Priming of Adult Incision Response by Early-Life Injury: Neonatal Microglial Inhibition Has Persistent But Sexually Dimorphic Effects in Adult Rats

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
O MoriartySuellen M Walker

Abstract

Neonatal hindpaw incision primes developing spinal nociceptive circuitry, resulting in enhanced hyperalgesia following reinjury in adulthood. Spinal microglia contribute to this persistent effect, and microglial inhibition at the time of adult reincision blocks the enhanced hyperalgesia. Here, we pharmacologically inhibited microglial function with systemic minocycline or intrathecal SB203580 at the time of neonatal incision and evaluated sex-dependent differences following adult reincision. Incision in adult male and female rats induced equivalent hyperalgesia and spinal dorsal horn expression of genes associated with microglial proliferation (Emr1) and transformation to a reactive phenotype (Irf8). In control adults with prior neonatal incision, the enhanced degree and duration of incision-induced hyperalgesia and spinal microglial responses to reincision were equivalent in males and females. However, microglial inhibition at the time of the neonatal incision revealed sex-dependent effects: the persistent mechanical and thermal hyperalgesia following reincision in adulthood was prevented in males but unaffected in females. Similarly, reincision induced Emr1 and Irf8 gene expression was downregulated in males, but not in femal...Continue Reading

Citations

Sep 24, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Ryan B HowardRobyn J Crook
Sep 24, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·S M Géranton
Oct 1, 2019·European Journal of Pain : EJP·Daniel SegelckeEsther M Pogatzki-Zahn
Aug 11, 2019·Journal of Neural Transmission·Chelsie L Brewer, Mark L Baccei
Mar 3, 2020·Frontiers in Pediatrics·Morika D Williams, B Duncan X Lascelles
Jan 21, 2020·Neuroscience Letters·Lauren M StyczynskiMark L Baccei
Mar 15, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Luke La Hausse De LalouviereMaria Fitzgerald
May 28, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Kufreobong E InyangGeoffroy Laumet
May 25, 2021·Frontiers in Behavioral Neuroscience·Douglas G RirieThomas J Martin
Jul 14, 2021·Pain·Ann M GregusMatthew W Buczynski

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biopsy
biopsies

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