Abstract
Sickle cell anemia is a manifestation of a single point mutation in hemoglobin, but inflammation and pain are the insignia of this disease which can start in infancy and continue throughout life. Earlier studies showed that mast cell activation contributes to neurogenic inflammation and pain in sickle mice. Morphine is the common analgesic treatment but also remains a major challenge due to its side effects and ability to activate mast cells. We, therefore, examined cannabinoid receptor-specific mechanisms to mitigate mast cell activation, neurogenic inflammation and hyperalgesia, using HbSS-BERK sickle and cannabinoid receptor-2-deleted sickle mice. We show that cannabinoids mitigate mast cell activation, inflammation and neurogenic inflammation in sickle mice via both cannabinoid receptors 1 and 2. Thus, cannabinoids influence systemic and neural mechanisms, ameliorating the disease pathobiology and hyperalgesia in sickle mice. This study provides ‘proof of principle’ for the potential of cannabinoid/cannabinoid receptor-based therapeutics to treat several manifestations of sickle cell anemia.
Original language | English (US) |
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Pages (from-to) | 566-577 |
Number of pages | 12 |
Journal | Haematologica |
Volume | 101 |
Issue number | 5 |
DOIs | |
State | Published - Apr 30 2016 |
Bibliographical note
Funding Information:Funding: this work was supported by NIH RO1 grants HL68802 and 103773 and UO1 HL117664 and Institute for Engineering in Medicine grants to KG. Confocal imaging was performed using the Olympus FluoView 1000 IX2 instrument at the University of Minnesota - University Imaging Centers, http://uic.umn.edu. The authors would like to thank Stefan Kren, Katherine NH Johnson, Sugandha Rajput, Ritu Jha and Susan Thompson for breeding, genotyping, phenotyping mice and/or technical assistance; Drs. Robert P. Hebbel and David Archer for providing breeder sickle mice; Drs. David Largaespada and Anindya Bagchi for advice on mouse genetics; Dr Donald A. Simone for a critical review of the manuscript; and Michael J. Franklin and Carol Taubert for editorial assistance.
Publisher Copyright:
© 2016 Ferrata Storti Foundation.
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Olympus Fluoview FV1000 IX2 Inverted Confocal with FLIM Detector
University Imaging CentersEquipment/facility: Equipment
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University Imaging Centers
Mark A Sanders (Program Director) & Guillermo Marques (Scientific Director)
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