# Real-time imaging of skeletal muscle innervating sensory neurons that signal pain and fatigue

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $479,680

## Abstract

Muscle pain and fatigue affect nearly all people at some time in their lives. At present, effective treatments for
short term muscle pain are clearly inadequate and adequate treatment for chronic muscle pain is even worse.
Considerable evidence indicates that peripheral sensory dysregulation of group III/IV muscle afferents, and
autonomic dysregulation may cause or contribute to both short-term and chronic muscle pain and fatigue.Our
long term goal is to determine the fundamental mechanisms that signal intense muscle pain, ache and fatigue
to sensory and motor systems. We have previously used discoveries in mouse models to prove that
combinations of protons, lactate, and ATP are necessary and sufficient to activate muscle sensory neurons. In
translational studies in human subjects we showed that combination of these three metabolites activated the
sensations of muscle ache and fatigue in human subjects. We propose here to use several transgenic mice
that will make it possible, for the first time, to determine the molecular, cellular, and structural mechanisms of
the sensory signaling pathways for the cognitive sensations of muscle pain and muscle fatigue. These mice
will also make it possible for us to determine the many different types of afferents that selectively signal the
many different aspects of autonomic function that allow us to function over a wide range of muscle blood flow.
Finally, these mice will make it possible for us to directly image not only the cell bodies of the muscle
innervating neurons, but to directly observe the activation of the nerve endings in skeletal muscles by both
metabolites and mechanical stimulation. These images may allow us to determine the mechanisms for “trigger
points”, the pulsating nature of muscle ache, lymphatic disease associated with muscle fatigue and pain, and
sympathetic activation of enhanced muscle pain.
The specific aims of this proposal are:
Aim 1: Define the different types of mechanosensitive, and metabosensitive sensory neurons
innervating skeletal muscle based on their responses to muscle contraction.
Aim 2: Determine if chemical mediators produced during muscle contraction are responsible for the
potentiation seen among a subset of mechanosensitive muscle sensory neurons during muscle
contraction.
Aim 3: Determine if metaboreceptors and metabo-nociceptors also respond to mechanical forces
generated during muscle contraction.
Aim 4: Determine the location and structure of skeletal muscle sensory neurons signaling pain and
fatigue via direct imaging of neuron terminals.

## Key facts

- **NIH application ID:** 10199073
- **Project number:** 5R01NS109140-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Charles Jeffery WOODBURY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $479,680
- **Award type:** 5
- **Project period:** 2018-09-18 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199073

## Citation

> US National Institutes of Health, RePORTER application 10199073, Real-time imaging of skeletal muscle innervating sensory neurons that signal pain and fatigue (5R01NS109140-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10199073. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*