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Digestive Diseases and Sciences

, Volume 57, Issue 5, pp 1213–1221 | Cite as

Anti-Stress Effects of Transcutaneous Electrical Nerve Stimulation (TENS) on Colonic Motility in Rats

  • Sazu Yoshimoto
  • Reji Babygirija
  • Anthony Dobner
  • Kirk Ludwig
  • Toku TakahashiEmail author
Original Article

Abstract

Background

Disorders of colonic motility may contribute to symptoms in patients with irritable bowel syndrome (IBS), and stress is widely believed to play a major role in developing IBS. Stress increases corticotropin releasing factor (CRF) of the hypothalamus, resulting in acceleration of colonic transit in rodents. In contrast, hypothalamic oxytocin (OXT) has an anti-stress effect via inhibiting CRF expression and hypothalamic–pituitary–adrenal axis activity. Although transcutaneous electrical nerve stimulation (TENS) and acupuncture have been shown to have anti-stress effects, the mechanism of the beneficial effects remains unknown.

Aims

We tested the hypothesis that TENS upregulates hypothalamic OXT expression resulting in reduced CRF expression and restoration of colonic dysmotility in response to chronic stress.

Methods

Male SD rats received different types of stressors for seven consecutive days (chronic heterotypic stress). TENS was applied to the bilateral hind limbs every other day before stress loading. Another group of rats did not receive TENS treatment.

Results

TENS significantly attenuated accelerated colonic transit induced by chronic heterotypic stress, which was antagonized by a central injection of an OXT antagonist. Immunohistochemical study showed that TENS increased OXT expression and decreased CRF expression at the paraventricular nucleus (PVN) following chronic heterotypic stress.

Conclusions

It is suggested that TENS upregulates hypothalamic OXT expression which acts as an anti-stressor agent and mediates restored colonic dysmotility following chronic stress. TENS may be useful to treat gastrointestinal symptoms associated with stress.

Keywords

Acupuncture Corticotropin releasing factor (CRF) Hypothalamic–pituitary–adrenal (HPA) axis Paraventricular nucleus (PVN) 

Abbreviations

CRF

Corticotropin releasing factor

HPA

Hypothalamus–pituitary–adrenal

OXT

Oxytocin

PVN

Paraventricular nucleus

SON

Supraoptic nucleus

TENS

Transcutaneous electrical nerve stimulation

Notes

Conflict of interest

None.

