Yonsei Med J.  2011 Nov;52(6):1016-1021. 10.3349/ymj.2011.52.6.1016.

Analgesic Mechanism of Electroacupuncture in an Arthritic Pain Model of Rats: A Neurotransmitter Study

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea. sjbai1@yuhs.ac
  • 2Medical Research Center, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
We investigated what kinds of neurotransmitters are related with electroacupuncture (EA) analgesia in an arthritic pain model of rats.
MATERIALS AND METHODS
One hundred rats were assigned to six groups: control, EA, opioid, adrenergic, serotonin and dopamine group. A standardized model of inflammatory arthritis was produced by injecting 2% carrageenan into the knee joint cavity. EA was applied to an acupoint for 30 min in all groups except fo the control group. In the opioid, adrenergic, serotonin and dopamine groups, each receptor antagonist was injected intraperitoneally to their respective group before initiating EA.
RESULTS
In the opioid receptor antagonist group, adrenergic receptor antagonist group, serotonin receptor antagonist group, dopamine receptor antagonist group and the control group weight-bearing force decreased significantly from 30 min to 180 min after EA in comparison with the EA group.
CONCLUSION
The analgesic effects of EA are related to opioid, adrenergic, serotonin and dopamine receptors in an arthritic pain model of rats.

Keyword

Arthritis; electroacupuncture; neurotransmitter; pain; weight-bearing

MeSH Terms

Acupuncture Analgesia/*methods
Adrenergic Antagonists/therapeutic use
Animals
Arthritis/chemically induced/drug therapy/physiopathology/*therapy
Carrageenan/toxicity
Dopamine Antagonists/therapeutic use
Electroacupuncture/*methods
Male
Neurotransmitter Agents/*metabolism
Pain/drug therapy/metabolism
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic/metabolism
Receptors, Dopamine/metabolism
Receptors, Opioid/antagonists & inhibitors/metabolism
Receptors, Serotonin/metabolism
Serotonin Antagonists/therapeutic use

Figure

  • Fig. 1 Effects of manual acupuncture on weight-bearing behavioral tests of rats with arthritis. Percent changes of weight-bearing force to body weight compared with responses before acupuncture were plotted. There were statistically significant differences in response between the acupuncture group and the control group at 30-180 min after the termination of acupuncture. There were no differences in response between the sham acupoint group and the control a group. Data were analyzed by one-way ANOVA with the Dunnett's (2-sided) post-hoc test for multiple comparisons. *Statistical significance was defined as p<0.05. ANOVA, analysis of variance.

  • Fig. 2 Effect of low frequency and high frequency electroacupuncture on weight-bearing behavioral tests of rats with arthritis. Percent changes of weight-bearing force to body weight compared with responses before electroacupuncture were plotted. There were statistically significant differences in response between the EA group and control group at 60-180 min after the termination of electroacupuncture. There were no differences in response between the sham acupoint group and the control group. Data were analyzed by one-way ANOVA with the Dunnett's (2-sided) post-hoc test for multiple comparisons. *Statistical significance was defined as p<0.05. EA, electroacupuncture; ANOVA, analysis of variance.

  • Fig. 3 Effect of neurotransmitter antagonists on weight bearing behavior test of rats with arthritis. Percent changes of weight-bearing force to body weight compared with responses before electroacupuncture were plotted. The neurotransmitter receptor antagonist groups and control group showed significant decrease in weight-bearing force from 30 min to 180 min after electroacupuncture in comparison with the EA group. Data were analyzed by one-way ANOVA with the Dunnett's (2-sided) post-hoc test for multiple comparisons. *Statistical significance was defined as p<0.05. EA, electroacupuncture; ANOVA, analysis of variance.


