# Chronic postoperative pain: Genetic and Neural Circuit Mechanisms

> **NIH NIH R35** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $211,966

## Abstract

PROJECT SUMMARY
This supplemental equipment request is for a complete electrophysiology setup to confirm the proper functioning
of DREADDs and opsins in experiments described in Projects 1 and 2. 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. The addition of
slice electrophysiology to these experiments would provide important additional mechanistic insight into the
actions of these transmitters. 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
a...

## Key facts

- **NIH application ID:** 10581162
- **Project number:** 3R35GM138168-03S1
- **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:** 2022
- **Award amount:** $211,966
- **Award type:** 3
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10581162

## Citation

> US National Institutes of Health, RePORTER application 10581162, Chronic postoperative pain: Genetic and Neural Circuit Mechanisms (3R35GM138168-03S1). Retrieved via AI Analytics 2026-06-04 from https://api.ai-analytics.org/grant/nih/10581162. Licensed CC0.

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