Digestive Diseases and Sciences

, Volume 51, Issue 8, pp 1493–1500 | Cite as

Electroacupuncture Elicits Dual Effects: Stimulation of Delayed Gastric Emptying and Inhibition of Accelerated Colonic Transit Induced by Restraint Stress in Rats

  • Masahiro Iwa
  • Yukiomi Nakade
  • Theodore N. Pappas
  • Toku Takahashi
Original Paper


Acupuncture has been used for treating functional gastrointestinal (GI) disorders. Animal studies have demonstrated that acupuncture antagonized various stress-induced responses. We investigated the effects of electroacupuncture (EA) at ST-36 (Zusanli; lower limb) on stress-induced alteration of GI motor activities. Solid gastric emptying was significantly delayed by restraint stress (29.6±2.4%; n=7) compared to that of controls (60.0±2.5%; n=8). Delayed gastric emptying was significantly improved by EA at ST-36 (47.2±1.8%). Intracisternal (IC) injection of corticotropin releasing factor (CRF; 1 μg) delayed gastric emptying to 25.4±3.1%, which was also improved by EA at ST-36, to 53.0±7.1% (n=8). The stimulatory effect of EA on stress-induced delayed gastric emptying was abolished by atropine (17.6±1.9%) but not by guanethidine (42.2±2.3%). Colonic transit was significantly accelerated by restraint stress (GC=7.2±0.3; n=8) compared to that of controls (GC=5.2±0.2; n=8). Accelerated colonic transit was significantly reduced by EA at ST-36 (GC=4.9±0.3). IC injection of CRF accelerated colonic transit (GC=6.9±0.2), which was also normalized by EA at ST-36 (GC=4.7±0.2). The inhibitory effect of EA on stress-induced acceleration of colonic transit was not affected by guanethidine (GC=4.6±0.3). In conclusion, EA at ST-36 showed dual effects: stimulation of stress-induced delayed gastric emptying and inhibition of stress-induced acceleration of colonic transit. The stimulatory effect of EA on stress-induced delayed gastric emptying is mediated via cholinergic pathways. The inhibitory effect of EA on stress-induced acceleration of colonic transit is independent of the sympathetic pathway.


Colonic transit Corticotropin releasing factor Electroacupuncture Gastric emptying Restraint stress 



This study was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases (DK55808; T.T.) and the National Center for Complementary and Alternative Medicine (AT 001588; T.T.).


  1. 1.
    Monnikes H, Tebbe JJ, Hildebrandt M, Arck P, Osmanoglou E, Rose M, Klapp B, Wiedenmann B, Heymann-Monnikes I (2001) Role of stress in functional gastrointestinal disorders. Evidence for stress-induced alterations in gastrointestinal motility and sensitivity. Dig Dis 19:201–211PubMedCrossRefGoogle Scholar
  2. 2.
    Holtmann G, Kutscher SU, Haag S, Langkafel M, Heuft G, Neufang-Hueber J, Goebell H, Senf W, Talley NJ (2004) Clinical presentation and personality factors are predictors of the response to treatment in patients with functional dyspepsia; a randomized, double-blind placebo-controlled crossover study. Dig Dis Sci 49:672–679PubMedCrossRefGoogle Scholar
  3. 3.
    Feinle-Bisset C, Andrews JM (2003) Treatment of functional dyspepsia. Curr Treat Options Gastroenterol 6:289–297PubMedCrossRefGoogle Scholar
  4. 4.
    Fukudo S, Suzuki J (1987) Colonic motility, autonomic function, and gastrointestinal hormones under psychological stress on irritable bowel syndrome. Tohoku J Exp Med 151:373–385PubMedCrossRefGoogle Scholar
  5. 5.
    Barone FC, Deegan JF, Price WJ, Fowler PJ, Fondacaro JD, Ormsbee HS 3rd (1990) Cold-restraint stress increases rat fecal pellet output and colonic transit. Am J Physiol 258:G329–G337PubMedGoogle Scholar
  6. 6.
    Monnikes H, Schmidt BG, Tache Y (1993) Psychological stress-induced accelerated colonic transit in rats involves hypothalamic corticotropin-releasing factor. Gastroenterology 104:716–723PubMedGoogle Scholar
  7. 7.
    Gue M, Junien JL, Bueno L (1991) Conditioned emotional response in rats enhances colonic motility through the central release of corticotropin-releasing factor. Gastroenterology 100:964–970PubMedGoogle Scholar
  8. 8.
    Tache Y, Martinez V, Wang L, Million M (2004) CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome. Br J Pharmacol 141:1321–1330PubMedCrossRefGoogle Scholar
  9. 9.
