Methylation Pattern and Pain Sensation in Children With Intellectual Disability

Completed

• Conditions: Intellectual Disability

• Registration Number: NCT06317506
• Lead Sponsor: IRCCS Burlo Garofolo

Brief Summary

Previous literature data indicate that children with intellectual disability (ID) experience more severe pain and more frequently than their cognitively healthy peers, during their daily life. Repeated and chronic pain exposure triggers a vicious circle of hyperalgesia and reduction of the impaired cognitive and adaptive function. Furthermore, these children are unable to rationalize any intervention targeted to contain potentially painful actions.

Epigenetics studies mechanisms responsible for a set of modifications that regulate gene expression without altering the DNA sequence itself. DNA methylation and posttranslational modification of histones are the main epigenetic mechanisms. It is widely accepted that these mechanisms can be engaged by environmental experience, such as early life trauma, pain or addiction leading to the idea of epigenetics as 'a bridge' between genes and environment.

Several epigenetic studies evaluated genes coding proteins involved in recycling of neurotransmitters (SCL6A4), in transmission of painful stimuli (TRPA1) and in response to analgesics (OPRM1). In particular, some studies assessed TRPA1 gene, coding for a cationic channel responsible for the transmission of thermal-painful sensations, and SCL6A4, a serotonin-recycling transmembrane protein presents at inter-synaptic level, have highlighted the importance of methylation in a pathological experience of chronic pain and anxiety disorder in the adult population. Opioid receptor OPRM1 is involved in the endogenous and exogenous opioid-mediated analgesia and a recent work in a group of adolescents treated for idiopathic scoliosis highlights a link between greater pain post-surgery and methylation of this gene. In this context, children with ID are at greater risk of undertreatment both for the difficulty in pain recognition and for the fear of medication-adverse reactions.

The epigenetic study of the aforementioned genes in children with ID associated with an evaluation of painful experiences and clinical history, could help understanding a scenario that it is still complex nowadays before the eyes of parents and caregivers and healthcare workers.The finding of a different methylation pattern in children with ID could in part explain the different pain experience.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-05-30
• Primary Completion: 2023-10-10
• Study Completion: 2023-10-10
• Status Verified: 2024-03
• Study First Submitted: 2024-03-12
• Study First Submitted QC: 2024-03-12
• Last Update Submitted: 2024-03-12
• Study First Posted: 2024-03-19
• Last Update Posted: 2024-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• Children with scheduled venipuncture or venous cannulation for diagnostic or therapeutic reasons, with and without severe intellectual disability.

Exclusion Criteria

• Presence of Autism spectrum disorder (ASD) according to DSM-V criteria.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Between groups differences in methylation levels	Through study completion, an average of 18 months	Evaluation of differences in methylation levels of three genes promoters (SCL6A4, OPRM1, TRPA1) in children with severe intellectual disability in comparison with their cognitively healthy peers

Trial Locations

Locations (1)

Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"; 🇮🇹 Trieste, Italy