Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats

Nicholas S Gregory; Phillip E Whitley; Kathleen A Sluka

doi:10.1371/journal.pone.0138576

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Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats

Journal article

Open access

Peer reviewed

Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats

Nicholas S Gregory, Phillip E Whitley and Kathleen A Sluka

PloS one, Vol.10(9), p.e0138576

2015

DOI: 10.1371/journal.pone.0138576

PMCID: PMC4574767

PMID: 26378796

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Abstract

Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans. These substances directly activate purinergic (P2X) and acid sensing ion channels (ASICs) on muscle nociceptors, and when combined, produce a greater increase in neuron firing than when given alone. Whether the enhanced effect of combining protons, lactate, and ATP is the sum of individual effects (additive) or more than the sum of individual effects (synergistic) is unknown. Using a rat model of muscle nociceptive behavior, we tested each of these compounds individually over a range of physiologic and supra-physiologic concentrations. Further, we combined all three compounds in a series of dilutions and tested their effect on muscle nociceptive behavior. We also tested a non-hydrolyzable form of ATP (α,β-meATP) alone and in combination with lactate and acidic pH. Surprisingly, we found no dose-dependent effect on muscle nociceptive behavior for protons, lactate, or ATP when given alone. We similarly found no effect after application of each two-metabolite combination. Only pH 4 saline and α,β-meATP produced hyperalgesia when given alone. When all 3 substances were combined, however, ATP (2.4μm), lactate (10mM), and acidic pH (pH 6.0) produced an enhanced effect greater than the sum of the effects of the individual components, i.e. synergism. α,β me ATP (3nmol), on the other hand, showed no enhanced effects when combined with lactate (10mM) or acidic pH (pH 6.0), i.e. additive. These data suggest that combining fatigue metabolites in muscle produces a synergistic effect on muscle nociception.

Protons

Hyperalgesia - metabolism

Lactic Acid - metabolism

Rats

Male

Pain - metabolism

Rats, Sprague-Dawley

Adenosine Triphosphate - analogs & derivatives

Animals

Adenosine Triphosphate - metabolism

Nociceptors - metabolism

Muscle Fatigue - physiology

Muscles - metabolism

Acid Sensing Ion Channels - metabolism

Hydrogen-Ion Concentration

Details

Title: Subtitle: Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats
Creators: Nicholas S Gregory - Neuroscience Graduate Program, University of Iowa, Iowa City, Iowa, United States of America
Phillip E Whitley - CFD Research Corporation, Huntsville, Alabama, United States of America
Kathleen A Sluka - Neuroscience Graduate Program, University of Iowa, Iowa City, Iowa, United States of America; Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, Iowa, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.10(9), p.e0138576
DOI: 10.1371/journal.pone.0138576
PMID: 26378796
PMCID: PMC4574767
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: R01 AR061371 / NIAMS NIH HHS T32 GM007337 / NIGMS NIH HHS T32 NS045549 / NINDS NIH HHS
Language: English
Date published: 2015
Academic Unit: Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
Record Identifier: 9984040011502771

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