Exploring Electrical Neuromodulation as an Alternative Therapeutic Approach in Inflammatory Bowel Diseases
Abstract
:1. Introduction
2. Fundamental Pathophysiological Mechanisms for the Anti-Inflammatory Property of Electrical Neuromodulation
2.1. Central Nervous System Involvement in the Pathophysiology of IBD
2.2. Enteric Nervous System Involvement in the Pathophysiology of IBD
2.3. Autonomic Nervous System Involvement in the Pathophysiology of IBD
2.4. Vagus Nerve System Involvement in the Pathophysiology of IBD
3. Vagus Nerve Stimulation in IBD Therapy
3.1. Devices and Mechanisms of VNS
3.2. VNS Efficacy in Animal Models
3.3. VNS Clinical Trials in IBD
Diseases | Population Size | Stimulation Sites | Pulse Features | Stimulation and Treatment Durations | Major Findings | Year | References |
---|---|---|---|---|---|---|---|
CD and UC | 23 patients (1 withdraw due to infection); 10 CD, 12 UC | Ta-VNS at Cymba conchae of the external left ear | 20 Hz, 0.3 ms pulse width, 300 s continuous ON | 5 min once daily (first 2 weeks); 5 min twice daily (Week 4 to 16) | Achieved clinical remission; reduced fecal calprotectin; improved quality of life | 2023 | [90] |
CD | 17 patients (16 analyzed) | VNS at left cervical vagus nerve | 0.25–2.0 mA, in 0.25 mA increments, 0.25 ms pulse width | 1 min once per day, gradually increased to 5 min; 16 weeks | Reduced CDAI; reduced fecal calprotectin; decreased mucosal inflammation; reduced serum levels of inflammatory cytokines; improved quality of life | 2023 | [91] |
CD | 9 patients | VNS at left cervical vagus nerve | 0.25 mA, 10 Hz, 0.25 or 0.5 ms pulse width, 30 s ON, 300 s OFF | 12 months | Achieved clinical and endoscopic remission; decreased C-reactive protein and fecal calprotectin; restored vagal tone and reduced digestive pain; changed cytokine profile | 2020 | [89] |
CD | 9 patients | VNS | 0.5–1.25 mA, 10 Hz, 0.5 ms pulse width, 30 s ON, 300 s OFF | 12 months | Reduced alpha activity was associated with improved clinical outcomes, reduced anxiety, and decreased fecal calprotectin | 2018 | [88] |
CD | 7 patients | VNS at left cervical vagus nerve | 0.25–1.25 mA, 10 Hz, 0.5 ms pulse width, 30 s ON, 300 s OFF | 6 months | Achieved clinical, biological, and endoscopic remission, with restored vagal tone; decreased CDAI, C-reactive protein, and fecal calprotectin | 2016 | [87] |
CD | A 49-year-old male | VNS at left cervical vagus nerve | 0.5–1 mA in 0.25 mA increments, 10 Hz, 0.5 ms pulse width, 30 s ON, 300 s OFF | 12 months | Achieved endoscopic remission; decreased CDAI, with increased parasympathetic tone | 2014 | [86] |
FI; OAB; UR; BPS/IC; FI; DI | Patients receiving implantable pulse generator: 20 OAB, 21 UR, 12 BPS/IC, 7 FI, 4 DI. | SNS at S3 sacral nerve root | N/A | 14–220 months | Improved clinical symptoms, quality of life, and satisfaction | 2021 | [92] |
FI; Low Anterior Resection Syndrome | 10 patients | SNS at S3 and S4 of sacral nerve | N/A | 14.7 days mean test stimulation | Significantly improved low anterior resection syndrome and fecal incontinence quality of life score; avoided permanent colostomy | 2021 | [93] |
UP in UC Patients | A 58-year-old female | SNS | 0.5–1.5 V, 14 Hz, 210 ms pulse width | 3-week temporary stimulation; 18 months permanent stimulation | Improved endoscopic and histologic scores; decreased rectal barrier permeability | 2015 | [94] |
FI in CD | 5 patients | SNS at S3 sacral nerve | 5 Hz, 0.1 ms pulse width | 3-week initial stimulation; 3–36 months permanent stimulation | Improved continence, with significant decrease in the Wexner scores; improved quality of life | 2008 | [95] |
CD, UC, and Undetermined Colitis | 12 patients (7 CD, 3 UC, 2 Undermined Colitis) | Posterior TNS (PTNS) | 10–30 mA, 10Hz, 0.2 ms pulse width | Several minutes per day; 3 months | Improved continence; improved quality of life | 2009 | [96] |
4. Other Methods of Electrical Neuromodulation
4.1. Sacral Nerve Stimulation in IBD Therapy
4.2. SNS Efficacy in Animal Models
