Long-lasting adverse effects of short-term stress during the suckling–mastication transition period on masticatory function and intraoral sensation in rats

Early-life stress affects brain development, eventually resulting in adverse behavioral and physical health consequences in adulthood. The present study assessed the hypothesis that short-term early-life stress during infancy before weaning, a period for the maturation of mastication and sleep, poses long-lasting adverse effects on masticatory function and intraoral sensations later in life. Rat pups were exposed to either maternal separation (MS) or intermittent hypoxia (IH-Infancy) for 6 h/day in the light/sleep phase from postnatal day (P)17 to P20 to generate “neglect” and “pediatric obstructive sleep apnea” models, respectively. The remaining rats were exposed to IH during P45–P48 (IH-Adult). Masticatory ability was evaluated based on the rats’ ability to chew pellets and bite pasta throughout the growth period (P21–P70). Intraoral chemical and mechanical sensitivities were assessed using two-bottle preference drinking tests, and hind paw pain thresholds were measured in adulthood (after P60). No differences were found in body weight, grip force, and hind paw sensitivity in MS, IH-Infancy, and IH-Adult rats compared with naïve rats. Masticatory ability was lower in MS and IH-Infancy rats from P28 to P70 than in naïve rats. MS and IH-Infancy rats exhibited intraoral hypersensitivity to capsaicin and mechanical stimulations in adulthood. The IH-Adult rats did not display inferior masticatory ability or intraoral hypersensitivity. In conclusion, short-term early-life stress during the suckling–mastication transition period potentially causes a persistent decrease in masticatory ability and intraoral hypersensitivity in adulthood. The period is a “critical window” for the maturation of oral motor and sensory functions.