Non-invasive Vagus Nerve Stimulation for Chronic Musculoskeletal Pain

Summary

Chronic musculoskeletal (MSK) pain affects an estimated 20-33% of the global population and is frequently associated with autonomic nervous system dysfunction, characterised by symptoms such as orthostatic intolerance, palpitations, gastrointestinal dysmotility, and fatigue. Conventional treatments often fail to address this autonomic component, limiting their effectiveness. This pilot study investigates whether non-invasive vagus nerve stimulation (nVNS) using the gammaCore Sapphire device can reduce autonomic symptom severity and improve pain in adults with chronic MSK pain and confirmed autonomic dysfunction.

RESTORE-MSK is a randomised, single-blind, sham-controlled, crossover pilot study. Twelve participants with chronic MSK pain (lasting 12 weeks or longer) and autonomic dysfunction (COMPASS-31 score of 17 or more) will be recruited from musculoskeletal clinics at Chapel Allerton Hospital, Leeds. Participants will be randomly allocated to receive either active nVNS or sham stimulation first, followed by a 2-week washout period, then crossover to the alternative treatment. Each treatment period lasts 14 days, with participants self-administering the device twice daily (morning and evening).

The primary outcome is change in autonomic symptom severity measured by the Composite Autonomic Symptom Score-31 (COMPASS-31). Secondary outcomes include physiological response to the NASA Lean Test, pain severity and interference (Brief Pain Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (EQ-5D-5L), intervention acceptability, and recruitment feasibility.

This pilot study aims to establish feasibility and proof of concept for a larger randomised controlled trial investigating nVNS as a non-pharmacological treatment option for chronic MSK pain with autonomic dysfunction.

Conditions

• Chronic Musculoskeletal Pain
• Autonomic Dysfunction
• Dysautonomia

Interventions

DEVICE

Active Vagus Nerve Stimulation

Stimulation parameters: The device delivers a proprietary electrical signal consisting of 5,000 Hz sine wave pulses repeated at 25 Hz. Intensity is set at a therapeutic level as advised by the research clinician, sufficient to activate the vagus nerve and produce perceptible muscle contractions in the neck.

DEVICE

Subtherapeutic Stimulation (Sham Control)

Stimulation parameters: The same gammaCore Sapphire device is used, with intensity set at a subtherapeutic level. This produces a perceptible sensation on the skin but does not activate the vagus nerve or cause the muscle contractions associated with therapeutic stimulation.

Sponsors & Collaborators

• The Leeds Teaching Hospitals NHS Trust

  collaborator OTHER

• University of Leeds

  lead OTHER

Principal Investigators

• Manoj Sivan, Prof · University of Leeds

• Darren C Greenwood, PhD · University of Leeds

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-14

Primary Completion

2026-07-09

Completion

2026-07-31

Countries

• United Kingdom

Study Locations