RGD Reference Report - Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats. - Rat Genome Database

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Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats.

Authors: Yang, JL  Xu, B  Li, SS  Zhang, WS  Xu, H  Deng, XM  Zhang, YQ 
Citation: Yang JL, etal., Mol Brain. 2012 May 30;5:18. doi: 10.1186/1756-6606-5-18.
RGD ID: 9491779
Pubmed: PMID:22647647   (View Abstract at PubMed)
PMCID: PMC3517515   (View Article at PubMed Central)
DOI: DOI:10.1186/1756-6606-5-18   (Journal Full-text)

BACKGROUND: Spinal glia, particularly microglia and astrocytes, are of the utmost importance in the development and maintenance of chronic pain. A recent study from our laboratory revealed that gabapentin, a recommended first-line treatment for multiple neuropathic conditions, could also efficiently antagonize thermal hyperalgesia evoked by complete Freund's adjuvant (CFA)-induced monoarthritis (MA). In the present study, we investigated whether the spinal glia are involved in the anti-hyperalgesic effect of gabapentin and how this event occurs. RESULTS: 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) alpha2/delta-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 alpha2/delta-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 alpha2/delta-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 alpha2/delta-1 subunits decreased CX3CL1 levels and blocked the development of thermal hyperalgesia in MA rats. CONCLUSIONS: 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 alpha2/delta-1 subunits might be involved in these events.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hyperalgesia treatmentISOCx3cl1 (Rattus norvegicus)9491779; 9491779associated with Arthritis and ExperimentalRGD 
Hyperalgesia  ISOCx3cr1 (Rattus norvegicus)9491779; 9491779associated with Arthritis more ...RGD 
Hyperalgesia treatmentIEP 9491779associated with Arthritis and ExperimentalRGD 
Hyperalgesia  IEP 9491779associated with Arthritis more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cx3cl1  (C-X3-C motif chemokine ligand 1)
Cx3cr1  (C-X3-C motif chemokine receptor 1)

Genes (Mus musculus)
Cx3cl1  (C-X3-C motif chemokine ligand 1)
Cx3cr1  (C-X3-C motif chemokine receptor 1)

Genes (Homo sapiens)
CX3CL1  (C-X3-C motif chemokine ligand 1)
CX3CR1  (C-X3-C motif chemokine receptor 1)


Additional Information