Acute physiological and electrical accentuation of vagal tone has no effect on pain or gastrointestinal motility in chronic pancreatitis

Abstract

Jacob Juel,1 Christina Brock,1–4 Søren S Olesen,1,2 Adnan Madzak,5 Adam D Farmer,5–7 Qasim Aziz,7 Jens B Frøkjær,2,5 Asbjørn Mohr Drewes1,2 1Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, 2Department of Clinical Medicine, Aalborg University, Aalborg, 3Department of Rheumatology, Aarhus University Hospital, Aarhus, 4Drug Design and Pharmacology, University of Copenhagen, Copenhagen, 5Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark; 6Department of Gastroenterology, University Hospitals of North Midlands, Stoke-on-Trent, 7Centre for Neuroscience and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK Background: The effective management of pain in chronic pancreatitis (CP) remains a therapeutic challenge. Analgesic drugs, such as opioids, and the underlying pathology can impair gut function. The autonomic nervous system influences hormone secretion and gut motility. In healthy volunteers, electrical (using noninvasive transcutaneous vagal nerve stimulation [t-VNS]) and physiological (using deep slow breathing [DSB]) modulation of parasympathetic tone results in pain attenuation and enhanced gut motility. Thus, the aims were to investigate whether t-VNS and DSB could enhance the parasympathetic tone, decrease pain sensitivity and improve gut motility in CP.Patients and methods: A total of 20 patients (12 males, mean age=61 years, range: 50–78 years) with CP were randomized to short-term (60 minutes) t-VNS and DSB, or their placebo equivalent, in a crossover design. Cardiometrically derived parameters of autonomic tone, quantitative sensory testing of bone and muscle pain pressure, conditioned pain modulation (CPM) and assessments of gastroduodenal motility with ultrasound were performed.Results: In comparison to sham, t-VNS and DSB increased cardiac vagal tone (CVT) (P<0.001). However, no changes in pain pressure thresholds for bone (P=0.95) or muscle (P=0.45) were seen. There was diminished CPM (P=0.04), and no changes in gastroduodenal motility were observed (P=0.3).Conclusion: This explorative study demonstrated that t-VNS and DSB increased CVT in patients with CP. However, this short-lasting increase did not affect pain sensitivity to musculoskeletal pain or gastroduodenal motility. The chronic pain in CP patients is complex, and future trials optimizing neuromodulation for pain relief and improved motility are needed. Keywords: pain, chronic pancreatitis, autonomic nervous system, vagus nerve, gut, motility

Keywords

• Pain
• Chronic pancreatitis
• Autonomic nervous system
• Vagus nerve
• Gut
• Motility