Background: Autism spectrum disorder (ASD) is often associated with acute pain, such as headache and migraine, which, in turn, may sometimes be accompanied by irritability or psychomotor agitation. A genetic basis of the association between ASD, headache, and migraine seems to come from the analysis of autistic individuals’ families and polygenic studies. From a clinical perspective, it may often be quite difficult for clinicians to detect headache and migraine among autistic subjects, as these individuals usually show difficulties in communicating feelings and emotions. Starting from these premises, it is fundamental to exclude a painful symptomatology in autistic patients showing irritability or psychomotor agitation. In this framework, the aim of this brief communication is to discuss some studies on the genetic basis of headache and migraine in ASD, give some insights into their diagnostic and clinical basis, and finally report some of the available therapeutic strategies.

Methods: To carry out this study, a literature search was conducted, mainly employing the PubMed Database from March to June 2025. The author focused on works dealing with the reciprocal relationship between headache, migraine, and ASD.

Results: It was found that both ASD and migraine share genetic mutations as well as neurotransmission and immune system dysregulation. Meanwhile, it seems that, given the communication difficulties of ASD subjects, migraine and headache diagnoses are quite hard to make among these individuals. Regarding therapeutic strategies, we may distinguish non-pharmacological strategies, including environmental modifications, and pharmacological ones, such as antipsychotics.

Conclusions: Migraine and headache among ASD subjects are frequently underdiagnosed. Further studies are needed to shed new light on pathophysiological mechanisms as well as on clinical aspects of these pathologies in ASD.