Share this article on:

Impact of human CA8 on thermal antinociception in relation to morphine equivalence in mice

Fu, Eugene S.a; Erasso, Diana M.a; Zhuang, Gerald Z.a; Upadhyay, Uditaa; Ozdemir, Mehtapa; Wiltshire, Timothyd; Sarantopoulos, Konstantinos D.a; Smith, Shad B.e; Maixner, Williame; Martin, Eden R.b,c; Levitt, Roy C.a,b,c

doi: 10.1097/WNR.0000000000000872
Clinical Neuroscience

Recently, we showed that murine dorsal root ganglion (DRG) Car8 expression is a cis-regulated eQTL that determines analgesic responses. In this report, we show that transduction through sciatic nerve injection of DRG with human wild-type carbonic anhydrase-8 using adeno-associated virus viral particles (AAV8-V5-CA8WT) produces analgesia in naive male C57BL/6J mice and antihyperalgesia after carrageenan treatment. A peak mean increase of about 4 s in thermal hindpaw withdrawal latency equaled increases in thermal withdrawal latency produced by 10 mg/kg intraperitoneal morphine in these mice. Allometric conversion of this intraperitoneal morphine dose in mice equals an oral morphine dose of about 146 mg in a 60-kg adult. Our work quantifies for the first time analgesia and antihyperalgesia in an inflammatory pain model after DRG transduction by CA8 gene therapy.

aDepartment of Anesthesiology, Perioperative Medicine and Pain Management

bJohn P. Hussman Institute for Human Genomics

cJohn T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida

dCenter for Pharmacogenetics and Individualized Therapy, University of North Caroline, Eshelman School of Pharmacy, Chapel Hill

eDepartment of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA

Correspondence to Roy C. Levitt, MD, Room 8052A (R-371), Rosenstiel Medical Sciences Building, Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami, FL 33136, USA Tel: +1 305 2431278; fax: +1 305 243 1373; e-mail: rlevitt@med.miami.edu

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/

Received July 16, 2017

Accepted August 9, 2017

© 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins