Prenatal endotoxin exposure alters behavioural pain responses to lipopolysaccharide in adult offspring

Abstract

Evidence suggests that exposure to bacterial endotoxin in early life can alter the production of pro-inflammatory cytokines in later life. This phenomenon may have significant consequences for pain and pain related behaviours as pro-inflammatory cytokines heighten pain sensitivity. This association has yet to be examined. As such, the aim of the present study was to characterize pain behaviours in adult rat offspring following prenatal endotoxin (PE) exposure. Pregnant F344 rats received endotoxin (200 µg/kg, s.c.) or saline on gestational days 16, 18 and 20. Pain thresholds were assessed in the adult PE offspring ( n = 23) and control offspring ( n = 24) prior to and 4 h following administration of lipopolysaccharide (LPS; 100 µg/kg, s.c.). Three assays of pain were employed — the hot plate, tail immersion and von Frey tests. Results demonstrated sex-specific effects of prenatal endotoxin on the offspring, with PE males displaying unaltered pain thresholds on the von Frey test post-LPS administration ( p < 0.01), while male control offspring ( n = 24) displayed the expected hyperalgesia. Male PE offspring also displayed increased pain thresholds on the tail immersion test ( p < 0.01), while no change in pain sensitivity was observed in control males following LPS exposure. No difference in response was observed between the female PE and control offspring on the von Frey test, however PE female offspring displayed increased thresholds on the tail immersion test compared to baseline — an effect not observed in the control female offspring. Pain sensitivity on the hot plate test was unaffected by prenatal exposure to endotoxin. These data suggest that prenatal exposure to products associated with bacterial infection have the capacity to alter pain responses, which are evident in the adult offspring.