Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons
Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons
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DOI：
10.1016/s0306-4522(00)00110-x
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发表时间：
2000-01-01
期刊：
影响因子：
3.3
通讯作者：
Mantyh, PW
中科院分区：
文献类型：
--
作者：
Honore, P;Rogers, SD;Mantyh, PW
本研究的目的是确定炎症性、神经性和癌症疼痛的小鼠模型是否各自具有脊髓和感觉神经元中一组独特的神经化学变化的特征。所有模型均在C3 H/HeJ小鼠中产生，并对痛觉过敏和异常性疼痛进行行为学表征。在脊髓和初级传入神经元中检测了与慢性疼痛的产生和维持有关的各种神经化学标志物，在将完全弗氏佐剂注射到后爪（持续性炎性疼痛的模型）中三天后，在脊髓中观察到P物质、降钙素基因相关肽、蛋白激酶C γ和P物质受体的增加。坐骨神经横断或L5脊神经结扎（持续性神经性疼痛的模型）后，在初级传入神经元和脊髓中观察到P物质和降钙素基因相关肽显著减少，甘丙肽和神经肽Y增加。相比之下，在股骨注射溶骨肉瘤细胞诱导的癌症疼痛模型中，初级传入神经元或脊髓中的任何这些标记物均未检测到变化。然而，在这种癌症疼痛模型中，在患癌肢体同侧的脊髓中观察到了包括大量星形胶质细胞肥大而无神经元损失、c-Fos神经元表达增加以及强啡肽免疫反应神经元数量增加的变化。在C3 H/HeJ小鼠中的神经性疼痛和癌症疼痛，并进一步表明癌症诱导独特的持续性疼痛状态。确定这些神经化学变化是否参与每种类型的持续性疼痛的产生和维持，可能会提供对这些疼痛状态下的机制的深入了解。(C)2000 IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
The aim of this investigation was to determine whether murine models of inflammatory, neuropathic and cancer pain are each characterized by a unique set of neurochemical changes in the spinal cord and sensory neurons. All models were generated in C3H/HeJ mice and hyperalgesia and allodynia behaviorally characterized. A variety of neurochemical markers that have been implicated in the generation and maintenance of chronic pain were then examined in spinal cord and primary afferent neurons.Three days after injection of complete Freund's adjuvant into the hindpaw (a model of persistent inflammatory pain) increases in substance P, calcitonin gene-related peptide, protein kinase C gamma, and substance P receptor were observed in the spinal cord. Following sciatic nerve transection or L5 spinal nerve ligation (a model of persistent neuropathic pain) significant decreases in substance P and calcitonin gene-related peptide and increases in galanin and neuropeptide Y were observed in both primary afferent neurons and the spinal cord. In contrast, in a model of cancer pain induced by injection of osteolytic sarcoma cells into the femur, there were no detectable changes in any of these markers in either primary afferent neurons or the spinal cord. However, in this cancer-pain model, changes including massive astrocyte hypertrophy without neuronal loss, increase in the neuronal expression of c-Fos, and increase in the number of dynorphin-immunoreactive neurons were observed in the spinal cord, ipsilateral to the limb with cancer.These results indicate that a unique set of neurochemical changes occur with inflammatory, neuropathic and cancer pain in C3H/HeJ mice and further suggest that cancer induces a unique persistent pain state. Determining whether these neurochemical changes are involved in the generation and maintenance of each type of persistent pain may provide insight into the mechanisms that underlie each of these pain states. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.