References

  1. 1.
    Vassallo M, Camilleri M, Phillips SF, Brown ML, Chapman NJ, Thomforde GM. Transit through the proximal colon influences stool weight in the irritable bowel syndrome. Gastroenterology. 1992;102:102–108.PubMedGoogle Scholar
  2. 2.
    Camilleri M, Mayer EA, Drossman DA, et al. Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist. Aliment Pharmacol Ther. 1999;13:1149–1159.PubMedCrossRefGoogle Scholar
  3. 3.
    Lenz HJ, Raedler A, Greten H, Vale WW, Rivier JE. Stress-induced gastrointestinal secretory and motor responses in rats are mediated by endogenous corticotropin-releasing factor. Gastroenterology. 1988;95:1510–1517.PubMedGoogle Scholar
  4. 4.
    Monnikes H, Schmidt BG, Raybould HE, Tache Y. CRF in the paraventricular nucleus mediates gastric and colonic motor response to restraint stress. Am J Physiol. 1992;262:G137–G143.PubMedGoogle Scholar
  5. 5.
    Nakade Y, Fukuda H, Iwa M, et al. Restraint stress stimulates colonic motility via central corticotropin-releasing factor and peripheral 5-HT3 receptors in conscious rats. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1037–G1044.PubMedCrossRefGoogle Scholar
  6. 6.
    Gomez F, Manalo S, Dallman MF. Androgen-sensitive changes in regulation of restraint-induced adrenocorticotropin secretion between early and late puberty in male rats. Endocrinology. 2004;145:59–70.PubMedCrossRefGoogle Scholar
  7. 7.
    Neumann ID. Brain oxytocin: a key regulator of emotional and social behaviours in both females and males. J Neuroendocrinol. 2008;20:858–865.PubMedCrossRefGoogle Scholar
  8. 8.
    Windle RJ, Kershaw YM, Shanks N, Wood SA, Lightman SL, Ingram CD. Oxytocin attenuates stress-induced c-fos mRNA expression in specific forebrain regions associated with modulation of hypothalamo–pituitary–adrenal activity. J Neurosci. 2004;24:2974–2982.PubMedCrossRefGoogle Scholar
  9. 9.
    Zheng J, Babygirija R, Bulbul M, Cerjak D, Ludwig K, Takahashi T. Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats. Am J Physiol Gastrointest Liver Physiol. 2010;299:G946–G953.PubMedCrossRefGoogle Scholar
  10. 10.
    Pitman DL, Ottenweller JE, Natelson BH. Plasma corticosterone levels during repeated presentation of two intensities of restraint stress: chronic stress and habituation. Physiol Behav. 1988;43:47–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Ostrander MM, Ulrich-Lai YM, Choi DC, Richtand NM, Herman JP. Hypoactivity of the hypothalamo–pituitary–adrenocortical axis during recovery from chronic variable stress. Endocrinology. 2006;147:2008–2017.PubMedCrossRefGoogle Scholar
  12. 12.
    Masere C, Nakade Y, Zheng J, Babygirija R, Ludwig K, Takahashi T. Chronic restraint stress has no more stimulatory effects on colonic motility in rats. Neurosci Lett. 2009;453:147–150.PubMedCrossRefGoogle Scholar
  13. 13.
    Zheng J, Dobner A, Babygirija R, Ludwig K, Takahashi T. Effects of repeated restraint stress on gastric motility in rats. Am J Physiol Regul Integr Comp Physiol. 2009;296:R1358–R1365.PubMedCrossRefGoogle Scholar
  14. 14.
    Yoshimoto S, Cerjak D, Babygirija R, Bulbul M, Ludwig K, Takahashi T. Hypothalamic circuit in regulating colonic transit following chronic stress in rats. Stress (in press).Google Scholar
  15. 15.
    Stock S, Uvnas-Moberg K. Increased plasma levels of oxytocin in response to afferent electrical stimulation of the sciatic and vagal nerves and in response to touch and pinch in anaesthetized rats. Acta Physiol Scand. 1988;132:29–34.PubMedCrossRefGoogle Scholar
  16. 16.
    Uvnas-Moberg K, Bruzelius G, Alster P, Lundeberg T. The antinociceptive effect of non-noxious sensory stimulation is mediated partly through oxytocinergic mechanisms. Acta Physiol Scand. 1993;149:199–204.PubMedCrossRefGoogle Scholar
  17. 17.
    Agren G, Lundeberg T, Uvnas-Moberg K, Sato A. The oxytocin antagonist 1-deamino-2-d-Tyr-(Oet)-4-Thr-8-Orn-oxytocin reverses the increase in the withdrawal response latency to thermal, but not mechanical nociceptive stimuli following oxytocin administration or massage-like stroking in rats. Neurosci Lett. 1995;187:49–52.PubMedCrossRefGoogle Scholar
  18. 18.
    Yang J, Yang Y, Chen JM, Liu WY, Wang CH, Lin BC. Effect of oxytocin on acupuncture analgesia in the rat. Neuropeptides. 2007;41:285–292.PubMedCrossRefGoogle Scholar
  19. 19.
