Larson A A, Giovengo S L, Shi Q, Velázquez R A, Kovacs K J
Department of Veterinary Pathobiology, University of Minnesota, St. Paul 55108, USA.
Pain. 2000 May;86(1-2):177-84. doi: 10.1016/s0304-3959(00)00244-x.
Kainic acid produces a persistent hyperalgesia when injected intraperitoneally (i.p.) in the rat or mouse. At higher doses than those needed to influence nociception, kainic acid induces seizures and translocation of histologically reactive zinc in the hippocampus. We tested the hypothesis that zinc, localized in a population of small diameter primary afferent neurons, plays a role in kainic acid-induced hyperalgesia similar to that in the hippocampus where zinc translocation accompanies kainic acid-induced seizures. The importance of zinc in the extracellular area was assessed by the influence of compounds that chelate divalent cations (disodium calcium ethylene diaminetetraacetate (CaEDTA)) or zinc (dipicolinic acid (DPA)) on kainic acid-induced hyperalgesia. When measured using the tail flick assay, thermal hyperalgesia was blocked by pretreatment intrathecally (i.t.) with either 10 nmol of NaCaEDTA or 1 nmol of DPA, drugs whose distribution is limited to the extracellular area. Injection of 10 ng zinc chloride i.t. had no long-term effect on nociception or on kainic acid-induced hyperalgesia. Whether zinc is translocated in response to a hyperalgesic dose of kainic acid was determined using the zinc-selective dye, N-(6-methoxy-8-quinolyl)-para-toluenensulfonamide (TSQ), which produces a delicate stain in the neuropil of the mouse spinal cord as well as a dense stain in the hippocampus. Injection of a hyperalgesic dose of kainic acid failed to alter TSQ fluorescence in either the spinal cord or hippocampus, in contrast to the distinct bleaching of TSQ in the hippocampus 24 h after a convulsant dose of kainic acid. Together these data suggest that, while not translocated, zinc in the extracellular area is necessary but not sufficient for the development of kainic acid-induced hyperalgesia.
当腹腔注射（i.p.）到大鼠或小鼠体内时，海藻酸会产生持续性痛觉过敏。在高于影响痛觉所需剂量时，海藻酸会诱发癫痫发作以及海马体中组织学上有反应的锌的移位。我们测试了这样一个假设：存在于一群小直径初级传入神经元中的锌，在海藻酸诱发的痛觉过敏中发挥的作用，类似于其在海马体中伴随海藻酸诱发癫痫发作时锌移位所起的作用。通过螯合二价阳离子的化合物（乙二胺四乙酸二钠钙（CaEDTA））或锌（吡啶甲酸（DPA））对海藻酸诱发的痛觉过敏的影响，评估了细胞外区域锌的重要性。当使用甩尾试验进行测量时，鞘内（i.t.）预先注射10 nmol的NaCaEDTA或1 nmol的DPA可阻断热痛觉过敏，这两种药物的分布仅限于细胞外区域。鞘内注射10 ng氯化锌对痛觉或海藻酸诱发的痛觉过敏没有长期影响。使用锌选择性染料N-(6-甲氧基-8-喹啉基)-对甲苯磺酰胺（TSQ）来确定锌是否会因痛觉过敏剂量的海藻酸而移位，该染料在小鼠脊髓的神经纤维网中产生细微染色，在海马体中产生浓密染色。与惊厥剂量的海藻酸给药24小时后海马体中TSQ明显褪色形成对比的是，注射痛觉过敏剂量的海藻酸未能改变脊髓或海马体中的TSQ荧光。这些数据共同表明，虽然锌不会移位，但细胞外区域的锌对于海藻酸诱发的痛觉过敏的发展是必要的，但不是充分的。
