# Novel target identification for treatment of chronic overlapping pain using multimodal brain imaging

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $2,980,325

## Abstract

Chronic overlapping pain conditions (COPCs) are idiopathic pain conditions that have minimal identifiable
origins in organic disease and represent a highly significant pain management challenge for physician and
patient. They occur in tens of millions of Americans with annual costs exceeding $100 billion. Epidemiological
data indicate many of these conditions overlap in presentation in the same patient, with odds of presenting 2 or
more conditions exceeding 50%. Often spatially separate areas of the body are affected (e.g.,
temporomandibular disorder (TMD) and irritable bowel syndrome (IBS)), which strongly suggests the
involvement of central nervous system mechanisms. Additionally, stress triggers or exacerbates many of these
conditions, which occur more frequently or exclusively in women. The convergence of pain from different
peripheral tissues and perceived stress most likely occurs in the brain. We propose an innovative
multidisciplinary discovery-driven approach to identify novel targets for therapeutic intervention to treat these
chronic pain conditions. We will use a recently reported rat model of comorbid pain hypersensitivity: masseter
muscle inflammation followed by stress inducing de novo chronic visceral hypersensitivity, a defining
characteristic of IBS. Combining visceral and orofacial pain measurement in awake animals, functional
magnetic resonance imaging, mass spectrometry imaging of brain sections, and genetic and molecular
approaches will allow identification of specific lipids and their metabolic pathways that change expression in
the brain during the transition from acute to chronic overlapping pain. A longitudinal design will allow changes
in brain activity in individual animals to be followed over weeks to months. In addition, areas of the brain that
contribute to known sex differences in the magnitude and duration of the stress-induced and comorbid
hypersensitivity should be identified. In three specific aims we will: 1) Identify changes in structure/function of
brain regions in response to stress alone and pain plus stress which correlate with changes in visceral
sensitivity and orofacial mechanosensitivity in male and female rats. Further, we will identify lipid moieties and
the underlying metabolic pathways that change between baseline, acute and chronic pain conditions; 2)
determine the effect of genetic knockdown of identified metabolic pathways in rat models of stress-induced and
comorbid pain hypersensitivity. siRNA microinjected into brain regions identified in Aim 1 will be used to
knockdown expression of enzymes that mediate the changes in lipid expression in the rat models. The effects
of siRNA on the sensory and affective components of pain will be examined to help identify “drugable targets”
for therapeutic intervention; and 3) Use pharmacological tools to test identified targets in order to confirm the
clinical utility in reversing these conditions. The proposed studies will significantly advance understandi...

## Key facts

- **NIH application ID:** 9966115
- **Project number:** 1R01DE029074-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Ohannes Kevork Melemedjian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,980,325
- **Award type:** 1
- **Project period:** 2020-09-10 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966115

## Citation

> US National Institutes of Health, RePORTER application 9966115, Novel target identification for treatment of chronic overlapping pain using multimodal brain imaging (1R01DE029074-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9966115. Licensed CC0.

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