    Chang L, Heitkemper MM. Gender differences in irritable bowel syndrome. Gastroenterology. 2002;123:1686–1701.PubMedCrossRefGoogle Scholar
  20. 20.
    Iwa M, Matsushima M, Nakade Y, Pappas TN, Fujimiya M, Takahashi T. Electroacupuncture at ST-36 accelerates colonic motility and transit in freely moving conscious rats. Am J Physiol Gastrointest Liver Physiol. 2006;290:G285–G292.PubMedCrossRefGoogle Scholar
  21. 21.
    Iwa M, Nakade Y, Pappas TN, Takahashi T. Electroacupuncture elicits dual effects: stimulation of delayed gastric emptying and inhibition of accelerated colonic transit induced by restraint stress in rats. Dig Dis Sci. 2006;51:1493–1500.PubMedCrossRefGoogle Scholar
  22. 22.
    Iwa M, Tateiwa M, Sakita M, Fujimiya M, Takahashi T. Anatomical evidence of regional specific effects of acupuncture on gastric motor function in rats. Auton Neurosci. 2007;137:67–76.PubMedCrossRefGoogle Scholar
  23. 23.
    Imai K, Ariga H, Chen C, Mantyh C, Pappas TN, Takahashi T. Effects of electroacupuncture on gastric motility and heart rate variability in conscious rats. Auton Neurosci. 2008;138:91–98.PubMedCrossRefGoogle Scholar
  24. 24.
    Ishiguchi T, Amano T, Matsubayashi H, Tada H, Fujita M, Takahashi T. Centrally administered neuropeptide Y delays gastric emptying via Y2 receptors in rats. Am J Physiol Regul Integr Comp Physiol. 2001;281:R1522–R1530.PubMedGoogle Scholar
  25. 25.
    Argiolas A, Melis MR, Vargiu L, Gessa GL. d(CH2)5Tyr(Me)-[Orn8]vasotocin, a potent oxytocin antagonist, antagonizes penile erection and yawning induced by oxytocin and apomorphine, but not by ACTH-(1–24). Eur J Pharmacol. 1987;134:221–224.PubMedCrossRefGoogle Scholar
  26. 26.
    Melis MR, Spano MS, Succu S, Argiolas A. The oxytocin antagonist d(CH2)5Tyr(Me)2-Orn8-vasotocin reduces non-contact penile erections in male rats. Neurosci Lett. 1999;265:171–174.PubMedCrossRefGoogle Scholar
  27. 27.
    Babygirija R, Zheng J, Bulbul M, Cerjak D, Ludwig K, Takahashi T. Sustained delayed gastric emptying during repeated restraint stress in oxytocin knockout mice. J Neuroendocrinol. 2010;22:1181–1186.PubMedCrossRefGoogle Scholar
  28. 28.
    Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 3rd ed. Orlando: Academic Press; 1997.Google Scholar
  29. 29.
    Sato A, Sato Y, Shimada F, Torigata Y. Changes in gastric motility produced by nociceptive stimulation of the skin in rats. Brain Res. 1975;87:151–159.PubMedCrossRefGoogle Scholar
  30. 30.
    Koizumi K, Sato A, Terui N. Role of somatic afferents in autonomic system control of the intestinal motility. Brain Res. 1980;182:85–97.PubMedCrossRefGoogle Scholar
  31. 31.
    Kametani H, Sato A, Sato Y, Simpson A. Neural mechanisms of reflex facilitation and inhibition of gastric motility to stimulation of various skin areas in rats. J Physiol (Lond). 1979;294:407–418.Google Scholar
  32. 32.
    Tatewaki M, Harris M, Uemura K, et al. Dual effects of acupuncture on gastric motility in conscious rats. Am J Physiol Regul Integr Comp Physiol. 2003;285:R862–R872.PubMedGoogle Scholar
  33. 33.
    Camilleri M, Malagelada JR, Kao PC, Zinsmeister AR. Effect of somatovisceral reflexes and selective dermatomal stimulation on postcibal antral pressure activity. Am J Physiol. 1984;247:G703–G708.PubMedGoogle Scholar
  34. 34.
    Liu S, Peng S, Hou X, Ke M, Chen JD. Transcutaneous electroacupuncture improves dyspeptic symptoms and increases high frequency heart rate variability in patients with functional dyspepsia. Neurogastroenterol Motil. 2008;20:1204–1211.PubMedCrossRefGoogle Scholar
  35. 35.
    Salansky N, Fedotchev A. Endogenous opioid peptide level changes under electrostimulation and their assessment by the EEG. Int J Neurosci. 1994;78:193–205.PubMedCrossRefGoogle Scholar
  36. 36.
    Han SH, Yoon SH, Cho YW, Kim CJ, Min BI. Inhibitory effects of electroacupuncture on stress responses evoked by tooth-pulp stimulation in rats. Physiol Behav. 1999;66:217–222.PubMedCrossRefGoogle Scholar
  37. 37.
    Li L, Yin-Xiang C, Hong X, Peng L, Da-Nian Z. Nitric oxide in vPAG mediates the depressor response to acupuncture in stress-induced hypertensive rats. Acupunct Electrother Res. 2001;26:165–170.PubMedGoogle Scholar
  38. 38.
    Yang CH, Lee BB, Jung HS, Shim I, Roh PU, Golden GT. Effect of electroacupuncture on response to immobilization stress. Pharmacol Biochem Behav. 2002;72:847–855.PubMedCrossRefGoogle Scholar
