Peripheral receptors and neuromediators involved in the antihyperalgesic effects of acupuncture: a state-of-the-art review

Pflügers Archiv - European Journal of Physiology (2021)Cite this article

Abstract

The present study aims to describe state-of-the-art of preclinical studies that have investigated peripheral receptors and neuromediators involved in the antihyperalgesic effects of acupuncture. The PubMed, Scopus, and Web of Science databases were searched using the integrative review method. Preclinical articles that involved the study of peripheral receptors and neuromediators on the pain control effects of acupuncture in rats or mice were selected using a predefined search strategy. From this search, 456 articles were found, and 29 of them met the inclusion criteria of the study. The selected articles addressed the following peripheral receptors: opioid (n = 9), adenosine (n = 5), cannabinoid (n = 5), transient receptor potential vanilloid (TRPV) (n = 3), histamine (n = 2), adrenergic (n = 1), muscarinic (n = 1), corticotrophin-releasing factor (CRF) (n = 2), IL-1 (n = 1), and endothelin (n = 1) receptors. The peripheral neuromediators correlated with the peripheral pain control effect were as follows: opioid peptides (n = 4), adenosine (n = 3), histamine (n = 1), substance P (n = 1) calcitonin gene-related peptide (CGRP) (n = 1), anandamide (n = 1), nitric oxide (n = 1), and norepinephrine (n = 1). This review summarizes the methods used to investigate the peripheral effects of acupuncture and discusses the main findings on each family of receptors and neuromediators. Ten families of peripheral receptors and 8 types of neuromediators were correlated with the antihyperalgesic effects of acupuncture in preclinical studies. Considering the benefits of a better understanding of the role of peripheral receptors and neuromediators in the context pain management, the findings of the present study highlight the importance of deepening the exploration of the peripheral mechanisms of acupuncture.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

US$ 39.95

Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. 1.

    Abraham TS, Chen ML, Ma SX (2011) TRPV1 expression in acupuncture points: response to electroacupuncture stimulation. J Chem Neuroanat 41:129–136. https://doi.org/10.1016/j.jchemneu.2011.01.001

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Cairns BE (2009) Peripheral receptor targets for analgesia: novel approaches to pain management, vol 1. Wiley, New Jersey

    Google Scholar 

  3. 3.

    Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824. https://doi.org/10.1038/39807

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Ceccherelli F, Gagliardi G, Ruzzante L, Giron G (2002) Acupuncture modulation of capsaicin-induced inflammation: effect of intraperitoneal and local administration of naloxone in rats. A blinded controlled study. J Altern Complement Med 8:341–349. https://doi.org/10.1089/10755530260128032

    Article  PubMed  Google Scholar 

  5. 5.

    Chai W, Tai Y, Shao X, Liang Y, Zheng GQ, Wang P, Fang J, Liu B (2018) Electroacupuncture alleviates pain responses and inflammation in a rat model of acute gout arthritis. Evid Based Complement Alternat Med 2018:2598975–2598915. https://doi.org/10.1155/2018/2598975

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Chen JX, Ibe BO, Ma SX (2006) Nitric oxide modulation of norepinephrine production in acupuncture points. Life Sci 79:2157–2164. https://doi.org/10.1016/j.lfs.2006.07.009

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Chen L, Zhang J, Li F, Qiu Y, Wang L, Li YH, Shi J, Pan HL, Li M (2009) Endogenous anandamide and cannabinoid receptor-2 contribute to electroacupuncture analgesia in rats. J Pain 10:732–739. https://doi.org/10.1016/j.jpain.2008.12.012

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Chung WY, Zhang HQ, Zhang SP (2011) Peripheral muscarinic receptors mediate the anti-inflammatory effects of auricular acupuncture. Chin Med 6:3. https://doi.org/10.1186/1749-8546-6-3

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Dai Y (2016) TRPs and pain. Semin Immunopathol 38:277–291. https://doi.org/10.1007/s00281-015-0526-0

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–1949. https://doi.org/10.1126/science.1470919

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Dussor G, Koerber HR, Oaklander AL, Rice FL, Molliver DC (2009) Nucleotide signaling and cutaneous mechanisms of pain transduction. Brain Res Rev 60:24–35. https://doi.org/10.1016/j.brainresrev.2008.12.013

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Fang JQ, Jiang YL, Qiu SC, He XF, Huang L, Shen YF, Yin XH (2013) Involvement of peripheral beta endorphin and Mu, delta, kappa opioid receptors in electroacupuncture analgesia for prolonged inflammatory pain of rats. 11:375–383. https://doi.org/10.1177/1721727X1301100208

  13. 13.

