Journal: Molecular Brain

Article Title: Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats

doi: 10.1186/1756-6606-5-18

Figure Lengend Snippet: Expression of CX3CL1 and its receptor CX3CR1 in the lumbar spinal cord. A , Double immunofluorescence staining shows that CX3CL1 is colocalized with the neuronal marker NeuN and VGCC α2/δ-1 subunits in all of the layers of the spinal dorsal horn. B , The western blot shows an increase in the level of CX3CL1 in the ipsilateral lumbar spinal dorsal horn at 4 hrs and 4 days after MA. C , Western blot analysis reveals that repeated Gab treatment significantly suppresses MA-induced upregulation of CX3CL1 in the lumbar spinal dorsal horn. D , Double immunofluorescence staining shows that CX3CR1 is colocalized with the microglial marker OX-42, but not the astrocytic marker GFAP. E , Western blot analysis reveals that repeated Gab treatment partially inhibits MA-induced upregulation of CX3CR1 in the lumbar spinal dorsal horn. * p < 0.05, ** p < 0.01 vs. control (sham MA or naïve); ++ P < 0.01 vs. MA.

Article Snippet: The specificity of the primary antibodies was verified by the preabsorption experiment (control peptide for CX3CL1 from Acris Antibodies; for CX3CR1 from Abcampare and Santa Cruz; for α2/δ-1 from LifeSpan).

Techniques: Expressing, Double Immunofluorescence Staining, Marker, Western Blot

Journal: Molecular Brain

Article Title: Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats

doi: 10.1186/1756-6606-5-18

Figure Lengend Snippet: A schematic illustration of spinal glial activation in monoarthritic pain. Joint inflammation may increase the release of nociceptive transmitters and modulators (such as EAAs, SP, ATP and CX3CL1) in the spinal dorsal horn from the primary afferent terminals ipsilateral to the inflammed joint . These events can initiate early focal microglial activation in ipsilateral spinal cord (within 4 hrs after MA). Activated microglia release several proinflammatory cytokines and chemokines that may spread to contralateral spinal cord, leading to the contralateral spinal microglial and astrocytic activation . Once the glia are activated, they release several glial products including proinflammatory cytokines, tumor necrosis factor-α, and inflammatory mediators. This leads to an exaggerated release of neurotransmitters from presynaptic neurons, sensitization of the post-synaptic membrane, activation of neighboring astrocytes, and enhancement of the microglial propagation of neuromediators . Such positive feedback loops sustain the perseverant release of pain mediators, facilitating the development of neuronal hypersensitivity, leading to exaggerated pain (such as thermal hyperalgesia) . Gabapentin might diminish the release of “pain” neurotransmitters/neuromodulators (such as CX3CL1) and activation of microglia in the spinal cord by modulating VGCC α2/δ-1 subunits, leading to a reduction in thermal hyperalgesia.

Article Snippet: The specificity of the primary antibodies was verified by the preabsorption experiment (control peptide for CX3CL1 from Acris Antibodies; for CX3CR1 from Abcampare and Santa Cruz; for α2/δ-1 from LifeSpan).

Techniques: Activation Assay