Mechanism on synergistic analgesia and intestinal motility antagonism of electroacupuncture combined with morphine

MIAO Yiwen; WANG Jinbo; WANG Tao; WANG Xinjun

doi:10.13703/j.0255-2930.20241218-0002

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Mechanism on synergistic analgesia and intestinal motility antagonism of electroacupuncture combined with morphine

Study on Mechanism | 更新时间：2026-05-12

- Mechanism on synergistic analgesia and intestinal motility antagonism of electroacupuncture combined with morphine
- Chinese Acupuncture & Moxibustion Vol. 46, Issue 5, Pages: 795-804(2026)
- 作者机构：
  
  南京中医药大学针灸推拿学院·养生康复学院，江苏　南京　210023
- 作者简介：
- 基金信息：
- DOI：10.13703/j.0255-2930.20241218-0002
  CLC：
- Received：18 December 2024，
  
  Online First：14 January 2026，
  
  Published：12 May 2026
- 稿件说明：
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MIAO Yiwen, WANG Jinbo, WANG Tao, et al. Mechanism on synergistic analgesia and intestinal motility antagonism of electroacupuncture combined with morphine[J]. Chinese Acupuncture & Moxibustion, 2026, 46(5): 795-804.
DOI：

MIAO Yiwen, WANG Jinbo, WANG Tao, et al. Mechanism on synergistic analgesia and intestinal motility antagonism of electroacupuncture combined with morphine[J]. Chinese Acupuncture & Moxibustion, 2026, 46(5): 795-804. DOI： 10.13703/j.0255-2930.20241218-0002.

摘要

目的：

观察电针联合吗啡的协同镇痛效应和肠动力拮抗效应，探讨针药结合“增效减毒”效应机制。

方法：

将60只SPF级雄性C57BL/6J小鼠随机分为空白组、模型组、假电针+生理盐水组、吗啡+假电针组、电针+生理盐水组、吗啡+电针组，每组10只。除空白组外，其余组小鼠以完全弗氏佐剂诱导炎性痛模型。造模成功后采用电针、吗啡及吗啡+电针分别对小鼠进行干预。电针穴取双侧“足三里”，连续波，频率2 Hz，电流2 mA，每次30 min，每天1次，连续7 d；吗啡干预每次给予24 mg/kg吗啡稀释液灌胃，每日2次，连续7 d。假电针不刺入、不接电。第0~8天运用热板法对小鼠热痛阈值进行测定。干预结束后，采用首粒黑便排出时间、2 h排便量及小肠推进率评估小鼠肠动力情况；采用免疫荧光法检测小鼠下丘脑μ阿片受体（MOR）、5-羟色胺1A受体（5-HT1AR）及小肠MOR、嘌呤能受体P2Y1（P2Y1R）阳性表达；ELISA法测定小鼠下丘脑β-内啡肽（β-EP）、5-羟色胺（5-HT）及小肠β-EP、三磷酸腺苷（ATP）含量。

结果：

与空白组比较，模型组小鼠热痛阈值降低（

0.05），下丘脑MOR、5-HT1AR阳性表达及5-HT含量降低（

0.05），下丘脑、小肠β-EP含量升高（

0.05）。与模型组比较，吗啡+假电针组热痛阈值升高（

0.05），首粒黑便排出时间增加（

0.05），2 h排便量、小肠推进率降低（

0.05），下丘脑、小肠MOR阳性表达增加（

0.05），小肠P2Y1R阳性表达、ATP含量降低（

0.05）；电针+生理盐水组热痛阈值升高（

0.05），下丘脑MOR、5-HT1AR及小肠P2Y1R阳性表达增加（

0.05），下丘脑β-EP、5-HT及小肠ATP含量增加（

0.05），小肠MOR阳性表达及β-EP含量降低（

0.05）；吗啡+电针组热痛阈值升高（

0.05），首粒黑便排出时间增加（

0.05），2 h排便量、小肠推进率降低（

0.05），下丘脑MOR、5-HT1AR阳性表达及β-EP、5-HT含量增加（

0.05），小肠β-EP含量降低（

0.05）。与吗啡+假电针组比较，吗啡+电针组首粒黑便排出时间缩短（

0.05），2 h排便量、小肠推进率增加（

0.05），下丘脑MOR、5-HT1AR阳性表达及β-EP、5-HT含量增加（

0.05），小肠MOR阳性表达及β-EP含量降低（

0.05），小肠P2Y1R阳性表达及ATP含量增加（

0.05）。与电针+生理盐水组比较，吗啡+电针组首粒黑便排出时间增加（

0.05），2 h排便量降低（

0.05），下丘脑、小肠MOR阳性表达及下丘脑β-EP含量增加（

0.05），小肠P2Y1R阳性表达、ATP含量降低（

0.05）。小肠MOR与P2Y1R存在共定位且阳性表达呈显著负相关（

=-0.868，

0.000 1）。

结论：

电针联合吗啡通过激动脑内MOR、5-HT1AR协同镇痛，通过抑制肠内MOR并激动P2Y1R改善肠动力，体现出针药结合“增效减毒”的特征。

Abstract

Objective

To observe the synergistic analgesia and intestinal motility antagonism of electroacupuncture (EA) combined with morphine

and explore the mechanism of the "effect-enhancing and toxicity-reducing" of the combined therapy with acupuncture and medication.

