New evidence for the involvement of spinal fractalkine receptor in pain facilitation and spinal glial activation in rat model of monoarthritis.
Fractalkine, a chemokine binding to only one known receptor CX3CR1, has recently been proposed to be a neuron-to-glia signal in the spinal cord leading to microglial activation and glially dependent pain facilitation. The previous studies explored that blockade of endogenous fractalkine, using anti-CX3CR1 neutralizing antibody, dose-dependently attenuated neuropathic pain. The present study examined the role of endogenous fractalkine in inflammatory pain. Intra-articular injection of complete Freund's adjuvant (CFA)-induced rat ankle joint monoarthritis (MA) model was used. Western blot analysis revealed that CX3CR1 expression in the spinal cord was significantly increased following CFA-induced MA. Intrathecal injection of anti-CX3CR1 neutralizing antibody both delayed the development of mechanical allodynia and thermal hyperalgesia, and reversed established pain facilitation. Furthermore, blockade of CX3CR1 significantly suppressed activation of spinal glia, especially microglia, evoked by MA. These data provided new evidence for the contribution of endogenous fractalkine to the initiation and early maintenance of inflammatory pain facilitation via activating spinal microglia.
Sun
Shan
S
Institutes of Brain Science, Institute of Neurobiology, Fudan University, 138 Yixueyuan, Shanghai 200032, China.
Cao
Hong
H
Han
Mei
M
Li
Ting-Ting
TT
Pan
Hai-Li
HL
Zhao
Zhi-Qi
ZQ
Zhang
Yu-Qiu
YQ
D000704:Analysis of Variance; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D000073883:CX3C Chemokine Receptor 1; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D009457:Neuroglia / Q000502:physiology*; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D018121:Receptors, Cytokine / Q000502:physiology*; D015728:Receptors, HIV / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology*
D000073883:CX3C Chemokine Receptor 1; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D005620:Freund's Adjuvant