    Martinez V, Tache Y (2001) Role of CRF receptor 1 in central CRF-induced stimulation of colonic propulsion in rats. Brain Res 893:29–35PubMedCrossRefGoogle Scholar
  10. 10.
    Martinez V, Wang L, Rivier J, Grigoriadis D, Tache Y (2004) Central CRF, urocortins and stress increase colonic transit via CRF1 receptors while activation of CRF2 receptors delays gastric transit in mice. J Physiol 556:221–234PubMedCrossRefGoogle Scholar
  11. 11.
    Nakade Y, Tsuchida D, Fukuda H, Iwa M, Pappas TN, Takahashi T (2005) Restraint stress delays solid gastric emptying via a central CRF and peripheral sympathetic neuron in rats. Am J Physiol Regul Integr Comp Physiol 288:R427–R432PubMedGoogle Scholar
  12. 12.
    Tache Y, Martinez V, Million M, Rivier J (1999) Corticotropin-releasing factor and the brain-gut motor response to stress. Can J Gastroenterol 13(Suppl A):18A–25APubMedGoogle Scholar
  13. 13.
    Maillot C, Million M, Wei JY, Gauthier A, Tache Y (2000) Peripheral corticotropin-releasing factor and stress-stimulated colonic motor activity involve type 1 receptor in rats. Gastroenterology 119:1569–1579PubMedCrossRefGoogle Scholar
  14. 14.
    Pothoulakis C, Castagliuolo I, Leeman SE (1998) Neuroimmune mechanisms of intestinal responses to stress. Role of corticotropin-releasing factor and neurotensin. Ann NY Acad Sci 840:635–648Google Scholar
  15. 15.
    Martinez V, Rivier J, Wang L, Tache Y (1997) Central injection of a new corticotropin-releasing factor (CRF) antagonist, astressin, blocks CRF- and stress-related alterations of gastric and colonic motor function. J Pharmacol Exp Ther 280:754–760PubMedGoogle Scholar
  16. 16.
    Williams CL, Peterson JM, Villar RG, Burks TF (1987) Corticotropin-releasing factor directly mediates colonic responses to stress. Am J Physiol 253:G582–G586PubMedGoogle Scholar
  17. 17.
    Monnikes H, Schmidt BG, Raybould HE, Tache Y (1992) CRF in the paraventricular nucleus mediates gastric and colonic motor response to restraint stress. Am J Physiol 262:G137–G143PubMedGoogle Scholar
  18. 18.
    Hurtak JJ (2002) An overview of acupuncture medicine. J Altern Complement Med 8:535–538PubMedCrossRefGoogle Scholar
  19. 19.
    Campbell A (2002) The origins of acupuncture. Acupunct Med 20:141PubMedCrossRefGoogle Scholar
  20. 20.
    National Institutes of Health (1997) Acupuncture. NIH Consens Statement 15:1–34Google Scholar
  21. 21.
    Morey SS (1998) NIH issues consensus statement on acupuncture. Am Fam Phys 57:2545–2546Google Scholar
  22. 22.
    Kunze M, Seidel HJ, Stube G (1990) [Comparative studies of the effectiveness of brief psychotherapy, acupuncture and papaverin therapy in patients with irritable bowel syndrome]. Z Gesamte Inn Med 45:625–627PubMedGoogle Scholar
  23. 23.
    Chan J, Carr I, Mayberry JF (1997) The role of acupuncture in the treatment of irritable bowel syndrome: a pilot study. Hepatogastroenterology 44:1328–1330PubMedGoogle Scholar
  24. 24.
    Fireman Z, Segal A, Kopelman Y, Sternberg A, Carasso R (2001) Acupuncture treatment for irritable bowel syndrome. A double-blind controlled study. Digestion 64:100–103Google Scholar
  25. 25.
    Diehl DL (1999) Acupuncture for gastrointestinal and hepatobiliary disorders. J Altern Complement Med 5:27–45PubMedCrossRefGoogle Scholar
  26. 26.
    Klauser AG, Rubach A, Bertsche O, Muller-Lissner SA (1993) Body acupuncture: effect on colonic function in chronic constipation. Z Gastroenterol 31:605–608PubMedGoogle Scholar
  27. 27.
    Chen K, Zhou S, Zhao Y (1992) Auriculoacupuncture therapy—A traditional Chinese method of treatment. J Tradit Chin Med 12:308–310PubMedGoogle Scholar
  28. 28.
    Broide E, Pintov S, Portnoy S, Barg J, Klinowski E, Scapa E (2001) Effectiveness of acupuncture for treatment of childhood constipation. Dig Dis Sci 46:1270–1275PubMedCrossRefGoogle Scholar
  29. 29.
