Purinergic Signalling

, Volume 11, Issue 2, pp 161–169 | Cite as

P2X7 receptor of rat dorsal root ganglia is involved in the effect of moxibustion on visceral hyperalgesia

  • Shuangmei Liu
  • Qingming Shi
  • Qicheng Zhu
  • Ting Zou
  • Guilin Li
  • An Huang
  • Bing Wu
  • Lichao Peng
  • Miaomiao Song
  • Qin Wu
  • Qiuyu Xie
  • Weijian Lin
  • Wei Xie
  • Shiyao Wen
  • Zhedong Zhang
  • Qiulan Lv
  • Lifang Zou
  • Xi Zhang
  • Mofeng Ying
  • Guodong Li
  • Shangdong LiangEmail author
Original Article


Irritable bowel syndrome (IBS) and inflammatory bowel disease often display visceral hypersensitivity. Visceral nociceptors after inflammatory stimulation generate afferent nerve impulses through dorsal root ganglia (DRG) transmitting to the central nervous system. ATP and its activated-purinergic 2X7 (P2X7) receptor play an important role in the transmission of nociceptive signal. Purinergic signaling is involved in the sensory transmission of visceral pain. Moxibustion is a therapy applying ignited mugwort directly or indirectly at acupuncture points or other specific parts of the body to treat diseases. Heat-sensitive acupoints are the corresponding points extremely sensitive to moxa heat in disease conditions. In this study, we aimed to investigate the relationship between the analgesic effect of moxibustion on a heat-sensitive acupoint “Dachangshu” and the expression levels of P2X7 receptor in rat DRG after chronic inflammatory stimulation of colorectal distension. Heat-sensitive moxibustion at Dachangshu acupoint inhibited the nociceptive signal transmission by decreasing the upregulated expression levels of P2X7 mRNA and protein in DRG induced by visceral pain, and reversed the abnormal expression of glial fibrillary acidic protein (GFAP, a marker of satellite glial cells) in DRG. Consequently, abdominal withdrawal reflex (AWR) score in a visceral pain model was reduced, and the pain threshold was elevated. Therefore, heat-sensitive moxibustion at Dachangshu acupoint can produce a therapeutic effect on IBS via inhibiting the nociceptive transmission mediated by upregulated P2X7 receptor.


Moxibustion Dorsal root ganglia Purinergic 2X7 receptor Satellite glial cell Visceral hyperalgesia Colorectal distension 



Irritable bowel syndrome


Adenosine triphosphate


Colorectal distention


Visceral hyperalgesic model


Abdominal withdrawal reflex


Heat-sensitive moxibustion


Dorsal root ganglia


Phosphate-buffered saline




Glial fibrillary acidic protein


Sodium dodecylsulfate


Horseradish peroxidase


Satellite glial cells



This work was supported by the grants (Nos: 81171184, 31060139, 30860086, 30860333, 30660048, 81460200, and 81200853) from the National Natural Science Foundation of China, the grants (Nos: 2010BSA09500 and 20111BBG70009-1) from the Technology Pedestal and Society Development Project of Jiangxi Province, the grant (Nos.: 20142BAB205028 and 20142BAB215027) from the Natural Science Foundation of Jiangxi Province, the second batch of Jiangxi province “Gan Po excellence talent 555 project”-leading talent project, the grant (No: 2009CB522902) from National Basic Research Program of China, and the grants (No: GJJ13155 and GJJ14319) from the Educational Department of Jiangxi Province. GL’s research was supported by the NMRC of Singapore (NMRC/CIRG/1334/2012).

Conflict of interest

The authors declare that there are no conflict of interest.


