Mucositis Pain and Its Temporal Relationship to White Cell Count

Background: Children who have received chemotherapy and/or radiotherapy treatment resulting in neutropenia can suffer painful mucositis. We explored the relationship between pain score and white cell count in children with mucositis due to immunosuppression and assessed the influence of opioid and ketamine analgesia.

Methods: Children with mucositis nursed in the pediatric oncology and hematology ward were invited to partake in this observational study following referral to the pediatric pain service for intravenous analgesia. Pain scores, white cell count, neutrophil count, and analgesia requirements were recorded daily until intravenous analgesia was either stopped or transitioned to oral analgesia. Data were analyzed using nonlinear mixed effects models that sought a relationship between white cell count and pain score using a sigmoid maximal effect (E_MAX) model. The impact of analgesic use on pain score was determined. The temporal relationship between white cell count and pain score was characterized by using a delayed effect model with an equilibration half-time.

Results: Fifty children were enrolled in the study from January 2022 to December 2023. The equilibration half-time relating the rise in white cell count and pain response was 0.29 days. The initial pain score (estimated in those children already started on treatment with paracetamol and tramadol) was 6.3 (maximum pain 10). The maximum pain reduction was 59% of that initial pain score. Morphine and ketamine further reduced pain; the maximum response for opioids was 38% reduction and that for ketamine was 11%.

Conclusion: Pain relief from mucositis is related to an increase in white cell count after a period of severe neutropenia, where white cell count is a surrogate for neutrophil count. There is a delay in analgesic response of approximately 1 day. This analgesic response to increasing white cell count had greater dominance than analgesia achieved using either opioids or ketamine.