Fukuizumi Tadaoki, Ohkubo Tsuyako, Kitamura Kenji
Department of Physiological Science & Molecular Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
Neurosci Lett. 2003 Jun 5;343(2):89-92. doi: 10.1016/s0304-3940(03)00332-x.
Our aim was to investigate the possible involvement of spinal voltage-dependent Ca(2+) channels (VDCCs) in vincristine-induced hyperalgesia and also to characterize this hyperalgesic state in the spinal cord. Mice receiving vincristine displayed significantly lower mechanical nociceptive thresholds than controls. Intrathecal omega-conotoxin GVIA (an N-type blocker) produced dose-dependent inhibition of the mechanical nociception, its antinociceptive effect being greater in vincristine-treated mice than in controls. The antinociception of omega-agatoxin IVA (a P/Q-type blocker) and calciseptine (an L-type blocker) were both slightly, but not significantly greater in vincristine-treated mice. An N-methyl-D-aspartate-receptor antagonist but not a tachykinin-NK1-receptor antagonist produced greater antinociception in vincristine-treated mice. These results suggest that vincristine-induced hyperalgesia involves a sensitization of the spinal processing of mechanical sensory information via a mechanism involving N-type but not P/Q- or L-type VDCCs. A spinal glutamatergic pathway also appears to be involved in this hyperalgesia.
我们的目的是研究脊髓电压依赖性钙通道（VDCCs）在长春新碱诱导的痛觉过敏中可能发挥的作用，并对脊髓中的这种痛觉过敏状态进行特征描述。接受长春新碱治疗的小鼠机械性伤害感受阈值显著低于对照组。鞘内注射ω-芋螺毒素GVIA（一种N型阻滞剂）对机械性伤害感受产生剂量依赖性抑制，其镇痛作用在长春新碱治疗的小鼠中比对照组更强。ω-阿加毒素IVA（一种P/Q型阻滞剂）和钙调蛋白（一种L型阻滞剂）的镇痛作用在长春新碱治疗的小鼠中虽略有增强，但不显著。一种N-甲基-D-天冬氨酸受体拮抗剂而非速激肽-NK1受体拮抗剂在长春新碱治疗的小鼠中产生了更强的镇痛作用。这些结果表明，长春新碱诱导的痛觉过敏涉及通过一种涉及N型而非P/Q型或L型VDCCs的机制使脊髓对机械性感觉信息的处理敏感化。脊髓谷氨酸能通路似乎也参与了这种痛觉过敏。
