White D M, Cousins M J
Department of Anaesthesia and Pain Management, Royal North Shore Hospital, St. Leonards, N.S.W., 2065, Australia.
Brain Res. 1998 Aug 10;801(1-2):50-8. doi: 10.1016/s0006-8993(98)00539-3.
Recent studies suggest that calcium contributes to peripheral neural mechanisms of hyperalgesia associated with nerve damage. In this animal behavioural study, we examined further the contribution of calcium in neuropathic pain by testing whether subcutaneous administration of either a calcium chelating agent or voltage-dependent calcium channel blockers attenuate nerve injury-induced hyperalgesia to mechanical stimulation. Studies were carried out in animals with partially ligated sciatic nerves, an established animal model of neuropathic pain. The nociceptive flexion reflex was quantified using an Ugo Basile Analgesymeter. Partial nerve injury induced a significant decrease in mechanical threshold compared to the sham operated controls. Daily subcutaneous injections of the calcium chelating agent, Quin 2 (20 microgram/2.5 microliter), significantly attenuated the nerve injury-induced hyperalgesia. Similarly, SNX-111, a N-type channel blocker, also significantly attenuated the nerve injury-induced hyperalgesia. SNX-230, a P and/or Q-type channel blocker, and nifedipine, a L-type channel blocker, had no effect on the hyperalgesia to mechanical stimulation. In control experiments, SNX-111 had no effect on mechanical thresholds when administered subcutaneously in either the hindpaw of normal animals or the back of the neck in nerve injury animals. This study shows that neuropathic pain involves a local calcium-dependent mechanism in the receptive field of intact neurons of an injured nerve, since it can be alleviated by subcutaneous injections of either a calcium chelating agent or SNX-111, a N-type calcium channel blocker. These agents may be effective, peripherally acting therapeutic agents for neuropathic pain.
最近的研究表明，钙参与了与神经损伤相关的痛觉过敏的外周神经机制。在这项动物行为学研究中，我们通过测试皮下注射钙螯合剂或电压依赖性钙通道阻滞剂是否能减轻神经损伤诱导的对机械刺激的痛觉过敏，进一步研究了钙在神经性疼痛中的作用。研究在坐骨神经部分结扎的动物身上进行，这是一种已确立的神经性疼痛动物模型。使用Ugo Basile镇痛仪对伤害性屈曲反射进行量化。与假手术对照组相比，部分神经损伤导致机械阈值显著降低。每天皮下注射钙螯合剂喹啉2（20微克/2.5微升）可显著减轻神经损伤诱导的痛觉过敏。同样，N型通道阻滞剂SNX-111也显著减轻了神经损伤诱导的痛觉过敏。P和/或Q型通道阻滞剂SNX-230以及L型通道阻滞剂硝苯地平对机械刺激痛觉过敏没有影响。在对照实验中，SNX-111皮下注射到正常动物的后爪或神经损伤动物的颈部背面时，对机械阈值没有影响。这项研究表明，神经性疼痛涉及受损神经完整神经元感受野中的局部钙依赖性机制，因为皮下注射钙螯合剂或N型钙通道阻滞剂SNX-111可以减轻这种疼痛。这些药物可能是有效的外周作用神经性疼痛治疗药物。
