Children and adolescents with sickle cell disease have worse cold and mechanical hypersensitivity during acute painful events

Abstract

Sickle cell disease (SCD) pain associates with cold temperature and touch. Patients and murine models with SCD have baseline thermal and mechanical pain. In SCD mice, the baseline hypersensitivity is exacerbated by experimental vaso-occlusive crises. We hypothesized that patients with SCD will similarly experience increased hypersensitivity to thermal and mechanical stimuli during acute painful events compared with baseline health. We conducted a prospective study of 24 patients with SCD aged 7 to 19 years. Patients underwent quantitative sensory testing to thermal (cold/heat) and mechanical stimuli on the thenar eminence of the nondominant hand (glabrous skin) and the lateral dorsum of the foot (hairy skin) during baseline health and within 48 hours of hospitalization for acute pain. Primary outcomes were changes in: (1) cold pain threshold (°C), (2) heat pain threshold (°C), and (3) mechanical pain threshold (g). Median age was 10.5 (interquartile range [IQR] 9-14.8) years, 67% were females, and 92% were on hydroxyurea. Patients with SCD had increased cold pain sensitivity in the hand during hospitalization compared with baseline (25.2°C [IQR 18.4-27.5°C] vs 21.3°C [IQR 4.9-26.2°C]; P = 0.011) and increased mechanical pain sensitivity in the foot during hospitalization (0.32 g [IQR 0.09-1.1 g] vs 1.7 g [IQR 0.4-8.3 g]; P = 0.003). There were no differences in heat pain sensitivity. The increased cold (P = 0.02) and mechanical (P = 0.0016) pain sensitivity during hospitalization persisted after adjusting for age, sex, hydroxyurea use, opioid consumption, and numeric pain score. Thus, cold and mechanical pain is significantly worse during an acute SCD painful event as compared to baseline health in patients with SCD.

Figure 1.

Differences in cold pain thresholds between baseline health and acute painful events. Boxplots displaying differences in median cold pain thresholds between SCD patients at baseline health and during acute pain (n=24, measured at both timepoints) analyzed using Wilcoxon signed-rank test. There was a significant increase in the median cold pain threshold in the hand (i.e., pain felt closer to 32°C) during acute pain as compared to baseline health reflecting increased cold pain sensitivity during acute pain. There were no measured differences in the foot. Note: open circles represent outliers.

Figure 2.

Differences in heat pain thresholds between baseline health and acute painful events. Boxplots displaying differences in median heat pain thresholds between SCD patients at baseline health and during acute pain (n=24, measured at both timepoints) analyzed using Wilcoxon signed-rank test. There were no differences in heat pain sensitivity between the two timepoints in the hand or the foot.

Figure 3.

Differences in mechanical pain thresholds between baseline health and acute painful events. Boxplots displaying differences in median mechanical pain thresholds between SCD patients at baseline health and during acute pain (n=24, measured at both timepoints) analyzed using Wilcoxon signed-rank test. There was a significant decrease in the mechanical pain threshold in the foot during acute pain as compared to baseline health reflecting an increase in mechanical pain sensitivity during acute pain. There was also a decrease in mechanical pain thresholds in the hand during acute pain as compared to baseline health that approached (but did not reach) significance in the direction of our hypothesis. Note: open circles and asterisks represent outliers.