Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease

Abstract

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.

Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia

“…To determine if HbF played any role in pain sensitivity, we assessed this association limited only to the sickle cell cohort which showed fetal hemoglobin was negatively associated with pain (β= =−0.338, p=0.006 for 512 mN; β=−0.368, p=0.005 for 256 mN). Because another report suggested that nociceptive processing in SCD is affected by opioid therapy [40], regressions restricted to sickle cell subjects not treated with opioids (n=17) showed comparable results for association with HbF (256 Δ pain score β=−0.322, standard error=0.171 with p=0.08 and 512 Δ pain score for β=−0.365, standard error=0.178 with p=0.06), and suggest this association is independent of opioids.…”

“…Although neither the regression with all subjects, nor regression excluding those taking opioids led to different conclusions, it is not possible to preclude opioid induced responses, especially in patients experiencing high pain burden that necessitates daily therapy. Indeed, a study of 38 SCD patients with high or low central sensitization showed high group responses were associated with opioid therapy [40]. Therefore, larger studies designed to determine the effect of opioids in sickle cell are needed [53].…”

Pain and opioid use after reversal of sickle cell disease following HLA‐matched sibling haematopoietic stem cell transplant

“…Interestingly, while none of our patients on short‐acting opioids experienced continued pain, use of long‐acting opioids was associated with continued pain. This may be a reflection of more severe disease in this group; however, contributions from other factors, such as opioid‐induced hyperalgesia, central sensitization or genetic predisposition cannot be ruled out (Campbell et al , ; Carroll et al , ).…”

Hematopoietic stem cell transplantation for sickle cell disease: Progress and challenges

“…Adults with SCD experience complications rarely seen in childhood, including leg ulcers, end‐stage kidney disease, restrictive lung disease, pulmonary hypertension, and retinopathy . Episodic acute pain may evolve into chronic pain due to peripheral nerve injury, central sensitization, and psychosocial factors . Men with SCD experience priapism, testicular infarction, and gonadal dysfunction; women have high peripartum morbidity and mortality risks .…”