# Resolution of postoperative pain by complementary approaches

> **NIH NIH P01** · DUKE UNIVERSITY · 2020 · $301,505

## Abstract

Abstract
Millions of individuals in the United States undergo surgery every year for medically necessary conditions and
are at risk for developing chronic pain especially following traumatic procedures like orthopedic surgery.
Excessive inflammation and unresolved pain remain leading causes of morbidity, in particular among the rapidly
growing elderly population. Our long-term goal is to define the mechanisms that underlie the conversion of acute
to persistent postoperative pain, and to provide safe and effective approaches to reduce this potentially
devastating complication. In the proposed study, we will model postoperative pain using a clinically relevant
model of orthopedic surgery (tibial fracture) combined with stress, which is a common to virtually every patient
undergoing major surgery. The overall objective of the work proposed in this project is to evaluate the role of
complementary and integrative health approaches to reduce, and possibly resolve, postoperative pain. Our
central hypothesis is that surgery-induced neuroinflammation is crucial to the modulation of postoperative pain,
and is exacerbated by a stressful event. Targeting of pro-resolving and vagal-mediated signaling can reverse
this persistent pain. This hypothesis is based on preliminary data acquired in the applicants’ laboratories, and
will be tested by pursuing 3 specific aims: 1) Analyze the effects of stress and sex on surgery-induced
neuroinflammation and pain behavior; 2) Determine the effects of natural compounds including docosahexaenoic
acids, menthol, and eucalyptol, on neuroinflammation and pain behavior after orthopedic surgery; and 3)
Characterize the ability of bioelectronic approaches (electroacupuncture and vagus nerve stimulation) to reduce
pain and neuroinflammation after orthopedic surgery. Feasibility for these models and techniques has been
established in the applicants’ hands. In this innovative approach, novel complementary bioelectronic strategies,
including minimally invasive vagus nerve stimulation, circuit mapping methods, and postmortem analyses of
clarified tissues will be combined with rigorous immunophenotyping and behavioral testing to define and
modulate pain-related signaling after surgery. The rationale for the proposed research is that successful
completion will advance and expand our understanding of how multiple complementary and integrative health
approaches affect fundamental molecular mechanisms of relevance to pain signaling and perioperative recovery.
Such knowledge is highly significant because it has the potential to improve surgical outcome, reduce opioid
requirements, and enhance quality of life for millions of patients in the United States.

## Key facts

- **NIH application ID:** 9703535
- **Project number:** 1P01AT009968-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Niccolo Terrando
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $301,505
- **Award type:** 1
- **Project period:** 2020-04-20 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9703535

## Citation

> US National Institutes of Health, RePORTER application 9703535, Resolution of postoperative pain by complementary approaches (1P01AT009968-01A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9703535. Licensed CC0.

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