Scientific Evidence-Based Mechanism of Acupuncture on Analgesia

Main Article Content

Nunnapas Jiwlawat
Sumit Durongphongtorn

Abstract

Traditional Chinese acupuncture has been routinely used worldwide as an adjunctive therapy for alleviating chronic pain because the long-term usage of analgesic drugs, prescribed in western medicine, may cause adverse side-effects or may provide unsatisfactory pain relief. However, the underlying analgesic mechanism of how acupuncture modulates the nervous system and pain pathways resulting in pain alleviation has not been revealed. In the last decade, more than 1,000 scientific researches have been published and proven that acupuncture interferes with pain signals at the various levels of nociception: peripheral, spinal cord, and brain. Acupuncture analgesic effects have significantly relied on the type of pain, type and location of acupuncture, frequency of electrical stimulation, and experience of the acupuncturist. Recent scientific evidence shows that the major analgesic effects of acupuncture are a result of the triggered release of endogenous-opioid in patients. Acupuncture induces serotonin and norepinephrine release which inhibit descending nociceptive transmission. Acupuncture also increases the pain threshold and reduces inflammatory reactions via a decreasing inflammatory mediator released from the peripheral nociceptive areas. In this review, we gather critical scientific proof from highlighted scientific research and summarize them into the analgesic mechanism of acupuncture. Lastly, we discuss challenges and future directions of scientific research on acupuncture.

Downloads

Download data is not yet available.

