Project Summary/Abstract A growing literature suggests autistic adults feel pain in a different manner than non-autistic adults and may experience more persistent pain than the general population. As pain is often the first sign of injury or illness, individual differences in pain perception or communication can significantly impact diagnosis and treatment of many health conditions. Alternatively, when pain is not addressed, this can lead to a pro-nociceptive pain profile, where endogenous systems facilitate pain instead of inhibiting it, potentially contributing to persistent pain. Autistic adults often experience sensitivity in other sensory domains that could extend to pain. For example, hyper-responsiveness can include pain-like reactions to everyday tactile stimuli like tags on clothing. At this point, several studies have demonstrated increased pain sensitivity2,3, increased pain-related anxiety2, and altered neural responses to pain1 in autistic individuals. Yet, several important questions remain that present barriers to improving pain treatment in autistic individuals. In this project, we propose to address several gaps in our current understanding, building a framework to investigate pain sensitivity in autism. First, we will address pain assessment and expression of pain in autistic adults. Currently, there is no consensus recommendation on pain assessment in autism. It is not clear if autistic individuals express pain in specific ways that differ from non- autistic individuals and if better pain assessment tools would improve pain management. In Aim 1, we propose to test different pain scales in self-reporting autistic adults to determine reliability. Additionally, we will assess how pain ratings on these scales correspond to observable pain behaviors. Secondly, we will address potential factors that may predict persistent pain in autism. It is currently unknown if hypersensitivity to pain extends from a general sensory hypersensitivity for autistic adults. In Aim 2, we will explore individual profiles of sensory reactivity to identify important relationships between pain and sensitivity in other sensory domains. We will also explore relationships with social and emotional factors that may impact persistent pain. Lastly, in Aim 3, we will address potential brain mechanisms of pain sensitivity in autistic adults. Our previous work indicated that autistic adults have a different neural response to heat pain across somatosensory and affective brain regions, but the functional connectivity of these regions and the relationship between neural responses and pain reports is not clear. Overall, we hypothesize that autistic adults have difficulty communicating their pain, leaving them at a greater risk for mismanagement of pain. Additionally, we hypothesize that autistic adults likely have a pro- nociceptive profile increasing the magnitude of pain. This combination of difficult pain communication and a pro- nociceptive profile leaves autistic...