The Modulating Effects Of Specific Modulators For Voltage-gated Sodium Channel On Rat Nociception And Epilepsy

In the present study, the modulating effects of specific voltage-gatedsodium channels modulators (BmK IT2 and BmK I ) from the venom ofscorpion Buthus martensi Karsch on rat nociception and epilepsy havebeen investigated using the means of behavioral test , micordialysis,immunohistochemistry and electrophysiological recording, and the possiblemechanisms involved in were discussed. The research includes three parts:1. The suppressive effects of BmK IT2 on rat nociceptive behavior andc-Fos expression in spinal cord induced by chemical stimulus(formalin and carrageenan). BmK IT2 has significant antinoceptive effectson spontaneous pain induced by formalin when subcutaneously injected intothe rat hindpaw. 1 min before or 10 min after formalin injection. Moreover,c-Fos expression induced by formalin was significantly inhibited in alllaminae of L4-5 spinal cord by pre- or post-treatment with BmK IT2. Inaddition, BmK IT2 can significantly inhibit rat mechanical hyperalgesiainduced by carrageengan in a dose-dependent manner. The inhibitoryeffects of BmK IT2 on nociception, hyperalgesia and c-Fos expression in ratspinal cord may be attributed to the modulation on voltage-gated sodiumchannel of peripheral nociceptors and primary afferents. BmK IT2 is worthyof being considered to be a kind of new algesia peptide drug. 3特异性钠通道调制剂对大鼠伤害性感受和癫痫发作的调制作用及其机制研究2. The dynamic release of amino acid transmitters from spinal dorsalhorn induced by scorpion BmK venom and a neurotoxin (BmK I). AfterBmK venom or BmK I was subcutaneously injected into rat hindpaw,glutamate and aspartate release could be evoked significantly within theinitial 30 minutes. However, GABA release could be laggardly evoked duringthe second 30 minutes by the venom, but not by BmK I. The resultsuggested that nociceptive afferent fibers could be activated to induceexcitatory amino acid release from spinal dorsal horn by nociceptive factorssuch as BmK I, but the delayed release of GABA might be attributed tomodulating role of some antinociceptive components in the venom.3. The rat epilepsy seizure induced by BmK I intrahippocampalinjection. The rat strong epileptic seizures in behavior and different epilepticdischarges in hippocampus were induced by intrahippocampal injection ofBmK I. In cultured rat hippocampus neurons, BmK I can significantly prolongthe inactivation of Na+ currents. In addition, c-Fos expression of rathippocampus with BmK administration was activated in a spatial andtemporal manner. The results show that the strong seizures and specificexpression of c-Fos induced by BmK I may be ascribed to, at least in part,the modulation on voltage-gated sodium channels in rat hippocampusneurons. The seizure rat induced by BmK I can serve as a useful animalmodel for studying epileptogenesis.