Muscle Reactive Oxygen Species (ROS) Contribute to Post-Incisional Guarding via the TRPA1 Receptor

Deep tissues and their afferents have unique responses to various stimuli and respond to injury distinctively. However, the types of receptors and endogenous ligands that have a key role in pain after deep tissue incision are unknown. TRPA1 has been shown to mediate pain-related responses in inflamm...

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Veröffentlicht in:PloS one 2017-01, Vol.12 (1), p.e0170410-e0170410
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description Deep tissues and their afferents have unique responses to various stimuli and respond to injury distinctively. However, the types of receptors and endogenous ligands that have a key role in pain after deep tissue incision are unknown. TRPA1 has been shown to mediate pain-related responses in inflammation- and nerve injury-induced pain models. We hypothesized that TRPA1 has an important role in pain behaviors after deep tissue incision. The effect of various doses of intraperitoneal (i.p.) TRPA1 antagonist, HC-030031, on pain behaviors after skin + deep tissue incision of the rat hind paw was measured. In vivo reactive oxygen species (ROS)-imaging and hydrogen peroxide (H2O2) levels after incision were also evaluated. Separate groups of rats were examined for H2O2-evoked pain-related behaviors after injections into the deep tissue or the subcutaneous tissue. Guarding pain behavior after skin + deep tissue incision was decreased by i.p. HC-030031. However, HC-030031 did not affect mechanical or heat responses after incision. Treatment either before or after incision was effective against incision-induced guarding behavior. ROS increased after skin + deep tissue incision in both the incised muscle and the skin. Tissue H2O2 also increased in both skin and muscle after incision. H2O2 injection produced pain behaviors when injected into muscle but not after subcutaneous injection. This study demonstrates that TRPA1 antagonist HC-030031 reduced spontaneous guarding pain behavior after skin + deep tissue incision. These data indicate that TRPA1 receptors on nociceptors are active in incised fascia and muscle but this is not evident in incised skin. Even though endogenous TRPA1 agonists like ROS and H2O2 were increased in both incised skin and muscle, those in skin do not contribute to nociceptive behaviors. This study suggests that endogenous TRPA1 ligands and the TRPA1 receptor are important targets for acute pain from deep tissue injury.
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However, the types of receptors and endogenous ligands that have a key role in pain after deep tissue incision are unknown. TRPA1 has been shown to mediate pain-related responses in inflammation- and nerve injury-induced pain models. We hypothesized that TRPA1 has an important role in pain behaviors after deep tissue incision. The effect of various doses of intraperitoneal (i.p.) TRPA1 antagonist, HC-030031, on pain behaviors after skin + deep tissue incision of the rat hind paw was measured. In vivo reactive oxygen species (ROS)-imaging and hydrogen peroxide (H2O2) levels after incision were also evaluated. Separate groups of rats were examined for H2O2-evoked pain-related behaviors after injections into the deep tissue or the subcutaneous tissue. Guarding pain behavior after skin + deep tissue incision was decreased by i.p. HC-030031. However, HC-030031 did not affect mechanical or heat responses after incision. 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Kang, Sinyoung ; Brennan, Timothy J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-ce3ed2b36f69704cb8257c9324a9266370ca699af4f764c6f16f79c7d0f704703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acetanilides - administration &amp; dosage</topic><topic>Analysis</topic><topic>Anesthesiology</topic><topic>Animal models</topic><topic>Animal tissues</topic><topic>Animals</topic><topic>Antagonists (Biochemistry)</topic><topic>Behavior</topic><topic>Biology and Life Sciences</topic><topic>Depth indicators</topic><topic>Fascia</topic><topic>Free radicals</topic><topic>Gene expression</topic><topic>Growth factors</topic><topic>Guarding behavior</topic><topic>Heat