# Vagal nerve stimulation to probe inflammation and brain in posttraumatic stress

> **NIH VA IK2** · VA SAN DIEGO HEALTHCARE SYSTEM · 2020 · —

## Abstract

Abstract:
Rates of posttraumatic stress disorder (PTSD) are high among combat Veterans with estimates of PTSD within
Iraq and Afghanistan veterans at nearly 17% of active duty and over 24% of reserve service members that screen
positive for PTSD. Studies from the current and prior wars have demonstrated that mental disorders, in particular
PTSD, are associated with higher rates of: 1) physical symptoms, 2) chronic physical illness and 3) overall
mortality. Rates of comorbid PTSD and chronic pain are exceedingly high among veterans with reports of 30%-
50% in both Vietnam and OEF/OIF Veterans, that suggest a shared pathophysiology. Excessive release of
peripheral pro-inflammatory cytokines has been implicated in the generation of: 1) pathologic chronic pain states
and 2) in PTSD. Perception of an aversive stimulus/threat activates peripheral inflammatory cytokine release,
while exogenous administration of an inflammatory stimulus (that also cause release of peripheral inflammatory
cytokines) increases the limbic (insular cortex and amygdala) response to aversive/threat stimuli as measured
by functional Magnetic Resonance Imaging (fMRI). Work by our group [Lerman et al., (2016)(15)], shows that
PTSD influences the: 1) nociceptive response, 2) intrathecal cytokine release and 3) peripheral cytokine release
in response to a painful stimulus when compared to responses of Veteran combat controls (CC). Vagus nerve
stimulation has been shown to decrease: 1) peripheral inflammatory cytokine release, 2) pain, and 3) anxiety.
Recent work by our group has shown that non-invasive vagal nerve stimulation (nVNS; using extradermal
stimulation) decreases peripheral inflammation in healthy control subjects and may similarly decrease
hyperinflammation observed in PTSD [Lerman et al., (2016)(22)]. In pilot work, we have obtained initial fMRI
evidence (preliminary data) suggests that in healthy controls, nVNS decreases insular response to painful stimuli,
which is known to be dysregulated in PTSD.
We plan to use nVNS as a probe in PTSD and CC to observe the effects of vagal nerve modulation on: 1) CNS
neural circuit function during pain and pain anticipation stimuli, and 2) peripheral inflammatory biomarker
measures. The long-term goal of this line of research is to use nVNS as a probe to obtain pilot data of: 1)
peripheral inflammatory biomarkers and 2) fMRI derived brain imaging response to pain, to advance our
understanding of fundamental pathophysiology of co-morbid pain and PTSD and to ultimately provide, targeted
neuromodulation based interventions for veterans with pain and PTSD. We will study two groups [(PTSD, CC),
(both without chronic pain diagnosis)], under two conditions (either nVNS or Sham stimulation), over three time
points (pre-nVNS/Sham), (7 days post-nVNS/Sham) and one month after treatment (one month post-
nVNS/Sham). The first objective of this proposal, is to measure peripheral inflammation in response to nVNS
treatment in order to delineate pe...

## Key facts

- **NIH application ID:** 9922130
- **Project number:** 5IK2RX002920-02
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Imanuel Ruvin Lerman
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922130

## Citation

> US National Institutes of Health, RePORTER application 9922130, Vagal nerve stimulation to probe inflammation and brain in posttraumatic stress (5IK2RX002920-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9922130. Licensed CC0.

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