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Muscle Reactive Oxygen Species (ROS) Contribute to Post-Incisional Guarding via the TRPA1 Receptor
Journal article   Open access   Peer reviewed

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

Daisuke Sugiyama, Sinyoung Kang and Timothy J Brennan
PloS one, Vol.12(1), pp.e0170410-e0170410
2017
DOI: 10.1371/journal.pone.0170410
PMCID: PMC5245866
PMID: 28103292
url
https://doi.org/10.1371/journal.pone.0170410View
Published (Version of record) Open Access

Abstract

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.
 Pain Threshold - physiology Reactive Oxygen Species - metabolism Acetanilides - administration & dosage Skin - metabolism Rats Male Muscle, Skeletal - innervation Muscle, Skeletal - metabolism Purines - administration & dosage Muscle, Skeletal - surgery Rats, Sprague-Dawley TRPC Cation Channels - antagonists & inhibitors Pain, Postoperative - metabolism Hydrogen Peroxide - metabolism Animals Hydrogen Peroxide - administration & dosage TRPA1 Cation Channel TRPC Cation Channels - metabolism Pain Threshold - drug effects Skin - innervation Nociceptors - metabolism Nociceptors - drug effects

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