%0 Journal Article
%T Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats
%A Jia-Le Yang
%A Bo Xu
%A Shuang-Shuang Li
%A Wei-Shi Zhang
%A Hua Xu
%A Xiao-Ming Deng
%A Yu-Qiu Zhang
%J Molecular Brain
%D 2012
%I BioMed Central
%R 10.1186/1756-6606-5-18
%X Unilateral intra-articular injection of CFA produced a robust activation of microglia and astrocytes. These cells exhibited large cell bodies, thick processes and increases in the ionized calcium binding adapter molecule 1 (Iba-1, a microglial marker) or the glia fibrillary acidic protein (GFAP, an astrocytic marker). These cells also displayed immunoreactive signals, and an upregulation of the voltage-gated calcium channels (VGCCs) ¦Á2/¦Ä-1 subunit, CX3CL1 and CX3CR1 expression levels in the spinal cord. These changes were associated with the development of thermal hyperalgesia. Immunofluorescence staining showed that VGCC ¦Á2/¦Ä-1 subunit, a proposed gabapentin target of action, was widely distributed in primary afferent fibers terminals and dorsal horn neurons. CX3CL1, a potential trigger to activate microglia, colocalized with VGCC ¦Á2/¦Ä-1 subunits in the spinal dorsal horn. However, its receptor CX3CR1 was mainly expressed in the spinal microglia. Multiple intraperitoneal (i.p.) gabapentin injections (100£¿mg/kg, once daily for 4£¿days with the first injection 60£¿min before intra-articular CFA) suppressed the activation of spinal microglia, downregulated spinal VGCC ¦Á2/¦Ä-1 subunits decreased CX3CL1 levels and blocked the development of thermal hyperalgesia in MA rats.Here we provide the first evidence that gabapentin diminishes CX3CL1 signaling and spinal microglia activation induced by joint inflammation. We also show that the VGCC ¦Á2/¦Ä-1 subunits might be involved in these events.
%K ¦Á2/¦Ä-1 subunit of Voltage-gated calcium channels
%K CX3CL1
%K CX3CR1
%K Gabapentin
%K Glial activation
%K Monoarthritis
%U http://www.molecularbrain.com/content/5/1/18/abstract