Chemokine (c-c motif) receptor 2 mediates mechanical and cold hypersensitivity in sickle cell disease mice
| Autor: | Katelyn E. Sadler, Cheryl L. Stucky, Katherine J. Zappia, Crystal L. O’Hara, Andy D. Weyer, Cheryl A. Hillery, Sarah N. Langer |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CCR2 Chemokine congenital hereditary and neonatal diseases and abnormalities Sensory Receptor Cells Receptors CCR2 CCR4 TRPV1 Mice Transgenic Anemia Sickle Cell CCL2 Article Proinflammatory cytokine 03 medical and health sciences Chemokine receptor Mice 0302 clinical medicine hemic and lymphatic diseases medicine Animals Spiro Compounds biology business.industry Chronic pain medicine.disease Cryopyrin-Associated Periodic Syndromes Benzoxazines Disease Models Animal 030104 developmental biology Anesthesiology and Pain Medicine Neurology Hyperalgesia Immunology biology.protein Neurology (clinical) business 030217 neurology & neurosurgery |
| Popis: | Approximately one-third of individuals with sickle cell disease (SCD) develop chronic pain. This debilitating pain is inadequately treated because the underlying mechanisms driving the pain are poorly understood. In addition to persistent pain, patients with SCD are also in a tonically proinflammatory state. Previous studies have revealed that there are elevated plasma levels of many inflammatory mediators including chemokine (c-c motif) ligand 2 (CCL2) in individuals with SCD. Using a transgenic mouse model of SCD, we investigated the contributions of CCL2 signaling to SCD-related pain. Inhibition of chemokine receptor 2 (CCR2), but not CCR4, alleviated the behavioral mechanical and cold hypersensitivity in SCD. Furthermore, acute CCR2 blockade reversed both the behavioral and the in vitro responsiveness of sensory neurons to an agonist of TRPV1, a neuronal ion channel previously implicated in SCD pain. These results provide insight into the immune-mediated regulation of hypersensitivity in SCD and could inform future development of analgesics or therapeutic measures to prevent chronic pain. |
| Databáze: | OpenAIRE |
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