4.3. SNS Clinical Studies in IBD and Other Conditions
4.4. Tibial Nerve Stimulation in IBD Therapy and Other Conditions
5. Electrical Neuromodulation for Concurrent GI Motility Disorders in Quiescent IBD
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Animal Models | Disease Models | Stimulation Type | Electrodes Locations | Pulse Features | Stimulation and Treatment Durations | Major Findings | References |
---|---|---|---|---|---|---|---|
Adult male Sprague-Dawley rats | TNBS-induced colitis | VNS | Wrapped around the left cervical vagus nerve and carotid | 1 mA, 5Hz, 500 us interval, 10 s ON, 90 s OFF; continuous cycle | 3 h per day; 5 consecutive days | Reduced weight loss, improved histology, lessened colitis and inflammation | [80] |
Adult male and female Sprague-Dawley rats | TNBS-induced colitis | VNS | Bipolar coil electrodes were placed around the left cervical vagus nerve and left carotid artery | 0.25 mA, 20 Hz, 500 ms pulse width, 30 s ON, 5 min OFF continuously | 3 h per day; 6 consecutive days | Lowered disease activity, reduced colonic damage, decreased myeloperoxidase, NO synthase, TNF-α, IL-6; inhibited MAPKs phosphorylation and NF-kB p65 translocation | [81] |
Adult male Sprague-Dawley rats | TNBS-induced colitis | VNS | One pair of electrodes implanted around the left cervical vagal nerve, 3–5 mm apart | VNS1: 1.0–3.0 mA, 25 Hz, 0.5 ms pulse width, 2 s ON, 3 s OFF VNS2: 1.0–3.0 mA. 40 Hz, 0.5 ms pulse width, 2 s ON, 3 s OFF VNS3: 1.0–3.0 mA, 5 Hz, 0.5 ms pulse width, 10 s ON, 90 s OFF | 3 h daily; 21 consecutive days | Reduced DAI, improved macroscopic and histological scores, decreased pro-inflammatory cytokines, increased vagal and decreased sympathetic activity | [82] |
Adult male Sprague-Dawley rats | TNBS-induced colitis | SNS | One pair of electrodes placed around the S3 nerve behind the sacral foramen | N/A mA, 5 Hz, 0.5 ms pulse width, 10 s ON, 90 s OFF | 1 h daily; 10 consecutive days | Lowered DAI, normalized colon length, increased acetylcholine and anti-inflammatory cytokines, decreased pro-inflammatory cytokines | [83] |
Adult male Sprague-Dawley rats | Colitis induced by 5% DSS | SNS | One pair of electrodes placed around S3 right sacral nerve | N/A mA, 5 Hz, 0.5 ms pulse width, 10 s ON, 90 s OFF | 1 h daily; 10 consecutive days | Reduced DAI and colonic damage, improved histology, lowered TNF-α, altered neurotransmitter levels | [84] |
Adult male Sprague-Dawley rats | TNBS-induced colitis | SNS | Bipolar: one pair of electrodes placed circumferentially around the nerve behind the right S3 sacral nerve, 3–4 mm apart; Unipolar: one electrode placed circumferentially around the nerve behind the right S3 sacral root; second electrode sutured on the muscle 10 mm apart; Bilateral: two electrodes in pair placed circumferentially around the right and left sacral roots | Optimized: N/A mA, 5 Hz, 0.5 ms pulse width, 10 s ON, 90 s OFF; Alternative: N/A mA, 14 Hz, 0.21 ms pulse width, continuous stimulation | 0.5 h, 1 h, and 3 h daily, with 1 h being the most effective; 10 consecutive days | 1h daily, 5 Hz bipolar SNS most effective; lowered DAI, reduced inflammation, balanced cytokine levels | [85] |
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Dilixiati, S.; Yan, J.; Qingzhuoga, D.; Song, G.; Tu, L. Exploring Electrical Neuromodulation as an Alternative Therapeutic Approach in Inflammatory Bowel Diseases. Medicina 2024, 60, 729. https://doi.org/10.3390/medicina60050729
Dilixiati S, Yan J, Qingzhuoga D, Song G, Tu L. Exploring Electrical Neuromodulation as an Alternative Therapeutic Approach in Inflammatory Bowel Diseases. Medicina. 2024; 60(5):729. https://doi.org/10.3390/medicina60050729
Chicago/Turabian StyleDilixiati, Suofeiya, Jiaxi Yan, De Qingzhuoga, Gengqing Song, and Lei Tu. 2024. "Exploring Electrical Neuromodulation as an Alternative Therapeutic Approach in Inflammatory Bowel Diseases" Medicina 60, no. 5: 729. https://doi.org/10.3390/medicina60050729