Highlights
- •Wide variability exists in the frequency of hospitalizations for pain among patients with sickle cell disease.
- •This pilot study explored the association between hospitalizations for pain and intrinsic resting state brain connectivity in the steady state of health.
- •Patients with frequent hospitalizations for pain showed patterns of increased pronociceptive and decreased antinociceptive brain connectivity.
Abstract
Sickle cell disease (SCD) is a hemoglobinopathy that affects more than 100,000 individuals
in the United States. The disease is characterized by the presence of sickle hemoglobin
and recurrent episodes of pain. Some individuals with SCD experience frequent hospitalizations
and a high burden of pain. The role of central mechanisms in SCD pain has not been
explored. Twenty-five adolescents and young adults with SCD underwent functional magnetic
resonance imaging. Participants were stratified into groups with high pain or low
pain based on the number of hospitalizations for pain in the preceding 12 months.
Resting state functional connectivity was analyzed using seed-based and dual regression
independent component analysis. Intrinsic brain connectivity was compared between
the high pain and low pain groups, and association with fetal hemoglobin, a known
modifier of SCD, was explored. Patients in the high pain group displayed an excess
of pronociceptive connectivity such as between anterior cingulate and default mode
network structures, such as the precuneus, whereas patients in the low pain group
showed more connectivity to antinociceptive structures such as the perigenual and
subgenual cingulate. Although a similar proportion of patients in both groups reported
that they were on hydroxyurea, the fetal hemoglobin levels were significantly higher
in the low pain group and were associated with greater connectivity to antinociceptive
structures. These findings support the role of central mechanisms in SCD pain. Intrinsic
brain connectivity should be explored as a complementary and objective outcome measure
in SCD pain research.
Perspective
Altered connectivity patterns associated with high pain experience in patients with sickle
cell disease suggest a possible role of central mechanisms in sickle cell pain. Resting
state brain connectivity studies should be explored as an effective methodology to
investigate pain in SCD.
Key words
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Article info
Publication history
Published online: August 17, 2015
Accepted:
July 28,
2015
Received in revised form:
July 11,
2015
Received:
May 15,
2015
Footnotes
This work was supported by the intramural research programs of the National Heart, Lung and Blood Institute; contract grant numbers: 1 ZIA HL006012; 1 ZIA HL006160 (J.G.T.). The authors declare no competing conflicts of interest.
Supplementary data accompanying this article are available online at www.jpain.org and www.sciencedirect.com.
Identification
Copyright
© 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.
