Eur J Pediatr Surg 2025; 35(01): 060-070
DOI: 10.1055/a-2482-5997
Original Article

Interferential Current Stimulation Enhances Rectal Motor Activity: Insights from an Isolated Perfused Porcine Model

1   Department of Pediatric Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany
2   Department of Neurophysiology, Mannheim Center vor Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany
,
Michael Boettcher
1   Department of Pediatric Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany
3   Mannheim Institute for Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany
,
Michaela Klinke Petrowsky
1   Department of Pediatric Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany
,
Nicolas Andres Hoyos
1   Department of Pediatric Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany
4   Department of Pediatric Surgery, SLK-Kliniken Heilbronn GmbH, Heilbronn, Baden-Württemberg, Germany
,
Irmgard Herrmann
6   Deutsches Zentrum Immuntherapie DZI, Erlangen University Hospital, Erlangen, Bayern, Germany
,
Walter Magerl*
2   Department of Neurophysiology, Mannheim Center vor Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany
,
Martin Herrmann*
1   Department of Pediatric Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany
5   Department of Medicine 3 Rheumatology and Immunology, Erlangen University Hospital, Erlangen, Bayern, Germany
6   Deutsches Zentrum Immuntherapie DZI, Erlangen University Hospital, Erlangen, Bayern, Germany
› Author Affiliations


Abstract

Introduction Interferential current (IFC) has been studied in several clinical trials for the treatment of bowel motility disorders, most often in children. However, only moderate effects are reported, and in contrast to IFC, the so-called placebo application is indiscernible. The mechanisms and neuroanatomic points of action remain elusive. Therefore, this therapy remains being questioned.

Methods To gain objective experimental data about IFC stimulation, we examined this method ex vivo in an isolated perfused porcine rectum including the mesorectum. To elucidate the role of plexus nerve fibers and enteric ganglia, we performed IFC stimulation also in the presence of tetrodotoxin (TTX) or hexamethonium (HXN). We applied the commonly used stimulation modes with a beat frequency sweeping between 5 and 25 Hz (IFCd5–25) and 80 and 150 Hz (IFCd80–150). We monitored intraluminal pressure and motility by online barometry and video recording, respectively. Motor activity, reflected by changes in the intraluminal pressure (cm H2O·s−1) and longitudinal movements (pixels·s−1), was quantified over time as root mean squares (RMSs).

Results After IFCd5–25, we observed a 30% increase in the rectal motility in the pressure changes which was sustained over 30 minutes post-stimulation (p < 0.02); only a minor effect was detected for IFCd80–150. Both TTX and HTX abolished the stimulation. This suggests neuronal modulation.

Conclusion IFCd5–25 stimulates rectal motor activity in the isolated perfused porcine rectum. Ganglia in the enteric nervous system are modulated to allow increased activity for at least 30 minutes. Therefore, the isolated porcine rectum is a suitable tool to study the effectiveness of various IFC settings in the rectum.

* These authors contributed equally to this work.




