Abstract：
BACKGROUND: Following amputation, peripheral nerves lack distal targets for regeneration, often resulting in symptomatic neuromas and debilitating neuropathic pain. Animal models can establish a practical method for symptomatic neuroma formation for better understanding of neuropathic pain pathophysiology through behavioral and histological assessments. We created a clinically translatable animal model of symptomatic neuroma to mimic neuropathic pain in patients and assess sexual differences in pain behaviors.
METHODS: Twenty-two male and female rats were randomly assigned to one of two experimental groups: (1) neuroma surgery, or (2) sham surgery. For the neuroma experimental group, the tibial nerve was transected in the thigh, and the proximal segment was placed under the skin for mechanical testing at the site of neuroma. For the sham surgery, rats underwent tibial nerve isolation without transection. Behavioral testing consisted of neuroma-site pain, mechanical allodynia, cold allodynia, and thermal hyperalgesia at baseline, and then weekly over 8 weeks.
RESULTS: Male and female neuroma rats demonstrated significantly higher neuroma-site pain response compared to sham groups starting at weeks 3 and 4, indicating symptomatic neuroma formation. Weekly assessment of mechanical and cold allodynia among neuroma groups showed a significant difference in pain behavior compared to sham groups (p < 0.001). Overall, males and females did not display significant differences in their pain responses. Histology revealed a characteristic neuroma bulb at week 8, including disorganized axons, fibrotic tissue, Schwann cell displacement, and immune cell infiltration.
CONCLUSIONS: This novel animal model is a useful tool to investigate underlying mechanisms of neuroma formation and neuropathic pain.
METHODS: Twenty-two male and female rats were randomly assigned to one of two experimental groups: (1) neuroma surgery, or (2) sham surgery. For the neuroma experimental group, the tibial nerve was transected in the thigh, and the proximal segment was placed under the skin for mechanical testing at the site of neuroma. For the sham surgery, rats underwent tibial nerve isolation without transection. Behavioral testing consisted of neuroma-site pain, mechanical allodynia, cold allodynia, and thermal hyperalgesia at baseline, and then weekly over 8 weeks.
RESULTS: Male and female neuroma rats demonstrated significantly higher neuroma-site pain response compared to sham groups starting at weeks 3 and 4, indicating symptomatic neuroma formation. Weekly assessment of mechanical and cold allodynia among neuroma groups showed a significant difference in pain behavior compared to sham groups (p < 0.001). Overall, males and females did not display significant differences in their pain responses. Histology revealed a characteristic neuroma bulb at week 8, including disorganized axons, fibrotic tissue, Schwann cell displacement, and immune cell infiltration.
CONCLUSIONS: This novel animal model is a useful tool to investigate underlying mechanisms of neuroma formation and neuropathic pain.
摘要：
背景：截肢后，周围神经缺乏再生的远端靶点，通常导致有症状的神经瘤和衰弱的神经性疼痛。动物模型可以建立症状性神经瘤形成的实用方法，以通过行为和组织学评估更好地了解神经性疼痛的病理生理学。我们创建了症状性神经瘤的临床可翻译动物模型，以模拟患者的神经性疼痛并评估疼痛行为的性别差异。
方法：将22只雄性和雌性大鼠随机分为两个实验组之一：（1）神经瘤手术，或（2）假手术。对于神经瘤实验组，胫骨神经在大腿被切断,并将近端节段置于皮肤下进行神经瘤部位的机械测试。为了假手术，大鼠接受了胫神经隔离术，没有横切。行为测试包括神经瘤部位疼痛，机械性异常性疼痛,冷异常性疼痛,和基线时的热痛觉过敏，然后每周超过8周。
结果：在第3周和第4周开始，雄性和雌性神经瘤大鼠表现出明显高于假手术组的神经瘤部位疼痛反应，表明有症状的神经瘤形成。每周对神经瘤组中机械性和冷异常性疼痛的评估显示，与假手术组相比，疼痛行为存在显着差异（p<0.001）。总的来说,男性和女性的疼痛反应没有显着差异。组织学显示8周有特征性的神经瘤球，包括轴突紊乱，纤维化组织,施万细胞置换，和免疫细胞浸润。
结论：这种新型动物模型是研究神经瘤形成和神经性疼痛的潜在机制的有用工具。
方法：将22只雄性和雌性大鼠随机分为两个实验组之一：（1）神经瘤手术，或（2）假手术。对于神经瘤实验组，胫骨神经在大腿被切断,并将近端节段置于皮肤下进行神经瘤部位的机械测试。为了假手术，大鼠接受了胫神经隔离术，没有横切。行为测试包括神经瘤部位疼痛，机械性异常性疼痛,冷异常性疼痛,和基线时的热痛觉过敏，然后每周超过8周。
结果：在第3周和第4周开始，雄性和雌性神经瘤大鼠表现出明显高于假手术组的神经瘤部位疼痛反应，表明有症状的神经瘤形成。每周对神经瘤组中机械性和冷异常性疼痛的评估显示，与假手术组相比，疼痛行为存在显着差异（p<0.001）。总的来说,男性和女性的疼痛反应没有显着差异。组织学显示8周有特征性的神经瘤球，包括轴突紊乱，纤维化组织,施万细胞置换，和免疫细胞浸润。
结论：这种新型动物模型是研究神经瘤形成和神经性疼痛的潜在机制的有用工具。
