An Evaluation of Central Sensitization in Patients With Sickle Cell Disease

Abstract

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.

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

“…Murine SCD models and individuals with SCD show increased sensitivity to experimental pain similar to that described in other groups with chronic pain [12, 16–18]. Recent murine and human studies have observed central sensitization in SCD [10, 14, 18–22]. Central sensitization is a process where repeated nociceptive signals from the periphery affect and alter pain processing in the central nervous system, leading to amplification of pain.…”

“…Tests of temporal summation are being considered as potential clinical assessment tools for characterizing central sensitization in other chronic pain conditions [41, 42], although central sensitization is not uniformly observed in chronic pain [14, 43]. Temporal summation is specific for increased responses by spinal dorsal horn or other central neurons to painful stimuli [41, 44, 45].…”

“…Temporal summation is specific for increased responses by spinal dorsal horn or other central neurons to painful stimuli [41, 44, 45]. Ezenwa et al showed that sixty percent of SCD adults had centralized pain using an algorithm assessing allodynia and hyperalgesia [20], while another SCD study showed a prevalence of 25% [14]. These results that suggest central sensitization may be a common element of pain in SCD.…”

“…While SCD studies have demonstrated increased sensitivity by static QST methods, the magnitude of these differences were significantly smaller than in fibromyalgia, [14, 18, 27, 28, 32]. Recent QST studies exploring central sensitization in SCD are promising [14], however its relationship with known disease modifiers has not been evaluated [4, 13, 14, 19, 20]. Indeed, recent resting state functional MRI showed a significant correlation between anti-nociceptive brain connectivity and fetal hemoglobin in low pain burden SCD patients [15].…”

Mechanisms of Pain in Sickle Cell Disease

“…Sickle Cell Disease -Pain and Common Chronic Complications 74 patients was recently evaluated using QST, questionnaires and daily pain diaries [29]. Those patients with higher scores for central sensitization exhibited worse manifestations of SCD.…”