# Core 2: Pain Mechanisms Core

> **NIH NIH P50** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $218,147

## Abstract

PROJECT SUMMARY / ABSTRACT 
 PAIN MECHANISMS CORE (PMC) 
The University of Michigan Fibromyalgia (FM) CORT proposes that presence of centralized pain will render 
individuals less responsive to analgesic therapies aimed at peripheral/nociceptive pain (surgery, biologics, 
opioids) and that this centralized pain phenotype has stereotypical clinical and neurobiological features similar 
to FM even when it is co-morbid with other musculoskeletal pain conditions with disparate underlying pain 
mechanisms. The PMC will use quantitative sensory testing (QST) and neuroimaging methods to characterize 
the degree of centralization in three cohorts of musculoskeletal pain patients: osteoarthritis of the hip, 
rheumatoid arthritis, and carpal tunnel syndrome. We will collect these same measures in individuals with FM 
and heathy controls, which will enable us to demonstrate that these neurobiological measures are increasingly 
abnormal in the transition from low (healthy controls) to high degrees of fibromyalgia (FM cohort). The Specific 
Aims of the CORT supported by the PMC are as follows: 1) To demonstrate that individuals with the highest 
FM Survey Criteria scores will have similar neurobiological findings of pain centralization, including abnormal 
QST findings and aberrant findings on functional, chemical and structural neuroimaging. We hypothesize that 
in all three musculoskeletal pain cohorts, the individuals with greater degrees of pain centralization (i.e. highest 
scores on the FM Survey Criteria) will demonstrate a) more hyperalgesia and decreased pain inhibition on 
QST and functional magnetic resonance imaging (fMRI), b) characteristic functional connectivity changes on 
fMRI (e.g., decreased functional connectivity to descending antinociceptive brain networks and increased 
connectivity to pronociceptive regions), c) increased CNS levels of excitatory neurotransmitters in 
pronociceptive regions on proton spectroscopy (i.e., glutamate in posterior insula), and d) increases in primary 
somatosensory/motor cortex volume. 2) To identify the clinical and mechanistic features of two important 
subsets of centralized pain: top-down activity independent centralization (i.e. previously termed primary FM) 
vs. bottom-up activity-dependent pain centralization or central sensitization (i.e. previously termed secondary 
FM) by exploring changes in QST/MRI measures in OA and carpel tunnel patients 6 months following surgery. 
It is critically important to better understand these mechanistic phenotypes of centralization since one group 
will benefit more from aggressive analgesic therapy aimed at the periphery.

## Key facts

- **NIH application ID:** 10266750
- **Project number:** 5P50AR070600-05
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** RICHARD E HARRIS
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $218,147
- **Award type:** 5
- **Project period:** 2016-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10266750

## Citation

> US National Institutes of Health, RePORTER application 10266750, Core 2: Pain Mechanisms Core (5P50AR070600-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10266750. Licensed CC0.

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