Gender-Specific Behavioural and Nociceptive Alterations in an Autism Model Induced by Prenatal Exposure to...

Autism spectrum disorders (ASD) are frequently associated with sensory abnormalities, particularly altered pain sensitivity, which may manifest as either hypo- or hypersensitivity to painful stimuli. Despite the higher prevalence of ASD in males, few studies have investigated sex differences in pain sensitivity within animal models of autism. This study evaluated thermal and mechanical pain sensitivity in male and female rats at juvenile, pubertal and adult stages, using a model of autism induced by prenatal exposure to lipopolysaccharide (LPS). Reduced social behaviour, a critical behaviour impairment in autism, was assessed, and molecular analyses of Oprm1 gene expression and mu-opioid receptor (MOR-1) protein levels in the periaqueductal grey (PAG) were performed in adulthood. At weaning, both male and female offspring prenatally exposed to LPS exhibited reduced social behaviour, consistent with behavioural phenotypes observed in ASD models. In mechanical nociceptive tests, males and females showed similar pain sensitivity at weaning, whereas only males displayed decreased sensitivity at puberty and adulthood. In thermal tests, males showed reduced nociceptive responses across all ages, whereas females exhibited this pattern only during the juvenile and pubertal stages. Both sexes in the LPS group showed increased Oprm1 gene expression in the PAG; however, MOR-1 protein content was decreased in males and increased in females in adulthood. Thus, our model of autism-induced hypoalgesia via enabling the opioid system, mainly in male rats. Sexual dimorphism was observed in both pain tests and MOR-1 protein levels in adult rats, with female rats being less sensitive to pain.