Intra-individual pain variability and phenotypes of pain in sickle cell disease: a secondary analysis from the Pain in Sickle Cell Disease Epidemiology Study (PiSCES).

ABSTRACT Mean pain intensity alone is insufficient to describe pain phenotypes in sickle cell disease (SCD). The objective of this study was to determine impact of day-to-day intra-individual pain variability on patient outcomes in SCD.We calculated metrics of pain variability and pain intensity for 139 participants with <10% missing data in the first 28-days of the Pain in Sickle Cell Epidemiology Study (PiSCES). We performed Spearman rank correlations between measures of intra-individual pain variability and outcomes. We then used k-means clustering to identify phenotypes of pain in SCD.We found that pain variability was inversely correlated with HRQoL, except in those with daily or near daily pain. Pain variability was positively correlated with affective coping, catastrophizing, somatic symptom burden, sickle cell stress, healthcare utilization and opioid use.We found 3 sub-groups or clusters of pain phenotypes in SCD. Cluster 1 included individuals with the lowest mean pain, lowest temporal instability and dependency, lowest proportion of days with pain and opioid use, and highest physical function. Cluster 2 included individuals with the highest mean pain, highest temporal dependency, highest proportion of days with pain and opioid use, and lowest physical function. Cluster 3 included individuals with high levels of mean pain, highest temporal instability, but with lower temporal dependency, proportion of days with pain and opioid use, and physical function compared to cluster 2.We conclude that intra-individual pain variability is associated with patient outcomes and psychological characteristics in SCD, and is useful in delineating phenotypes of pain in SCD.