    Fernandes MR, Lima NV, Rezende KS, Santos ICM, Silva IS, Guimarães RCA (2016) Animal models of obesity in rodents. An integrative review. Acta Cir Bras 31:840–844. https://doi.org/10.1590/s0102-865020160120000010

    Article  PubMed  Google Scholar 

  14. 14.

    Fijan S, Frauwallner A, Langerholc T, Krebs B, ter Haar (née Younes) JA, Heschl A, Mičetić Turk D, Rogelj I (2019) Efficacy of using probiotics with antagonistic activity against pathogens of wound infections: an integrative review of literature. Biomed Res Int 2019:2019–2021. https://doi.org/10.1155/2019/7585486

    CAS  Article  Google Scholar 

  15. 15.

    Fox A, Kesingland A, Gentry C, McNair K, Patel S, Urban L, James I (2001) The role of central and peripheral cannabinoid1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain. Pain 92:91–100. https://doi.org/10.1016/s0304-3959(00)00474-7

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Franco-Cereceda A, Henke H, Lundberg JM, Petermann JB, Hokfelt T, Fischer JA (1987) Calcitonin gene-related peptide (CGRP) in capsaicin-sensitive substance P-immunoreactive sensory neurons in animals and man: distribution and release by capsaicin. Peptides 8:399–410. https://doi.org/10.1016/0196-9781(87)90117-3

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Fraser GL, Gaudreau GA, Clarke PB, Ménard DP, Perkins MN (2000) Antihyperalgesic effects of δ opioid agonists in a rat model of chronic inflammation. Br J Pharmacol 129:1668–1672

    CAS  Article  Google Scholar 

  18. 18.

    Fujita T, Feng C, Takano T (2017) Presence of caffeine reversibly interferes with efficacy of acupuncture-induced analgesia. Sci Rep 7:3397. https://doi.org/10.1038/s41598-017-03542-x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Goldman N, Chen M, Fujita T, Xu Q, Peng W, Liu W, Jensen TK, Pei Y, Wang F, Han X, Chen JF, Schnermann J, Takano T, Bekar L, Tieu K, Nedergaard M (2010) Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci 13:883–888. https://doi.org/10.1038/nn.2562

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Huang M, Wang X, Xing B, Yang H, Sa Z, Zhang D, Yao W, Yin N, Xia Y, Ding G (2018) Critical roles of TRPV2 channels, histamine H1 and adenosine A1 receptors in the initiation of acupoint signals for acupuncture analgesia. Sci Rep 8:6523. https://doi.org/10.1038/s41598-018-24654-y

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Huang M, Zhang D, Sa ZY, Xie YY, Gu CL, Ding GH (2012) In adjuvant-induced arthritic rats, acupuncture analgesic effects are histamine dependent: potential reasons for acupoint preference in clinical practice. Evid Based Complement Alternat Med 2012:810512–810516. https://doi.org/10.1155/2012/810512

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Hurt JK, Zylka MJ (2012) PAPupuncture has localized and long-lasting antinociceptive effects in mouse models of acute and chronic pain. Mol Pain 8:28. https://doi.org/10.1186/1744-8069-8-28

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Hwang SW, Cho H, Kwak J, Lee SY, Kang CJ, Jung J, Cho S, Min KH, Suh YG, Kim D, Oh U (2000) Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances. Proc Natl Acad Sci U S A 97:6155–6160. https://doi.org/10.1073/pnas.97.11.6155

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Kashiba H, Ueda Y (1991) Acupuncture to the skin induces release of substance P and calcitonin gene-related peptide from peripheral terminals of primary sensory neurons in the rat. Am J Chin Med 19:189–197. https://doi.org/10.1142/S0192415X91000260

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Lang PM, Tracey DJ, Irnich D, Sippel W, Grafe P (2002) Activation of adenosine and P2Y receptors by ATP in human peripheral nerve. Naunyn Schmiedeberg's Arch Pharmacol 366:449–457. https://doi.org/10.1007/s00210-002-0624-0

    CAS  Article  Google Scholar 

  26. 26.

