Peripheral block of the hyperpolarization-activated cation current (Ih) reduces mechanical allodynia in animal models of postoperative and neuropathic pain
Peripheral block of the hyperpolarization-activated cation current (Ih) reduces mechanical allodynia in animal models of postoperative and neuropathic pain
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DOI：
10.1016/j.rapm.2005.01.010
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发表时间：
2005-05-01
影响因子：
5.1
通讯作者：
Eisenach, JC
中科院分区：
文献类型：
--
作者：
Dalle, C;Eisenach, JC
背景和目标：阻断超极化激活的内向电流（I-h）可降低刺激期间外周轴突的兴奋性，并减少轴突切断的感觉神经元的异位放电。DRG神经元中I-h表达的变化已被认为是神经损伤和炎症后致敏的部分基础。我们假设轴突上的I-h外周阻滞将在术后和神经病性疾病中产生抗异常性疼痛作用，并且我们测试了神经周给予ZD 7288（一种I-h特异性阻滞剂）对神经病性和术后疼痛动物模型中疼痛相关行为的影响。方法：在氟烷麻醉下，如前所述对成年雄性大鼠进行部分坐骨神经损伤或后爪切口。通过应用校准的von Frey细丝证明缩爪阈值降低来推断机械性异常性疼痛。手术后，动物接受生理盐水或ZD 7288解决方案无论是通过坐骨神经周围注射或通过intraplantarinjection.Results：神经周围注射ZD 7288（100 AM）显着减少机械异常性疼痛引起的部分坐骨神经损伤和后爪切口。生理盐水和ZD 7288的10 AM对机械性异常性疼痛没有显著影响。在神经损伤后，ZD 7288，100 AM的同侧给药不影响同侧缩爪阈值。足底注射ZD 7288不能减轻神经损伤后的机械性异常性疼痛。镇静和运动的影响没有observed.Conclusions：目前的研究表明，外周阻滞的I-H产生的抗异常性疼痛的效果，这表明，I-H通道代表一个新的目标，神经阻滞治疗术后和神经病理性疼痛。
Background and Objectives: Block of the hyperpolarization-activated inward current (I-h) reduces excitability of peripheral axons during stimulation and decreases ectopic discharges in axotomized sensory neurons. Changes in I-h expression in DRG neurons have been suggested to partially underlie sensitization after nerve injury and inflammation. We hypothesized that peripheral block of I-h on axons would produce an antiallodynic effect in postoperative as well as neuropathic conditions, and we tested perineural administration of ZD 7288, a specific blocker of I-h, on pain-associated behavior in animal models of neuropathic and postoperative pain.Methods: Under halothane anesthesia, partial sciatic nerve injury or hind-paw incision were performed on adult male rats as previously described. Mechanical allodynia was inferred by demonstration of a decrease in paw withdrawal threshold by application of calibrated von Frey filaments. After surgery, animals received either a saline or a ZD 7288 solution either by sciatic perineural injection or by intraplantar injection.Results: Perineural administration of ZD 7288 (100 AM) significantly reduced mechanical allodynia induced by partial sciatic nerve injury and hind-paw incision. Saline and 10 AM of ZD 7288 had no significant effect on mechanical allodynia. Contralateral administration of ZD 7288, 100 AM, did not affect ipsilateral paw withdrawal threshold after nerve injury. Intraplantar injection of ZD 7288 failed to reduce mechanical allodynia after nerve injury. Sedation and motor effects were not observed.Conclusions: The current study shows that peripheral block of I-h produces an antiallodynic effect, which suggests that I-h channels represent a novel target for nerve block treatment of postoperative and neuropathic pain.