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

Fu, Eugene S.; 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.
doi: 10.1097/WNR.0000000000000872
Clinical neuroscience: PDF Only

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.

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