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Autism spectrum disorder (ASD) is a neurodevelopmental disorder, which affects 1 in 44 children and may cause severe disabilities. Besides socio-communicational difficulties and repetitive behaviors, ASD also presents as atypical sensorimotor function and pain reactivity. While chronic pain is a frequent co-morbidity in autism, pain management in this population is often insufficient because of difficulties in pain evaluation, worsening their prognosis and perhaps driving higher mortality rates. Previous observations have tended to oversimplify the experience of pain in autism as being insensitive to painful stimuli. Various findings in the past 15 years have challenged and complicated this dogma. However, a relatively small number of studies investigates the physiological correlates of pain reactivity in ASD. We explore the possibility that atypical pain perception in people with ASD is mediated by alterations in pain perception, transmission, expression and modulation, and through interactions between these processes. These complex interactions may account for the great variability and sometimes contradictory findings from the studies. A growing body of evidence is challenging the idea of alterations in pain processing in ASD due to a single factor, and calls for an integrative view. We propose a model of the pain cycle that includes the interplay between the molecular and neurophysiological pathways of pain processing and it conscious appraisal that may interfere with pain reactivity and coping in autism. The role of social factors in pain-induced response is also discussed. Pain assessment in clinical care is mostly based on subjective rather than objective measures. This review clarifies the strong need for a consistent methodology, and describes innovative tools to cope with the heterogeneity of pain expression in ASD, enabling individualized assessment. Multiple measures, including self-reporting, informant reporting, clinician-assessed, and purely physiological metrics may provide more consistent results. An integrative view on the regulation of the pain cycle offers a more robust framework to characterize the experience of pain in autism.