# The role of expectation in the pain-trauma co-morbidity among Veterans

> **NIH VA I01** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2024 · —

## Abstract

Posttraumatic Stress Disorder (PTSD) is highly co-morbid with chronic pain conditions. Pain contributes to
more severe PTSD (and vice versa) as evidenced by greater disability, more frequent use of harmful opioid
analgesics and increased pain severity. Biomechanisms underlying the entanglement of pain and trauma in
Veterans are incompletely understood. This is a renewal application (CSR&D Merit Review CX000816) to
continue deciphering the neural networks underlying pain and PTSD co-morbidity in Veterans. The long-term
goal is to determine biological markers of heterogeneity within pain-trauma co-morbidity in order to improve
symptom prevention and treatments. Understanding unique and overlapping impact of pain and/or trauma
symptoms on the underlying neurocircuitry has the potential to optimize existing and pave way to developing
new, biologically targeted interventions. The objective of this renewal is to build upon our prior findings and
identify the role of expectation in pain-trauma comorbidity in diagnostically heterogeneous Veterans with
combat trauma and chronic pain. Our current hypotheses are based on our published and strong preliminary
data. We propose to test the “two-component” expectation or anticipation model whereby neural systems
underlying anticipation of pain onset (broken in traumatic stress) and pain offset (broken in chronic pain)
interact to create biomechanistic vulnerability for pain-trauma comorbidity. We will examine the integrity (i.e.,
connectivity) and capability (i.e., function) of neural networks underlying pain and pain relief anticipation in
diagnostically heterogeneous cohort of Veterans. We will employ advanced neuroimaging (rest and task-based
functional MRI) and advanced statistical approaches to uncover multivariable anticipatory biophenotypes within
Veterans with comorbid pain and trauma. Aim1: To determine the degree to which traumatic stress affects the
capability and integrity of pain anticipation Hypothesis 1a: Traumatic stress will be associated with abnormal
pain anticipation response within insula and amygdala during task-based fMRI; Hypothesis 1b: Traumatic
stress will disrupt fronto-amygdala-insular connectivity at rest. Aim2: To determine the degree to which chronic
pain affects the capability and integrity of relief anticipation. Hypothesis 2a: Chronic pain will be associated with
abnormal pain relief anticipation within insula and cingulate during task-based fMRI; Hypothesis 2b: Chronic
pain will disrupt fronto-striatal-insula connectivity at rest. Exploratory Aim3: Build robust biophenotypes based
on subgrouping anticipatory mechanisms. We will utilize clustering approaches including, but not limited to,
graph-based models. The best model will be determined through analysis of training, test, and validation
samples. Hypothesis 3: We will be able to separate pain anticipation vs. relief anticipation biophenotypes in
diagnostically heterogeneous Veterans with combat trauma and chronic pain. This ...

## Key facts

- **NIH application ID:** 10804928
- **Project number:** 2I01CX000816-05A2
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Irina A Strigo
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10804928

## Citation

> US National Institutes of Health, RePORTER application 10804928, The role of expectation in the pain-trauma co-morbidity among Veterans (2I01CX000816-05A2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10804928. Licensed CC0.

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