    Li QH, Xie WX, Li XP, Huang KT, Du ZH, Cong WJ, Zhou LH, Ye TS, Chen JF (2015) Adenosine A2A receptors mediate anti-inflammatory effects of electroacupuncture on synovitis in mice with collagen-induced arthritis. Evid Based Complement Alternat Med 2015:809560–809511. https://doi.org/10.1155/2015/809560

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Liao HY, Hsieh CL, Huang CP, Lin YW (2017) Electroacupuncture attenuates CFA-induced inflammatory pain by suppressing Nav1.8 through S100B, TRPV1, opioid, and adenosine pathways in mice. Sci Rep 7:42531. https://doi.org/10.1038/srep42531

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Liu LY (2015) A new type of signaling pathways as pilomotor lines along skin for transmitting acupuncture signals to produce acupuncture effects. Chin J Physiol 58:165–177. https://doi.org/10.4077/CJP.2015.BAD290

    Article  PubMed  Google Scholar 

  29. 29.

    Liu LY, Zhang H, Pan J, Pen A (2005) The existence of a linear system consisted of sympathetic endings in the rat’s skin. Anat Embryol 210:91–100. https://doi.org/10.1007/s00429-005-0007-7

    CAS  Article  Google Scholar 

  30. 30.

    Loeser JD, Treede RD (2008) The Kyoto protocol of IASP basic pain terminology. Pain 137:473–477. https://doi.org/10.1016/j.pain.2008.04.025

    Article  PubMed  Google Scholar 

  31. 31.

    Lund ILT (2015) Effects triggered in the periphery by acupuncture. Acupunct Relat Therap:24–34. https://doi.org/10.1016/j.arthe.2015.08.002

  32. 32.

    Ma SX (2003) Enhanced nitric oxide concentrations and expression of nitric oxide synthase in acupuncture points/meridians. J Altern Complement Med 9:207–215. https://doi.org/10.1089/10755530360623329

    Article  PubMed  Google Scholar 

  33. 33.

    Macpherson LJ, Geierstanger BH, Viswanath V, Bandell M, Eid SR, Hwang S, Patapoutian A (2005) The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin. Curr Biol 15:929–934. https://doi.org/10.1016/j.cub.2005.04.018

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Macpherson LJ, Hwang SW, Miyamoto T, Dubin AE, Patapoutian A, Story GM (2006) More than cool: promiscuous relationships of menthol and other sensory compounds. Mol Cell Neurosci 32:335–343

    CAS  Article  Google Scholar 

  35. 35.

    Mazzardo-Martins L, Salm DC, Winkelmann-Duarte EC, Ferreira JK, Ludtke DD, Frech KP, Belmonte LAO, Horewicz VV, Piovezan AP, Cidral-Filho FJ, More AOO, Martins DF (2018) Electroacupuncture induces antihyperalgesic effect through endothelin-B receptor in the chronic phase of a mouse model of complex regional pain syndrome type I. Pflugers Arch - Eur J Physiol 470:1815–1827. https://doi.org/10.1007/s00424-018-2192-2

    CAS  Article  Google Scholar 

  36. 36.

    McDonald JL, Cripps AW, Smith PK (2015) Mediators, receptors, and signalling pathways in the anti-inflammatory and antihyperalgesic effects of acupuncture. Evid Based Complement Alternat Med 2015:975632–975610. https://doi.org/10.1155/2015/975632

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, Pertwee RG, Griffin G, Bayewitch M, Barg J, Vogel Z (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90. https://doi.org/10.1016/0006-2952(95)00109-d

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Miller LK, Devi LA (2011) The highs and lows of cannabinoid receptor expression in disease: mechanisms and their therapeutic implications. Pharmacol Rev 63:461–470. https://doi.org/10.1124/pr.110.003491

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    More AO, Cidral-Filho FJ, Mazzardo-Martins L, Martins DF, Nascimento FP, Li SM, Santos AR (2013) Caffeine at moderate doses can inhibit acupuncture-induced analgesia in a mouse model of postoperative pain. J Caffe Res 3:143–148. https://doi.org/10.1089/jcr.2013.0014

    CAS  Article  Google Scholar 

  40. 40.