    Zhu Z, Li H, Chen L, Wang G, Kan C (2003) Acupuncture treatment of habitual constipation. J Tradit Chin Med 23:133PubMedGoogle Scholar
  30. 30.
    Su Z (1992) Acupuncture treatment of infantile diarrhea: a report of 1050 cases. J Tradit Chin Med 12:120–121PubMedGoogle Scholar
  31. 31.
    Anastasi JK, McMahon DJ (2003) Testing strategies to reduce diarrhea in persons with HIV using traditional Chinese medicine: acupuncture and moxibustion. J Assoc Nurses AIDS Care 14:28–40PubMedCrossRefGoogle Scholar
  32. 32.
    Burgmann T, Rawsthorne P, Bernstein CN (2004) Predictors of alternative and complementary medicine use in inflammatory bowel disease: Do measures of conventional health care utilization relate to use? Am J Gastroenterol 99:889–893PubMedCrossRefGoogle Scholar
  33. 33.
    Chen XH, Geller EB, Adler MW (1996) Electrical stimulation at traditional acupuncture sites in periphery produces brain opioid-receptor-mediated antinociception in rats. J Pharmacol Exp Ther 277:654–660PubMedGoogle Scholar
  34. 34.
    Han JS (2003) Acupuncture: neuropeptide release produced by electrical stimulation of different frequencies. Trends Neurosci 26:17–22PubMedCrossRefGoogle Scholar
  35. 35.
    Han JS, Terenius L (1982) Neurochemical basis of acupuncture analgesia. Annu Rev Pharmacol Toxicol 22:193–220PubMedCrossRefGoogle Scholar
  36. 36.
    Hahm ET, Lee JJ, Lee WK, Bae HS, Min BI, Cho YW (2004) Electroacupuncture enhancement of natural killer cell activity suppressed by anterior hypothalamic lesions in rats. Neuroimmunomodulation 11:268–272PubMedCrossRefGoogle Scholar
  37. 37.
    Yu Y, Kasahara T, Sato T, Asano K, Yu G, Fang J, Guo S, Sahara M, Hisamitsu T (1998) Role of endogenous interferon-gamma on the enhancement of splenic NK cell activity by electroacupuncture stimulation in mice. J Neuroimmunol 90:176–186PubMedCrossRefGoogle Scholar
  38. 38.
    Wu B (1995) [Effect of acupuncture on the regulation of cell-mediated immunity in the patients with malignant tumors]. Zhen Ci Yan Jiu 20:67–71PubMedGoogle Scholar
  39. 39.
    Li L, Yin-Xiang C, Hong X, Peng L, Da-Nian Z (2001) Nitric oxide in vPAG mediates the depressor response to acupuncture in stress-induced hypertensive rats. Acupunct Electrother Res 26:165–170PubMedGoogle Scholar
  40. 40.
    Yang CH, Lee BB, Jung HS, Shim I, Roh PU, Golden GT (2002) Effect of electroacupuncture on response to immobilization stress. Pharmacol Biochem Behav 72:847–855PubMedCrossRefGoogle Scholar
  41. 41.
    Han SH, Yoon SH, Cho YW, Kim CJ, Min BI (1999) Inhibitory effects of electroacupuncture on stress responses evoked by tooth-pulp stimulation in rats. Physiol Behav 66:217–222PubMedCrossRefGoogle Scholar
  42. 42.
    Liao YY, Seto K, Saito H, Fujita M, Kawakami M (1980) Effects of acupuncture on adrenocortical hormone production. (II) Effect of acupuncture on the response of adrenocortical hormone production to stress. Am J Chin Med 8:160–166Google Scholar
  43. 43.
    Shen D, Liu B, Wi D, Zhang F, Chen Y (1994) [Effects of electroacupuncture on central and peripheral monoamine neurotransmitter in the course of protecting rat stress peptic ulcer]. Zhen Ci Yan Jiu 19:51–54PubMedGoogle Scholar
  44. 44.
    Xiang L, Zhu F, Ma Y, Weng E, Tang G (1993) [Influences of acupuncture on gastroduodenal mucosal lesion and electrical changing induced by stress in rats]. Zhen Ci Yan Jiu 18:53–57PubMedGoogle Scholar
  45. 45.
    Tatewaki M, Harris M, Uemura K, Ueno T, Hoshino E, Shiotani A, Pappas TN, Takahashi T (2003) Dual effects of acupuncture on gastric motility in conscious rats. Am J Physiol Regul Integr Comp Physiol 285:R862–R872PubMedGoogle Scholar
  46. 46.