  1. 1.
    Bradesi S, Herman J, Mayer EA (2008) Visceral analgesics: drugs with a great potential in functional disorders? Curr Opin Pharmacol 8:697–703CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Dunlop SP, Jenkins D, Spiller RC (2003) Distinctive clinical, psychological, and histological features of postinfective irritable bowel syndrome. Am J Gastroenterol 98:1578–1583CrossRefPubMedGoogle Scholar
  3. 3.
    Nozu T, Okumura T (2011) Visceral sensation and irritable bowel syndrome; with special reference to comparison with functional abdominal pain syndrome. J Gastroenterol Hepatol 26(Suppl 3):122–127CrossRefPubMedGoogle Scholar
  4. 4.
    Blackshaw LA, Brookes SJ, Grundy D, Schemann M (2007) Sensory transmission in the gastrointestinal tract. Neurogastroenterol Motil 19(Suppl 1):1–19CrossRefPubMedGoogle Scholar
  5. 5.
    Cervero F (1994) Sensory innervation of the viscera: peripheral basis of visceral pain. Physiol Rev 74:95–138PubMedGoogle Scholar
  6. 6.
    Burnstock G (2012) Discovery of purinergic signalling, the initial resistance and current explosion of interest. Brit J Pharmacol 167:238–255CrossRefGoogle Scholar
  7. 7.
    Burnstock G (2013) Purinergic mechanisms and pain—an update. Eur J Pharmacol 716:24–40CrossRefPubMedGoogle Scholar
  8. 8.
    Burnstock G, Krügel U, Abbracchio MP, Illes P (2011) Purinergic signalling: from normal behaviour to pathological brain function. Prog Neurobiol 95:229–274CrossRefPubMedGoogle Scholar
  9. 9.
    Kong FJ, Liu SM, Xu CS, Liu J, Li GD, Li GL, Gao Y, Lin H, Tu GH, Peng HY, Qiu SY, Fan B, Zhu QC, Yu SC, Zheng CR, Liang S (2013) Electrophysiological studies of upregulated P2X7 receptors in rat superior cervical ganglia after myocardial ischemic injury. Neurochem Int 63:230–237CrossRefPubMedGoogle Scholar
  10. 10.
    Liu J, Li GL, Peng HY, Tu GH, Kong FJ, Li GL, Liu SM, Gao Y, Xu H, Qiu SY, Fan B, Zhu QC, Yu SC, Zheng CR, Wu B, Li GD, Liang SD (2013) Sensory-sympathetic coupling in superior cervical ganglia after myocardial ischemic injury facilitates sympathoexcitatory action via P2X7 receptor. Purinergic Signal 9:463–479CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Tu GH, Li GL, Peng HY, Hu J, Liu J, Kong FJ, Liu SM, Gao Y, Xu CS, Xu XL, Qiu SY, Fan B, Zhu QC, Yu SC, Zheng CR, Wu B, Peng LC, Song MM, Wu Q, Liang SD (2013) P2X7 inhibition in stellate ganglia prevents the increased sympathoexcitatory reflex via sensory-sympathetic coupling induced by myocardial ischemic injury. Brain Res Bull 96:71–85CrossRefPubMedGoogle Scholar
  12. 12.
    Xu H, Wu B, Jiang FQ, Xiong SH, Zhang BP, Li GL, Liu SM, Gao Y, Xu CS, Tu GH, Peng HY, Liang SD, Xiong HG (2013) High fatty acids modulate P2X7 expression and IL-6 release via the p38 MAPK pathway in PC12 cells. Brain Res Bull 94:63–70CrossRefPubMedGoogle Scholar
  13. 13.
    Zhang J, Li X, Gao Y, Guo GH, Xu CS, Li GL, Liu SM, Tu GH, Peng HY, Qiu SY, Fan B, Zhu QC, Yu SC, Zheng CR, Liang SD (2013) Effects of puerarin on the inflammatory role of burn-related procedural pain mediated by P2X7 receptors. Burn 39:610–618CrossRefGoogle Scholar
  14. 14.
    Burnstock G (2009) Purinergic mechanosensory transduction and visceral pain. Mol Pain 5:69CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Marques CC, Castelo-Branco MT, Pacheco RG, Buongusto F, do Rosário A Jr, Schanaider A, Coutinho-Silva R, de Souza HSP (2014) Prophylactic systemic P2X7 receptor blockade prevents experimental colitis. Biochim Biophys Acta 1842:65–78CrossRefPubMedGoogle Scholar
