Cervical transcutaneous vagal neuromodulation in chronic pancreatitis patients with chronic pain: A randomised sham controlled clinical trial

Janusiya Anajan Muthulingam, Søren Schou Olesen, Tine Maria Hansen, Christina Brock, Asbjørn Mohr Drewes, Jens Brøndum Frøkjær, Janusiya Anajan Muthulingam, Søren Schou Olesen, Tine Maria Hansen, Christina Brock, Asbjørn Mohr Drewes, Jens Brøndum Frøkjær

Abstract

Background & aims: Chronic abdominal pain is the primary symptom of chronic pancreatitis, but unfortunately it is difficult to treat. Vagal nerve stimulation studies have provided evidence of anti-nociceptive effect in several chronic pain conditions. We investigated the pain-relieving effects of transcutaneous vagal nerve stimulation in comparison to sham treatment in chronic pancreatitis patients.

Methods: We conducted a randomised double-blinded, sham-controlled, crossover trial in patients with chronic pancreatitis. Patients were randomly assigned to receive a two-week period of cervical transcutaneous vagal nerve stimulation using the gammaCore device followed by a two-week sham stimulation, or vice versa. We measured clinical and experimental endpoints before and after each treatment. The primary clinical endpoint was pain relief, documented in a pain diary using a visual analogue scale. Secondary clinical endpoints included Patients' Global Impression of Change score, quality of life and Brief Pain Inventory questionnaire. Secondary experimental endpoints included cardiac vagal tone and heart rate.

Results: No differences in pain scores were seen in response to two weeks transcutaneous vagal nerve stimulation as compared to sham treatment (difference in average pain score (visual analogue scale): 0.17, 95%CI (-0.86;1.20), P = 0.7). Similarly, no differences were seen for secondary clinical endpoints, except from an increase in the appetite loss score (13.9, 95%CI (0.5:27.3), P = 0.04). However, improvements in maximum pain scores were seen for transcutaneous vagal nerve stimulation and sham treatments as compared to their respective baselines: vagal nerve stimulation (-1.3±1.7, 95%CI (-2.21:-0.42), P = 0.007), sham (-1.3±1.9, 95%CI (-2.28:-0.25), P = 0.018). Finally, heart rate was decreased after two weeks transcutaneous vagal nerve stimulation in comparison to sham treatment (-3.7 beats/min, 95%CI (-6.7:-0.6), P = 0.02).

Conclusion: In this sham-controlled crossover study, we found no evidence that two weeks transcutaneous vagal nerve stimulation induces pain relief in patients with chronic pancreatitis.

Trial registration number: The study is registered at NCT03357029; www.clinicaltrials.gov.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. CONSORT diagram.
Fig 1. CONSORT diagram.
Study enrolment and randomisation.
Fig 2. Study design & treatment procedure:…
Fig 2. Study design & treatment procedure: Patients were instructed to self-administer the treatment bilaterally on the neck three times per day for two weeks at home.
The treatment was delivered via two stainless steel contact surfaces that were covered with conductive gel before each treatment.
Fig 3
Fig 3
Average pain score during the two study periods for the two sequences (nVNS/sham in black and sham/nVNS in grey). VAS = visual analogue scale.

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