Perineural resiniferatoxin prevents the development of hyperalgesia produced by loose ligation of the sciatic nerve in rats
Perineural resiniferatoxin prevents the development of hyperalgesia produced by loose ligation of the sciatic nerve in rats
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DOI：
10.1213/01.ane.0000260296.01813.62
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发表时间：
2007-05-01
影响因子：
5.7
通讯作者：
Bradley, Edwin L., Jr.
中科院分区：
文献类型：
--
作者：
Kissin, Igor;Freitas, Cristina F.;Bradley, Edwin L., Jr.
背景：香草受体（TRPV1）存在于周围神经纤维中；辣椒素对其刺激导致降钙素基因相关肽和其他参与神经炎症的神经肽的释放。另一方面，神经损伤后释放的各种炎症介质可激活或致敏TRPV1受体。这些发现共同提示TRPV1受体阻断在神经病变中的保护作用。在本研究中，我们验证了一种假设，即神经周围树脂化毒素（RTX）可以预防因在坐骨神经周围放置松散收缩结扎而引起的痛觉过敏。方法：雄性Sprague-Dawley大鼠在坐骨神经处单次经皮注射RTX （0.0005%, 0.1 mL）或载药剂，3 h后行手术，在给药侧神经周围松绑4根。评估了对有害热的反应（戒断潜伏期、爪子抬起持续时间）、von Frey纤维的重复刺激和后爪姿势的变化（脚趾伸展、腹屈和足外展）。结果：术前给予神经周围RTX完全阻止结扎引起的戒断潜伏期减少，足部抬起时间增加和von Frey纤维戒断频率增加。RTX对后爪姿势缺陷的预防作用明显但不完全，如术后第7天，RTX组的累积爪姿评分（0-6）为1.69 +/- 0.92，vehicle组为4.06 +/- 1.68 （P < 0.005）。RTX对已经发展的神经病变的影响仅限于持续相对较短时间的热痛觉减退。结论：围神经RTX可防止因在坐骨神经上松紧性结扎而引起的神经病变的发展。围手术期使用通过TRPV1受体作用的药物可能有望预防手术后周围神经的神经性疼痛。
BACKGROUND: The vanilloid receptors (TRPV1) are found in peripheral nerve fibers; their stimulation by capsaicin leads to release of calcitonin gene-related peptide and other neuropeptides participating in neuroinflammation. On the other hand, various inflammatory mediators, released after nerve damage, can activate or sensitize the TRPV1 receptors. These findings together suggest a protective effect of TRPV1 receptor blockade in neuropathy. In the present study, we tested the hypothesis that perineural resiniferatoxin (RTX) can prevent the development of hyperalgesia caused by placing loosely constrictive ligatures around the sciatic nerve.METHODS: Male Sprague-Dawley rats received a single percutaneous injection of RTX (0.0005%, 0.1 mL) or vehicle at the sciatic nerve, and underwent surgery 3 h later to place four loose ligatures around the nerve on the side of drug administration. Responses to noxious heat (withdrawal latency, paw-lift duration), repetitive stimulation with von Frey filaments, and changes in hindpaw posture (toe spread, ventroflexion, and foot exorotation) were assessed.RESULTS: Perineural RTX administered before surgery completely prevented ligation-induced reduction in withdrawal latency, increase in paw lift duration and increase in withdrawal frequency to von Frey filaments. The preventive effect of RTX on the development of deficits in hindpaw posture was pronounced but not complete, e.g., on day 7 after surgery, the cumulative paw-posture score (0-6) was 1.69 +/- 0.92 with RTX and 4.06 +/- 1.68 with vehicle (P < 0.005). The effect of RTX used against the background of already developed neuropathy was limited to thermal hypoalgesia lasting for a relatively short period.CONCLUSION: Perineural RTX prevents the development of neuropathy caused by placing loosely constrictive ligatures on the sciatic nerve. Perioperative use of drugs acting via the TRPV1 receptors may hold the promise for preventing neuropathic pain after surgery on peripheral nerves.