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

Eugene S. Fu, Diana M. Erasso, Gerald Z. Zhuang, Udita Upadhyay, Mehtap Ozdemir, Timothy Wiltshire, Konstantinos D. Sarantopoulos, Shad B. Smith, William Maixner, Eden R. Martin, Roy C. Levitt

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1215-1220
Number of pages6
JournalNeuroreport
Volume28
Issue number18
DOIs
StatePublished - Jan 1 2017

Keywords

  • CA8 gene therapy
  • analgesia
  • antihyperalgesia
  • antinociception
  • carbonic anhydrase-8
  • inflammatory pain
  • morphine

ASJC Scopus subject areas

  • Neuroscience(all)

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