Intrathecal administration of clonidine attenuates spinal neuroimmune activation in a rat model of neuropathic pain with existing hyperalgesia.
Central neuroimmune activation contributes to the initiation and maintenance of neuropathic pain after nerve injury. The current study was aimed to examine the modulation of neuroimmune activation in the spinal cord by the alpha(2) adrenoceptor agonist, clonidine, in a rat model of neuropathic pain induced by partial sciatic nerve ligation (PSNL). Animals were randomly assigned into 6 groups: sham-operation with 20 microg clonidine or saline; and PSNL with clonidine (5, 10, and 20 microg) or saline. Fourteen days post-operation, various doses of clonidine or saline were injected intrathecally. The paw pressure threshold and paw withdrawal latencies were measured before and at 30, 60, 90, and 120 min after the injection of clonidine. Glial activation markers such as macrophage antigen complex-1 (mac-1) and glial fibrillary acidic protein (GFAP), interleukin (IL)-1beta and IL-6, nuclear factor-kappa B (NF-kappaB) activation, and p-p38 mitogen-activated protein kinase (MAPK) activation in the lumbar spinal cord were determined as well. Administration of clonidine resulted in a dose-dependent attenuation in PSNL-induced mechanical and thermal hyperalgesia. Furthermore, clonidine could markedly inhibit neuroimmune activation characterized by glial activation, production of cytokines, NF-kappaB activation as well as p38 activation. The antihyperalgesic effect of intrathecal clonidine in rats receiving PSNL might partly attribute to the inhibition of neuroimmune activation associated with the maintenance of neuropathic pain.
Feng
Xiaomei
X
Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.
Zhang
Fujun
F
Dong
Rong
R
Li
Weiyan
W
Liu
Jian
J
Zhao
Xin
X
Xue
Qingsheng
Q
Yu
Buwei
B
Xu
Jianguo
J
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D003000:Clonidine / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006930:Hyperalgesia / Q000150:complications*; D007278:Injections, Spinal; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects*; D010146:Pain / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D016328:NF-kappa B; D048051:p38 Mitogen-Activated Protein Kinases; D003000:Clonidine