Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms.
Integrative approaches such as electroacupuncture, devoid of drug effects are gaining prominence for treating pain. Understanding the mechanisms of electroacupuncture induced analgesia would benefit chronic pain conditions such as sickle cell disease (SCD), for which patients may require opioid analgesics throughout life. Mouse models are instructive in developing a mechanistic understanding of pain, but the anesthesia/restraint required to administer electroacupuncture may alter the underlying mechanisms. To overcome these limitations, we developed a method to perform electroacupuncture in conscious, freely moving, unrestrained mice. Using this technique we demonstrate a significant analgesic effect in transgenic mouse models of SCD and cancer as well as complete Freund's adjuvant-induced pain. We demonstrate a comprehensive antinociceptive effect on mechanical, cold and deep tissue hyperalagesia in both genders. Interestingly, individual mice showed a variable response to electroacupuncture, categorized into high-, moderate-, and non-responders. Mechanistically, electroacupuncture significantly ameliorated inflammatory and nociceptive mediators both peripherally and centrally in sickle mice correlative to the antinociceptive response. Application of sub-optimal doses of morphine in electroacupuncture-treated moderate-responders produced equivalent antinociception as obtained in high-responders. Electroacupuncture in conscious freely moving mice offers an effective approach to develop a mechanism-based understanding of analgesia devoid of the influence of anesthetics or restraints.
Vascular Biology Center, Division of Hematology, Oncology &Transplantation, Department of Medicine, University of Minnesota, 14-100 PWB, 516 Delaware ST SE, Minneapolis, MN 55455, USA.
Ying
Y
Wang
Vascular Biology Center, Division of Hematology, Oncology &Transplantation, Department of Medicine, University of Minnesota, 14-100 PWB, 516 Delaware ST SE, Minneapolis, MN 55455, USA.
Jianxun
J
Lei
Department of Neurosurgery, University of California San Diego, 200 West Arbor Drive #8893, La Jolla, CA 92103-8893, USA.
Mihir
M
Gupta
Vascular Biology Center, Division of Hematology, Oncology &Transplantation, Department of Medicine, University of Minnesota, 14-100 PWB, 516 Delaware ST SE, Minneapolis, MN 55455, USA.
Fei
F
Peng
Vascular Biology Center, Division of Hematology, Oncology &Transplantation, Department of Medicine, University of Minnesota, 14-100 PWB, 516 Delaware ST SE, Minneapolis, MN 55455, USA.
Sarah
S
Lam
Vascular Biology Center, Division of Hematology, Oncology &Transplantation, Department of Medicine, University of Minnesota, 14-100 PWB, 516 Delaware ST SE, Minneapolis, MN 55455, USA.
Ritu
R
Jha
Vascular Biology Center, Division of Hematology, Oncology &Transplantation, Department of Medicine, University of Minnesota, 14-100 PWB, 516 Delaware ST SE, Minneapolis, MN 55455, USA.
Ellis
E
Raduenz
Department of Veterinary and Biomedical Sciences, University of Minnesota, 295 Animal Science/Veterinary Medicine Bldg, 1988 Fitch Ave, St. Paul, MN 55108, USA.
Al J
AJ
Beitz
Vascular Biology Center, Division of Hematology, Oncology &Transplantation, Department of Medicine, University of Minnesota, 14-100 PWB, 516 Delaware ST SE, Minneapolis, MN 55455, USA.
Kalpna
K
Gupta
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