Human Informatics Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, 305-8568, Japan.
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8577, Japan.
Sci Rep. 2017 Jun 27;7(1):4305. doi: 10.1038/s41598-017-04677-7.
The antineoplastic agent oxaliplatin induces a painful peripheral neuropathy characterized by an acute cold hypersensitivity. There is a lack of effective treatments to manage oxaliplatin-induced cold hypersensitivity which is due, in part, to a lack of understanding of the pathophysiology of oxaliplatin-induced cold hypersensitivity. Thus, brain activity in oxaliplatin-treated macaques was examined using functional magnetic resonance imaging (fMRI). Oxaliplatin treatment reduced tail withdrawal latency to a cold (10 °C) stimulus, indicating cold hypersensitivity and increased activation in the secondary somatosensory cortex (SII) and the anterior insular cortex (Ins) was observed. By contrast, no activation was observed in these areas following cold stimulation in untreated macaques. Systemic treatment with an antinociceptive dose of the serotonergic-noradrenergic reuptake inhibitor duloxetine decreased SII and Ins activity. Pharmacological inactivation of SII and Ins activity by microinjection of the GABA receptor agonist muscimol increased tail withdrawal latency. The current findings indicate that SII/Ins activity is a potential mediator of oxaliplatin-induced cold hypersensitivity.
奥沙利铂等抗肿瘤药物可引起以急性冷感觉过敏为特征的痛性周围神经病。目前缺乏有效的治疗方法来控制奥沙利铂引起的冷感觉过敏，部分原因是对奥沙利铂引起的冷感觉过敏的病理生理学缺乏了解。因此，使用功能磁共振成像（fMRI）检查了奥沙利铂处理的猕猴的大脑活动。奥沙利铂治疗可降低对冷（10°C）刺激的尾巴退缩潜伏期，表明冷感觉过敏，并观察到次级体感皮层（SII）和前岛叶皮层（Ins）的激活增加。相比之下，未处理的猕猴在冷刺激后这些区域没有观察到激活。全身给予抗伤害性剂量的血清素-去甲肾上腺素再摄取抑制剂度洛西汀可降低 SII 和 Ins 的活性。通过注射 GABA 受体激动剂 muscimol 使 SII 和 Ins 活性失活可增加尾巴退缩潜伏期。目前的研究结果表明，SII/Ins 活性可能是奥沙利铂引起的冷感觉过敏的潜在介导物。
