Xiao W H, Bennett G J
Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, USA.
J Pharmacol Exp Ther. 1995 Aug;274(2):666-72.
In patients and animals with painful peripheral neuropathies, spontaneous ectopic discharge from injured primary afferents is hypothesized to maintain a central state of hyperexcitability that underlies hyperalgesia and allodynia. Temporary suppression of this discharge allows the central state to normalize, such that hyperalgesia and allodynia are absent or reduced until the resumption of the discharge rekindles central hyperexcitability. Previous work suggests that Ca++ channels are involved in the genesis of spontaneous discharge from injured afferents. We applied SNX-111 and SNX-124 (0.1-3.0 micrograms), synthetic homologs of omega-conopeptides (MVIIA and GVIA, respectively) and potent blockers of neuronal N-type voltage-sensitive Ca++ channels, to the site of nerve injury via chronically implanted perineural cannulae in rats with an experimental painful peripheral neuropathy (the chronic constriction injury model). Heat-hyperalgesia and mechano-allodynia were reduced for at least 3 hr. Drug application to a normal nerve had no effect on responses to heat or mechanical stimuli. These results suggest that N-type Ca++ channel blockers may be useful in the treatment of the abnormal pains that occur after nerve injury.
在患有疼痛性周围神经病变的患者和动物中，据推测，受损初级传入神经的自发性异位放电会维持一种中枢性的过度兴奋状态，这种状态是痛觉过敏和异常性疼痛的基础。暂时抑制这种放电可使中枢状态恢复正常，从而使痛觉过敏和异常性疼痛消失或减轻，直到放电恢复重新引发中枢性过度兴奋。先前的研究表明，钙离子通道参与了受损传入神经自发性放电的产生。我们通过在患有实验性疼痛性周围神经病变（慢性压迫损伤模型）的大鼠中慢性植入神经周围套管，将SNX - 111和SNX - 124（0.1 - 3.0微克），即ω - 芋螺毒素（分别为MVIIA和GVIA）的合成类似物以及神经元N型电压敏感性钙离子通道的强效阻滞剂，应用于神经损伤部位。热痛觉过敏和机械性异常性疼痛至少减轻了3小时。将药物应用于正常神经对热或机械刺激的反应没有影响。这些结果表明，N型钙离子通道阻滞剂可能对治疗神经损伤后出现的异常疼痛有用。
