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

Eugene 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 Citations (Scopus)

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

Fingerprint

Spinal Ganglia
Morphine
Hot Temperature
Virion
Analgesia
Dependovirus
Carbonic Anhydrases
Carrageenan
Sciatic Nerve
Inbred C57BL Mouse
Genetic Therapy
Analgesics
Pain
Injections
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Impact of human CA8 on thermal antinociception in relation to morphine equivalence in mice. / Fu, Eugene; Erasso, Diana M.; Zhuang, Gerald Z.; Upadhyay, Udita; Ozdemir, Mehtap; Wiltshire, Timothy; Sarantopoulos, Konstantinos D.; Smith, Shad B.; Maixner, William; Martin, Eden R; Levitt, Roy C.

In: NeuroReport, Vol. 28, No. 18, 01.01.2017, p. 1215-1220.

Research output: Contribution to journalArticle

Fu, E, Erasso, DM, Zhuang, GZ, Upadhyay, U, Ozdemir, M, Wiltshire, T, Sarantopoulos, KD, Smith, SB, Maixner, W, Martin, ER & Levitt, RC 2017, 'Impact of human CA8 on thermal antinociception in relation to morphine equivalence in mice', NeuroReport, vol. 28, no. 18, pp. 1215-1220. https://doi.org/10.1097/WNR.0000000000000872
Fu, Eugene ; Erasso, Diana M. ; Zhuang, Gerald Z. ; Upadhyay, Udita ; Ozdemir, Mehtap ; Wiltshire, Timothy ; Sarantopoulos, Konstantinos D. ; Smith, Shad B. ; Maixner, William ; Martin, Eden R ; Levitt, Roy C. / Impact of human CA8 on thermal antinociception in relation to morphine equivalence in mice. In: NeuroReport. 2017 ; Vol. 28, No. 18. pp. 1215-1220.
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