Project Summary/Abstract As pain is often the first sign of injury or illness, individual differences in pain perception or communication can impact diagnosis and treatment of dangerous health conditions. In this proposal, we will investigate differences in pain perception for autistic adults who may have difficulty communicating about pain due to autism-related communication difficulties. Emerging evidence suggests autistic adults experience pain differently than non- autistic adults. Autistic adults report higher pain intensity and more pain-related anxiety compared to non-autistic adults. Additionally, the pattern of neural responses to pain in autistic adults suggests altered central processing of pain. However, most of these studies have been conducted in younger autistic adults (<40yrs). This is concerning as many painful chronic medical conditions become prevalent in mid-adulthood (e.g., back pain, arthritis, diabetes) and reports suggest autistic adults experience these conditions are an even greater rate, increasing the potential for disparate pain management in this population. In non-autistic populations, older age is consistently associated with decreased pain sensitivity. Endogenous modulation of pain in aging is associated with increased central sensitization (facilitation of pain), and less efficient descending pain modulation (inhibition of pain). Our preliminary data suggests that autistic adults are affected with persistent pain in adulthood and that this increases with age. Our conceptual framework suggests that autistic adults may experience persistent pain in adulthood due to 3 factors: 1) increased pain sensitivity, 2) altered endogenous pain modulation, and 3) difficulty in pain assessment. The overall goal of this cross-sectional study is to investigate how pain differs in autistic adults (n=40, ages 30- 70 yrs) compared to age, race, and sex matched non-autistic adults (n=40). To examine how pain perception may differ for autistic adults, this exploratory R21 will address two targeted knowledge gaps. In Aim 1, we will use a standard battery of multi-modality (heat and pressure) quantitative sensory testing to address both sensory and affective pain sensitivity. In Aim 2, we will examine differences in endogenous pain modulatory systems in autistic adults using both temporal summation (to address pain facilitation) and conditioned pain modulation (to address pain inhibition). At the end of this study, we will better understand critical differences in pain perception that may place autistic adults at risk for persistent pain in adulthood. For autistic adults, differences in pain processing and endogenous pain modulation, coupled with difficulty in social communication and healthcare access, could lead to poor pain outcomes. The knowledge gained from this study on mechanistic differences in pain sensitivity and endogenous pain modulation will help build a framework for development of new pain assessment tools and targeted pa...