What are Electroceuticals?

Electrical impulses that are used to modulate the body’s neural circuits for medical intervention are called “Electroceuticals.”  The general field of study, bioelectronics, seeks to develop the medical applications as a companion to – or possibly replacement of – molecular medicines.  The pharmaceutical giant GSK launched a program with a $1 million prize to stimulate early developments in the field.[1]

Here we present one possible application of Electroceuticals to a specific medical condition.

Treatment Idea

The proposed application of an Electroceutical proof of principle is for the treatment of gastroparesis, a condition in which the muscles in the stomach wall work poorly or not at all.  Ordinarily, strong muscular contractions propel food through the digestive tract, preventing the stomach from emptying properly. Gastroparesis can interfere with digestion and cause problems with blood sugar levels and nutrition.[2]  Symptoms include nausea, vomiting, gastroesophageal reflux, and diarrhea.  Diabetes mellitus is the most common cause of gastroparesis.

There is currently no cure for gastroparesis. Dietary changes may help some patients cope with gastroparesis signs and symptoms.  Gastroparesis medications may offer some relief, but can cause serious side effects.  Gastroparesis is believed to be caused by damage to the vagus nerve that controls the stomach muscles.  This provides an opportunity for a direct electroceutical effect through modulation of neural signals of a known nerve.

Proof of Principle Approach

The vagus nerve runs along the esophagus to the fundus of the stomach, providing a low complexity point of intervention.  The electroceutical impulse at this point can return stomach wall muscles to working order.

While the specific regimen of impulses must be determined for an electroceutical approach, guidelines from the literature are available.  For example, Mintchev et al. (1998) used anaesthetized canines with a 50 Hertz, 14 volt rectangular trains for four seconds with 4-second delays between pulses.  Here they also describe placement of four electrodes (two active and two ground) about 8–10 cm proximal to the stomach pylorus in a human patient.  Other voltage regimens are summarized by Bortolotti (2011).

The FDA-approved Enterra device (see below) includes intramuscular stomach leads, which are surgically placed on the greater curvature of the stomach.  A pulse generator is implanted in a subcutaneous pocket, usually in the abdomen.

Briefly, the proposal is to replace the invasive Enterra system with an electroceutical approach that is less invasive and more readily controlled.  Such a device will be welcomed in the medical and diabetes communities.

Meeting Some Outlined Criteria

  1. Prospect of Disease Effect:  Gastric electrical stimulation of neural signals as therapy for gastroparesis has been attempted for over 50 years (Bortolotti 2011).  Three principal methods have been tried, with sequential neural gastric electrical stimulation (SN-GES) being the most promising.   SN-GES has been used in animals (Mintchev et al., 1998) and a single human patient (Mintchev et al., 2000).  To date none of the current technologies has consistently accelerated gastric emptying or improved all symptoms in all patients with gastroparesis.  Soffer (2012) reviews the use of gastric electrical stimulation (GES) on gastroparesis.  The implanted Enterra system (Medtronic), a unipolar intramuscular lead, is FDA approved for the treatment of chronic, drug refractory nausea and vomiting secondary to gastroparesis of diabetic or idiopathic etiology.[3]  The intramuscular stomach leads are implanted via laparoscopy.  While controlled studies using the Enterra system have been performed (see Bortolotti, 2011), patient response may have suffered from incorrect positioning of electrodes and in opiate use during implantation surgery.  The Enterra system suffers from numerous other problems such as infection, device erosion, and other device-related shortcomings – which may even be fatal (Forster et al., 2003).  Despite the one fatality, Forster et al. concluded that GES significantly improved symptoms and quality of life for many patients with gastroperesis.  Parkman et al. (2010) report over 3500 Enterra devices were placed in US patients.  What might be best at improving gastric emptying and symptoms, low-frequency/high-energy GES (gastric electrical pacing with long pulse stimulation), requires a device that is too large and heavy for implantation.
  2. Complexity and Access:  The targeted vagus nerve provides a low complexity intervention with demonstrated access to the nerve intervention point.  This is evidenced by the fact that electrical stimulus is currently applied in cases of severe gastroperesis.  This method as currently practiced requires surgical intervention.  In an editorial, Bortolotti (2011) hoped that electronic technology could enable an easily implantable device to monitor contractile activity for human patients.
  3. Patient Population and Unmet Need:  While functional dyspepsia is estimated to affect 20% of the adult population in the United States (Parkman et al., 2004), the prevalence of gastroparesis is difficult to assess.  Jung et al. (2009) concluded it is a rare condition in the general population with incidences of 2.5 and 9.8 per 100,000 for men and women, respectively (Jung, 2010).  Gastroparesis affects about 5 million individuals in the US, including 5 to 12% of patients with diabetes (Parkman et al., 2010).  Hospitalizations for gastroperesis in the US were 231,140 in 2009 (Nusrat and Bielefeldt, 2013).  As noted above, there is no known cure.
  4. Animal Models:  Gastroperesis intervention has been described for animals in the literature, primarily using canines. See Parkman et al. (2010).  Canine models have been used to demonstrate efficacy of an electrical impulse treatment (cf. Kelly et al., 1972; Bellahsène et al., 1992; Johnson et al., 1990).
  5. Clinical proof of successful intervention can be readily demonstrated by methods used by the Mayo Clinic and others to diagnose the presence and extent of gastroparesis.  Measurement of the rate of stomach emptying is performed by endoscopy or by scanning the body after consumption of a radioactive tracer, often as a 99mTc sulfur colloid-labeled egg sandwich (Tougas et al., 2000).  Several other methods are outlined by the American College of Gastroenterology.[4]



