Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Section of Neurology, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan.
Hum Brain Mapp. 2013 Oct;34(10):2733-46. doi: 10.1002/hbm.22105. Epub 2012 Apr 21.
Persistent neuropathic pain due to peripheral nerve degeneration in diabetes is a stressful symptom; however, the underlying neural substrates remain elusive. This study attempted to explore neuroanatomical substrates of thermal hyperalgesia and burning pain in a diabetic cohort due to pathologically proven cutaneous nerve degeneration (the painful group). By applying noxious 44°C heat stimuli to the right foot to provoke neuropathic pain symptoms, brain activation patterns were compared with those of healthy control subjects and patients with a similar degree of cutaneous nerve degeneration but without pain (the painless group). Psychophysical results showed enhanced affective pain ratings in the painful group. After eliminating the influence of different pain intensity ratings on cerebral responses, the painful group displayed augmented responses in the limbic and striatal structures, including the perigenual anterior cingulate cortex (ACC), superior frontal gyrus, medial thalamus, anterior insular cortex, lentiform nucleus (LN), and premotor area. Among these regions, blood oxygen level-dependent (BOLD) signals in the ACC and LN were correlated with pain ratings to thermal stimulations in the painful group. Furthermore, activation maps of a simple regression analysis as well as a region of interest analysis revealed that responses in these limbic and striatal circuits paralleled the duration of neuropathic pain. However, in the painless group, BOLD signals in the primary somatosensory cortex and ACC were reduced. These results suggest that enhanced limbic and striatal activations underlie maladaptive responses after cutaneous nerve degeneration, which contributed to the development and maintenance of burning pain and thermal hyperalgesia in diabetes.
糖尿病导致的周围神经退行性病变引起的持续性神经病理性疼痛是一种应激症状；然而，其潜在的神经基础仍难以捉摸。本研究试图探讨病理性证实的皮肤神经退行性病变（疼痛组）导致的糖尿病患者的热痛觉过敏和烧灼感的神经解剖学基础。通过将有害的 44°C 热刺激施加到右脚以引发神经病理性疼痛症状，比较了大脑激活模式与健康对照组和具有相似程度皮肤神经退行性病变但无疼痛的患者（无痛组）。心理物理学结果显示疼痛组的情感疼痛评分增加。在消除不同疼痛强度评分对大脑反应的影响后，疼痛组显示出边缘和纹状体结构的反应增强，包括前扣带回皮质（ACC）的围生区、额上回、内侧丘脑、前岛叶、豆状核（LN）和运动前区。在这些区域中，ACC 和 LN 中的血氧水平依赖性（BOLD）信号与疼痛组对热刺激的疼痛评分相关。此外，简单回归分析的激活图和感兴趣区分析表明，这些边缘和纹状体回路的反应与神经病理性疼痛的持续时间平行。然而，在无痛组中，初级体感皮层和 ACC 中的 BOLD 信号减少。这些结果表明，皮肤神经退行性病变后，边缘和纹状体的过度激活是适应性反应的基础，这有助于糖尿病中烧灼感和热痛觉过敏的发展和维持。