Article Details

Section
Review Article

References

1. Pergolizzi J, Ahlbeck K, Aldington D, Alon E, Coluzzi F, Dahan A, Huygen F, Kocot-Kępska M, Mangas A, Mavrocordatos P, Morlion B, Müller-Schwefe G, Nicolaou A, Pérez Hernández C, Sichère P, Schäfer M, Varrassi G. The development of chronic pain: physiological CHANGE necessitates a multidisciplinary approach to treatment. Curr Med Res Opin. 2013;29(9):1127-35.
2. Bergh I, Steen G, Waern M, Johansson B, Odén A, Sjöström B, Steen B. Pain and its relation to cognitive function and depressive symptoms: a Swedish population study of 70-year-old men and women. J Pain Symptom Manage. 2003;26(4):903-12.
3. Wells N, Pasero C, McCaffery M. Improving the Quality of Care Through Pain Assessment and Management. In: Hughes RG, editor. Patient safety and quality: An evidence-based handbook for nurses. Rockville (MD): Agency for Healthcare Research and Quality; 2008.
4. Glowacki D. Effective pain management and improvements in patients’ outcomes and satisfaction. Crit Care Nurse. 2015;35(3):33-41.
5. National Institutes of Health. National Institutes of Health Consensus Conference. Acupuncture. JAMA. 1998;280(17):1518-24.
6. Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report. 2008(12):1-23.
7. World Health Organization. Acupuncture: review and analysis of reports on controlled clinical trials. Geneva: World Health Organization; 2002. 81 p.
8. Zhang R, Lao L, Ren K, Berman BM. Mechanisms of acupuncture-electroacupuncture on persistent pain. Anesthesiology. 2014;120(2):482-503.
9. Ulett GA, Han S, Han JS. Electroacupuncture: mechanisms and clinical application. Biol Psychiatry. 1998;44(2):129-38.
10. Merskey HaB, N. Classification of chronic pain: a Current list with definitions and notes on usage. 2nd ed. Seattle: International Association for the Study of Pain Press; 1994.
11. Muir WW, 3rd, Woolf CJ. Mechanisms of pain and their therapeutic implications. J Am Vet Med Assoc. 2001;219(10):1346-56.
12. Institute of Medicine Committee on Pain, Disability, Chronic Illness Behavior. Pain and Disability: Clinical, Behavioral, and Public Policy Perspectives. In: Osterweis M, Kleinman A, Mechanic D, editors. Pain and Disability: Clinical, Behavioral, and Public Policy Perspectives. Washington (DC): National Academies Press; 1987.
13. Rainville P. Brain mechanisms of pain affect and pain modulation. Curr Opin Neurobiol. 2002;12(2):195-204.
14. Dong ZQ, Ma F, Xie H, Wang YQ, Wu GC. Changes of expression of glial cell line-derived neurotrophic factor and its receptor in dorsal root ganglions and spinal dorsal horn during electroacupuncture treatment in neuropathic pain rats. Neurosci Lett. 2005;376(2):143-8.
15. Kimura K, Masuda K, Wakayama I. Changes in skin blood flow and skin sympathetic nerve activity in response to manual acupuncture stimulation in humans. Am JChin Med. 2006;34(2):189-96.
16. Dougherty DD, Kong J, Webb M, Bonab AA, Fischman AJ, Gollub RL. A combined [11C] diprenorphine PET study and fMRI study of acupuncture analgesia. Behav Brain Res. 2008;193(1):63-8.
17. Hui KK, Liu J, Makris N, Gollub RL, Chen AJ, Moore CI, Kennedy DN, Rosen BR, Kwong KK. Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects. Hum Brain Mapp. 2000;9(1):13-25.
18. Stacher G, Wancura I, Bauer P, Lahoda R, Schulze D. Effect of acupuncture of pain threshold and pain tolerance determined by electrical stimulation of the skin: a controlled study. Am J Chin Med (Gard City N Y). 1975;3(2):143-9.
19. Wu S, Yamaguchi H, Shibutani K. Effect of acupuncture on perception threshold: a randomised controlled trial. Acupunct Med. 2012;30(1):32-6.
20. Baeumler PI, Fleckenstein J, Takayama S, Simang M, Seki T, Irnich D. Effects of acupuncture on sensory perception: a systematic review and meta-analysis. PLoS One. 2014;9(12):e113731.
21. Research Group of Acupuncture Analgesia, Beijing Medical College. The effect of acupuncture on pain threshold of the skin on human volunteers. Chin Med J. 1973;3:151-7.
22. Lao L, Zhang RX, Zhang G, Wang X, Berman BM, Ren K. A parametric study of electroacupuncture on persistent hyperalgesia and Fos protein expression in rats. Brain Res. 2004;1020(1-2):18-29.