  1. Bellahsène BE, Lind CD, Schirmer BD, Updike OL, McCallum RW. Acceleration of gastric emptying with electrical stimulation in a canine model of gastroparesis. Am J Physiol 1992; 262: G826-G834.
  2. Bortolotti, M. Gastric electrical stimulation for gastroparesis: A goal greatly pursued, but not yet attained. World J Gastroenterol 2011 January 21; 17(3):273-282.
  3. Forster J, Sarosiek I, Lin Z, Durham S, Denton S, Roeser K, McCallum RW. Further experience with gastric stimulation to treat drug refractory gastroparesis. Am J Surg 2003; 186:690-695.
  4. Johnson B, Familoni B, Abell TL, Verkman R, Wood G. Development of a canine model for gastric pacing. Gastroenterology 1990; 98:A36.
  5. Jung HK, Choung RS, Locke GR 3rd, Schleck CD, Zinsmeister AR, Szarka LA, Mullan B, Talley NJ. The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. Gastroenterology. 2009 Apr; 136(4):1225-1233.
  6. Jung HK. The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. J Neurogastroenterol Motil, Vol. 16 No. 1, January, 2010. DOI: 10.5056/jnm.2010.16.1.99
  7. Kelly KA, La Force RC. Pacing the canine stomach with electric stimulation. Am J Physiol 1972; 222:588-594.
  8. Mintchev MP, Sanmiguel CP, Otto SJ, Bowes KL. Microprocessor controlled movement of liquid gastric content using sequential neural electrical stimulation. Gut 1998; 43:607-661.
  9. Mintchev MP, Sanmiguel CP, Amaris M, Bowes KL. Microprocessor-controlled movement of solid gastric content using sequential neural electrical stimulation. Gastroenterology 2000; 118: 258-263.
  10. Nusrat S, Bielefeldt K. Gastroparesis on the rise: incidence vs awareness? Neurogastroenterol Motil (2013) 25, 16–22.
  11. Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004; 127:1592-1622.
  12. Parkman HP, Camilleri M, Farrugia G, McCallum RW, Bharucha AE, Mayer EA, Tack JF, Spiller R, Horowitz M, et al. Gastroparesis and functional dyspepsia: excerpts from the AGA/ANMS meeting. Neurogastroenterol Motil. 2010 Feb; 22(2):113-133.
  13. Soffer EE, Gastric Electrical Stimulation for Gastroparesis. J Neurogastroenterol Motil. 2012 April; 18(2): 131–137.
  14. Tougas GH, Eaker EY, Abell TL, Abrahamsson H, Boivin PL, Chen J, Hocking MP, Quigley EM, Koch KL, Tokayer AZ, Stanghellini V, Chen Y, Huizinga JD, Ryden J, Bourgeois I, McCallum RW. Assessment of gastric emptying using a low fat meal: Establishment of international control values. Am J Gastroenterol 2000; 95:1456–1462.

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