1 Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
2 Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Mol Pain. 2018 Jan-Dec;14:1744806918810099. doi: 10.1177/1744806918810099. Epub 2018 Oct 16.
Evidence suggests that there are both nociceptive and neuropathic components of cancer-induced pain. We have observed that changes in intrinsic membrane properties and excitability of normally non-nociceptive Aβ sensory neurons are consistent in rat models of peripheral neuropathic pain and cancer-induced pain. This has prompted a comparative investigation of the intracellular electrophysiological characteristics of sensory neurons and of the ultrastructural morphology of the dorsal horn in rat models of neuropathic pain and cancer-induced pain. Neuropathic pain model rats were induced with a polyethylene cuff implanted around a sciatic nerve. Cancer-induced pain model rats were induced with mammary rat metastasis tumour-1 rat breast cancer or MATLyLu rat prostate cancer cells implanted into the distal epiphysis of a femur. Behavioural evidence of nociception was detected using von Frey tactile assessment. Aβ-fibre low threshold mechanoreceptor neurons in both cancer-induced pain and neuropathic pain models exhibited slower dynamics of action potential genesis, including a wider action potential duration and lower action potential amplitude compared to those in control animals. Enhanced excitability of Aβ-fibre low threshold mechanoreceptor neurons was also observed in cancer-induced pain and neuropathic pain models. Furthermore, both cancer-induced pain and neuropathic pain models showed abundant abnormal axonal sprouting in bundles of myelinated axons in the ipsilateral spinal laminae IV and V. The patterns of changes show consistency between rat models of cancer-induced pain and neuropathic pain. These findings add to the body of evidence that animal models of cancer-induced pain and neuropathic pain share features that may contribute to the peripheral and central sensitization and tactile hypersensitivity in both pain states.
有证据表明,癌症引起的疼痛既有伤害性疼痛成分,也有神经性疼痛成分。我们观察到,在周围神经病理性疼痛和癌症引起的疼痛的大鼠模型中,正常非伤害性 Aβ 感觉神经元的固有膜性质和兴奋性的变化是一致的。这促使我们对感觉神经元的细胞内电生理特性和背角的超微结构形态进行了比较研究,这些研究分别在神经病理性疼痛和癌症引起的疼痛的大鼠模型中进行。神经病理性疼痛模型大鼠通过在坐骨神经周围植入聚乙烯袖套来诱导。癌症引起的疼痛模型大鼠通过植入乳腺癌 1 号大鼠乳腺癌或 MATLyLu 大鼠前列腺癌细胞到股骨远端骺来诱导。使用 von Frey 触觉评估来检测伤害性感受的行为证据。在癌症引起的疼痛和神经病理性疼痛模型中,Aβ 纤维低阈值机械感受器神经元的动作电位发生动力学较慢,与对照组动物相比,其动作电位持续时间较宽,动作电位幅度较低。在癌症引起的疼痛和神经病理性疼痛模型中,还观察到 Aβ 纤维低阈值机械感受器神经元的兴奋性增强。此外,在同侧脊髓 IV 和 V 层的有髓轴突束中,两种疼痛模型均表现出丰富的异常轴突发芽。变化模式在癌症引起的疼痛和神经病理性疼痛的大鼠模型之间表现出一致性。这些发现增加了证据,表明癌症引起的疼痛和神经病理性疼痛的动物模型具有共同的特征,这些特征可能导致两种疼痛状态中的外周和中枢敏化以及触觉过敏。