    More AO, Tesser CD, da Silva JB, Min LS (2016) Status and impact of acupuncture research: a bibliometric analysis of Global and Brazilian Scientific Output from 2000 to 2014. J Altern Complement Med 22:429–436. https://doi.org/10.1089/acm.2015.0281

    Article  PubMed  Google Scholar 

  41. 41.

    World Health Organization (1996) Acupuncture: review and analysis of reports on controlled clinical trials. http://whqlibdoc.who.int/publications/2002/9241545437.pdf

  42. 42.

    Pertwee RG (2009) Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br J Pharmacol 156:397–411. https://doi.org/10.1111/j.1476-5381.2008.00048.x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Quiroz-González S, Olivera Toro A, García Piceno Y, Jiménez-Estrada I, Fossion R (2019) Psychoneurobiomodulation: an emerging concept to understand the systemic effects of neurophysiological acupuncture. Longhua Chin Med 2

  44. 44.

    Quiroz-González S, Torres-Castillo S, López-Gómez RE, Estrada IJ (2017) Acupuncture points and their relationship with multireceptive fields of neurons. J Acupunct Meridian Stud 10(2):81–89.https://doi.org/10.1016/j.jams.2017.01.006

  45. 45.

    Sandkuhler J (2009) Models and mechanisms of hyperalgesia and allodynia. Physiol Rev 89:707–758. https://doi.org/10.1152/physrev.00025.2008

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Sawynok J (2007) Adenosine and ATP receptors. Handb Exp Pharmacol:309–328. https://doi.org/10.1007/978-3-540-33823-9_11

  47. 47.

    Scholz J, Woolf CJ (2002) Can we conquer pain? Nat Neurosci 5(Suppl):1062–1067. https://doi.org/10.1038/nn942

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Sekido R, Ishimaru K, Sakita M (2003) Differences of electroacupuncture-induced analgesic effect in normal and inflammatory conditions in rats. Am J Chin Med 31:955–965. https://doi.org/10.1142/S0192415X03001491

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Sekido R, Ishimaru K, Sakita M (2004) Corticotropin-releasing factor and interleukin-1β are involved in the electroacupuncture-induced analgesic effect on inflammatory pain elicited by carrageenan. Am J Chin Med 32:269–279. https://doi.org/10.1142/S0192415X04001928

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Siemens J, Zhou S, Piskorowski R, Nikai T, Lumpkin EA, Basbaum AI, King D, Julius D (2006) Spider toxins activate the capsaicin receptor to produce inflammatory pain. Nature 444:208–212. https://doi.org/10.1038/nature05285

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Silberstein M (2013) Is acupuncture “stimulation” a misnomer? A case for using the term “blockade”. BMC Complement Altern Med 13:68. https://doi.org/10.1186/1472-6882-13-68

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Souza MT, Silva MD, Carvalho R (2010) Revisão integrativa: o que é e como fazer. Integrative review: what is it? How to do it? Einstein (São Paulo) 8(1 Pt 1):102–106. https://doi.org/10.1590/s1679-45082010rw1134

    Article  Google Scholar 

  53. 53.

    Stein C (1995) The control of pain in peripheral tissue by opioids. N Engl J Med 332:1685–1690. https://doi.org/10.1056/NEJM199506223322506

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Stein C, Hassan AH, Lehrberger K, Giefing J, Yassouridis A (1993) Local analgesic effect of endogenous opioid peptides. Lancet 342:321–324. https://doi.org/10.1016/0140-6736(93)91471-w

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Su TF, Zhang LH, Peng M, Wu CH, Pan W, Tian B, Shi J, Pan HL, Li M (2011) Cannabinoid CB2 receptors contribute to upregulation of beta-endorphin in inflamed skin tissues by electroacupuncture. Mol Pain 7:98. https://doi.org/10.1186/1744-8069-7-98

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Su TF, Zhao YQ, Zhang LH, Peng M, Wu CH, Pei L, Tian B, Zhang J, Shi J, Pan HL, Li M (2012) Electroacupuncture reduces the expression of proinflammatory cytokines in inflamed skin tissues through activation of cannabinoid CB2 receptors. Eur J Pain 16:624–635. https://doi.org/10.1002/j.1532-2149.2011.00055.x

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, Yamashita A, Waku K (1995) 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 215:89–97. https://doi.org/10.1006/bbrc.1995.2437

    CAS  Article  Google Scholar 

  58. 58.

