Laboratoire de Neurobiologie, CNRS UMR 7637, Ecole Supérieure de Physique et de Chimie Industrielles, 10 rue Vauquelin, 75005, Paris, France,
J Mol Neurosci. 2013 Nov;51(3):880-92. doi: 10.1007/s12031-013-0095-4. Epub 2013 Aug 23.
Vincristine is one of the most common anti-cancer drug therapies administered for the treatment of many types of cancer. Its dose-limiting side effect is the emergence of peripheral neuropathy, resulting in chronic neuropathic pain in many patients. This study sought to understand the mechanisms underlying the development of neuropathic pain by vincristine-induced neurotoxicity. We focused on signs of functional changes and revealed that deep layers of the spinal cord (III-IV) experience increased neuronal activity both in the absence of peripheral stimulation and, as a result of tactile mechanical stimulations. These laminae and superficial laminae I-II were also subject to structural changes as evidenced by an increase in immunoreactivity of Piccolo, a marker of active presynaptic elements. Further investigations performed, using DNA microarray technology, describe a large number of genes differentially expressed in dorsal root ganglions and in the spinal dorsal horn after vincristine treatment. Our study describes an important list of genes differentially regulated by vincristine treatment that will be useful for future studies and brings forward evidence for molecular and anatomical modifications of large diameter sensory neurons terminating in deep dorsal horn laminae, which could participate in the development of tactile allodynia.
长春新碱是最常用的抗癌药物疗法之一，用于治疗多种类型的癌症。其剂量限制的副作用是外周神经病变的出现，导致许多患者出现慢性神经性疼痛。本研究旨在通过长春新碱诱导的神经毒性来了解神经病理性疼痛发展的机制。我们专注于功能变化的迹象，并揭示了脊髓深层（III-IV）在没有外周刺激的情况下以及由于触觉机械刺激而经历增强的神经元活动。这些层和浅层 I-II 也经历了结构变化，表现为 Piccolo 的免疫反应性增加，Piccolo 是活跃的突触前元件的标志物。使用 DNA 微阵列技术进行的进一步研究描述了在长春新碱处理后背根神经节和脊髓背角中大量差异表达的基因。我们的研究描述了长春新碱处理差异调节的重要基因列表，这将对未来的研究有用，并为终止于深背角层的大直径感觉神经元的分子和解剖学修饰提供证据，这些修饰可能参与触觉过敏的发展。
