# Acute-to-Chronic Transition in Ergonomic Muscle Pain: Nociceptor Mechanisms

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $621,503

## Abstract

Abstract
Chronic musculoskeletal pain is a very common and frequently disabling condition that affects up to 50% of the
adult population worldwide, having a huge impact on quality of life and economic burden, loses related to
medical expenses, lower labor productivity and increased compensation claims. Unfortunately, our lack of
understanding of the mechanisms underlying this condition has precluded the development of rationale, safe
and effective therapies. While some people display resilience to chronic musculoskeletal pain, research has
only focused on the psychological aspects involved in such resilience. However, growing evidence suggests
that, in addition to psychological factors, a physical component is critical to achieve resilience to chronic pain
and that failure to display adequate reparative and/or regenerative responses is associated with persistent
pain. The phenomenon of repeated bout effect (RBE) is a common and natural example of the involvement of
an endogenous reparative response (i.e., physical resilience) to muscle injury and persistent pain. Initial
exposure to strenuous muscle activity produces significant pain, loss of force and tissue damage, which over
time resolves without any external intervention. Re-exposure to the same activity, will however, produce much
less pain, dysfunction and tissue damage, suggesting that physical resilience is enhanced by the muscle
activity. Although recent research has underlined the importance of immune, endocrine and neural responses
in muscle repair and regeneration, whether they also contribute to recovery from persistent musculoskeletal
pain is unknown. Furthermore, whether exposure to stress or repetitive ergonomic tasks interferes with
physical resilience, leading to chronic musculoskeletal pain, remains unknown. We plan to combine our
expertise in several experimental approaches and our new preclinical model of RBE to study physical
resilience, to achieve the three major goals of this proposal: (1) elucidate the role of muscle activity in physical
resilience, with emphasis on mechanisms of ergonomic injury-induced chronic muscle pain; (2) evaluate the
interaction between stress and physical resilience on chronic musculoskeletal pain, especially in regard to the
role of early-life interventions on physical resilience and muscle nociceptor hyperexcitability; and, (3) assess
the effect of physical resilience on neuropathic muscle pain, with emphasis on cellular and molecular
mechanisms of muscle nociceptor dysfunction.
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## Key facts

- **NIH application ID:** 9872987
- **Project number:** 5R01AR063312-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** JON DAVID LEVINE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $621,503
- **Award type:** 5
- **Project period:** 2013-03-05 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872987

## Citation

> US National Institutes of Health, RePORTER application 9872987, Acute-to-Chronic Transition in Ergonomic Muscle Pain: Nociceptor Mechanisms (5R01AR063312-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9872987. Licensed CC0.

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