利多卡因和Nav1.8阻滞剂A803467在糖尿病大鼠中的抗伤害感受活性
Antinociceptive activities of lidocaine and the nav1.8 blocker a803467 in diabetic rats.
作者信息
Mert Tufan, Gunes Yasemin
机构信息
Department of Biophysics, School of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey.
出版信息
J Am Assoc Lab Anim Sci. 2012;51(5):579-85.
The streptozocin-induced diabetic rat is a model of chronic pain that shows signs of hyperalgesia and allodynia and may replicate signs in diabetic humans. Here we investigated the antinociceptive effects of A803467, a highly selective blocker of Nav1.8 channels, in diabetic rats with painful neuropathy. We systemically (intraperitoneal) or locally (intraplantar) administered A803467 (or lidocaine, a nonselective sodium channel blocker, as a control) to diabetic rats with hyperalgesia and allodynia and then measured thermal latencies and mechanical thresholds. With intraperitoneal administration, A803467 led to 6-fold greater reduction of hyperalgesia and 2-fold greater reduction of allodynia than did lidocaine. Whereas the antihyperalgesic effects of lidocaine and A803467 were similar after intraplantar administration, A803467 (1 mg) was at least 2 times more effective as an antiallodynic than was lidocaine (0.5 mg). These results suggest that compared with lidocaine, systemic or local blockade of Nav1.8 channels by A803467 may more effectively relieve hyperalgesia and allodynia in diabetic neuropathy.
链脲佐菌素诱导的糖尿病大鼠是一种慢性疼痛模型，表现出痛觉过敏和异常性疼痛的症状，可能会重现糖尿病患者的症状。在此，我们研究了Nav1.8通道的高度选择性阻滞剂A803467对患有疼痛性神经病变的糖尿病大鼠的镇痛作用。我们对患有痛觉过敏和异常性疼痛的糖尿病大鼠进行全身（腹腔内）或局部（足底内）给予A803467（或作为对照的非选择性钠通道阻滞剂利多卡因），然后测量热潜伏期和机械阈值。腹腔内给药时，与利多卡因相比，A803467使痛觉过敏的减轻程度高6倍，异常性疼痛的减轻程度高2倍。足底内给药后，利多卡因和A803467的抗痛觉过敏作用相似，但A803467（1毫克）作为抗异常性疼痛药物的效果至少是利多卡因（0.5毫克）的2倍。这些结果表明，与利多卡因相比，A803467对Nav1.8通道的全身或局部阻断可能更有效地缓解糖尿病神经病变中的痛觉过敏和异常性疼痛。
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