23. Kong J, Fufa DT, Gerber AJ, Rosman IS, Vangel MG, Gracely RH, Gollub RL. Psychophysical outcomes from a randomized pilot study of manual, electro, and sham acupuncture treatment on experimentally induced thermal pain. J Pain. 2005;6(1):55-64.
24. Du J, He L. Alterations of spinal dorsal horn substance P following electroacupuncture analgesia--a study of the formalin test with immunohistochemistry and densitometry. Acupunct Electrother Res. 1992;17(1):1-6.
25. Lee JH, Jang KJ, Lee YT, Choi YH, Choi BT. Electroacupuncture inhibits inflammatory edema and hyperalgesia through regulation of cyclooxygenase synthesis in both peripheral and central nociceptive sites. Am J Chin Med. 2006;34(6):981-8.
26. Xu FY, Gan JH, Li WP, Yang M, Liu X. Effect of electroacupuncture on the level of IL-1beta and TNF-alpha in patients with osteoarthritis. Zhongguo Zhen Jiu. 2009;29(7):529-31.
27. Yuan SY, Qin Z, Liu DS, Yin WQ, Zhang ZL, Li SG. Acupuncture for chronic pelvic pain syndromes (CPPS) and its effect on cytokines in prostatic fluid. Zhongguo Zhen Jiu. 2011;31(1):11-4.
28. Pasternak GW. Pharmacological mechanisms of opioid analgesics. Clin Neuropharmacol. 1993;16(1):1-18.
29. Zhang RX, Lao L, Wang L, Liu B, Wang X, Ren K, Berman BM. Involvement of opioid receptors in electroacupuncture-produced anti-hyperalgesia in rats with peripheral inflammation. Brain Res. 2004;1020(1-2):12-7.
30. Zhang GG, Yu C, Lee W, Lao L, Ren K, Berman BM. Involvement of peripheral opioid mechanisms in electroacupuncture analgesia. Explore (NY). 2005;1(5):365-71.
31. Han JS. Acupuncture and endorphins. Neurosci Lett. 2004;361(1-3):258-61.
32. Han JS. Acupuncture: neuropeptide release produced by electrical stimulation of different frequencies. Trends Neurosci. 2003;26(1):17-22.
33. Kim HY, Wang J, Lee I, Kim HK, Chung K, Chung JM. Electroacupuncture suppresses capsaicin-induced secondary hyperalgesia through an endogenous spinal opioid mechanism. Pain. 2009;145(3):332-40.
34. Harris RE, Zubieta JK, Scott DJ, Napadow V, Gracely RH, Clauw DJ. Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs). Neuroimage. 2009;47(3):1077-85.
35. Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci. 2007;27(37):10000-6.
36. Xie GX, Han JS, Hollt V. Electroacupuncture analgesia blocked by microinjection of anti-beta-endorphin antiserum into periaqueductal gray of the rabbit. Int J Neurosci. 1983;18(3-4):287-91.
37. Li X, Eisenach JC. alpha2A-adrenoceptor stimulation reduces capsaicin-induced glutamate release from spinal cord synaptosomes. J Pharmacol Exp Ther. 2001;299(3):939-44.
38. Sun RQ, Wang HC, Wan Y, Jing Z, Luo F, Han JS, Wang Y. Suppression of neuropathic pain by peripheral electrical stimulation in rats: mu-opioid receptor and NMDA receptor implicated. Exp Neurol. 2004;187(1):23-9.
39. Choi BT, Kang J, Jo UB. Effects of electroacupuncture with different frequencies on spinal ionotropic glutamate receptor expression in complete Freund’s adjuvantinjected rat. Acta Histochem. 2005;107(1):67-76.
40. Ma C, Li CX, Yi JL, Yan LP. Effects of electroacupuncture on glutamate and aspartic acid contents in the dorsal root ganglion and spinal cord in rats with neuropathic pain. Zhen Ci Yan Jiu. 2008;33(4):250-4.
41. Park JH , Han JB , Kim SK , Park JH , Go DH , Sun B , Min BI. Spinal GABA receptors mediate the suppressive effect of electroacupuncture on cold allodynia in rats. Brain Res. 2010;1322:24-9.
42. Kim SK, Park JH, Bae SJ, Kim JH, Hwang BG, Min BI, Park DS, Na HS. Effects of electroacupuncture on cold allodynia in a rat model of neuropathic pain: mediation by spinal adrenergic and serotonergic receptors. Exp Neurol. 2005;195(2):430-6.
43. Qiao LN, Yang YS, Wang JY, Gao YH, Han YJ, Chen SP, Ji CF, Liu JL. Effects of electroacupuncture at “Futu” (LI18), etc. on expression of spinal 5-HT 1 AR mRNA, 5-HT 2 AR mRNA and protein in rats with neck incision pain. Zhen Ci Yan Jiu. 2011;36(6):391-6.
