Central sensitization (CS), nociceptive hyper-excitability known to amplify and maintain clinical pain, has been identified as a leading culprit responsible for maintaining pain in several chronic pain conditions. Recent evidence suggests that it may explain differences in the symptom experience of individuals with sickle cell disease (SCD). Quantitative sensory testing (QST) can be used to examine CS and identify individuals that may have a heightened CS profile. The present study categorized patients with SCD based on QST responses into a high or low CS phenotype and compared these groups on measures of clinical pain, vaso-occlusive crises, psychosocial factors, and sleep continuity. Eighty-three adult patients with SCD completed QST, questionnaires, daily sleep and pain diaries over a three-month period, weekly phone calls for three months, and monthly phone calls for 12 months. Patients were divided into CS groups (i.e. No/Low CS [n=17] vs. High CS [n=21]), based on thermal and mechanical temporal summation and aftersensations, which were norm-referenced to 47 healthy controls. High CS subjects reported more clinical pain, vaso-occlusive crises, catastrophizing, and negative mood, and poorer sleep continuity (p’s<0.05) over the 18-month follow-up period. Future analyses should investigate whether psychosocial disturbances and sleep mediate the relationship between central sensitization and pain outcomes.
Perspective
In general, sickle cell disease patients with greater central sensitization had higher clinical pain, more crises, worse sleep, and more psychosocial disturbances compared to the low CS group.
Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis), central sensitization, depression, and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not.
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