School of Paediatrics and Reproductive Health, University of Adelaide, SA 5005, Australia.
Physiol Behav. 2010 May 11;100(2):143-7. doi: 10.1016/j.physbeh.2010.02.013. Epub 2010 Feb 23.
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 (200microg/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 4h following administration of lipopolysaccharide (LPS; 100microg/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.
有证据表明，生命早期接触细菌内毒素会改变生命后期促炎细胞因子的产生。这种现象可能对疼痛及其相关行为产生重大影响，因为促炎细胞因子会提高疼痛敏感性。目前尚未对此进行研究。因此，本研究的目的是描述产前内毒素（PE）暴露后成年大鼠后代的疼痛行为。在妊娠第 16、18 和 20 天，F344 大鼠皮下注射内毒素（200μg/kg）或生理盐水。在 LPS（100μg/kg，皮下注射）给药前和给药后 4 小时，对 PE 后代（n=23）和对照后代（n=24）进行疼痛阈值评估。采用三种疼痛测定法——热板法、尾巴浸入法和冯·弗雷测试。结果表明，产前内毒素对后代具有性别特异性影响，PE 雄性在 LPS 给药后冯·弗雷测试中疼痛阈值不变（p<0.01），而雄性对照后代（n=24）表现出预期的痛觉过敏。PE 雄性后代在尾巴浸入测试中也表现出较高的疼痛阈值（p<0.01），而 LPS 暴露后对照雄性后代的疼痛敏感性没有变化。在冯·弗雷测试中，PE 雌性和对照雌性后代之间没有观察到反应差异，但 PE 雌性后代在尾巴浸入测试中的阈值升高，而对照雌性后代则没有观察到这种影响。在热板测试中，产前暴露于内毒素对疼痛敏感性没有影响。这些数据表明，生命早期接触与细菌感染相关的产物有能力改变疼痛反应，这些反应在成年后代中表现明显。
