title: Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation.
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.
authors.affiliation: Vascular Biology Center, Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Lucile
authors.initials: L
authors.lastname: Vincent
authors.affiliation: Vascular Biology Center, Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Vang
authors.affiliation: Vascular Biology Center, Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Nguyen
authors.affiliation: Vascular Biology Center, Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Benson
authors.affiliation: Vascular Biology Center, Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Lei
authors.affiliation: Vascular Biology Center, Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA gupta014@umn.edu.
authors.forename: Kalpna
authors.initials: K
authors.lastname: Gupta
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications*; D000818:Animals; D001522:Behavior, Animal; D002186:Cannabinoids / Q000494:pharmacology; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D000860:Hypoxia / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020078:Neurogenic Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D010147:Pain Measurement; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism*
chemical_list: D002186:Cannabinoids; D043882:Receptors, Cannabinoid