Abstract
Colonic electrical stimulation (CES) is expected to be a valuable alternative to drug therapy and surgical procedures for the treatment of constipation.
During the past two decades, CES has been reported to enhance motility of the colon in animal models and in human subjects with constipation. Various pulse configurations and stimulation sites of CES have been evaluated for their ability to modulate colonic motility. In this chapter, CES studies were introduced from two aspects: single-channel stimulation and multichannel stimulation.
The mechanism of CES that promotes colonic motility is still unclear, which hinders the improvement and utilization of this technique. Neurological pathways, the interstitial cells of Cajal, rectal pacemakers, colonic contractions, rectoanal coordination, etc. may all be involved in the process.
Problems with the therapy remain. Up to now, no consensus has been reached regarding which modes and sites of stimulation should be used for different types of constipation. There are different electrophysiological properties of specific colon segments. The gastrointestinal (GI) tract may get fatigued with long duration CES. CES may cause dysfunction of other parts of the GI tract. And a new type of CES system characterized by less energy consumption, recharge capability, greater safety, and permanent implantation is required.
Although CES is a safe and promising choice for the treatment of constipation, there’s still a long way to go for the clinical application of CES for constipation.
Keywords
Colonic electrical stimulation, Colonic transit, Constipation, Gastrointestinal (GI) motility, Mechanism
Outline
Single-Channel Stimulation 1427
Multichannel Stimulation 1430
Mechanism of Action (MOA) 1432
Summary 1433
References 1433
Normal gastrointestinal (GI) motility is regulated by its own bioelectrical activity, and GI dysmotilities are often accompanied by abnormal, bioelectrical activity in the GI tract. Therefore, improving of GI motility can theoretically be achieved through external, electrical stimulation to adjust bioelectrical activity. Gastrointestinal electrical stimulation (GIES) is exactly achieved by delivering external, electrical pulses to electrodes, implanted in the GI tract, thereby controlling bioelectrical activity and regulating GI motility ( ). The most significant advancement in this field has been made in research on gastric electrical stimulation (GES) since 1960s, which has been approved as a clinical treatment method for obesity and gastroparesis, in some European and American countries ( ). The promising results with GES also spurred great interest in the study of colonic electrical stimulation (CES).
ONE modality of GIES, CES, was initially proposed in a study by Linkens, in which disorganization rather than improvement of colonic slow waves was observed, under CES. This finding was explained by the weak coupling between electrical pulses and colonic slow waves that is unlike the strong coupling of slow waves in the stomach and small intestine. It seems that these discouraging results impeded the progress of the research on CES until , when Hughes et al. reported that CES, using appropriate parameters in a canine colonic pouch, could promote contraction and evacuation. This finding unveiled the potential of CES, as a treatment for constipation. CES, over the past two decades, has been reported to initiate myoelectrical activity, evoke migrating, motor complexes, and enhance motility of the colon in animal models and in constipation of human subjects. CES is expected to become a valuable alternative to drug therapy and surgical procedures for the treatment of constipation.
Various pulse configurations and stimulation sites of CES have been evaluated for their ability to modulate colonic motility. According to the pulse configuration, CES can be categorized into long-pulse stimulation, short-pulse stimulation, and stimulation with pulse trains. Different stimulation electrodes, serosal electrodes, intramuscular electrodes, and intraluminal or mucosal electrodes have been adopted for CES studies. CES can also be divided into single-channel stimulation and multichannel stimulation depending on the numbers of electrical channels used ( Table 120.1 ). To make CES closer to clinical practice, CES studies were introduced from two aspects of single-channel stimulation and multichannel stimulation.
