Clinical Interpretation of Quantitative Sensory Testing as a Measure of Pain Sensitivity in Patients With Sickle Cell Disease

Abstract

Patients with sickle cell disease (SCD) display significantly lower mean/median thermal and mechanical pain thresholds compared to controls. This suggests impaired pain sensitivity where stimuli produce exaggerated pain. Despite these mean/median differences, clinicians need to understand if patients meet criteria for impaired pain sensitivity. We defined thresholds for impaired cold, heat, and mechanical pain sensitivity in SCD patients. Using quantitative sensory testing (QST) we assessed cold, heat, and mechanical pain thresholds in SCD patients and African American controls ≥ 7 years. Impaired pain sensitivity was defined as: 1) cold pain threshold one standard deviation (SD) above control median threshold; 2) heat pain threshold one SD below control median threshold; 3) mechanical pain threshold one SD below control median threshold. Fifty-five SCD patients and 57 controls participated. Impaired pain sensitivity thresholds were: 1) cold: 17.01°C, 2) heat: 43.91°C, 3) mechanical: 4.42g. Impaired cold pain sensitivity was the most common finding (63.6%), then heat (60%), and mechanical (38.2%). Impaired pain sensitivity to ≥1 testing modalities occurred in 81.8% of SCD patients. Determining impaired pain sensitivity thresholds increases clinical utility of QST. QST could be a screening tool to phenotype SCD pain, an outcome for pain interventional trials, or guide pain neurobiology investigations.

Quantitative sensory testing in children with sickle cell disease: additional insights and future possibilities

“…In a follow‐up report, Brandow and Panepinto () proposed cpt and hpt cut‐off values indicative of impairment in children with SCD. When we apply these cut‐offs to our African American cohort, we find that 50 (83%) of the controls and 49 (82%) of the SCD group would be considered to have impaired cpt and 51 (85%) of the controls and the SCD group would be considered to have impaired hpt.…”

“…Several groups have recently reported on QST in SCD (Brandow et al, 2013(Brandow et al, , 2019O'Leary et al, 2014;Jacob et al, 2015;Brandow & Panepinto, 2016;Campbell et al, 2016a;Ezenwa et al, 2016;Bakshi et al, 2017;Veluswamy et al, 2018), raising interest in the use of QST as a modality to help elucidate the mechanisms of pain in SCD. Interestingly, Veluswamy et al (2018) demonstrated stronger and more rapid vasoconstriction in SCD subjects in response to thermal stimuli, most significantly cold, compared to controls, suggesting that heightened vascular autonomic reactivity may be linked to cold-related VOC in SCD.…”

Mouse Models of Pain in Sickle Cell Disease

“…Similarities exist between clinical features of pain in SCD and in BERK and Townes mouse models. Increased sensitivity to heat, cold, and mechanical stimuli observed in mice has also been observed in patients with SCD using quantitative sensory testing (QST) (Bakshi, Lukombo, Belfer, & Krishnamurti, ; Brandow & Panepinto, ; Brandow, Stucky, Hillery, Hoffmann, & Panepinto, ; Cain et al., ; Campbell et al., ; Darbari et al., ; Ezenwa et al., ; Hillery et al., ; Jacob et al., ; Kohli et al., ; Lei, Benson, Tran, Ofori‐Acquah, & Gupta, ). For both BERK and Townes sickle mice, females show increased hyperalgesia compared to age‐matched males (Kohli et al., ; Lei et al., ).…”

A QST‐based Pain Phenotype in Adults With Sickle Cell Disease: Sensitivity and Specificity of Quality Descriptors

“…The pain of SCD, however, is complex and may vary by an underlying etiology that involves some dysfunction of the nervous system such as peripheral and central sensitization . Studies have revealed altered peripheral nerve architecture in animal models of SCD and evidence of sensitization in humans with SCD . Neuropathic pain is associated with pain of increased duration and intensity that is less responsive than nociceptive pain to typical doses of opioid analgesics .…”

“…QST and self‐report questionnaires are useful to characterize the sensitization and neuropathic pain experiences of patients with SCD . In particular, QST results in African Americans with SCD reveal the presence of an abnormal thermal pain threshold (sensitivity) and/or a reduced mechanical pain threshold (sensitivity) .…”