Attenuation of Unevoked Mechanical and Cold Pain Hypersensitivities Associated With Experimental Neuropathy in Mice by Angiotensin II Type-2 Receptor Antagonism

Recent findings from a phase II clinical trial showed analgesic effects of an angiotensin II type-2 receptor (AT2R) antagonist in postherpetic neuralgia patients. This study aimed to investigate whether AT2R antagonism could provide effective analgesia in voluntary measures of unevoked/ongoing pain-like behaviors in mice with experimental neuropathy. Mice were subjected to spared nerve injury to induce neuropathy and tested in 2 operant behavioral tests to measure ongoing mechanical and cold pain hypersensitivities. Systemic administration of an AT2R antagonist provided effective analgesia in these behavioral measures of mechanical and cold pain in spared nerve injury mice, suggesting its effectiveness in neuropathic pain. Accepted for publication September 6, 2018. Funding: This study was supported by a pilot and feasibility grant from the Washington University Nutrition Obesity Research Center National Institutes of Health grant P30DK056341 (to A.J.S.) and by start-up funds from the Department of Anesthesiology, Washington University Pain Center and Washington University School of Medicine (to D.P.M.). The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Andrew J. Shepherd, PhD, Department of Anesthesiology and Washington University Pain Center, Washington University School of Medicine in St Louis, St Louis, MO 63110. Address e-mail to a.shepherd@wustl.edu; and Durga P. Mohapatra, PhD, Department of Anesthesiology and Washington University Pain Center, Washington University School of Medicine in St Louis, St Louis, MO 63110. Address e-mail to d.p.mohapatra@wustl.edu. © 2018 International Anesthesia Research Society

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