Kiani Faisal Ayub, Li Hao, Guo Panpan, Zhang Qiulin, Abouelfetouh Mahmoud M, Ding Mingxing, Ding Yi
Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Department of Clinical Sciences, Faculty of Veterinary Sciences, Bahauddin Zakariyah University, Multan, Pakistan.
Animal Model Exp Med. 2024 Jul 11. doi: 10.1002/ame2.12458.
Existing remedial approaches for relieving neuropathic pain (NPP) are challenging and open the way for alternative therapeutic measures such as electroacupuncture (EA). The mechanism underlying the antinociceptive effects of repeated EA sessions, particularly concerning the regulation of the Adora3 receptor and its associated enzymes, has remained elusive.
This study used a mouse model of spared nerve injury (SNI) to explore the cumulative analgesic effects of repeated EA at ST36 (Zusanli) and its impact on Adora3 regulation in the spinal cord dorsal horn (SCDH). Forty-eight male mice underwent SNI surgery for induction of neuropathic pain and were randomly assigned to the SNI, SNI + 2EA, SNI + 4EA, and SNI + 7EA groups. Spinal cord (L4-L6) was sampled for immunofluorescence, adenosine (ADO) detection and for molecular investigations following repeated EA treatment.
Following spared nerve injury (SNI), there was a significant decrease in mechanical withdrawal thresholds (PWTs) and thermal nociceptive withdrawal latency (TWL) in the ipsilateral hind paw on the third day post-surgery, while the contralateral hind paw PWTs showed no significant changes. On subsequent EA treatments, the SNI + EA groups led to a significant increase in pain thresholds (p < 0.05). Repeated EA sessions in SNI mice upregulated Adenosine A3 (Adora3) and cluster of differentiation-73 (CD73) expression while downregulating adenosine deaminase (ADA) and enhancing neuronal instigation in the SCDH. Colocalization analysis of Neun-treated cells revealed increased Adora3 expression, particularly in the SNI + 7EA group.
In conclusion, cumulative electroacupuncture treatment reduced neuropathic pain by regulating Adora3 and CD73 expression, inhibiting ADA and most likely increasing neuronal activation in the SCDH. This study offers a promising therapeutic option for managing neuropathic pain, paving the way for further research.
现有的缓解神经性疼痛（NPP）的治疗方法具有挑战性，为电针（EA）等替代治疗措施开辟了道路。重复进行电针治疗产生抗伤害性作用的机制，尤其是关于Adora3受体及其相关酶的调节机制，仍然不清楚。
本研究使用 spared 神经损伤（SNI）小鼠模型，探讨在足三里（ST36）重复进行电针的累积镇痛效果及其对脊髓背角（SCDH）中Adora3调节的影响。48只雄性小鼠接受SNI手术以诱导神经性疼痛，并随机分为SNI、SNI + 2次电针、SNI + 4次电针和SNI + 7次电针组。重复电针治疗后，采集脊髓（L4 - L6）进行免疫荧光、腺苷（ADO）检测和分子研究。
在 spared 神经损伤（SNI）后，术后第三天同侧后爪的机械性退缩阈值（PWTs）和热痛觉退缩潜伏期（TWL）显著降低，而对侧后爪的PWTs无显著变化。在随后的电针治疗中，SNI + 电针组导致疼痛阈值显著升高（p < 0.05）。在SNI小鼠中重复进行电针治疗可上调腺苷A3（Adora3）和分化簇73（CD73）的表达，同时下调腺苷脱氨酶（ADA）并增强SCDH中的神经元激发。对Neun处理细胞的共定位分析显示Adora3表达增加，特别是在SNI + 7次电针组中。
总之,累积电针治疗通过调节Adora3和CD73表达、抑制ADA并很可能增加SCDH中的神经元激活来减轻神经性疼痛。本研究为治疗神经性疼痛提供了一个有前景的治疗选择，为进一步研究铺平了道路。