44. Chang FC, Tsai HY, Yu MC, Yi PL, Lin JG. The central serotonergic system mediates the analgesic effect of electroacupuncture on ZUSANLI (ST36) acupoints. J Biomed Sci. 2004;11(2):179-85.
45. Yoo YC, Oh JH, Kwon TD, Lee YK, Bai SJ. Analgesic mechanism of electroacupuncture in an arthritic pain model of rats: a neurotransmitter study. Yonsei Med J. 2011;52(6):1016-21.
46. 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(1-2):181-5.
47. 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(1-2):11-9.
48. Zhang Y, Zhang RX, Zhang M, Shen XY, Li A, Xin J, Ren K, Berman BM, Tan M, Lao L. Electroacupuncture inhibition of hyperalgesia in an inflammatory pain rat model: involvement of distinct spinal serotonin and norepinephrine receptor subtypes. Br J Anaesth. 2012;109(2):245-52.
49. Li A, Wang Y, Xin J, Lao L, Ren K, Berman BM, Zhang RX. Electroacupuncture suppresses hyperalgesia and spinal Fos expression by activating the descending inhibitory system. Brain Res. 2007;1186:171-9.
50 Wu MT, Sheen JM, Chuang KH, Yang P, Chin SL, Tsai CY, Chen CJ, Liao JR, Lai PH, Chu KA, Pan HB, Yang CF. Neuronal specificity of acupuncture response: a fMRI study with electroacupuncture. Neuroimage. 2002;16(4):1028-37.
51. Zhang WT, Jin Z, Huang J, Zhang L, Zeng YW, Luo F, Chen AC, Han JS. Modulation of cold pain in human brain by electric acupoint stimulation: evidence from fMRI. Neuroreport. 2003;14(12):1591-6.
52. Mayer DJ. Analgesia produced by electrical stimulation of the brain. Prog Neuro-psychopharmacol Biol Psychiatry. 1984;8(4-6):557-64.
53. Adams JE. Naloxone reversal of analgesia produced by brain stimulation in the human. Pain. 1976;2(2):161-6.
54. Zhang RX, Lao L, Wang X, Fan A, Wang L, Ren K, Berman BM. Electroacupuncture attenuates inflammation in a rat model. J Altern Complement Med. 2005;11(1):135-42.
55. Dallman MF, Akana SF, Strack AM, Scribner KS, Pecoraro N, La Fleur SE, Houshyar H, Gomez F. Chronic stress-induced effects of corticosterone on brain: direct and indirect. Ann N Y Acad Sci. 2004;1018:141-50.
56. Sarchielli P, Alberti A, Candeliere A, Floridi A, Capocchi G, Calabresi P. Glial cell line-derived neurotrophic factor and somatostatin levels in cerebrospinal fluid of patients affected by chronic migraine and fibromyalgia. Cephalalgia. 2006;26(4):409-15.
57. Kvorning N, Akeson J. Plasma adrenaline increases in anesthetized patients given electro-acupuncture before surgery. Pain Med. 2010;11(7):1126-31.
58. Millan MJ. Descending control of pain. Prog Neurobiol. 2002;66(6):355-474.
59. Binder W, Mousa SA, Sitte N, Kaiser M, Stein C, Schafer M. Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue. Eur J Neurosci. 2004;20(1):92-100.
60. Bliss TV, Cooke SF. Long-term potentiation and longterm depression: a clinical perspective. Clinics. 2011;66 Suppl 1:3-17.
61. Xing GG, Liu FY, Qu XX, Han JS, Wan Y. Long-term synaptic plasticity in the spinal dorsal horn and its modulation by electroacupuncture in rats with neuropathic pain. Exp Neurol. 2007;208(2):323-32.
62. Ma C, Feng KH, Yan LP. [Effects of electroacupuncture on long-term potentiation of synaptic transmission in spinal dorsal horn in rats with neuropathic pain]. Zhen Ci Yan Jiu. 2009;34(5):324-8.
63. Jeong HJ, Hong SH, Nam YC, Yang HS, Lyu YS, Baek SH, Lee HJ, Kim HM. The effect of acupuncture on proinflammatory cytokine production in patients with chronic headache: a preliminary report. Am J Chin Med. 2003;31(6):945-54.
64. Gao YH, Wang JY, Qiao LN, Chen SP, Tan LH, Xu QL, Liu JL. NK cells mediate the cumulative analgesic effect of electroacupuncture in a rat model of neuropathic pain. BMC Complement Altern Med. 2014;14:316.
65. Huang C, Hu ZP, Jiang SZ, Li HT, Han JS, Wan Y. CCK(B) receptor antagonist L365,260 potentiates the efficacy to and reverses chronic tolerance to electroacupuncture-induced analgesia in mice. Brain Res Bull. 2007;71(5):447-51.
66. Li M, Tjen ALSC, Guo ZL, Longhurst JC. Electroacupuncture modulation of reflex hypertension in rats: role of cholecystokinin octapeptide. Am J Physiol Regul Integr Comp Physiol. 2013;305(4):R404-13.
