Paroxetine alleviates rat limb post-ischemia induced allodynia through GRK2 upregulation in superior cervical ganglia.
Long-lasting neuroplastic changes induced by transient decrease in G protein-coupled receptor kinase 2 (GRK2) in nociceptors enhances and prolongs inflammatory hyperalgesia. Here, we investigated the effects of paroxetine (a selective serotonin reuptake inhibitor and GRK2 inhibitor) on GRK2 expression in superior cervical ganglion (SCG) in a rat model of complex regional pain syndrome type I (CRPS-I). After ischemia-reperfusion (I/R) injury, the ipsilateral 50% paw withdrawal thresholds (PWTs) to mechanical stimuli and the expression levels of GRK2 protein and mRNA in the ipsilateral SCGs all decreased significantly; the ipsilateral cold allodynia scores increased significantly. No significant differences were found in the contralateral side except GRK2 mRNA reduced significantly at day 2-day 9 after I/R injury, but still higher than those in ipsilateral SCGs. After paroxetine administration, the ipsilateral 50% PWTs at day 2, 7, 14, and 21 were significantly higher than those in control group; The GRK2 protein and mRNA levels in ipsilateral SCGs were also significantly up-regulated after day1; The ipsilateral cold allodynia scores were significantly reduced after day7. No significant differences were found in the contralateral 50% PWTs, cold allodynia scores, and GRK2 protein level except GRK2 mRNA levels increased significantly at day1-day7 after paroxetine 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 paroxetine might alleviate this allodynia through GRK2 protein upregulation in SCGs.
Department of Anesthesiology, Jinshan Hospital, Fudan University Shanghai, China.
Jun
J
Tang
Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital 650 Xin Songjiang Road, Shanghai 201620, China.
Jing
J
Dong
Department of Anesthesiology, Jinshan Hospital, Fudan University Shanghai, China.
Li
L
Yang
Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital 650 Xin Songjiang Road, Shanghai 201620, China.
Lingqi
L
Gao
Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital 650 Xin Songjiang Road, Shanghai 201620, China.
Jijian
J
Zheng
G protein-coupled receptor kinase 2; complex regional pain syndrome type I; mechanical and cold allodynia; paroxetine; selective serotonin reuptake inhibitor; superior cervical ganglion neurons