Inflammation During Pregnancy Increases Reduced Uterine Perfusion Pressure-induced Hyperalgesia and Spinal Cord Inflammation in Dam Rats
Marianne H. Lee1, Eric Chen2, Jhanel J. Greene6, Jonathan W. Lee2, Jumi Chung4,5, Norma B. Ojeda2, Xiaoli Dai3, Hyun Joon Lee4,5, and Lir-Wan Fan2
1Mississippi INBRE Research Scholar, Mississippi College, Clinton, MS
2Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS
3Department of Anesthesiology, University of Mississippi Medical Center, Jackson, MS
4Department of Neurology, University of Mississippi Medical Center, Jackson, MS
5Research Services, G.V. (Sonny) Montgomery Veterans Administration Medical Center, Jackson, MS
6Mississippi INBRE Research Scholar, Tougaloo College, Tougaloo, MS
Emerging epidemiological and experimental studies suggest that systemic inflammation induced by preeclampsia during pregnancy may affect CNS functions including pain signal processing. Our previous studies in rats with reduced uterine perfusion pressure (RUPP) demonstrated that systemic inflammation during pregnancy induced CNS inflammation of rat dams, which has shown to increase pain sensitivity in other pathological conditions. This study was designed to further examine whether maternal inflammation via lipopolysaccharide (LPS) exposure enhances pain sensitivity associated with RUPP in dams. LPS (100 µg/kg) was administered intraperitoneally into pregnant rats on day 13 of gestation (G13) and RUPP surgery was performed on G14. The dams were subjected to tail flick testing via thermal stimuli and von Frey filament testing via mechanical stimuli. Spinal inflammation and unmyelinated c-fiber projections were examined on day 21 after delivery. All induced inflammation groups (Saline+RUPP, LPS+Sham, and LPS+RUPP) showed significant increases in thermal sensitivity across postnatal days, but only the LPS+RUPP group showed significantly increased sensitivity to mechanical stimuli across postnatal days. Additional LPS exposure enhanced the RUPP-induced microglia and astrocyte activation and unmyelinated c-fiber projections in the lumbar spinal cords of dams on day 21 after delivery. Collectively, LPS-induced systemic inflammation during pregnancy exacerbates RUPP-induced nociceptive afferent plasticity, altering spinal pain signal processing, and contributes to the development of nociceptive hypersensitivity in rat dams. Keywords: Lipopolysaccharide, reduced uterine perfusion pressure, nociceptive hypersensitivity, unmyelinated c-fiber projections, microglia. Supported by Mississippi INBRE Research Scholars Program, NIH grant NH/NINDS R01NS080844, and Newborn Medicine Funds from the Department of Pediatrics, University of Mississippi Medical Center.