Pain hypersensitivity in a pharmacological mouse model of Attention-Deficit/Hyperactivity Disorder (ADHD)

Authors
O Bouchatta, F Aby, W Sifeddine et al

Lab
University of Bordeaux, CNRS, Institute of Neurodegenerative Diseases, IMN, UMR 5293, Bordeaux, France

Journal
ResearchSquare

Abstract
Recent clinical evidence suggests that pain hypersensitivity develops in subjects with attention deficit hyperactivity disorder (ADHD). However, the mechanisms and neural circuits involved in these interactions remain unknown because of the paucity of studies in animal models. In our previous work, we validated a mouse model obtained by neonatal 6-Hydroxydopamine (6-OHDA) injection, to mimic ADHD syndrome. Here, we demonstrated that 6-OHDA mice exhibited a marked decrease of withdrawal thresholds to thermal and mechanical stimuli, suggesting that ADHD conditions increase nociceptive sensitivity. Moreover, sensitization to pathological inflammatory pain is amplified in 6-OHDA mice as compared to shams. Conversely, ADHD-related hyperactivity and anxiety, but not inattention and impulsivity, are worsened in the inflammatory pain model. Our data indicated that ADHD-induced allodynia and hyperalgesia are accompanied by neuronal hyperexcitability in the dorsal spinal cord. Next, we tested the hypothesis that descending controls are responsible for pain alterations. By combining in vivo electrophysiology, optogenetic stimulation and behavioral analyses, we demonstrated that the anterior cingulate cortex (ACC) hyperactivity alters the ÔACC Ð posterior insulaÕ circuit, and triggers changes in spinal networks that underlie pain sensitization. Altogether, our results point to unprecedented mechanisms underlying the comorbidity between ADHD and pain sensitization. They indicate that ADHD and pain sensitization are mutually worsening comorbid disorders. The identification of shared mechanisms, engaging overlapping neuronal circuits and underlying both disorders, is key to better treatments.

BIOSEB Instruments Used:
Cold Hot Plate Test (BIO-CHP)