    Ishiguchi T, Amano T, Matsubayashi H, Tada H, Fujita M, Takahashi T (2001) Centrally administered neuropeptide Y delays gastric emptying via Y2 receptors in rats. Am J Physiol Regul Integr Comp Physiol 281:R1522–R1530PubMedGoogle Scholar
  47. 47.
    Ishiguchi T, Tada H, Nakagawa K, Yamamura T, Takahashi T (2002) Hyperglycemia impairs antro-pyloric coordination and delays gastric emptying in conscious rats. Auton Neurosci 95:112–120PubMedCrossRefGoogle Scholar
  48. 48.
    Fukumoto S, Tatewaki M, Yamada T, Fujimiya M, Mantyh C, Voss M, Eubanks S, Harris M, Pappas TN, Takahashi T (2003) Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. Am J Physiol Regul Integr Comp Physiol 284:R1269–R1276PubMedGoogle Scholar
  49. 49.
    Martinez V, Wang L, Million M, Rivier J, Tache Y (2004) Urocortins and the regulation of gastrointestinal motor function and visceral pain. Peptides 25:1733–1744PubMedCrossRefGoogle Scholar
  50. 50.
    Tsukada F, Nagura Y, Abe S, Sato N, Ohkubo Y (2003) Effect of restraint and footshock stress and norepinephrine treatment on gastric emptying in rats. Biol Pharm Bull 26:368–370PubMedCrossRefGoogle Scholar
  51. 51.
    Mistiaen W, Blockx P, Van Hee R, Bortier H, Harrisson F (2002) The effect of stress on gastric emptying rate measured with a radionuclide tracer. Hepatogastroenterology 49:1457–1460PubMedGoogle Scholar
  52. 52.
    Lenz HJ, Burlage M, Raedler A, Greten H (1988) Central nervous system effects of corticotropin-releasing factor on gastrointestinal transit in the rat. Gastroenterology 94:598–602PubMedGoogle Scholar
  53. 53.
    Enck P, Merlin V, Erckenbrecht JF, Wienbeck M (1989) Stress effects on gastrointestinal transit in the rat. Gut 30:455–459PubMedCrossRefGoogle Scholar
  54. 54.
    Muraoka M, Mine K, Kubo C (1998) A study of intestinal dysfunction induced by restraint stress in rats. Scand J Gastroenterol 33:806–810PubMedCrossRefGoogle Scholar
  55. 55.
    Kalin NH, Takahashi LK, Chen FL (1994) Restraint stress increases corticotropin-releasing hormone mRNA content in the amygdala and paraventricular nucleus. Brain Res 656:182–186PubMedCrossRefGoogle Scholar
  56. 56.
    Liu JH, Yan J, Yi SX, Chang XR, Lin YP, Hu JM (2004) Effects of electroacupuncture on gastric myoelectric activity and substance P in the dorsal vagal complex of rats. Neurosci Lett 356:99–102PubMedCrossRefGoogle Scholar
  57. 57.
    Sato A, Sato Y, Suzuki A, Uchida S (1993) Neural mechanisms of the reflex inhibition and excitation of gastric motility elicited by acupuncture-like stimulation in anesthetized rats. Neurosci Res 18:53–62PubMedCrossRefGoogle Scholar
  58. 58.
    Chang CS, Chou JW, Wu CY, Chang YH, Ko CW, Chen GH (2002) Atropine-induced gastric dysrhythmia is not normalized by electroacupuncture. Dig Dis Sci 47:2466–2472PubMedCrossRefGoogle Scholar
  59. 59.
    Ouyang H, Yin J, Wang Z, Pasricha PJ, Chen JD (2002) Electroacupuncture accelerates gastric emptying in association with changes in vagal activity. Am J Physiol Gastrointest Liver Physiol 282:G390–G396PubMedGoogle Scholar
  60. 60.
    Monnikes H, Raybould HE, Schmidt B, Tache Y (1993) CRF in the paraventricular nucleus of the hypothalamus stimulates colonic motor activity in fasted rats. Peptides 14:743–747PubMedCrossRefGoogle Scholar
  61. 61.
    Monnikes H, Schmidt BG, Tebbe J, Bauer C, Tache Y (1994) Microinfusion of corticotropin releasing factor into the locus coeruleus/subcoeruleus nuclei stimulates colonic motor function in rats. Brain Res 644:101–108PubMedCrossRefGoogle Scholar
  62. 62.
    Million M, Wang L, Martinez V, Tache Y (2000) Differential Fos expression in the paraventricular nucleus of the hypothalamus, sacral parasympathetic nucleus and colonic motor response to water avoidance stress in Fischer and Lewis rats. Brain Res 877:345–353PubMedCrossRefGoogle Scholar
  63. 63.
