Neuroirritability is defined as persistent or recurrent episodes of pain behaviors which, after assessment and management of potential nociceptive sources, can most likely be attributed to abnormal signaling of the central nervous system. Neuroirritability is frequently associated with other comorbid conditions (e.g., prematurity, hypoxic brain injury, genetic syndromes, developmental and communication delays, autonomic storming), and is very unlikely to be seen in neurotypical children. Although neuroirritability can present at any time, patients most commonly present during the newborn period, at the onset of adolescence, or in relation to neurotrauma that may happen later in life.