  16. 16.
    Liu B, Hu YM, Tenner SM (2000) A randomized controlled trial of acupuncture for irritable bowel syndrome. Am J Gastroenterol 95:2498CrossRefGoogle Scholar
  17. 17.
    Zhou E, Liu H, Wu H, Shi Y, Wang X, Tan L, Yao L, Zhong Y, Jiang Y, Zhang L (2009) Suspended moxibustion relieves chronic visceral hyperalgesia via serotonin pathway in the colon. Neurosci Lett 451:144–147CrossRefPubMedGoogle Scholar
  18. 18.
    Kim SY, Chae Y, Lee SM, Lee H, Park HJ (2011) The effectiveness of moxibustion: an overview during 10 years. Evid-Based Compl Alt 19 pp. [Article ID 306515]Google Scholar
  19. 19.
    Xiong X, Liu W, Yang X, Feng B, Wang J (2014) Moxibustion for essential hypertension. Complement Ther Med 22:187–195CrossRefPubMedGoogle Scholar
  20. 20.
    Gao XY, Chong CY, Zhang SP, Cheng KWE, Zhu B (2012) Temperature and safety profiles of needle-warming techniques in acupuncture and moxibustion. Evid-Based Compl Alt 6 pp. [Article ID 168393]Google Scholar
  21. 21.
    Lee MS, Kang JW, Ernst E (2010) Does moxibustion work? An overview of systematic reviews. BMC Res Notes 3:284CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Lin JG, Chen YH (2011) The mechanistic studies of acupuncture and moxibustion in Taiwan. Chin J Integr Med 17:177–186CrossRefPubMedGoogle Scholar
  23. 23.
    Chen RX, Kang MF (2006) A new therapy: moxibustion on heat-sensitive acupoint. People’s Medical Publishing House, BeijingGoogle Scholar
  24. 24.
    Hu D, Kang M, Xiong J, Deng P (2012) Irritable bowel syndrome with diarrhea (1BS-D) treated with moxibustion on heat-sensitive acupoints: a randomized controlled trial. World J Acupunct-Moxibustion (WJAM) 22:1–4CrossRefGoogle Scholar
  25. 25.
    Al-Chaer ED, Kawasaki M, Pasricha PJ (2000) A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. Gastroenterology 119:1276–1285CrossRefPubMedGoogle Scholar
  26. 26.
    Huang LX, Zhao JS, Han Z (2006) Nomenclature and location of acupoints. GB/T 12346–2006. China Zhijian Publishing House 11, BeijingGoogle Scholar
  27. 27.
    Sun YJ, Wu YC, Zhang JF, Zhang P, Tang ZY (2013) Effects of electroacupuncture on muscle state and electrophysiological changes in rabbits with lumbar nerve root compression. Chin J Integr Med 19:446–452CrossRefPubMedGoogle Scholar
  28. 28.
    Chen RX, Chen MR, Kang MF (2009) Practical reading of heat-sensitization moxibustion. People’s Medical Publishing House 4, BeijingGoogle Scholar
  29. 29.
    Xiao AJ, Chen RX, Kang MF, Tan SH (2012) Heat-sensitive moxibustion attenuates the inflammation after focal cerebral ischemia/reperfusion injury. Neural Regen Res 7:2600–2606PubMedCentralPubMedGoogle Scholar
  30. 30.
    Hucho T, Levine JD (2007) Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron 55(3):365–376CrossRefPubMedGoogle Scholar
  31. 31.
    Donnelly-Roberts DL, Jarvis MF (2007) Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states. Brit J Pharmacol 151:571–579CrossRefGoogle Scholar
  32. 32.
    Skaper SD, Debetto P, Giusti P (2010) The P2X7 purinergic receptor: from physiology to neurological disorders. FASEB J 24:337–345CrossRefPubMedGoogle Scholar
  33. 33.
    Sperlagh B, Vizi ES, Wirkner K, Illes P (2006) P2X7 receptors in the nervous system. Prog Neurobiol 78:327–346CrossRefPubMedGoogle Scholar
  34. 34.
