Mast cell activation contributes to sickle cell pathobiology and pain in mice

Lucile Vincent, Derek Vang, Julia Nguyen, Mihir Gupta, Kathryn Luk, Marna E. Ericson, Donald A. Simone, Kalpna Gupta

Research output: Contribution to journalArticlepeer-review

168 Scopus citations


Sickle cell anemia (SCA) is an inherited disorder associated with severe lifelong pain and significant morbidity. The mechanisms of pain in SCA remain poorly understood. We show that mast cell activation/degranulation contributes to sickle pain pathophysiology by promoting neurogenic inflammation and nociceptor activation via the release of substance P in the skin and dorsal root ganglion. Mast cell inhibition with imatinib ameliorated cytokine release from skin biopsies and led to a correlative decrease in granulocyte-macrophage colony-stimulating factor and white blood cells in transgenic sickle mice. Targeting mast cells by genetic mutation or pharmacologic inhibition with imatinib ameliorates tonic hyperalgesia and prevents hypoxia/reoxygenation-induced hyperalgesia in sickle mice. Pretreatment with the mast cell stabilizer cromolyn sodium improved analgesia following low doses of morphine that were otherwise ineffective. Mast cell activation therefore underlies sickle pathophysiology leading to inflammation, vascular dysfunction, pain, and requirement for high doses of morphine. Pharmacological targeting of mast cells with imatinib may be a suitable approach to address pain and perhaps treat SCA.

Original languageEnglish (US)
Pages (from-to)1853-1862
Number of pages10
Issue number11
StatePublished - 2013

Bibliographical note

Publisher Copyright:
© 2013 by The American Society of Hematology.


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