treatment</topic><topic>Hydrogen</topic><topic>Hydrogen peroxide</topic><topic>Hydrogen Peroxide - administration &amp; dosage</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>Injection</topic><topic>Injuries</topic><topic>Laboratory animals</topic><topic>Ligands</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Muscle, Skeletal - innervation</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - surgery</topic><topic>Muscles</topic><topic>Neurosciences</topic><topic>Nociceptors</topic><topic>Nociceptors - drug effects</topic><topic>Nociceptors - metabolism</topic><topic>Oxidative stress</topic><topic>Oxygen</topic><topic>Pain</topic><topic>Pain management</topic><topic>Pain perception</topic><topic>Pain Threshold - drug effects</topic><topic>Pain Threshold - physiology</topic><topic>Pain, Postoperative - metabolism</topic><topic>Purines - administration &amp; 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However, the types of receptors and endogenous ligands that have a key role in pain after deep tissue incision are unknown. TRPA1 has been shown to mediate pain-related responses in inflammation- and nerve injury-induced pain models. We hypothesized that TRPA1 has an important role in pain behaviors after deep tissue incision. The effect of various doses of intraperitoneal (i.p.) TRPA1 antagonist, HC-030031, on pain behaviors after skin + deep tissue incision of the rat hind paw was measured. In vivo reactive oxygen species (ROS)-imaging and hydrogen peroxide (H2O2) levels after incision were also evaluated. Separate groups of rats were examined for H2O2-evoked pain-related behaviors after injections into the deep tissue or the subcutaneous tissue. Guarding pain behavior after skin + deep tissue incision was decreased by i.p. HC-030031. However, HC-030031 did not affect mechanical or heat responses after incision. Treatment either before or after incision was effective against incision-induced guarding behavior. ROS increased after skin + deep tissue incision in both the incised muscle and the skin. Tissue H2O2 also increased in both skin and muscle after incision. H2O2 injection produced pain behaviors when injected into muscle but not after subcutaneous injection. This study demonstrates that TRPA1 antagonist HC-030031 reduced spontaneous guarding pain behavior after skin + deep tissue incision. These data indicate that TRPA1 receptors on nociceptors are active in incised fascia and muscle but this is not evident in incised skin. Even though endogenous TRPA1 agonists like ROS and H2O2 were increased in both incised skin and muscle, those in skin do not contribute to nociceptive behaviors. This study suggests that endogenous TRPA1 ligands and the TRPA1 receptor are important targets for acute pain from deep tissue injury.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28103292</pmid><doi>10.1371/journal.pone.0170410</doi><oa>free_for_read</oa></addata></record>
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subjects Acetanilides - administration & dosage
Analysis
Anesthesiology
Animal models
Animal tissues
Animals
Antagonists (Biochemistry)
Behavior
Biology and Life Sciences
Depth indicators
Fascia
Free radicals
Gene expression
Growth factors
Guarding behavior
Heat treatment
Hydrogen
Hydrogen peroxide
Hydrogen Peroxide - administration & dosage
Hydrogen Peroxide - metabolism
Injection
Injuries
Laboratory animals
Ligands
Male
Medical research
Medicine
Medicine and Health Sciences
Muscle, Skeletal - innervation
Muscle, Skeletal - metabolism
Muscle, Skeletal - surgery
Muscles
Neurosciences
Nociceptors
Nociceptors - drug effects
Nociceptors - metabolism
Oxidative stress
Oxygen
Pain
Pain management
Pain perception
Pain Threshold - drug effects
Pain Threshold - physiology
Pain, Postoperative - metabolism
Purines - administration & dosage
Rats
Rats, Sprague-Dawley
Reactive oxygen species
Reactive Oxygen Species - metabolism
Receptors
Research and Analysis Methods
Rodents
Skin
Skin - innervation
Skin - metabolism
Surgery
Tissues
TRPA1 Cation Channel
TRPC Cation Channels - antagonists & inhibitors
TRPC Cation Channels - metabolism
title Muscle Reactive Oxygen Species (ROS) Contribute to Post-Incisional Guarding via the TRPA1 Receptor
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