Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：缓解神经性疼痛（NPP）的现有补救方法具有挑战性，并为诸如电针（EA）等替代治疗措施开辟了道路。反复EA会话的抗伤害作用的潜在机制，特别是关于Adora3受体及其相关酶的调节，仍然难以捉摸。
方法：本研究采用备用神经损伤(SNI)小鼠模型，探讨ST36(足三里)重复电针的累积镇痛效应及其对脊髓背角Adora3调节(SCDH)的影响。48只雄性小鼠接受了SNI手术以诱导神经性疼痛，并被随机分配到SNI，SNI+2EA,SNI+4EA,和SNI+7EA组。脊髓（L4-L6）取样用于免疫荧光，腺苷（ADO）检测和重复EA治疗后的分子研究。
结果：保留神经损伤（SNI）后，手术后第3天，同侧后爪的机械退缩阈值（PWTs）和热伤害性退缩潜伏期（TWL）显着降低，而对侧后爪PWTs无明显变化。在随后的EA治疗中，SNI+EA组导致疼痛阈值显著增加(p<0.05).SNI小鼠中反复的EA会上调腺苷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中的神经元激励。Neun处理细胞的共定位分析显示Adora3表达增加，特别是在SNI+7EA组中。
结论：结论：累积电针治疗通过调节Adora3和CD73表达减少神经病理性疼痛，抑制ADA和最有可能增加SCDH中的神经元激活。这项研究为管理神经性疼痛提供了一个有前途的治疗选择，为进一步研究铺平道路。
方法：本研究采用备用神经损伤(SNI)小鼠模型，探讨ST36(足三里)重复电针的累积镇痛效应及其对脊髓背角Adora3调节(SCDH)的影响。48只雄性小鼠接受了SNI手术以诱导神经性疼痛，并被随机分配到SNI，SNI+2EA,SNI+4EA,和SNI+7EA组。脊髓（L4-L6）取样用于免疫荧光，腺苷（ADO）检测和重复EA治疗后的分子研究。
结果：保留神经损伤（SNI）后，手术后第3天，同侧后爪的机械退缩阈值（PWTs）和热伤害性退缩潜伏期（TWL）显着降低，而对侧后爪PWTs无明显变化。在随后的EA治疗中，SNI+EA组导致疼痛阈值显著增加(p<0.05).SNI小鼠中反复的EA会上调腺苷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中的神经元激励。Neun处理细胞的共定位分析显示Adora3表达增加，特别是在SNI+7EA组中。
结论：结论：累积电针治疗通过调节Adora3和CD73表达减少神经病理性疼痛，抑制ADA和最有可能增加SCDH中的神经元激活。这项研究为管理神经性疼痛提供了一个有前途的治疗选择，为进一步研究铺平道路。
