Abstract：
OBJECTIVE: Diabetic neuropathic pain (DNP) is one of the most prevalent symptoms of diabetes. The alteration of proteins in the spinal cord dorsal horn (SCDH) plays a significant role in the genesis and the development of DNP. Our previous study has shown electroacupuncture could effectively relieve DNP. However, the potential mechanism inducing DNP\'s genesis and development remains unclear and needs further research.
METHODS: This study established DNP model rats by intraperitoneally injecting a single high-dose streptozotocin; 2 Hz electroacupuncture was used to stimulate Zusanli (ST36) and Kunlun (BL60) of DNP rats daily from day 15 to day 21 after streptozotocin injection. Behavioral assay, quantitative PCR, immunofluorescence staining, and western blotting were used to study the analgesic mechanism of electroacupuncture.
RESULTS: The bradykinin B1 receptor (B1R) mRNA, nuclear factor-κB p65 (p65), substance P, and calcitonin gene-related peptide (CGRP) protein expression were significantly enhanced in SCDH of DNP rats. The paw withdrawal threshold was increased while body weight and fasting blood glucose did not change in DNP rats after the electroacupuncture treatment. The expression of B1R, p65, substance P, and CGRP in SCDH of DNP rats was also inhibited after the electroacupuncture treatment.
CONCLUSIONS: This work suggests that the potential mechanisms inducing the allodynia of DNP rats were possibly related to the increased expression of B1R, p65, substance P, and CGRP in SCDH. Downregulating B1R, p65, substance P, and CGRP expression levels in SCDH may achieve the analgesic effect of 2 Hz electroacupuncture treatment.
METHODS: This study established DNP model rats by intraperitoneally injecting a single high-dose streptozotocin; 2 Hz electroacupuncture was used to stimulate Zusanli (ST36) and Kunlun (BL60) of DNP rats daily from day 15 to day 21 after streptozotocin injection. Behavioral assay, quantitative PCR, immunofluorescence staining, and western blotting were used to study the analgesic mechanism of electroacupuncture.
RESULTS: The bradykinin B1 receptor (B1R) mRNA, nuclear factor-κB p65 (p65), substance P, and calcitonin gene-related peptide (CGRP) protein expression were significantly enhanced in SCDH of DNP rats. The paw withdrawal threshold was increased while body weight and fasting blood glucose did not change in DNP rats after the electroacupuncture treatment. The expression of B1R, p65, substance P, and CGRP in SCDH of DNP rats was also inhibited after the electroacupuncture treatment.
CONCLUSIONS: This work suggests that the potential mechanisms inducing the allodynia of DNP rats were possibly related to the increased expression of B1R, p65, substance P, and CGRP in SCDH. Downregulating B1R, p65, substance P, and CGRP expression levels in SCDH may achieve the analgesic effect of 2 Hz electroacupuncture treatment.
摘要：
目的：糖尿病神经性疼痛（DNP）是糖尿病最常见的症状之一。脊髓背角（SCDH）中蛋白质的改变在DNP的发生和发展中起着重要作用。我们先前的研究表明，电针可以有效缓解DNP。然而,DNP发生发展的潜在机制尚不清楚，有待进一步研究。
方法：本研究通过腹腔注射单一高剂量链脲佐菌素建立DNP大鼠模型；链脲佐菌素注射后第15天至第21天，每天用2Hz电针刺激DNP大鼠的足三里（ST36）和昆仑（BL60）。行为分析，定量PCR,免疫荧光染色，采用免疫印迹法研究电针的镇痛机制。
结果：缓激肽B1受体（B1R）mRNA，核因子-κBp65(p65),P物质,降钙素基因相关肽（CGRP）蛋白在DNP大鼠SCDH中表达显著增强。电针治疗后，DNP大鼠的爪缩阈值增加，而体重和空腹血糖没有变化。B1R的表达，p65,P物质,电针治疗后，DNP大鼠SCDH中的CGRP也受到抑制。
结论：这项工作表明，诱导DNP大鼠异常性疼痛的潜在机制可能与B1R的表达增加有关，p65,P物质,和CGRP在SCDH。下调B1R,p65,P物质,SCDH中CGRP的表达水平可能达到2Hz电针治疗的镇痛效果。
方法：本研究通过腹腔注射单一高剂量链脲佐菌素建立DNP大鼠模型；链脲佐菌素注射后第15天至第21天，每天用2Hz电针刺激DNP大鼠的足三里（ST36）和昆仑（BL60）。行为分析，定量PCR,免疫荧光染色，采用免疫印迹法研究电针的镇痛机制。
结果：缓激肽B1受体（B1R）mRNA，核因子-κBp65(p65),P物质,降钙素基因相关肽（CGRP）蛋白在DNP大鼠SCDH中表达显著增强。电针治疗后，DNP大鼠的爪缩阈值增加，而体重和空腹血糖没有变化。B1R的表达，p65,P物质,电针治疗后，DNP大鼠SCDH中的CGRP也受到抑制。
结论：这项工作表明，诱导DNP大鼠异常性疼痛的潜在机制可能与B1R的表达增加有关，p65,P物质,和CGRP在SCDH。下调B1R,p65,P物质,SCDH中CGRP的表达水平可能达到2Hz电针治疗的镇痛效果。