Reference

1. Hunter DJ, Lo GH. The management of osteoarthritis: an overview and call to appropriate conservative treatment. Med Clin North Am. 2009. 93:127–143.
Article
2. Ezzo J, Berman B, Hadhazy VA, Jadad AR, Lao L, Singh BB. Is acupuncture effective for the treatment of chronic pain? A systematic review. Pain. 2000. 86:217–225.
Article
3. ter Riet G, Kleijnen J, Knipschild P. Acupuncture and chronic pain: a criteria-based meta-analysis. J Clin Epidemiol. 1990. 43:1191–1199.
Article
4. Lin JG, Chen WL. Acupuncture analgesia: a review of its mechanisms of actions. Am J Chin Med. 2008. 36:635–645.
5. Ulett GA, Han S, Han JS. Electroacupuncture: mechanisms and clinical application. Biol Psychiatry. 1998. 44:129–138.
6. Huang C, Hu ZP, Long H, Shi YS, Han JS, Wan Y. Attenuation of mechanical but not thermal hyperalgesia by electroacupuncture with the involvement of opioids in rat model of chronic inflammatory pain. Brain Res Bull. 2004. 63:99–103.
Article
7. Koo ST, Lim KS, Chung K, Ju H, Chung JM. Electroacupuncture-induced analgesia in a rat model of ankle sprain pain is mediated by spinal alpha-adrenoceptors. Pain. 2008. 135:11–19.
Article
8. Oh JH, Bai SJ, Cho ZH, Han HC, Min SS, Shim I, et al. Pain-relieving effects of acupuncture and electroacupuncture in an animal model of arthritic pain. Int J Neurosci. 2006. 116:1139–1156.
Article
9. Min SS, Han JS, Kim YI, Na HS, Yoon YW, Hong SK, et al. A novel method for convenient assessment of arthritic pain in voluntarily walking rats. Neurosci Lett. 2001. 308:95–98.
Article
10. Han JS, Terenius L. Neurochemical basis of acupuncture analgesia. Annu Rev Pharmacol Toxicol. 1982. 22:193–220.
11. Han JS, Xie GX, Zhou ZF, Folkesson R, Terenius L. Acupuncture mechanisms in rabbits studied with microinjection of antibodies against beta-endorphin, enkephalin and substance P. Neuropharmacology. 1984. 23:1–5.
Article
12. Zhang WT, Jin Z, Cui GH, Zhang KL, Zhang L, Zeng YW, et al. Relations between brain network activation and analgesic effect induced by low vs. high frequency electrical acupoint stimulation in different subjects: a functional magnetic resonance imaging study. Brain Res. 2003. 982:168–178.
Article
13. Kishioka S, Miyamoto Y, Fukunaga Y, Nishida S, Yamamoto H. Effects of a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) on Met-enkephalin-, beta-endorphin-, dynorphin-(1-13)- and electroacupuncture-induced antinociception in rats. Jpn J Pharmacol. 1994. 66:337–345.
14. Kayser V, Elfassi IE, Aubel B, Melfort M, Julius D, Gingrich JA, et al. Mechanical, thermal and formalin-induced nociception is differentially altered in 5-HT1A-/-, 5-HT1B-/-, 5-HT2A-/-, 5-HT3A-/- and 5-HTT-/- knock-out male mice. Pain. 2007. 130:235–248.
Article
15. Takagi J, Yonehara N. Serotonin receptor subtypes involved in modulation of electrical acupuncture. Jpn J Pharmacol. 1998. 78:511–514.
Article
16. Baek YH, Choi DY, Yang HI, Park DS. Analgesic effect of electroacupuncture on inflammatory pain in the rat model of collagen-induced arthritis: mediation by cholinergic and serotonergic receptors. Brain Res. 2005. 1057:181–185.
Article
17. Xie CW, Tang J, Han JS. Takagi H, Simon EJ, editors. Central norepinephrine in acupuncture analgesia. Differential effects in brain and spinal cord. Advances in endogenous and exogenous opioids. 1981. Tokyo: Kodansha;288–290.
Article
18. Kim SK, Park JH, Bae SJ, Kim JH, Hwang BG, Min BI, et al. Effects of electroacupuncture on cold allodynia in a rat model of neuropathic pain: mediation by spinal adrenergic and serotonergic receptors. Exp Neurol. 2005. 195:430–436.
Article
19. Wang YQ, Cao XD, Li KY, Wu GC. Relationship between electroacupuncture analgesia and dopamine receptors in nucleus accumbens. Zhongguo Yao Li Xue Bao. 1997. 18:494–496.
20. Zhu CB, Li XY, Zhu YH, Xu SF. Binding sites of mu receptor increased when acupuncture analgesia was enhanced by droperidol: an autoradiographic study. Zhongguo Yao Li Xue Bao. 1995. 16:311–314.
21. King MA, Bradshaw S, Chang AH, Pintar JE, Pasternak GW. Potentiation of opioid analgesia in dopamine 2 receptor knock-out mice: evidence for a tonically active anti-opioid system. J Neurosci. 2001. 21:7788–7792.
Article
22. Wang Y, Zhang Y, Wang W, Cao Y, Han JS. Effects of synchronous or asynchronous electroacupuncture stimulation with low versus high frequency on spinal opioid release and tail flick nociception. Exp Neurol. 2005. 192:156–162.
Article
23. He LF. Involvement of endogenous opioid peptides in acupuncture analgesia. Pain. 1987. 31:99–121.
Article
24. Acupuncture. NIH Consens Statement. 1997. 15:1–34.
25. Ernst E, White A. Acupuncture: a scientific appraisal. 1999. Oxford: Butterworth Heinemann;11–30.
Full Text Links
  • YMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr