Department of Pharmacology, Federal University of Paraná, P.O. Box 19031, 81540-970 Curitiba, PR, Brazil.
Department of General Biology, Federal University of Minas Gerais, P.O. Box 486, 31270-901 Belo Horizonte, MG, Brazil.
Pharmacol Biochem Behav. 2017 Sep;160:63-69. doi: 10.1016/j.pbb.2017.08.004. Epub 2017 Aug 17.
Acute and chronic ethanol exposure increases the risk of infection by altering the innate host's defense system. Adolescence is a critical period for brain development. Insults during this period may have long-lasting consequences. The present study investigated the effects of binge-like ethanol exposure in adolescent rats on mechanical hyperalgesia during sickness syndrome that was induced by a systemic injection of lipopolysaccharide (LPS) or an intracerebroventricular (i.c.v.) injection of interleukin-1β (IL-1β) after the cessation of ethanol exposure. Male Wistar rats were exposed to ethanol from postnatal day (PND) 25 to PND 38 in a binge-like pattern. Hyperalgesia was assessed on the right hindpaw after an intraperitoneal injection of LPS (5 and 50μg/kg, intraperitoneally) on PND 51 and PND 63 or an i.c.v. or intraplantar (i.pl.) injection of IL-β (3 and 1ng, respectively) on PND 51. Ethanol exposure during adolescence did not alter mechanical thresholds which increased normally with age. The systemic injection of LPS (0.5-50μg/kg) in adult rats induced dose-related mechanical hyperalgesia. Binge-like ethanol exposure significantly increased mechanical hyperalgesia that was induced by 50μg/kg LPS on PND 51 and 63, which lasted until 24h after the injection. This change was not observed at a lower dose of LPS (5μg/kg). Acute oral treatment with ethanol 24h prior to LPS administration did not alter mechanical hyperalgesia. The i.c.v. injection of IL-1β (1-10ng) also induced dose-related mechanical hyperalgesia in the right hindpaw in non-exposed animals. In animals that were exposed to binge-like ethanol, the i.c.v. or i.pl. injection of IL-1β also increased hyperalgesia on PND 51. These results suggest that binge-like ethanol exposure during adolescence causes alterations in the central nervous system that can increase mechanical hyperalgesia that is observed during sickness syndrome, and this effect can be observed until adulthood after the cessation of ethanol exposure.
急性和慢性乙醇暴露通过改变先天宿主的防御系统增加感染的风险。青春期是大脑发育的关键时期。在此期间受到的伤害可能会产生持久的后果。本研究探讨了青春期大鼠在停止乙醇暴露后，通过单次腹腔内（ip）注射脂多糖（LPS）或脑室内（icv）注射白细胞介素-1β（IL-1β）诱导的疾病综合征期间，类似 binge 样的乙醇暴露对机械性痛觉过敏的影响。雄性 Wistar 大鼠在类似 binge 样的模式下从出生后第 25 天（PND）到第 38 天（PND）暴露于乙醇。在 PND 51 和 PND 63 时，通过腹腔内注射 LPS（5 和 50μg/kg）或 icv 或足底（i.pl.）注射 IL-β（3 和 1ng）后，评估右侧后爪的痛觉过敏。青春期的乙醇暴露不会改变机械阈值，而机械阈值会随着年龄的增长而正常增加。在成年大鼠中，全身注射 LPS（0.5-50μg/kg）会引起剂量依赖性的机械性痛觉过敏。类似 binge 样的乙醇暴露显著增加了 PND 51 和 63 时 50μg/kg LPS 诱导的机械性痛觉过敏，这种变化持续到注射后 24 小时。在较低剂量的 LPS（5μg/kg）时，未观察到这种变化。在 LPS 给药前 24 小时给予急性口服乙醇治疗不会改变机械性痛觉过敏。在未暴露于乙醇的动物中，icv 注射 IL-1β（1-10ng）也会引起右侧后爪的剂量依赖性机械性痛觉过敏。在暴露于 binge 样乙醇的动物中，icv 或 i.pl.注射 IL-1β也会增加 PND 51 时的痛觉过敏。这些结果表明，青春期类似 binge 样的乙醇暴露会导致中枢神经系统发生变化，从而增加疾病综合征期间观察到的机械性痛觉过敏，这种效应可以在停止乙醇暴露后直到成年期才会消失。
