High-Impact Chronic Pain in Sickle Cell Linked to Poor Health Outcomes

Nitya Bakshi, MBBS, MS

Credit: Yale School of Medicine

Individuals with high-impact chronic pain (HICP) and sickle cell disease (SCD) demonstrated a greater burden of pain and worse health outcomes in an analysis of data from the Pain in Sickle Cell Epidemiology Study (PiSCES).¹

Compared with those with SCD without HICP, those with HICP exhibited worse mean daily pain intensity on days without crises and more days with pain, healthcare utilization, home opioid use, and higher levels of stress. There was no significant evidence to suggest a higher daily pain intensity on days with crises.

“In this study, we built on previous observations from PiSCES and provide empirical evidence to support the heterogeneity of the chronic pain phenotype in SCD and the stratification of chronic pain based on the frequency of pain interference, that is, the presence of HICP, to identify a severely affected subgroup of chronic pain that experienced greater pain burden and worse health outcomes,” wrote the investigative team, led by Nitya Bakshi, MBBS, MS, division of pediatric hematology-oncology at the Yale University School of Medicine.

SCD is defined by both acute episodes of and chronic pain, which has been linked to substantial morbidity and poorer health outcomes. In the pivotal PiSCES study, more than half of the studied individuals had chronic pain, with approximately one-third experiencing daily or near-daily pain.²

Current pain definitions are comprised of frequency (pain on most days) and duration (≥6 months), but do not include the impact of pain on a patient.³ A recent US National Pain Strategy report has called for separating a severely affected population with chronic pain, who experience restrictions in work, social, or self-care activities, as having HICP.⁴

Although recent data have pointed to the presence of subgroups of chronic pain within SCD, there is a notable gap in systematic efforts to examine HICP as a phenotype within patients with SCD.⁵ Using data from PiSCES, Baskhi and colleagues compared the HICP phenotype in SCD with individuals who had chronic pain, but not HICP.¹

PiSCES enrolled participants with SCD aged ≥16 from July 2002 to August 2004. Each participant provided baseline demographic, clinical, health-related quality of life (HRQoL), and psychological data and completed a daily pain diary for 6 months on SCD-related daily pain intensity, interference, medication use, and healthcare utilization.

Those who had completed pain diaries for ≥5 months and reported pain on >50% of reported days were identified as a cohort with HICP in PiSCES. The full analysis cohort included 63 patients with SCD and chronic pain, of which 48 experienced HICP. No differences were observed in demographic and clinical characteristics between the two pain cohorts.

Upon analysis, the mean, median, and 90th percentile of daily pain intensity and interference, and the proportion of pain days and days with interference, were significantly higher for patients with HICP. Those with HICP also experienced higher mean pain on days without crises and without healthcare utilization and a greater number of days with home opioid use.

However, Bakshi and colleagues identified no statistically significant differences between the HICP and non-HICP cohorts in mean daily pain intensity among days with crises or days with healthcare utilization.

Notably, they found SCD-related stress was significantly higher in those with HICP, while psychological characteristics, including depression and anxiety, were not statistically different between the cohorts. This remained in line with evidence on the role of stress in chronic pain for disorders other than SCD.

“Given the known associations of psychological comorbidities with HICP, this should be examined in larger prospective studies of HICP in SCD,” Bakshi and colleagues added.

References

1. _{Jagtiani A, Chou E, Gillespie SE, et al. High-impact chronic pain in sickle cell disease: insights from the Pain in Sickle Cell Epidemiology Study (PiSCES). Pain. Published online May 23, 2024. doi:10.1097/j.pain.0000000000003262}
2. _{Smith WR, Penberthy LT, Bovbjerg VE, et al. Daily assessment of pain in adults with sickle cell disease. Ann Intern Med. 2008;148(2):94-101. doi:10.7326/0003-4819-148-2-200801150-00004}
3. _{Dampier C, Palermo TM, Darbari DS, Hassell K, Smith W, Zempsky W. AAPT Diagnostic Criteria for Chronic Sickle Cell Disease Pain. J Pain. 2017;18(5):490-498. doi:10.1016/j.jpain.2016.12.0162}
4. _{National Pain Strategy Report. A comprehensive population health-level strategy for pain. Available at: https://www.iprcc.nih.gov/sites/default/files/documents/NationalPainStrategy_508C.pdf.}
5. _{Bakshi N, Gillespie S, McClish D, McCracken C, Smith WR, Krishnamurti L. Intraindividual pain variability and phenotypes of pain in sickle cell disease: a secondary analysis from the Pain in Sickle Cell Epidemiology Study. Pain. 2022;163(6):1102-1113. doi:10.1097/j.pain.0000000000002479}