Meregalli Cristina, Monza Laura, Jongen Joost L M
School of Medicine and Surgery, Experimental Neurology Unit and Milan Center for Neuroscience, University of Milano-Bicocca, Monza, Italy.
Department of Neurology, Brain Tumor Center, Erasmus MC Cancer Institute, Rotterdam, Netherlands.
Front Pain Res (Lausanne). 2022 Dec 13;3:1066069. doi: 10.3389/fpain.2022.1066069. eCollection 2022.
Neuropathic pain is a frequent complication of chemotherapy-induced peripheral neurotoxicity (CIPN). Chemotherapy-induced peripheral neuropathies may serve as a model to study mechanisms of neuropathic pain, since several other common causes of peripheral neuropathy like painful diabetic neuropathy may be due to both neuropathic and non-neuropathic pain mechanisms like ischemia and inflammation. Experimental studies are ideally suited to study changes in morphology, phenotype and electrophysiologic characteristics of primary afferent neurons that are affected by chemotherapy and to correlate these changes to behaviors reflective of evoked pain, mainly hyperalgesia and allodynia. However, hyperalgesia and allodynia may only represent one aspect of human pain, i.e., the sensory-discriminative component, while patients with CIPN often describe their pain using words like annoying, tiring and dreadful, which are affective-emotional descriptors that cannot be tested in experimental animals. To understand why some patients with CIPN develop neuropathic pain and others not, and which are the components of neuropathic pain that they are experiencing, experimental and clinical pain research should be combined. Emerging evidence suggests that changes in subsets of primary afferent nerve fibers may contribute to specific aspects of neuropathic pain in both preclinical models and in patients with CIPN. In addition, the role of cutaneous neuroimmune interactions is considered. Since obtaining dorsal root ganglia and peripheral nerves in patients is problematic, analyses performed on skin biopsies from preclinical models as well as patients provide an opportunity to study changes in primary afferent nerve fibers and to associate these changes to human pain. In addition, other biomarkers of small fiber damage in CIPN, like corneal confocal microscope and quantitative sensory testing, may be considered.
神经性疼痛是化疗引起的周围神经毒性（CIPN）的常见并发症。化疗引起的周围神经病变可作为研究神经性疼痛机制的模型，因为周围神经病变的其他一些常见原因，如疼痛性糖尿病神经病变，可能是由于缺血和炎症等神经性和非神经性疼痛机制共同导致的。实验研究非常适合研究受化疗影响的初级传入神经元的形态、表型和电生理特征的变化，并将这些变化与反映诱发性疼痛的行为（主要是痛觉过敏和异常性疼痛）相关联。然而，痛觉过敏和异常性疼痛可能仅代表人类疼痛的一个方面，即感觉辨别成分，而CIPN患者通常用烦人、疲惫和可怕等词语来描述他们的疼痛，这些都是情感-情绪描述词，无法在实验动物中进行测试。为了理解为什么有些CIPN患者会出现神经性疼痛而有些则不会，以及他们所经历的神经性疼痛的组成部分是什么，实验性和临床性疼痛研究应该结合起来。新出现的证据表明，初级传入神经纤维亚群的变化可能在临床前模型和CIPN患者中都对神经性疼痛的特定方面有影响。此外，还考虑了皮肤神经免疫相互作用的作用。由于获取患者的背根神经节和周围神经存在问题，对临床前模型以及患者的皮肤活检进行的分析为研究初级传入神经纤维的变化并将这些变化与人类疼痛联系起来提供了机会。此外，CIPN中小纤维损伤的其他生物标志物，如角膜共聚焦显微镜和定量感觉测试，也可以考虑。
