Impact of Psychological Covariates on Experimental Pain Sensitivity in Children and Adolescents with SCD

Background: Children with Sickle Cell Disease (SCD) have increased sensitivity to heat and cold pain (Brandow et al) during steady state. However, the role of psychological factors such as anxiety, depressive symptoms and catastrophizing on pain sensitivity is not known in SCD. Characterization of these factors may provide an insight into the study of their possible roles in the transition to chronic pain.

Aim:To determine if psychological factors impact pain sensitivity in patients with SCD.

Methods: Patients with SCD were offered quantitative sensory testing (QST) when at steady state (at least 2 weeks following a VOE). QST procedures included estimation of pressure, mechanical and thermal pain thresholds (minimum intensity of stimulus which is first perceived as painful) and tolerances (maximum intensity of a pain-producing stimulus that a participant is willing to accept in a given situation) as well as windup values (increased pain perception to repetitive painful stimuli). At each time point, participants completed the PROMIS measures of pain intensity, pain interference, anxiety, depressive symptoms, sleep, fatigue and peer relationships. Participants also completed the Pain Catastrophizing Scale ((PCS)-Sullivan et al), Child Somatization Inventory (Walker et al), Pain Coping Inventory (Varni et al)* as well as Peds QL Generic and SCD specific measures of Quality of life*.

Results:We determined the experimental pain phenotype (sensitivity to pressure, mechanical and thermal pain) of 29 patients with SCD during steady state (> 2 weeks from a vaso-occlusive episode). These participants were not receiving long-term opioids or adjunctive medications for pain. The median age of participants was 15 (IQR 10-19) and majority (69 %) were female.  Approximately half of the study sample had HbSS. Three quarters of the study sample were prescribed hydroxyurea. The median Hb level was 11.1 (IQR 10.2-11.6). The median number of VOC’s in the year prior to testing was 1(IQR 0-2) and in 3 years prior to testing was 3 (IQR 2-5). The median PROMIS pain intensity T-score was 37.8, PROMIS pain interference T-score was 48.75, PROMIS Depressive symptom T-score was 44.35 and PROMIS anxiety was 43.9; these scores were not higher than the average T- score of 50 described in the pediatric population. High catastrophizing scores were reported on the PCS, with median score being 29. The median cold pain threshold was 23.6 degrees C (IQR 15.8-26.7) and median heat pain threshold was 39.1 degrees C (IQR 37.5- 40.9).

We noted that increase in scores on PROMIS depressive symptoms was associated with lower heat (Spearman’s rho= -0.55), cold (Spearman’s rho= 0.57) and mechanical (Spearman’s rho= -0.4) pain thresholds. Scores on PROMIS depressive symptoms predicted heat and cold pain thresholds independent of age and VOC’s in the past 3 years. Increased PROMIS anxiety scores were associated with lower mechanical pain thresholds (Spearman’s rho= -0.43) and lower cold detection thresholds (Spearman’s rho= 0.46). Increased scores on PCS were associated with lower heat detection thresholds (Spearman’s’ rho= -0.39). (All p-values were<0.05)

Outcome	Depressive symptoms		VOCs in 3 years prior to study		Age (years)		Model sig	n
	Coeff	p-value	Coeff	p-value	Coeff	p-value
Cold Pain Threshold	0.4	0.003	-0.19	0.6	-0.41	0.16	<0.01	27
Heat Pain Threshold	-0.12	0.013	0.38	0.012	0.2	0.068	<0.001	28

Conclusions: Depressive symptoms and anxiety are associated with lower experimental pain thresholds in patients with SCD. Higher scores on PROMIS depressive symptoms predict increased sensitivity to heat and cold pain independent of age and number of VOCs experienced in the past 3 years. Further studies are needed to determine the contribution of psychological factors in the transition to chronic pain in SCD.

Acknowledgements: 1- Sickle Cell Disease Association of America 2- *PedsQL™ contact information and permission to use: Mapi Research Trust, Lyon, France. E-mail: PROinformation@mapi-trust.org – Internet: www.Mapi-trust.org and http://www.pedsql.org/index.html