ALTERED NOCICEPTIVE RESPONDING IN A PRECLINICAL MODEL OF AUTISM IS ASSOCIATED WITH SEX-DEPENDANT TRANSCRIPTIONAL CHANGES IN THE DORSAL HORN OF THE SPINAL CORD

Atypical pain sensitivity is frequently reported in autism. Prenatal valproic acid (VPA) exposure, an animal autism model, is associated with thermal and mechanical hyposensitivity¹. This study further examined nociceptive behaviour in the VPA model, the underlying neurobiological mechanisms, and if such effects are sex-dependent. Male and female rats prenatally exposed to VPA (500mg/kg) or saline were assessed for mechanical, cold and thermal responding, anxiety-like behaviour and affective pain responding prior to and following Complete Freund’s adjuvant (CFA, 50ul/intraplantar) or sham injection. Ipsilateral dorsal horn spinal cord (DHSC) tissue was collected for analyses.
Prenatal VPA exposure induced hyposensitivity to static and dynamic mechanical stimuli hyposensitivity, but no change in responding to heat or cold stimuli, when compared to saline-treated counterparts. Following CFA, VPA-exposed rats exhibited an attenuated CFA-induced mechanical hypersensitivity and diminished affective pain responding, while thermal and anxiety-like behaviours were unaffected. There was no effect of sex on any of the behavioural parameters assessed however, sex-specific DHCS transcriptional alterations were noted. Prenatal VPA-exposure increased Calca, Slc12a5 and Itgam expression and reduced tac1 expression in male, but not female rats. CFA increased Calca and reduced Tac1 expression in Saline-males, and reduced Calca and Itgam expression in Saline-females. In VPA male rats, CFA reduced the expression of Calca and Slc12a5, and increased Tac1. In comparison, CFA reduced Calca and increased Itgam expression in VPA-females compared with VPA-Sham and SAL-CFA treated counterparts respectively. These data provide evidence for atypical pain responding and sex-dependant spinal gene expression in the VPA model of autism.