Methods

Sixty SPF-grade male C57BL/6J mice were randomly divided into a blank group

a model group

a sham-EA+normal saline (NS) group

a morphine+sham-EA group

an EA+NS group

and a morphine+EA group

with 10 mice in each group. Except in the blank group

the mice in the other groups were prepared to be inflammatory pain models induced by complete Freundʹs adjuvant. After successful modeling

the interventions were administered with EA

morphine

or morphine+EA

respectively. EA was delivered at "Zusanli" (ST36) bilaterally

with continuous wave

at a frequency of 2 Hz and a current of 2 mA

for 30 min

once daily and for 7 consecutive days. Intragastric administration with diluted morphine hydrochloride solution (24 mg/kg) was operated

twice daily and for 7 consecutive days. Sham-EA was obtained by no access to needle puncture and electric stimulation. The thermal pain threshold was measured using the hot plate method from day 0 to day 8. Intestinal motility was evaluated by time to first passage of melena

2-hour fecal output and small intestinal transit rate. Immunofluorescence was used to detect the positive expression of μ-opioid receptor (MOR) and 5-hydroxytryptamine 1A receptor (5-HT1AR) in the hypothalamus

and that of MOR and purinergic receptor P2Y1 (P2Y1R) in the small intestine. ELISA was employed to measure the contents of β-endorphin (β-EP) and serotonin (5-HT) in the hypothalamus

and those of β-EP and adenosine triphosphate (ATP) in the small intestine.

Results

Compared with the blank group

the thermal pain threshold of mice decreased (

0.05)

the positive expression of MOR and 5-HT1AR and the content of 5-HT in the hypothalamus were reduced (

0.05)

the contents of β-EP in the hypothalamus and small intestine increased (

0.05) in the model group. When compared with the model group

in the morphine+sham-EA group

the thermal pain threshold increased (

0.05)

the time to first passage of melena was prolonged (

0.05)

and the 2-hour fecal output and small intestinal transit rate decreased (

0.05)

and the positive expression of MOR in the hypothalamus and small intestine increased (

0.05)

while the positive expression of P2Y1R and the content of ATP in the small intestine decreased (

0.05); in the EA+NS group

the thermal pain threshold was higher (

0.05)

the positive expression of MOR and 5-HT1AR in the hypothalamus and that of P2Y1R in the small intestine increased (

0.05)

and the contents of β-EP and 5-HT in the hypothalamus

and the content of ATP in the small intestine were elevated (

0.05)

the positive expression of MOR and the content of β-EP in the small intestine were reduced (

0.05); in the morphine+EA group

the thermal pain threshold was higher (

0.05)

the time to first passage of melena was prolonged (

0.05)

the 2-hour fecal output and small intestinal transit rate were declined (

0.05)

and the positive expression of MOR and 5-HT1AR and the contents of β-EP and 5-HT in the hypothalamus increased (

0.05)

while the content of β-EP in the small intestine decreased (

0.05). In comparison with the morphine+sham-EA group

the morphine+EA group showed the decrease in the time to first passage of me

lena (

0.05)

the increase in the 2-hour fecal output and small intestinal transit rate (

0.05)

and the increase in the positive expression of MOR and 5-HT1AR and the contents of β-EP and 5-HT in the hypothalamus (

0.05)

the decrease in the positive expression of MOR and the content of β-EP in the small intestine (

0.05)

and the increase in the positive expression of P2Y1R and the content of ATP in the small intestine (

0.05). Compared with the EA+NS group

the morphine+EA group demonstrated the increase in the time to first passage of melena (

0.05)

the decrease in the 2-hour fecal output (

0.05)

and the increase in the positive expression of MOR in the hypothalamus and the small intestine and the content of β-EP in the hypothalamus (

0.05)

and the decrease in the positive expression of P2Y1R and the content of ATP in the small intestine (

0.05). MOR and P2Y1R were co-located and the positive expression of them in the small intestine showed a significant negative correlation (

=-0.868

0.000 1).

Conclusion

Electroacupuncture combined with morphine exerts synergistic analgesia by agonizing MOR and 5-HT1AR in the brain

and improves intestinal motility by inhibiting MOR and agonizing P2Y1R in the intestine

demonstrating the characteristic of "effect-enhancing and toxicity-reducing" in the combined therapy with acupuncture and medication.

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