Chronic muscle pain syndromes (e.g. low back pain, myofascial pain, and pain induced by repeated exertion or exposure to mechanical vibrations), are common, debilitating, and very costly to society. Chronic muscle pain remains extremely difficult to treat, in large part due to the lack of understanding of underlying mechanisms. Much current muscle pain research focuses on the effects of strain on muscle and tendon tissue, but does not address pathophysiological mechanisms specifically responsible for chronic muscle pain. Importantly, virtually nothing is known about the cellular mechanisms underlying the critical transition from acute to chronic muscle pain. We propose an approach that will directly target the pathophysiological mechanisms of muscle pain, focusing on the transition from acute to chronic pain states. This investigation will integrate behavioral, electrophysiological and cell biological methods to link observations on cellular mechanisms to pain-related behavior in the animal.
In Specific Aim 1, we will characterize the acute pain state, identifying the pronociceptive effects of two mediators and second messengers produced by abnormal activity in muscle that affect primary afferent nerve fiber function.
In Specific Aim 2, we will investigate the cellular mechanisms engaged by the acute pain state that cause it to evolve into a chronic condition of prolonged hyperalgesia. We have already performed critical preliminary studies that have revealed a profound, long- lasting muscle hyperalgesia produced by inflammation and data that strongly suggest our approach can reveal fundamental mechanisms of muscle pain syndromes. In this application, we propose to study cellular mechanisms of the transition from acute to chronic muscle pain in animal models of muscle pain syndromes. These studies have the potential to identify novel targets for the development of new pharmacological therapies for the treatment of this debilitating condition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR054635-05
Application #
8122306
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Tonkins, William P
Project Start
2007-08-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$309,385
Indirect Cost
Name
University of California San Francisco
Department
Dentistry
Type
Schools of Dentistry
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Reichling, David B; Green, Paul G; Levine, Jon D (2013) The fundamental unit of pain is the cell. Pain 154 Suppl 1:S2-9
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Hendrich, J; Alvarez, P; Chen, X et al. (2012) GDNF induces mechanical hyperalgesia in muscle by reducing I(BK) in isolectin B4-positive nociceptors. Neuroscience 219:204-13
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Bogen, Oliver; Alessandri-Haber, Nicole; Chu, Carissa et al. (2012) Generation of a pain memory in the primary afferent nociceptor triggered by PKCε activation of CPEB. J Neurosci 32:2018-26

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