title: Dexmedetomidine alleviates rat post-ischemia induced allodynia through GRK2 upregulation in superior cervical ganglia.
abstract: A transient decrease in G protein-coupled receptor kinase 2 (GRK2) in nociceptors can produce long-lasting neuroplastic changes in nociceptor function, eventually enhancing and prolonging inflammatory hyperalgesia. Here, we investigated the effects of selective α2-adrenoceptor agonist dexmedetomidine (DMED) on GRK2 expression in superior cervical ganglion (SCG) in a rat model of complex regional pain syndrome type I (CRPS-I). The ipsilateral 50% paw withdrawal thresholds (PWTs) to mechanical stimuli decreased significantly starting from 24 h after ischemia-reperfusion (I/R) injury, and lasted for over 3 weeks; the ipsilateral cold allodynia scores, GRK2 protein and mRNA levels in SCGs all increased significantly. No significant differences were found in the contralateral side except GRK2 mRNA reduced significantly after 48 h I/R injury, but still higher than those in the ipsilateral side. Following daily injection of 10 μg/kg of DMED for a maximum of 7 days, the ipsilateral PWTs on days 1, 2, 7, 14, and 21 after DMED administration were significantly higher than those in control group; the GRK2 protein and mRNA expressions in the ipsilateral SCGs were also significantly upregulated; the ipsilateral cold allodynia scores were significantly reduced. No significant differences were found in the contralateral 50%PWTs, cold allodynia scores, and GRK2 protein level except GRK2 mRNA levels increased significantly on days 1 to 7 after DMED administration. Therefore, a transient decrease of GRK2 expression in SCG neurons might be involved in the development and maintenance of allodynia in CRPS-I and DMED might alleviate this allodynia through GRK2 upregulation in SCG neurons.
authors.affiliation: Department of Anesthesiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University affiliated Shanghai First People's Hospital, Shanghai 201620, China. Electronic address: dongjingmn@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, Jinshan Hospital, Fudan University, Shanghai, China. Electronic address: liyangmagic@sina.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Jinshan Hospital, Fudan University, Shanghai, China. Electronic address: mdtangj@sina.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Anesthesiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University affiliated Shanghai First People's Hospital, Shanghai 201620, China. Electronic address: zhengjijian626@sina.com.
authors.forename: Jijian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000627:therapeutic use*; D000818:Animals; D020927:Dexmedetomidine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005552:Forelimb / Q000503:physiopathology; D007839:Functional Laterality; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control*; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D007511:Ischemia / Q000150:complications / Q000188:drug therapy; D009474:Neurons / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy; D018709:Statistics, Nonparametric; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; C496569:Grk2 protein, rat; D054769:G-Protein-Coupled Receptor Kinase 2
keywords: Complex regional pain syndrome type I; Dexmedetomidine; G protein-coupled receptor kinase 2; Mechanical and cold allodynia; Superior cervical ganglion neurons; α(2)-Adrenoceptor