    Valentino RJ, Page ME, Luppi PH, Zhu Y, Van Bockstaele E, Aston-Jones G (1994) Evidence for widespread afferents to Barrington’s nucleus, a brainstem region rich in corticotropin-releasing hormone neurons. Neuroscience 62:125–143PubMedCrossRefGoogle Scholar
  64. 64.
    Lewis TD (1999) Morphine and gastroduodenal motility. Dig Dis Sci 44:2178–2186PubMedCrossRefGoogle Scholar
  65. 65.
    Qian LW, Lin YP (1993) [Effect of electroacupuncture at zusanli (ST36) point in regulating the pylorus peristaltic function]. Zhongguo Zhong Xi Yi Jie He Za Zhi 13(324):336–339PubMedGoogle Scholar
  66. 66.
    Boscan P, Pickering AE, Paton JF (2002) The nucleus of the solitary tract: an integrating station for nociceptive and cardiorespiratory afferents. Exp Physiol 87:259–266PubMedCrossRefGoogle Scholar
  67. 67.
    Kaptchuk TJ (2002) Acupuncture: theory, efficacy, and practice. Ann Intern Med 136:374–383PubMedGoogle Scholar
  68. 68.
    Travagli RA, Gillis RA, Vicini S (1992) Effects of thyrotropin-releasing hormone on neurons in rat dorsal motor nucleus of the vagus, in vitro. Am J Physiol 263:G508–G517PubMedGoogle Scholar
  69. 69.
    Washabau RJ, Fudge M, Price WJ, Barone FC (1995) GABA receptors in the dorsal motor nucleus of the vagus influence feline lower esophageal sphincter and gastric function. Brain Res Bull 38:587–594PubMedCrossRefGoogle Scholar
  70. 70.
    Travagli RA, Gillis RA, Rossiter CD, Vicini S (1991) Glutamate and GABA-mediated synaptic currents in neurons of the rat dorsal motor nucleus of the vagus. Am J Physiol 260:G531–G536PubMedGoogle Scholar
  71. 71.
    Sivarao DV, Krowicki ZK, Abrahams TP, Hornby PJ (1999) Vagally-regulated gastric motor activity: evidence for kainate and NMDA receptor mediation. Eur J Pharmacol 368:173–182PubMedCrossRefGoogle Scholar
  72. 72.
    Sivarao DV, Krowicki ZK, Hornby PJ (1998) Role of GABAA receptors in rat hindbrain nuclei controlling gastric motor function. Neurogastroenterol Motil 10:305–313PubMedCrossRefGoogle Scholar
  73. 73.
    Valentino RJ, Miselis RR, Pavcovich LA (1999) Pontine regulation of pelvic viscera: pharmacological target for pelvic visceral dysfunctions. Trends Pharmacol Sci 20:253–260PubMedCrossRefGoogle Scholar
  74. 74.
    Gamboa-Esteves FO, Lima D, Batten TF (2001) Neurochemistry of superficial spinal neurones projecting to nucleus of the solitary tract that express c-fos on chemical somatic and visceral nociceptive input in the rat. Metab Brain Dis 16:151–164PubMedCrossRefGoogle Scholar
  75. 75.
    Lee CH, Jung HS, Lee TY, Lee SR, Yuk SW, Lee KG, Lee BH (2001) Studies of the central neural pathways to the stomach and Zusanli (ST36). Am J Chin Med 29:211–220PubMedCrossRefGoogle Scholar
  76. 76.
    Liu JH, Li J, Yan J, Chang XR, Cui RF, He JF, Hu JM (2004) Expression of c-fos in the nucleus of the solitary tract following electroacupuncture at facial acupoints and gastric distension in rats. Neurosci Lett 366:215–219PubMedCrossRefGoogle Scholar
  77. 77.
    Toney GM, Mifflin SW (2000) Sensory modalities conveyed in the hindlimb somatic afferent input to nucleus tractus solitarius. J Appl Physiol 88:2062–2073PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Masahiro Iwa
    • 1
    • 2
  • Yukiomi Nakade
    • 1
  • Theodore N. Pappas
    • 1
  • Toku Takahashi
    • 1
    • 3
  1. 1.Department of SurgeryDuke University and Durham Veterans Affairs Medical CenterDurhamUSA
  2. 2.Department of Health Promoting Acupuncture and MoxibustionMeiji University of Oriental Medicine Hiyoshi-choFunai-gunJapan
  3. 3.Department of SurgerySurgical Service 112, VA Medical CenterDurhamUSA

Personalised recommendations