# Chronic postoperative pain: Genetic and Neural Circuit Mechanisms

> **NIH NIH R35** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $381,250

## Abstract

PROJECT SUMMARY
Chronic (or persistent) postoperative pain (CPOP) is a potentially devastating outcome from an otherwise
successful surgical procedure. It affects millions of patients every year, with pain lasting for months to years,
resulting in patient suffering and resulting economic hardship. The surgeries with the highest incidence of chronic
postoperative pain are amputations, thoracotomies, cardiac, and breast surgery. Other risk factors include
preoperative pain, psychological factors, demographics, and the intensity of acute postoperative pain. Attempts
to prevent chronic postoperative pain have largely been unsuccessful, with no change in the incidence despite
increased use of regional and multimodal analgesia. Therefore, further research is needed to identify biomarkers
to accurately predict those at risk for developing chronic postoperative pain and treatments that reduce the
incidence. We hypothesize that Diffuse Noxious Inhibitory Control (DNIC) efficiency is predictive of who will
develop chronic postoperative pain. Thus, a better understanding of the mechanisms responsible for DNIC will
result in more efficacious treatments. We would expect that patients or animal models with less efficient DNIC
would be ‘at risk’ for developing chronic pain when exposed to the painful stimulus of surgery. Our overall
objectives in this application are to use a new model of persistent postoperative pain, the Dahl S rat, to investigate
the involvement of serotonin, catecholamine and dopamine systems on DNIC using pharmacologic,
chemogenetic and optogenetic approaches. We will also investigate which genetic polymorphism(s) are
responsible for the persistent postoperative pain experienced by the Dahl S rat. This will be accomplished in
three projects. Project 1: will determine the relationship between DNIC and CPOP. DNIC responses will be
abolished in Sprague Dawley rats and restored in Dahl S rats, and the resultant effects on postoperative pain
persistence ascertained. We will also test the hypothesis that the absent DNIC response in SS rats is a result
of increased nociceptive facilitation by serotonergic “on cells” in the rostral ventral medulla by optogenetically
inhibiting serotonergic neurons in the spinal cord. Project 2 will examine the role of periaqueductal gray
dopamine neurons on DNIC and postoperative pain using a Dahl S rat expressing a novel variant of the
Catecholamine-O-methyltransferase gene that increases dopaminergic tone. Project 3 will use a powerful
physiologic genomics approach, the use of consomic and congenic rats, to identify the gene polymorphism(s)
responsible for the absent DNIC response and persistent postoperative pain exhibited by Dahl S rats. We expect
our studies to provide genetic and phenotypic biomarkers to guide diagnosis and treatment decisions in chronic
postoperative pain.

## Key facts

- **NIH application ID:** 10029233
- **Project number:** 1R35GM138168-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Norman Taylor
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10029233

## Citation

> US National Institutes of Health, RePORTER application 10029233, Chronic postoperative pain: Genetic and Neural Circuit Mechanisms (1R35GM138168-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10029233. Licensed CC0.

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