊：
影响因子：
7.4
通讯作者：
Iadarola MJ
中科院分区：
文献类型：
--
作者：
Bates BD;Mitchell K;Keller JM;Chan CC;Swaim WD;Yaskovich R;Mannes AJ;Iadarola MJ
目前用于治疗眼科手术或损伤后疼痛的镇痛药受到短暂有效性和不良或不良副作用的限制。角膜主要受表达TRPV1（瞬时受体电位通道，V亚家族，成员1）的小直径c纤维感觉神经元支配，TRPV1是一种钠/钙离子通道，由痛觉神经元大量表达，因此是疼痛控制的靶点。树脂干扰素（RTX）是一种有效的TRPV1激动剂，当外周注射时，通过过量的钙流入使表达TRPV1的神经末梢失活，从而产生短暂的镇痛作用。本研究的目的是评估局部RTX作为角膜镇痛药。在大鼠角膜中，单次应用RTX剂量依赖性消除或减少辣椒素擦眼反应3-5天，5-7天恢复正常的伤害性反应。RTX单独产生短暂但强烈的有害反应，类似于辣椒素，需要用局部麻醉预处理角膜。在RTX之前使用局部利多卡因，可阻断RTX的急性伤害性反应，而不损害随后的镇痛效果。重要的是，RTX镇痛(a)不影响上皮伤口愈合，(b)使眨眼反射完好无损，(c)对角膜没有可检测到的组织学损伤。免疫组织化学显示，CGRP免疫反应性（trpv1表达纤维的替代标志物）的丧失至少延伸到角膜-巩膜边界，并表现出进行性恢复，与辣椒素敏感性的恢复一致。这些数据表明RTX可能是一种安全有效的治疗术后或损伤后眼痛的方法。
Analgesics currently available for the treatment of pain following ophthalmic surgery or injury are limited by transient effectiveness and undesirable or adverse side effects. The cornea is primarily innervated by small-diameter C-fiber sensory neurons expressing TRPV1 (transient receptor potential channel, subfamily V, member 1), a sodium/calcium cation channel expressed abundantly by nociceptive neurons and consequently a target for pain control. Resiniferatoxin (RTX), a potent TRPV1 agonist, produces transient analgesia when injected peripherally by inactivating TRPV1-expressing nerve terminals through excessive calcium influx. The aim of the present study was to evaluate topical RTX as a corneal analgesic. In rat cornea, a single application of RTX dose-dependently eliminated or reduced the capsaicin eye wipe response for 3–5 days, with normal nociceptive responses returning by 5–7 days. RTX alone produced a brief but intense noxious response, similar to capsaicin, necessitating pretreatment of the cornea with a local anesthetic. Topical lidocaine, applied prior to RTX, blocks acute nociceptive responses to RTX without impairing the subsequent analgesic effect. Importantly, RTX analgesia (a) did not impair epithelial wound healing, (b) left the blink reflex intact and (c) occurred without detectable histological damage to the cornea. Immunohistochemistry showed that loss of CGRP immunoreactivity, a surrogate marker for TRPV1-expressing fibers, extended at least to the corneal-scleral boundary and displayed a progressive return, coincident with the return of capsaicin sensitivity. These data suggest RTX may be a safe and effective treatment for postoperative or post-injury ophthalmic pain.
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