    Taguchi R, Taguchi T, Kitakoji H (2010) Involvement of peripheral opioid receptors in electroacupuncture analgesia for carrageenan-induced hyperalgesia. Brain Res 1355:97–103. https://doi.org/10.1016/j.brainres.2010.08.014

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Takano T, Chen X, Luo F, Fujita T, Ren Z, Goldman N, Zhao Y, Markman JD, Nedergaard M (2012) Traditional acupuncture triggers a local increase in adenosine in human subjects. J Pain 13:1215–1223. https://doi.org/10.1016/j.jpain.2012.09.012

    Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Tani E, Senba E, Kokumai S, Masuyama K, Ishikawa T, Tohyama M (1990) Histamine application to the nasal mucosa induces release of calcitonin gene-related peptide and substance P from peripheral terminals of trigeminal ganglion: a morphological study in the guinea pig. Neurosci Lett 112:1–6. https://doi.org/10.1016/0304-3940(90)90312-w

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Torres-Rosas R, Yehia G, Pena G, Mishra P, del Rocio T-BM, Moreno-Eutimio MA, Arriaga-Pizano LA, Isibasi A, Ulloa L (2014) Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat Med 20:291–295. https://doi.org/10.1038/nm.3479

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Vickers AJ, Vertosick EA, Lewith G, MacPherson H, Foster NE, Sherman KJ, Irnich D, Witt CM, Linde K, Acupuncture Trialists C (2018) Acupuncture for chronic pain: update of an individual patient data meta-analysis. J Pain 19:455–474. https://doi.org/10.1016/j.jpain.2017.11.005

    Article  PubMed  Google Scholar 

  63. 63.

    Wang Y, Gehringer R, Mousa SA, Hackel D, Brack A, Rittner HL (2014) CXCL10 controls inflammatory pain via opioid peptide-containing macrophages in electroacupuncture. PLoS One 9:e94696. https://doi.org/10.1371/journal.pone.0094696

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Wang Y, Hackel D, Peng F, Rittner HL (2013) Long-term antinociception by electroacupuncture is mediated via peripheral opioid receptors in free-moving rats with inflammatory hyperalgesia. Eur J Pain 17:1447–1457. https://doi.org/10.1002/j.1532-2149.2013.00325.x

    CAS  Article  PubMed  Google Scholar 

  65. 65.

    Wu SY, Chen WH, Hsieh CL, Lin YW (2014) Abundant expression and functional participation of TRPV1 at Zusanli acupoint (ST36) in mice: mechanosensitive TRPV1 as an “acupuncture-responding channel”. BMC Complement Altern Med 14:96. https://doi.org/10.1186/1472-6882-14-96

    Article  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Xu H, Blair NT, Clapham DE (2005) Camphor activates and strongly desensitizes the transient receptor potential vanilloid subtype 1 channel in a vanilloid-independent mechanism. J Neurosci 25:8924–8937. https://doi.org/10.1523/JNEUROSCI.2574-05.2005

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Yuan XC, Wang Q, Su W, Li HP, Wu CH, Gao F, Xiang HC, Zhu H, Lin LX, Hu XF, Cao J, Li JJ, Li M (2018) Electroacupuncture potentiates peripheral CB2 receptor-inhibited chronic pain in a mouse model of knee osteoarthritis. J Pain Res 11:2797–2808. https://doi.org/10.2147/JPR.S171664

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Zhang D, Spielmann A, Wang L, Ding G, Huang F, Gu Q, Schwarz W (2012) Mast-cell degranulation induced by physical stimuli involves the activation of transient-receptor-potential channel TRPV2. Physiol Res 61:113–124

    CAS  Article  Google Scholar 

  69. 69.

