# Boosting mind-body mechanisms and outcomes for chronic pain

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $2,181,778

## Abstract

Abstract
While many mind-body therapies have shown promise for chronic pain, the efficacy of any single-modality
treatment is typically modest, and finding a way to boost clinical outcomes is a crucially important goal. It is
well documented, and recommended in the recent Institute of Medicine (IOM) report on pain, that a multimodal
approach is optimal for pain management. Multimodal analgesic strategies are thought to enhance benefits to
patients by simultaneously targeting multiple pathways that contribute to chronic pain. Mind-body therapies
have shown promise for pain, and many such therapies (e.g., mindfulness meditation (MM) training) are
actually characterized as predominantly “mind,” taking advantage of top-down brain-based mechanisms of
action, without fully integrating bottom-up “body”-based mechanisms. A greater use of “mind” and “body”
elements via a multimodal therapeutic approach may enhance clinical outcomes through neurophysiological
integration within the central nervous system (i.e., brain). Our overall goal in this proposal is to evaluate how
and where such integration takes place for a common chronic pain disorder - migraine. Our 3 Projects will
target 3 critical and inter-related pathophysiological processes that characterize migraine headache, and how
both “top-down” and “bottom-up” interventions mitigate this pathology. To augment MM training, we propose a
specifically-targeted, bottom-up therapy that has also shown promise for migraine - transcutaneous vagus
nerve stimulation (tVNS). We will use a recently developed optimized tVNS approach that gates stimulation to
the respiratory rhythm (i.e., respiratory-gated auricular vagal afferent nerve stimulation, RAVANS), which
enhances the potential synergy, both conceptually and neurophysiologically, of combining tVNS with MM, with
its own focus of non-judgmental attention on breathing with a calm and alert mind. All three projects will apply
neuroimaging and other physiological and behavioral tools at baseline and following 8-weeks of a combination
of RAVANS or Sham tVNS with MM or education control. Aim 1, addressed by Project 1, will investigate
brainstem and cortical mechanisms for reducing cortical/subcortical hyperexcitability. Aim 2, addressed by
Project 2, will evaluate MM+RAVANS tVNS improvements in autonomic and central autonomic network
dysfunction. Aim 3, addressed by Project 3, will use multimodal PET/MR imaging and a recently developed
ligand for glial activation to assess anti-neuroinflammatory effects of MM+RAVANS tVNS therapy. Aim 4 will
investigate how the neurobiological changes assessed in Aims 1 to 3 are inter-related through mediation and
other analyses performed by the Neuroimaging and Biostatistical Core, while the Clinical Core and
Administrative Core will support recruitment and administration of our synergistic study design.

## Key facts

- **NIH application ID:** 10456004
- **Project number:** 5P01AT009965-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** VITALY NAPADOW
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,181,778
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456004

## Citation

> US National Institutes of Health, RePORTER application 10456004, Boosting mind-body mechanisms and outcomes for chronic pain (5P01AT009965-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10456004. Licensed CC0.

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