Thermal A-δ Nociceptors, Identified by Transcriptomics, Express Higher Levels of Anesthesia-Sensitive Receptors Than Thermal C-Fibers and Are More Suppressible by Low-Dose Isoflurane

We investigated the effect of isoflurane on 2 main types of thermal nociceptors: A-δ and C-fibers. Surprisingly, 1% inhaled isoflurane led to a hyperalgesic response to C-fiber thermal stimulation, whereas responses to A-δ thermal stimulation were blunted. We explored the hypothesis that differences in withdrawal behavior are mediated by differential expression of isoflurane-sensitive proteins between these types of thermal nociceptors. Multiple transcriptomic databases of peripheral neurons were integrated to reveal that isoflurane-susceptible proteins Htr3a, Kcna2, and Scn8a were enriched in thermosensitive A-δ neurons. This exploratory analysis highlights the differing role that volatile anesthetics might have on nociceptors in the peripheral nervous system. Accepted for publication August 24, 2017. Funding: This study was supported by the intramural research program of the National Institutes of Health (NIH), Clinical Center. S.J.R. was supported by the NIH Medical Research Scholars Program, a public–private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, The American Association for Dental Research, the Colgate-Palmolive Company, Genentech, alumni of student research programs, and other individual supporters. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Michael J. Iadarola, PhD, Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bldg 10, Room 2C401, 10 Center Dr, MSC 1510, Bethesda, MD 20892. Address e-mail to miadarol@cc.nih.gov. © 2017 International Anesthesia Research Society

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