A mini-review: Bridging the gap between autism spectrum disorder and pain comorbidities

Abstract

Background Pain is a complex neurobiological response with a multitude of causes; however, patients with autism spectrum disorder (ASD) often report chronic pain with no known etiology. Recent research has been aimed toward identifying the causal mechanisms of pain in mouse and human models of ASD. In recent years, efforts have been made to better document and explore secondary phenotypes observed in ASD patients in the clinic. As new sequencing studies have become more powered with larger cohorts within ASD, specific genes and their variants are often left uncharacterized or validated. In this review we highlight ASD risk genes often presented with pain comorbidities. Aims This mini-review bridges the gap between two fields of literature, neurodevelopmental disorders and pain research. We discuss the importance of the genetic landscape of ASD and its links to pain phenotypes. Results Among the numerous genes implicated in ASD, few have been implicated with varying severities of pain comorbidity. Mutations in these genes, such as SCN9A, SHANK3 , and CNTNAP2 , lead to altered neuronal function that produce different responses to pain, shown in both mouse and human models. Conclusion There is a necessity to use new technologies to advance the current understanding of ASD risk genes and their contributions to pain. Secondly, there is a need to power future ASD risk genes associated with pain with their own cohort, because a better understanding is needed of this subpopulation.

Exploring polygenic contributors to subgroups of comorbid conditions in autism spectrum disorder

“…Nevertheless, although both pain and pain sensory issues may share susceptibility genes with ASD 38 , 39 , our findings suggest that ASD may be more likely to correlate with abnormality in pain tolerance at the gene level compared to allergies. This is consistent with our findings that PRS pain might contribute, at least to a slightly higher degree, to the corresponding topic enriched with sensory processing issues than that of allergies and that combining PRS ASD and PRS pain strengthened the association with the corresponding comorbid conditions.…”

The Current View on the Paradox of Pain in Autism Spectrum Disorders

“…To conclude, a body of evidence suggests atypical neuronal processing of pain in ASD. Although some recent results indicate possible alterations in nociceptors (46) or suggest possible excitatory/inhibitory imbalance in the spinal cord level (5), most of the findings focus on atypical brain processing. Together with evidence of hypoactivation in areas of the second and third order brain areas, more consistently in (pre-)frontal cortex, scientific findings support the hypothesis of a "feed-back defect" or "altered top-down regulation" in pain processing, in ASD (62).…”

“…ASD significantly decreases the person's educational, social and employment opportunities. Among other comorbidities, pain is frequent, sometimes undiagnosed or diagnosed with delay in children with ASD (5)(6)(7)(8). Children with autism are about twice as likely as their typical peers to experience chronic or recurrent pain (9).…”

Exploring Polygenic Contributors To Subgroups of Comorbid Conditions In Autism Spectrum Disorder

“…Nevertheless, although both pain and pain sensation issues may share susceptibility genes with ASD, 19,20 our findings suggest that ASD may be more likely to correlate with abnormality in pain sensation at the gene level compared to allergies. This is consistent with our findings that PRS pain might contribute, at least to a slightly higher degree, to the corresponding topic enriched with sensory processing issues than that of allergies and that combining PRS ASD and PRS pain strengthened the association with the corresponding comorbid conditions.…”