Caregivers of children diagnosed with severe neurological impairment (SNI), a term used to describe children with illnesses impacting the nervous system in various ways, report pain as their child’s primary complaint. Symptoms of SNI include difficulties with thinking, speaking, and moving, as well as effects on other body parts. Children with SNI have trouble communicating their pain, making it difficult to diagnose and treat. Pain and irritability of unknown origin (PIUO) is the term used to describe discomfort-like behaviors when no obvious source of the pain can be found. Those children with SNI who appear in the emergency department of a tertiary pediatric hospital reporting pain or agitation were the focus of this investigation into the clinical care they received upon admission. Results were compared to the PIUO pathway, a unified clinical method for diagnosing and treating the root causes of discomfort and distress in kids who had trouble expressing their feelings. A retrospective chart review identified children (aged 0-18) with SNI-compatible diagnoses who presented with discomfort, irritation, or inexplicable crying and required hospitalization between January 1 and December 31, 2019. Children in whom the cause of the pain was discovered were compared to those in whom it was not using descriptive statistics to examine the clinical care they got. The PIUO pathway was compared to the results of the examinations conducted on children for whom no etiology of their pain could be determined. About 6 different kids made up 8 total hospital admissions that were studied. In 3 individuals, the underlying reason for their discomfort and agitation was determined and treated. There were inadequacies in the history taking, physical examination, and investigations that could have helped pinpoint the source of discomfort and irritation in children with PIUO. During each hospital stay, the patient’s level of discomfort was measured using the r-FLACC pain scale, and a variety of pain and irritation drugs were administered. The discomfort and irritation of children with SNI admitted to a tertiary pediatric hospital were not investigated consistently. The PIUO pathway is a standardized technique to lower and treat pain in children with SNI, and its efficacy should be investigated in future studies.