Gabapentin normalizes spinal neuronal responses that correlate with behavior in a rat model of cancer-induced bone pain
Gabapentin normalizes spinal neuronal responses that correlate with behavior in a rat model of cancer-induced bone pain
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DOI：
10.1097/00000542-200501000-00022
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发表时间：
2005-01-01
期刊：
影响因子：
8.8
通讯作者：
Urch, CE
中科院分区：
文献类型：
--
作者：
Donovan-Rodriguez, T;Dickenson, AH;Urch, CE
背景：癌症引起的骨痛是一个主要的临床问题，目前的治疗缺乏充分的疗效。加巴喷丁被许可用于神经性疼痛，但也有效对抗动物的炎症刺激。方法：建立了使用MRMT-1细胞系注射到胫骨中的癌症诱导的骨痛的大鼠模型，以研究急性化疗的疗效。（10，30，100 mg/kg）和慢性（30 mg/kg）全身性加巴喷丁对自然和有害电刺激的电生理浅表背角神经元反应的影响，结果：在电生理研究中，加巴喷丁急性（100 mg/kg）和慢性（30 mg/kg）均能使超兴奋的浅表背角神经元反应正常化，显著降低电诱发和机械诱发反应，但对热诱发反应无影响。行为学研究表明，慢性加巴喷丁（30 mg/kg）显著减弱MRMT-1大鼠的疼痛行为，使反应恢复至术前基线水平，并且这种减弱伴随着恢复至正常（非MRMT-1）宽动态范围：伤害性特异性浅表背角神经元轮廓。在这种癌症诱发的骨痛大鼠模型中，疼痛相关行为与浅表背角神经元群体的过度兴奋密切相关。加巴喷丁使癌症引起的骨痛引起的背角神经元变化正常化并减弱疼痛行为。因此，它可能为癌症引起的骨痛提供新的临床治疗。
Background: Cancer-induced bone pain is a major clinical problem for which current treatments lack full efficacy. Gabapentin is licensed for use in neuropathic pain yet is also effective against inflammatory stimuli in animals.Methods: A rat model of cancer-induced bone pain using the MRMT-1 cell line injected into the tibia was established to investigate the efficacy of acute (10, 30, 100 mg/kg) and chronic (30 mg/kg) systemic gabapentin on electrophysiological superficial dorsal horn neuronal responses to natural and noxious electrical stimuli, as well as on pain-related behavior.Results: In electrophysiological studies gabapentin worked both acutely (100 mg/kg) and chronically (30 mg/kg) to normalize the hyperexcitable superficial dorsal horn neuronal response, significantly reducing electrical-evoked and mechanical-evoked but not thermal-evoked responses. The behavioral study showed that chronic gabapentin (30 mg/kg) significantly attenuated pain behavior in MRMT-1 rats, restoring responses to preoperative baseline degrees, and that this attenuation was accompanied by a reversion to normal (non-MRMT-1) wide-dynamic-range: nociceptive specific superficial dorsal horn neuronal profiles.Conclusions. Pain-related behavior in this rat model of cancer-induced bone pain is strongly linked to hyperexcitability of a population of superficial dorsal horn neurones. Gabapentin normalizes the cancer-induced bone pain induced dorsal horn neuronal changes and attenuates pain behavior. it may therefore provide a novel clinical treatment for cancer-induced bone pain.