Stimulation Type | Electrodes Location | Pulse Parameters | Authors | ||
---|---|---|---|---|---|
Frequency | Amplitude | Duration (ms) | |||
Single-channel | 5, 10, 20, and 25 cm proximal to the anus (cat) | 10, 40 Hz | 0–50 mA | 0.1, 1 | |
1 cm distal to the cecocolonic junction (rat) | 40 Hz | 10 mA | 4 | ||
10 cm distal to the cecum (dog) | 20 pulses/min | 2–6 mA | 300 | ||
40 Hz | 2–6 mA | 6 | |||
Rectosigmoid junction (human) | 15% higher than the basal frequency | 5 mA | 200 | ||
Rectosigmoid junction (human) | 10 Hz | 2 V | 0.15 | ||
Rectum (human) | 2–110 Hz | 30–35 V | 0.36–0.96 | ||
Multichannel | Two electrode pairs in isolated colonic loops (dog) | 10 Hz | 30–35 mA | 0.5 | |
Four electrode pairs in the descending colon (dog) | 50 Hz | 20 V | 10 | ||
Four electrode pairs in the descending colon (dog) | 50 Hz | 8–10 V | 10 | ||
Three electrode pairs in the cecum (pig) | 120 Hz | 7–15 mA | 1 | ||
Three electrode pairs in the cecum (pig) | 120 Hz | 10 V | 1 | ||
Two electrode pairs in the proximal colon and rectosigmoid junction (dog) | 40 Hz | 2.5–6 mA | 4 | ||
Five wire electrodes in the descending colon (rat) | 2–40 Hz | 4–10 mA | 0.15–30 | ||
Nine wire electrodes in the descending colon (pig) | 10 Hz | 9–30 mA | 0.03–3 | ||
Four electrode pairs in the cecum (pig) | 40 Hz | 10 V | 3 | ||
Two electrode pairs in the midtransverse colon and colosigmoid junction (human) | 15% higher than the basal frequency | 5 mA | 200 | ||
Four electrode pairs in the ileocecal junction, the cecocolonic junction, the midtransverse colon, and the colosigmoid junction (human) | 15% higher than the basal frequency | 5 mA | 200 |
Single-Channel Stimulation
Before the implementation of CES, stimulation site, pulse configuration, and the magnitude of parameters should be determined. and first assessed the optimal stimulation parameters and electrode sites for single-channel stimulation of CES, in cats with spinal cord injury (SCI). Two pairs of electrodes were separately implanted in a semicircular fashion, around the colon, at approximately 10 and 25 cm, respectively, proximal to the anus. Each electrode of a third electrode pair was separately implanted, parallel to the longitudinal axis of the intestine, at approximately 5 and 20 cm, respectively, proximal to the anus. The three electrode pairs were stimulated separately to determine the optimal stimulation site. Frequency (10 and 40 Hz), pulse width (0.1 and 1.0 ms), and pulse amplitude (0–50 mA) were respectively tested for each pair of electrodes to determine the optimal stimulation parameters. The results of colonic, transit measurement supported that CES could improve colonic transit. The electrode pair, which was most effective at promoting colonic transit, was located semicircularly, 10 cm proximal to the anus. The stimulation parameters were optimized for frequency at 40 Hz, for pulse width at 1 ms, and pulse amplitude between 25 and 35 mA. , however, proved that luminal content propulsion is highly dependent on pressure waves of the proximal colon; therefore, the proximal colon was chosen as the stimulation site in some CES studies. evaluated the acute effects of single-channel CES in rats. One pair of pacing wires was implanted on the serosal surface of the proximal colon, 1 cm distal to the cecocolonic junction, the point at which a fistula was made for phenol red injection to measure colonic transit. The electrical stimulus was composed of pulse trains with a train on-time of 2 s and train off-time of 3 s, a pulse frequency of 40 Hz, a pulse width of 4 ms, and pulse amplitude of 10 mA. The results, when compared to the control session, showed that the CES session exhibited a significantly higher output of phenol red, which indicated CES of the proximal colon could also accelerate colonic transit.
