School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Trauma and Orthopedics, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Pain Physician. 2019 May;22(3):E215-E224.
Approximately 30% to 80% of patients with brachial plexus avulsion (BPA) developed neuropathic pain. It is an intolerable neuropathic pain, which brings heavy burden to family and society. In addition to motor and sensory deficits, neuropathic pain can be another serious sequela that equally influences the patient. The development of a microsurgical technique has promoted the treatment and rehabilitation of brachial plexus injury, but pain relief after BPA is still a difficult problem.
The present study aimed to semi-quantify changes in the behavior, spinal cord and cerebral metabolism in a neuropathic pain model following BPA injury in rats.
Controlled animal study.
Institute of Rehabilitation Medicine, Shanghai, China.
A total of 15 Sprague-Dawley rats, weighing 200 to 220 g, were randomly divided into 2 groups: experimental group (n = 10) and control group (n = 5). In the experimental group, neuropathic pain induced by BPA was established by directly avulsing the C5, C6, C7, C8, and T1 roots on the right side from the spinal cord. Rats in the control group only received open-close surgery. The autotomic behavior of biting their own digits was recorded and scored at 2 months after the surgery. Small animal positron emission tomography/computed tomography (PET/CT) images after injection of a 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) tracer were acquired to evaluate glucose metabolism in pain-related brain regions before and after the surgery, respectively. Semi-quantitative values of cortical to cerebellum standardized uptake value (SUV) ratios were calculated. Then, the animals were euthanized and the cervical segments of the spinal cord were removed for detection of glial fibrillary acidic protein (GFAP) expression in the astrocytes by immunohistochemical assay.
Nine of the 10 rats (90%) in the experimental group showed autotomic behavior at 2 months after the surgery. Slight autotomic behavior was noted only in one of 5 rats (20%) from the control group. The autotomic score in the experimental group was significantly higher than that in the control group (5.4 ± 1.0 vs. 0.2 ± 0.4, P < 0.05). The experimental group showed significantly higher SUV ratio in both the right and left thalamus, compared to the control group (P < 0.05). Immunohistochemical assay demonstrated that GFAP positive astrocytes in the dorsal horn at the injured side significantly increased compared to the control group (P < 0.05).
There are differences between small animals and human beings, and the structure and function of the human brain is more complex than in rodents. Therefore, extrapolation of the present conclusion should be cautious.
The present study reported a unique model of neuropathic pain following total BPA in rodents, which was demonstrated by a higher rate and score of autotomic behavior. More astrocytes were found activated in the spinal cord at the corresponding level of C5 and C6 spinal cord. In the small animal PET/CT imaging, significantly higher standardized glucose metabolic activity was found in both the right and left thalamus in the experimental group. The present study semi-quantified the neuropathic pain behavior in rats and explored the plastic changes in the spinal and brain metabolism.
Brachial plexus avulsion, small animal PET/CT, glucose metabolism, neuropathic pain, astrocyte, 18F-FDG.
约 30%至 80%的臂丛神经撕脱伤（BPA）患者会出现神经病理性疼痛。这是一种难以忍受的神经病理性疼痛，给家庭和社会带来了沉重的负担。除了运动和感觉功能障碍外，神经病理性疼痛还可能是另一个严重的后遗症，同样会影响患者。显微外科技术的发展促进了臂丛神经损伤的治疗和康复，但 BPA 后疼痛缓解仍然是一个难题。
本研究旨在半定量分析大鼠臂丛神经撕脱伤后神经病理性疼痛模型行为、脊髓和大脑代谢的变化。
对照动物研究。
中国上海康复医学研究所。
共 15 只体重 200 至 220 克的 Sprague-Dawley 大鼠随机分为 2 组：实验组（n = 10）和对照组（n = 5）。在实验组中，通过直接从脊髓上撕脱右侧 C5、C6、C7、C8 和 T1 神经根，建立神经病理性疼痛模型。对照组仅行开-闭手术。术后 2 个月记录并评分大鼠自咬其指的自主行为。分别在手术前后注射 2-[18F]-氟-2-脱氧-D-葡萄糖（18F-FDG）示踪剂后，采集小动物正电子发射断层扫描/计算机断层扫描（PET/CT）图像，评估疼痛相关脑区的葡萄糖代谢情况。计算皮质与小脑标准化摄取值（SUV）比值的半定量值。然后，处死动物，取出颈椎段脊髓，通过免疫组化法检测星形胶质细胞中胶质纤维酸性蛋白（GFAP）的表达。
实验组 10 只大鼠中有 9 只（90%）在术后 2 个月出现自主行为，对照组 5 只大鼠中有 1 只（20%）出现轻微自主行为。实验组的自主行为评分明显高于对照组（5.4 ± 1.0 vs. 0.2 ± 0.4，P < 0.05）。实验组右侧和左侧丘脑的 SUV 比值均明显高于对照组（P < 0.05）。免疫组化法显示，损伤侧背角的 GFAP 阳性星形胶质细胞明显增多（P < 0.05）。
小动物与人之间存在差异，且人脑的结构和功能比啮齿动物更为复杂。因此，对本研究结论的外推应谨慎。
本研究报道了一种独特的臂丛神经完全撕脱后神经病理性疼痛模型，其表现为自主行为的发生率和评分更高。在相应的 C5 和 C6 脊髓水平，发现更多的脊髓背角星形胶质细胞被激活。在小动物 PET/CT 成像中，实验组右侧和左侧丘脑的标准化葡萄糖代谢活性明显升高。本研究半定量评估了大鼠的神经病理性疼痛行为，并探讨了脊髓和大脑代谢的可塑性变化。
臂丛神经撕脱伤；小动物 PET/CT；葡萄糖代谢；神经病理性疼痛；星形胶质细胞；18F-FDG。