Publication History

Received: 27 March 2024

Accepted: 22 November 2024

Accepted Manuscript online:
25 November 2024

Article published online:
11 December 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Vlismas LJ, Wu W, Ho V. Idiopathic slow transit constipation: pathophysiology, diagnosis, and management. Medicina (Kaunas) 2024; 60 (01) 108
  • 2 Song G, Trujillo S, Fu Y, Shibi F, Chen J, Fass R. Transcutaneous electrical stimulation for gastrointestinal motility disorders. Neurogastroenterol Motil 2023; 35 (11) e14618
  • 3 Vriesman MH, Rajindrajith S, Koppen IJN. et al. Quality of life in children with functional constipation: a systematic review and meta-analysis. J Pediatr 2019; 214: 141-150
  • 4 López J, Barba MG, Fernández SN. et al. Protocol for treatment of constipation with polyethylene glycol 3350 plus electrolytes in critically ill children. An Pediatr (Engl Ed) 2023; 99 (03) 176-184
  • 5 Ford AC, Suares NC. Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis. Gut 2011; 60 (02) 209-218
  • 6 Agharezaee M, Mahnam A. A computational study to evaluate the activation pattern of nerve fibers in response to interferential currents stimulation. Med Biol Eng Comput 2015; 53 (08) 713-720
  • 7 Yik YI, Hutson J, Southwell B. Home-based transabdominal interferential electrical stimulation for six months improves paediatric slow transit constipation (STC). Neuromodulation 2018; 21 (07) 676-681
  • 8 Clarke MC, Chase JW, Gibb S. et al. Decreased colonic transit time after transcutaneous interferential electrical stimulation in children with slow transit constipation. J Pediatr Surg 2009; 44 (02) 408-412
  • 9 Ismail KA, Chase J, Gibb S. et al. Daily transabdominal electrical stimulation at home increased defecation in children with slow-transit constipation: a pilot study. J Pediatr Surg 2009; 44 (12) 2388-2392
  • 10 Yik YI, Ismail KA, Hutson JM, Southwell BR. Home transcutaneous electrical stimulation to treat children with slow-transit constipation. J Pediatr Surg 2012; 47 (06) 1285-1290
  • 11 Leong LC, Yik YI, Catto-Smith AG, Robertson VJ, Hutson JM, Southwell BR. Long-term effects of transabdominal electrical stimulation in treating children with slow-transit constipation. J Pediatr Surg 2011; 46 (12) 2309-2312
  • 12 Hutson JM, Dughetti L, Stathopoulos L, Southwell BR. Transabdominal electrical stimulation (TES) for the treatment of slow-transit constipation (STC). Pediatr Surg Int 2015; 31 (05) 445-451
  • 13 Lu ML, He J, Lu S. Electrical stimulation therapy for slow transit constipation in children: a systematic review. Int J Colorectal Dis 2015; 30 (05) 697-702
  • 14 Ladi-Seyedian SS, Sharifi-Rad L, Yousefi A, Alimadadi H, Farahmand F, Motamed F. Management of intractable functional constipation in children by interferential therapy: transabdominal or pelvic floor. Dig Dis Sci 2023; 68 (06) 2510-2517
  • 15 Chase J, Robertson VJ, Southwell B, Hutson J, Gibb S. Pilot study using transcutaneous electrical stimulation (interferential current) to treat chronic treatment-resistant constipation and soiling in children. J Gastroenterol Hepatol 2005; 20 (07) 1054-1061
  • 16 Kajbafzadeh AM, Sharifi-Rad L, Nejat F, Kajbafzadeh M, Talaei HR. Transcutaneous interferential electrical stimulation for management of neurogenic bowel dysfunction in children with myelomeningocele. Int J Colorectal Dis 2012; 27 (04) 453-458
  • 17 Ladi-Seyedian SS, Sharifi-Rad L, Manouchehri N, Ashjaei B. A comparative study of transcutaneous interferential electrical stimulation plus behavioral therapy and behavioral therapy alone on constipation in postoperative Hirschsprung disease children. J Pediatr Surg 2017; 52 (01) 177-183
  • 18 Vitton V, Mion F, Leroi AM. et al. Interferential therapy for chronic constipation in adults: The CON-COUR randomized controlled trial. United European Gastroenterol J 2023; 11 (04) 337-349
  • 19 Pauwels N, Willemse C, Hellemans S. et al. The role of neuromodulation in chronic functional constipation: a systematic review. Acta Gastroenterol Belg 2021; 84 (03) 467-476
  • 20 Moore JS, Gibson PR, Burgell RE. Neuromodulation via interferential electrical stimulation as a novel therapy in gastrointestinal motility disorders. J Neurogastroenterol Motil 2018; 24 (01) 19-29
  • 21 Tan AYF, Sourial M, Hutson JM, Southwell BR. Short-term interferential transabdominal electrical stimulation did not change oral-rectal transit time in piglets. Neuromodulation 2018; 21 (07) 669-675
  • 22 Fuentes C J, Armijo-Olivo S, Magee DJ, Gross DP. A preliminary investigation into the effects of active interferential current therapy and placebo on pressure pain sensitivity: a random crossover placebo controlled study. Physiotherapy 2011; 97 (04) 291-301
  • 23 Southwell BR. Electro-neuromodulation for colonic disorders-review of meta-analyses, systematic reviews, and RCTs. Neuromodulation 2020; 23 (08) 1061-1081
