Effects of binge-like ethanol exposure during adolescence on the hyperalgesia observed during sickness syndrome in rats

Abstract

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.