    Zhang GG, Yu C, Lee W, Lao L, Ren K, Berman BM (2005) Involvement of peripheral opioid mechanisms in electroacupuncture analgesia. Explore 1:365–371. https://doi.org/10.1016/j.explore.2005.06.006

    Article  PubMed  Google Scholar 

  70. 70.

    Zhang J, Chen L, Su T, Cao F, Meng X, Pei L, Shi J, Pan HL, Li M (2010) Electroacupuncture increases CB2 receptor expression on keratinocytes and infiltrating inflammatory cells in inflamed skin tissues of rats. J Pain 11:1250–1258. https://doi.org/10.1016/j.jpain.2010.02.013

    CAS  Article  PubMed  Google Scholar 

  71. 71.

    Zhang N, Oppenheim JJ (2005) Crosstalk between chemokines and neuronal receptors bridges immune and nervous systems. J Leukoc Biol 78:1210–1214. https://doi.org/10.1189/jlb.0405224

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Zhang R, Lao L, Ren K, Berman BM (2014) Mechanisms of acupuncture-electroacupuncture on persistent pain. Anesthesiology 120:482–503. https://doi.org/10.1097/ALN.0000000000000101

    Article  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Zhang ZJ, Wang XM, McAlonan GM (2012) Neural acupuncture unit: a new concept for interpreting effects and mechanisms of acupuncture. Evid Based Complement Alternat Med 2012:429412–429423. https://doi.org/10.1155/2012/429412

    Article  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Zhao YX, He W, Jing XH, Liu JL, Rong PJ, Ben H, Liu K, Zhu B (2012) Transcutaneous auricular vagus nerve stimulation protects endotoxemic rat from lipopolysaccharide-induced inflammation. Evid Based Complement Alternat Med 2012:627023–627010. https://doi.org/10.1155/2012/627023

    Article  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Zhao ZQ (2008) Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 85:355–375. https://doi.org/10.1016/j.pneurobio.2008.05.004

    Article  PubMed  Google Scholar 

  76. 76.

    Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sorgard M, Di Marzo V, Julius D, Hogestatt ED (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452–457. https://doi.org/10.1038/22761

    CAS  Article  PubMed  Google Scholar 

  77. 77.

    Zylka MJ (2010) Needling adenosine receptors for pain relief. Nat Neurosci 13:783–784. https://doi.org/10.1038/nn0710-783

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Li Shih Min for the critical review of the initial research project related to this article, Mayara Trento Salvador for the language correction and Dr. Mike Cummings for the critical review of the manuscript.

Author information

Affiliations

  1. Federal University of Santa Catarina , Florianópolis, Santa Catarina, Brazil

    Maísa Maria Spagnol Trento

  2. Integrative Medicine and Acupuncture Service, University Hospital, Federal University of Santa Catarina, R. Profa. Maria Flora Pausewang, s/n - Trindade, Florianópolis, Santa Catalina, CEP: 88036-800, Brazil

    Ari Ojeda Ocampo Moré

  3. Departament of Morphological Science, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil

    Elisa Cristiana Winkelmann Duarte

  4. Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil

    Daniel Fernandes Martins

  5. Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil

    Daniel Fernandes Martins

Authors
  1. Maísa Maria Spagnol Trento
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ari Ojeda Ocampo Moré
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elisa Cristiana Winkelmann Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniel Fernandes Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All the authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Maísa Maria Spagnol Trento e Ari Ojeda Ocampo Moré. All the authors commented on previous versions of the manuscript and approved the final manuscript.

Corresponding author

Correspondence to Ari Ojeda Ocampo Moré.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Trento, M.M.S., Moré, A.O.O., Duarte, E.C.W. et al. Peripheral receptors and neuromediators involved in the antihyperalgesic effects of acupuncture: a state-of-the-art review. Pflugers Arch - Eur J Physiol (2021). https://doi.org/10.1007/s00424-020-02503-0

Download citation

Keywords

  • Acupuncture
  • Electroacupuncture
  • Pain
  • Hyperalgesia
  • Peripheral receptors
  • Peripheral neuromediators acupuncture-induced analgesia
  • Rat
  • Mouse