  • 24 Nussbaum-Krammer CI, Neto MF, Brielmann RM, Pedersen JS, Morimoto RI. Investigating the spreading and toxicity of prion-like proteins using the metazoan model organism C. elegans . J Vis Exp 2015; (95) 52321
  • 25 Fukuda TY, Echeimberg JO, Pompeu JE. et al. Root mean square value of the electromyographic signal in the isometric torque of the quadriceps, hamstrings and brachial biceps muscles in female subjects. J Appl Res 2010; 10 (01) 32-39
  • 26 Krogh-Lund C, Jørgensen K. Changes in conduction velocity, median frequency, and root mean square-amplitude of the electromyogram during 25% maximal voluntary contraction of the triceps brachii muscle, to limit of endurance. Eur J Appl Physiol Occup Physiol 1991; 63 (01) 60-69
  • 27 Gonzalez LM, Moeser AJ, Blikslager AT. Porcine models of digestive disease: the future of large animal translational research. Transl Res 2015; 166 (01) 12-27
  • 28 Yin L, Yang H, Li J. et al. Pig models on intestinal development and therapeutics. Amino Acids 2017; 49 (12) 2099-2106
  • 29 Brown DR, Timmermans J-P. Lessons from the porcine enteric nervous system. Neurogastroenterol Motil 2004; 16 (Suppl. 01) 50-54
  • 30 Ortego-Isasa I, Ortega-Morán JF, Lozano H. et al. Colonic electrical stimulation for chronic constipation: a perspective review. Biomedicines 2024; 12 (03) 481
  • 31 Smith TK, Park KJ, Hennig GW. Colonic migrating motor complexes, high amplitude propagating contractions, neural reflexes and the importance of neuronal and mucosal serotonin. J Neurogastroenterol Motil 2014; 20 (04) 423-446
  • 32 Pervez M, Ratcliffe E, Parsons SP, Chen JH, Huizinga JD. The cyclic motor patterns in the human colon. Neurogastroenterol Motil 2020; 32 (05) e13807
  • 33 Spencer NJ, Dinning PG, Brookes SJ, Costa M. Insights into the mechanisms underlying colonic motor patterns. J Physiol 2016; 594 (15) 4099-4116
  • 34 Dinning PG, Wiklendt L, Gibbins I. et al. Low-resolution colonic manometry leads to a gross misinterpretation of the frequency and polarity of propagating sequences: Initial results from fiber-optic high-resolution manometry studies. Neurogastroenterol Motil 2013; 25 (10) e640-e649
  • 35 Bassotti G, Crowell MD, Whitehead WE. Contractile activity of the human colon: lessons from 24 hour studies. Gut 1993; 34 (01) 129-133
  • 36 Larauche M, Wang Y, Wang PM. et al. The effect of colonic tissue electrical stimulation and celiac branch of the abdominal vagus nerve neuromodulation on colonic motility in anesthetized pigs. Neurogastroenterol Motil 2020; 32 (11) e13925
  • 37 Cheng LK, Nagahawatte ND, Avci R, Du P, Liu Z, Paskaranandavadivel N. Strategies to refine gastric stimulation and pacing protocols: experimental and modeling approaches. Front Neurosci 2021; 15: 645472
  • 38 Hughes SF, Scott SM, Pilot MA, Williams NS. Electrically stimulated colonic reservoir for total anorectal reconstruction. Br J Surg 1995; 82 (10) 1321-1326
  • 39 Bennett A, Stockley HL. Electrically induced contractions of guinea-pig isolated ileum resistant to tetrodotoxin. Br J Pharmacol 1973; 48 (02) 359P-360P
  • 40 Rae MG, Fleming N, McGregor DB, Sanders KM, Keef KD. Control of motility patterns in the human colonic circular muscle layer by pacemaker activity. J Physiol 1998; 510 (Pt 1): 309-320
  • 41 Oda K, Araki K, Totoki T, Shibasaki H. Nerve conduction study of human tetrodotoxication. Neurology 1989; 39 (05) 743-745
  • 42 Sia TC, Brookes SJ, Dinning PG, Wattchow DA, Spencer NJ. Peristalsis and propulsion of colonic content can occur after blockade of major neuroneuronal and neuromuscular transmitters in isolated guinea pig colon. Am J Physiol Gastrointest Liver Physiol 2013; 305 (12) G933-G939
  • 43 Dib-Hajj SD, Yang Y, Black JA, Waxman SG. The Na(V)1.7 sodium channel: from molecule to man. Nat Rev Neurosci 2013; 14 (01) 49-62
  • 44 Kocmalova M, Kollarik M, Canning BJ. et al. Control of neurotransmission by NaV1.7 in human, guinea pig, and mouse airway parasympathetic nerves. J Pharmacol Exp Ther 2017; 361 (01) 172-180
  • 45 Ridolfi TJ, Tong WD, Takahashi T, Kosinski L, Ludwig KA. Sympathetic and parasympathetic regulation of rectal motility in rats. J Gastrointest Surg 2009; 13 (11) 2027-2033 , discussion 2033
  • 46 Aellen S, Wiesel PH, Gardaz JP. et al. Electrical stimulation induces propagated colonic contractions in an experimental model. Br J Surg 2009; 96 (02) 214-220
  • 47 Akasu T, Nishimura T. Synaptic transmission and function of parasympathetic ganglia. Prog Neurobiol 1995; 45 (05) 459-522
  • 48 Alkadhi KA, Alzoubi KH, Aleisa AM. Plasticity of synaptic transmission in autonomic ganglia. Prog Neurobiol 2005; 75 (02) 83-108
  • 49 Horn CC, Ardell JL, Fisher LE. Electroceutical targeting of the autonomic nervous system. Physiology (Bethesda) 2019; 34 (02) 150-162
  • 50 Noble JG, Henderson G, Cramp AFL, Walsh DM, Lowe AS. The effect of interferential therapy upon cutaneous blood flow in humans. Clin Physiol 2000; 20 (01) 2-7