    Antonioli L, Colucci R, Pellegrini C, Giustarini G, Tuccori M, Blandizzi C, Fornai M (2013) The role of purinergic pathways in the pathophysiology of gut diseases: pharmacological modulation and potential therapeutic applications. Pharmacol Ther 139:157–188CrossRefPubMedGoogle Scholar
  35. 35.
    Kurashima Y, Amiya T, Nochi T, Fujisawa K, Haraguchi T, Iba H, Tsutsui H, Sato S, Nakajima S, Iijima H, Kubo M, Kunisawa J, Kiyono H (2012) Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors. Nat Commun 3:1034CrossRefPubMedCentralPubMedGoogle Scholar
  36. 36.
    Roberts JA, Lukewich MK, Sharkey KA, Furness JB, Mawe GM, Lomax AE (2012) The roles of purinergic signaling during gastrointestinal inflammation. Curr Opin Pharmacol 12:659–666CrossRefPubMedCentralPubMedGoogle Scholar
  37. 37.
    Dublin P, Hanani M (2007) Satellite glial cells in sensory ganglia: their possible contribution to inflammatory pain. Brain Behav Immun 21:592–598CrossRefPubMedGoogle Scholar
  38. 38.
    Hanani M (2005) Satellite glial cells in sensory ganglia: from form to function. Brain Res Rev 48:457–476CrossRefPubMedGoogle Scholar
  39. 39.
    Pannese E (2010) The structure of the perineuronal sheath of satellite glial cells (SGCs) in sensory ganglia. Neuron Glia Biol 6:3–10CrossRefPubMedGoogle Scholar
  40. 40.
    Takeda M, Takahashi M, Matsumoto S (2009) Contribution of the activation of satellite glia in sensory ganglia to pathological pain. Neurosci Biobehav R 33:784–792CrossRefGoogle Scholar
  41. 41.
    Jarvis MF (2010) The neural-glial purinergic receptor ensemble in chronic pain states. Trends Neurosci 33:48–57CrossRefPubMedGoogle Scholar
  42. 42.
    Kushnir R, Cherkas PS, Hanani M (2011) Peripheral inflammation upregulates P2X receptor expression in satellite glial cells of mouse trigeminal ganglia: a calcium imaging study. Neuropharmacology 61:739–746CrossRefPubMedGoogle Scholar
  43. 43.
    Liu FY, Sun YN, Wang FT, Li Q, Su L, Zhao ZF, Meng XL, Zhao H, Wu X, Sun Q, Xing GG, Wan Y (2012) Activation of satellite glial cells in lumbar dorsal root ganglia contributes to neuropathic pain after spinal nerve ligation. Brain Res 1427:65–77CrossRefPubMedGoogle Scholar
  44. 44.
    Zhou EH, Wang XM, Ding GH, Wu HG, Qi L, Liu HR, Zhang SJ (2011) Suspended moxibustion relieves chronic visceral hyperalgesia and decreases hypothalamic corticotropin-releasing hormone levels. World J Gastroenterol 17:662–665CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Shuangmei Liu
    • 1
  • Qingming Shi
    • 4
  • Qicheng Zhu
    • 1
  • Ting Zou
    • 1
  • Guilin Li
    • 1
  • An Huang
    • 5
  • Bing Wu
    • 1
  • Lichao Peng
    • 1
  • Miaomiao Song
    • 1
  • Qin Wu
    • 1
  • Qiuyu Xie
    • 2
  • Weijian Lin
    • 2
  • Wei Xie
    • 2
  • Shiyao Wen
    • 2
  • Zhedong Zhang
    • 2
  • Qiulan Lv
    • 1
  • Lifang Zou
    • 1
  • Xi Zhang
    • 1
  • Mofeng Ying
    • 1
  • Guodong Li
    • 6
  • Shangdong Liang
    • 1
    • 3
    Email author
  1. 1.Department of Physiology, Medical SchoolNanchang UniversityNanchangPeople’s Republic of China
  2. 2.2012 Grade of Department of Clinical MedicineNanchang UniversityNanchangPeople’s Republic of China
  3. 3.Institute of Life ScienceNanchang UniversityNanchangPeople’s Republic of China
  4. 4.Orthopedics Department of Second Affiliated Hospital, Medical SchoolNanchang UniversityNanchangPeople’s Republic of China
  5. 5.Jiangxi University of Finance and EconomicsNanchangPeople’s Republic of China
  6. 6.Department of Clinical ResearchSingapore General HospitalSingaporeSingapore

Personalised recommendations