67. Chae Y, Park HJ, Hahm DH, Yi SH, Lee H. Individual differences of acupuncture analgesia in humans using cDNA microarray. J Physiol Sci. 2006;56(6):425-31.
68. Cao W, Deng Y, Dong X, Wang Y, Lu Z. Effects of electroacupuncture at different frequencies on the nociceptive response and central contents of GABA and glutamic acid in arthritic rats. Zhen Ci Yan Jiu. 1993;18(1):48-52.
69. Cheng LL, Ding MX, Xiong C, Zhou MY, Qiu ZY, Wang Q. Effects of electroacupuncture of different frequencies on the release profile of endogenous opioid peptides in the central nerve system of goats. Evid Based Complement Alternat Med. 2012;2012:476457.
70. Parmen V. Electroacupuncture analgesia in a rabbit ovariohysterectomy. J Acupunct Meridian Stud. 2014;7(1):15-24.
71. Park JY, Park JJ, Jeon S, Doo AR, Kim SN, Lee H, Chae Y, Maixner W, Lee H, Park HJ. From peripheral to central: the role of ERK signaling pathway in acupuncture analgesia. J Pain. 2014;15(5):535-49.
72. Han JS. Acupuncture analgesia: areas of consensus and controversy. Pain. 2011;152(3 Suppl):S41-8.
73. Lu TW, Wei IP, Liu YH, Hsu WC, Wang TM, Chang CF, Lin JG. Immediate effects of acupuncture on gait patterns in patients with knee osteoarthritis. Chin Med J. 2010;123(2):165-72.
74. Xu Q, Liu T, Chen S, Gao Y, Wang J, Qiao L, Liu J. Correlation between the cumulative analgesic effect of electroacupuncture intervention and synaptic plasticity of hypothalamic paraventricular nucleus neurons in rats with sciatica. Neural Regen Res. 2013;8(3):218-25.
75. Shokrani O, Saghaei M, Ashrafi F, Sadeghi A. Electrical stimulation of acupuncture points for analgesia during bone marrow aspiration and biopsy: A randomized double-blind placebo-controlled trial. Adv Biomed Res. 2014;3:125.
76. Li X, Zhou K, Zhang E, Qi Z, Sun W, Xu L, Cai Y, Wang R. Therapeutic effect of electroacupuncture, massage, and blocking therapy on external humeral epicondylitis. J Tradit Chin Med. 2014;34(3):261-6.
77. Weiss J, Quante S, Xue F, Muche R, Reuss-Borst M. Effectiveness and acceptance of acupuncture in patients with chronic low back pain: results of a prospective, randomized, controlled trial. J Altern Complement Med. 2013;19(12):935-41.
78. Stival RS, Cavalheiro PR, Stasiak CE, Galdino DT, Hoekstra BE, Schafranski MD. Acupuncture in fibromyalgia: a randomized, controlled study addressing the immediate pain response. Rev Bras Reumatol. 2014;54(6):431-6.
79. Tao W, Luo X, Cui B, Liang D, Wang C, Duan Y, Li X, Zhou S, Zhao M, Li Y, He Y, Wang S, Kelley KW, Jiang P, Liu Q. Practice of traditional Chinese medicine for psycho-behavioral intervention improves quality of life in cancer patients: A systematic review and meta-analysis. Oncotarget. 2015;6(37):39725-39.
80. Jiwlawat S, Durongphongtorn S. The Antinociceptive Effects of Tramadol on the Thermal Threshold Response in Cats. The Thai Journal of Veterinary Medicine. 2011;41(2):171-8.
81. Zaslawski CJ, Cobbin D, Lidums E, Petocz P. The impact of site specificity and needle manipulation on changes to pain pressure threshold following manual acupuncture: a controlled study. Complement Ther Med. 2003;11(1):11-21.
82. Bai L, Qin W, Tian J, Dong M, Pan X, Chen P,Dai J, Yang W, Liu Y. Acupuncture modulates spontaneous activities in the anticorrelated resting brain networks. Brain Res. 2009;1279:37-49.
83. Wang KF, Zhang LJ, Lu F, Lu YH, Yang CH. Can Ashi points stimulation have specific effects on shoulder pain? A systematic review of randomized controlled trials. Chinese J Integr Med. 2016;22(6):467-72.
84. Inoue M, Kitakoji H, Ishizaki N, Tawa M, Yano T, Katsumi Y, Kawakita K. Relief of low back pain immediately after acupuncture treatment--a randomised, placebo controlled trial. Acupunct Med. 2006;24(3):103-8.
85. Miao EY. Clinical critical qualitative evaluation of the selected randomized controlled trials in current acupuncture researches for low back pain. Zhong Xi Yi Jie He Xue Bao. 2010;8(12):1133-46.
86. Yi M, Zhang H, Lao L, Xing GG, Wan Y. Anterior cingulate cortex is crucial for contra- but not ipsi-lateral electro-acupuncture in the formalin-induced inflammatory pain model of rats. Mol Pain. 2011;7:61.