  39. 39.
    Manni L, Aloe L, Fiore M. Changes in cognition induced by social isolation in the mouse are restored by electro-acupuncture. Physiol Behav. 2009;98:537–542.PubMedCrossRefGoogle Scholar
  40. 40.
    Imai K, Ariga H, Takahashi T. Electroacupuncture improves imbalance of autonomic function under restraint stress in conscious rats. Am J Chin Med. 2009;37:45–55.PubMedCrossRefGoogle Scholar
  41. 41.
    Wu HG, Jiang B, Zhou EH, et al. Regulatory mechanism of electroacupuncture in irritable bowel syndrome: preventing MC activation and decreasing SP VIP secretion. Dig Dis Sci. 2008;53:1644–1651.PubMedCrossRefGoogle Scholar
  42. 42.
    Tian XY, Bian ZX, Hu XG, Zhang XJ, Liu L, Zhang H. Electro-acupuncture attenuates stress-induced defecation in rats with chronic visceral hypersensitivity via serotonergic pathway. Brain Res. 2006;1088:101–108.PubMedCrossRefGoogle Scholar
  43. 43.
    Ma XP, Tan LY, Yang Y, et al. Effect of electro-acupuncture on substance P, its receptor and corticotropin-releasing hormone in rats with irritable bowel syndrome. World J Gastroenterol. 2009;15:5211–5217.PubMedCrossRefGoogle Scholar
  44. 44.
    Hollifield M, Sinclair-Lian N, Warner TD, Hammerschlag R. Acupuncture for posttraumatic stress disorder: a randomized controlled pilot trial. J Nerv Ment Dis. 2007;195:504–513.PubMedCrossRefGoogle Scholar
  45. 45.
    Windle RJ, Shanks N, Lightman SL, Ingram CD. Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats. Endocrinology. 1997;138:2829–2834.PubMedCrossRefGoogle Scholar
  46. 46.
    Neumann ID. Involvement of the brain oxytocin system in stress coping: interactions with the hypothalamo–pituitary–adrenal axis. Prog Brain Res. 2002;139:147–162.PubMedCrossRefGoogle Scholar
  47. 47.
    Rogers RC, Hermann GE. Oxytocin, oxytocin antagonist, TRH, and hypothalamic paraventricular nucleus stimulation effects on gastric motility. Peptides. 1987;8:505–513.PubMedCrossRefGoogle Scholar
  48. 48.
    Liu MT, Rayport S, Jiang Y, Murphy DL, Gershon MD. Expression and function of 5-HT3 receptors in the enteric neurons of mice lacking the serotonin transporter. Am J Physiol Gastrointest Liver Physiol. 2002;283:G1398–G1411.PubMedGoogle Scholar
  49. 49.
    Wu CL, Doong ML, Wang PS. Involvement of cholecystokinin receptor in the inhibition of gastrointestinal motility by oxytocin in ovariectomized rats. Eur J Pharmacol. 2008;580:407–415.PubMedCrossRefGoogle Scholar
  50. 50.
    Welch MG, Anwar M, Chang CY, et al. Combined administration of secretin and oxytocin inhibits chronic colitis and associated activation of forebrain neurons. Neurogastroenterol Motil. 2010;22:654–e202.PubMedCrossRefGoogle Scholar
  51. 51.
    Babygirija R, Zheng J, Ludwig K, Takahashi T. Central oxytocin is involved in restoring impaired gastric motility following chronic repeated stress in mice. Am J Physiol Regul Integr Comp Physiol. 2010;298:R157–R165.PubMedCrossRefGoogle Scholar
  52. 52.
    Matsunaga M, Konagaya T, Nogimori T, et al. Inhibitory effect of oxytocin on accelerated colonic motility induced by water-avoidance stress in rats. Neurogastroenterol Motil. 2009;21:856–e59.PubMedCrossRefGoogle Scholar
  53. 53.
    Babygirija R, Zheng J, Bulbul M, Ludwig K, Takahashi T. Beneficial effects of social attachment to overcome daily stress. Brain Res. 2010;1352:43–49.PubMedCrossRefGoogle Scholar
  54. 54.
    Olff M, Langeland W, Witteveen A, Denys D. A psychobiological rationale for oxytocin in the treatment of posttraumatic stress disorder. CNS Spectr. 2010;15:522–530.PubMedGoogle Scholar
  55. 55.
    Johansen PO, Krebs TS. How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationale. J Psychopharmacol. 2009;23:389–391.PubMedCrossRefGoogle Scholar
  56. 56.
    Sluka KA, Walsh D. Transcutaneous electrical nerve stimulation: basic science mechanisms and clinical effectiveness. J Pain. 2003;4:109–121.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Sazu Yoshimoto
    • 1
  • Reji Babygirija
    • 1
  • Anthony Dobner
    • 1
  • Kirk Ludwig
    • 1
  • Toku Takahashi
    • 1
    Email author
  1. 1.Department of Surgery, Zablocki VA Medical CenterMedical College of WisconsinMilwaukeeUSA

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