Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adults worldwide. It often coexists with anxiety, depression or alterations in sensitivity. Patients with ADHD report sensitization to pain and the prevalence of generalized pain is higher in ADHD patients (up to 80%) compared to control population (17%) (Stray LL et al., 2013). However, the mechanisms involved remain unknown. Neuroanatomical studies confirm that attentiveness and central mechanisms involved in pain transmission use identical neural networks (i.e., the anterior cingulate cortex (ACC) connection to insula). Thus, alterations in this circuit may underlie both behavioral outcomes.We previously validated a mouse model of ADHD obtained by neonatal 6-hydroxydopamine (6-OHDA) lesion. We demonstrated that 6-OHDA mice exhibit increased nociception, showing higher sensitization to thermal and mechanical stimuli compared to sham animals. By combining in vivo electrophysiology and optogenetics, we demonstrated that ACC hyperactivity alters the ACC–posterior insula circuit that underlie nociceptive sensitization. Using microendoscopic calcium imaging in freely moving mice, we monitored population neuron activity in ACC under ADHD-like conditions. Interestingly, the in vivo calcium imaging showed different firing patterns between ACC neurons from 6-OHDA mice and sham mice under nociceptive stimulation.We provide functional evidence that nociceptive sensitization relies on ACC hyperexcitability. Our data indicate that ADHD and persistent pain are mutually worsening comorbid disorders with reciprocal worsening of nociceptive sensitization and hyperactivity, and new treatments should target overlapping mechanisms for better efficiency.