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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Fu, ES; Erasso, DM; Zhuang, GZ; Upadhyay, U; Ozdemir, M; Wiltshire, T; Sarantopoulos, KD; Smith, SB; Maixner, W; Martin, ER; Levitt, RC

Published Date

  • December 13, 2017

Published In

Volume / Issue

  • 28 / 18

Start / End Page

  • 1215 - 1220

PubMed ID

  • 28902707

Pubmed Central ID

  • PMC5685868

Electronic International Standard Serial Number (EISSN)

  • 1473-558X

Digital Object Identifier (DOI)

  • 10.1097/WNR.0000000000000872

Language

  • eng

Conference Location

  • England