# Central oxytocin mechanisms of pain recovery following nerve injury

> **NIH NIH P01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $333,000

## Abstract

Oxytocin produces antinociception in rodents in a variety of pain states, however the
mechanisms by which this occurs and the importance of peripheral versus central effects are
unclear. Prior studies have typically used systemic administration of oxytocin, with dosing-to-
effect strategies in the absence of pharmacokinetic data or consideration of brain penetrance.
These studies can only be extrapolated to the clinic after relevant dosing parameters have been
determined experimentally to achieve peripheral and central oxytocin exposure across rodents
and humans, and using such parameters to compare antinociceptive efficacy against different
outcome measures, with subsequent exploration of potential mechanisms. This Project
translates and is informed by Projects 1 and 3 to define the pharmacokinetics of oxytocin in
awake and anesthetized rats in brain and blood and determine the relevance of peripheral and
central action of oxytocin on complex behaviors following nerve injury. Three specific aims are
proposed. The first aim will define the pharmacokinetics of oxytocin in plasma and brain using
i.v. bolus, and these data will be used to design targeted concentration infusion paradigms in
the PK/PD core. The rate of brain entry and loss will also be assessed. The second aim will take
advantage of a novel transgenic rat developed by our group that expresses Cre recombinase
selectively in oxytocinergic neurons. We will determine the role of endogenous oxytocin circuits
in modulation of complex behaviors after peripheral nerve injury using Cre dependent neuronal
ablative strategies, expressing mutated caspase 3 in targeted neurons. We have developed
novel behavioral methods that assess impairment of attention, fear avoidance, and affective and
sensory modalities of pain after nerve injury and use these innovative behavioral methods for
this aim. The third aim combines the knowledge gained from Aims 1 and 2 to assess the
efficacy of oxytocin in mitigating the behavioral changes induced by peripheral nerve injury,
tests the potential for oxytocin to produce long-lasting, disease-modifying effects in behavior
and afferent physiology, and the role of endogenous circuits in these effects. This project
interacts with Project 1 to assess the contribution of altered primary sensory afferent signaling in
complex behaviors and the relevance of oxytocin and with Project 3 to target relevant peripheral
levels of oxytocin in humans for peripheral and central action.

## Key facts

- **NIH application ID:** 10332264
- **Project number:** 1P01NS119159-01A1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** THOMAS JEFFREY MARTIN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $333,000
- **Award type:** 1
- **Project period:** 2022-04-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10332264

## Citation

> US National Institutes of Health, RePORTER application 10332264, Central oxytocin mechanisms of pain recovery following nerve injury (1P01NS119159-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10332264. Licensed CC0.

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