Past Projects

The PIUO Project is based on a pilot project conducted by Dr. Harold Siden and Dr. Tim Oberlander



Becoming Pain Detectives

Over the years we have seen many children in our practice experiencing pain without any obvious correctable source. In 2010 we piloted the PIUO Pathway in a study with 10 non-verbal children with SNI. The children ranged in age from 5 to 17 years and their SNI had a wide variety of causes, with high degrees of medical complexity and communication impairment.

In the proposal for the pilot study we were focussed on medications for PIUO and wanted to ask 6 physicians specializing in pediatric pain and/or palliative medicine to test the PIUO Pathway. We also wanted them to tell us what medications/therapies they routinely used in treating PIUO and in which order they would prescribe certain medications.

However, in documenting the work-up which had been done for the 10 study participants to determine the cause of their pain, the results were surprising: while it might be assumed that evaluation for pain and irritability would be thorough and revealing, just the opposite occurred in these children. We found that:

  • No child in the pilot study had been fully evaluated for PIUO before enrolling. PIUO assessment was conducted in a disorganized, scatter-shot manner, with each child receiving only partial elements of a comprehensive evaluation.

  • Even multiple attempts by diverse care teams were unable to resolve PIUO. Children continued to experience PIUO despite assessments by 6 to 14 different clinical teams and primary care providers prior to enrollment.

  • Pediatric symptom management experts could not agree on treatment strategies. For example, there was a complete lack of consensus about optimal pharmacotherapy for PIUO.

The objective of our pilot study was to get an idea of whether following the PIUO Pathway would increase our probability of succeeding as “pain detectives” for children and families dealing with frequent or constant, inexplicable and poorly managed pain.

For pilot study participants, PIUO was resolved for 63% in ~13 weeks (median). These children had shown signs of PIUO for 1-2 years prior to study entry, but our step-wise evaluation and treatment sequence (led by an RN and MD) resolved it for nearly two-thirds of the children in 1-25 weeks.


We recognize that the PIUO Pathway is not 100% succesful at detecting causes of PIUO in children and treat them. Sometimes medications that we know relieve pain are the best next step, but clinicians disagree about which medications to prescribe and ind which order.

We presented a case vignette to the 6 physicians who participated in the PIUO pilot study.  The physicians were presented with a case study of a child with a neurological condition displaying pain-like behaviors. Physicians were asked to list their top 5 medications and the order in which they would trial them. From the answers we got, we concluded that medication choices and sequences are highly empiric. The variation in suggested medication sequences stems from the fact that we do not fully understand the disruptions resulting in pain in children with rare neurological conditions, nevertheless, this lack of consensus leads to ineffectiveness and frustration for families and professionals alike.

We plan to conduct further studies into the optimal medications and their sequence in treating PIUO in children with SNI, for whom the PIUO Pathway does not reveal the source of their pain.




You can read more about our pilot study and similar studies in the following research publications: 

  • "Physician variability in treating pain and irritability of unknown origin in children with severe neurological impairment", 2013, by Harold Siden, Bruce Carleton, and Tim Oberlander (link to full text pdf)

  • "Pain Management for Children with a Developmental Disability in a Primary Care Setting", 2008, by Harold Siden and Tim Oberlander in Pain in Children: A Practical Guide for Primary Care, p. 29-37 (link to publication)

  • You can also view this poster explaining the case vignette study and results