Besides stimulation of different sites, different pulse configurations were used in CES studies. To investigate the most effective pulse configuration, ) compared long-pulse CES and trains of pulses CES on colonic contractions and transit in a conscious canine model with a proximal colon cannula. For CES, one pair of serosal electrodes was placed and sutured, 10 cm distal to the cecum. In the long-pulse CES session, CES was applied with a pulse frequency of 20 pulses/min, a pulse width of 300 ms, and pulse amplitude of 2–6 mA (according to the tolerance of each animal). In the pulse-train CES session, CES was performed using a train on-time of 2 s and off-time of 3 s, a pulse frequency of 40 Hz, a pulse width of 6 ms, and a pulse amplitude of 2–6 mA (according to the tolerance of each animal). They found that, when compared with sham CES, pulse-train CES, but not long-pulse CES, significantly increased colonic contraction, accelerated colonic transit, and induced defecation.
In clinical research on CES, Shafik et al., in their early studies, determined the rectosigmoid junction, which played the role of functional sphincter in defecation, as the potential pacemaker site of rectal electrical activity ( ). After that, in 10 constipation patients with rectal inertia, they implanted one pair of stimulation electrodes and two pairs of recording electrodes into the rectosigmoid junction mucosa for rectal pacing ( ). The electrical stimulator delivered long pulses with a pulse width of 200 ms, an amplitude of 5 mA, and a frequency that was 15% higher than the frequency of the basal, rectal waves already recorded. All patients were trained for electrical stimulation treatments at home, with instructions to perform rectal electrical stimulation 30–60 min after breakfast and lunch and record the daily number of induced and spontaneous bowel evacuations. With rectal pacing, rectal electrical activity of 10 patients was recovered at different degrees, and bowel evacuation was induced in 7/10. The other 3/10 who exhibited low electrical activity showed no significant response to the rectal pacing treatment. Three of the seven patients could evacuate spontaneously without pacing after having performed daily pacing for 5–6 months, and their pacing devices were removed thereafter. The study period was well tolerated, acceptable to the patients, and performed without complication. Similarly, also chose the rectosigmoid junction to conduct electrical stimulation on two patients with refractory, slow-transit constipation. One pair of electrodes was placed into the muscular layer of the rectosigmoid junction under laparoscopy. The stimulation parameters used were a frequency of 10 Hz, a pulse width of 150 μs, and pulse amplitude of 2 V in a continuous mode for 30 days. After 30 days, the mode was changed to a cyclical mode, with electrical stimulation, 2 min on and 20 min off. During the follow-up of 19 months and 6 months, respectively, in these two patients, the number of bowel movements per week increased significantly. Both patients no longer needed laxatives, enemas, or any other assistance for defecation.
In addition to the clinical research mentioned earlier, a noninvasive electrical stimulation therapy using an anal plug has been applied to treat functional constipation. The first trial of this therapy was conducted by . They treated a 25-year-old female patient with functional constipation who displayed impaired, rectal sensation without slow-transit or paradoxical pelvic floor contraction. After receiving electrical stimulation therapy, her constipation symptoms and impaired rectal sensations improved dramatically. After this case report, the authors selected 22 patients, who also had functional constipation with impaired rectal sensation, to compare electrical stimulation therapy with biofeedback therapy ( ). The stimulation parameters used were scheduled individually and within the range of a frequency of 2–110 Hz, a pulse width of 360–960 μs, and amplitude of 30–35 V. The stimulation therapy was performed once a day for 20 min, over 10–12 sessions. They showed that the efficacy of electrical stimulation treatment is comparable to the efficacy of biofeedback therapy in this subgroup of constipated patients, and that the frequency of the sense of “wanting to defecate” improved only in the group treated with electrical stimulation. reported on the efficacy of this therapy that was based on five years of clinical experience from 147 patients with chronic, functional constipation. They found that electrical stimulation with the anal plug was successful for the treatment of patients with chronic, functional constipation, refractory to biofeedback therapy, rectal hyposensitivity, and anal pain. Electrical stimulation therapy, however, provided no significant improvement in colonic transit time in their patients.