Newly Published
Pain Medicine  |   June 2017
H2O2 Induces Muscle Nociception via Transient Receptor Potential Ankyrin 1 Receptors
Author Notes
  • From the Departments of Anesthesia (D.S., S.K., N.A., P.A., T.J.B.) and Pharmacology (Y.M.U., T.J.B.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa.
  • Submitted for publication February 16, 2017. Accepted for publication May 19, 2017.
    Submitted for publication February 16, 2017. Accepted for publication May 19, 2017.×
  • Acknowledgments: The authors are grateful to Durga P. Mohapatra, Ph.D. (Department of Anesthesiology, Washington University, St. Louis, Missouri), for providing TRPA1–/– mice. The authors also acknowledge Alberto Subieta, B.S. (Department of Anesthesia, University of Iowa, Iowa City, Iowa), Brandt Uitermarkt, M.A. (Department of Anesthesia, University of Iowa, Iowa City, Iowa), He Gu M.D., Ph.D. (Department of Anesthesia, University of Iowa, Iowa City, Iowa), and John Kennedy, M.D. ( Department of Anesthesia, University of Iowa, Iowa City, Iowa), for technical assistance.
    Acknowledgments: The authors are grateful to Durga P. Mohapatra, Ph.D. (Department of Anesthesiology, Washington University, St. Louis, Missouri), for providing TRPA1–/– mice. The authors also acknowledge Alberto Subieta, B.S. (Department of Anesthesia, University of Iowa, Iowa City, Iowa), Brandt Uitermarkt, M.A. (Department of Anesthesia, University of Iowa, Iowa City, Iowa), He Gu M.D., Ph.D. (Department of Anesthesia, University of Iowa, Iowa City, Iowa), and John Kennedy, M.D. ( Department of Anesthesia, University of Iowa, Iowa City, Iowa), for technical assistance.×
  • Research Support: Supported in part by grant No. NS092851 from the National Institutes of Health (Bethesda, Maryland; to Dr. Usachev) and by the Foundation of Anesthesia Education and Research (Schaumberg, Illinois; to Dr. Kang).
    Research Support: Supported in part by grant No. NS092851 from the National Institutes of Health (Bethesda, Maryland; to Dr. Usachev) and by the Foundation of Anesthesia Education and Research (Schaumberg, Illinois; to Dr. Kang).×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Kang: Department of Anesthesia, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa 52242. sinyoung-kang@uiowa.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Pain Medicine
Pain Medicine   |   June 2017
H2O2 Induces Muscle Nociception via Transient Receptor Potential Ankyrin 1 Receptors
Anesthesiology Newly Published on June 22, 2017. doi:10.1097/ALN.0000000000001756
Anesthesiology Newly Published on June 22, 2017. doi:10.1097/ALN.0000000000001756
Abstract

Background: H2O2 has a variety of actions in skin wounds but has been rarely studied in deep muscle tissue. Based on response to the transient receptor potential ankyrin 1 antagonists after plantar incision, we hypothesized that H2O2 exerts nociceptive effects via the transient receptor potential ankyrin 1 in muscle.

Methods: Nociceptive behaviors in rats (n = 269) and mice (n = 16) were evaluated after various concentrations and volumes of H2O2 were injected into the gastrocnemius muscle or subcutaneous tissue. The effects of H2O2 on in vivo spinal dorsal horn neuronal activity and lumbar dorsal root ganglia neurons in vitro were evaluated from 26 rats and 6 mice.

Results: Intramuscular (mean ± SD: 1,436 ± 513 s) but not subcutaneous (40 ± 58 s) injection of H2O2 (100 mM, 0.6 ml) increased nociceptive time. Conditioned place aversion was evident after intramuscular (–143 ± 81 s) but not subcutaneous (–2 ± 111 s) injection of H2O2. These H2O2-induced behaviors were blocked by transient receptor potential ankyrin 1 antagonists. Intramuscular injection of H2O2 caused sustained in vivo activity of dorsal horn neurons, and H2O2 activated a subset of dorsal root ganglia neurons in vitro. Capsaicin nerve block decreased guarding after plantar incision and reduced nociceptive time after intramuscular H2O2. Nociceptive time after intramuscular H2O2 in transient receptor potential ankyrin 1 knockout mice was shorter (173 ± 156 s) compared with wild-type mice (931 ± 629 s).

Conclusions: The greater response of muscle tissue to H2O2 may help explain why incision that includes deep muscle but not skin incision alone produces spontaneous activity in nociceptive pathways.