The cellular distribution and changes in CX3CL1/fractalkine and its receptor CX3CR1 protein levels in the trigeminal subnucleus caudalis (TSC) of rats with unilateral infraorbital nerve ligation (IONL) were investigated on postoperation days 1, 3, 7, and 14 (POD1, POD3, POD7, and POD14, respectively) and compared with those of sham-operated and naïve controls. Behavioral tests revealed a significant increase in tactile hypersensitivity bilaterally in the vibrissal pads of both sham- and IONL-operated animals from POD1 to POD7, with a trend towards normalization in sham controls at POD14. Image analysis revealed increased CX3CL1 immunofluorescence (IF) intensities bilaterally in the TSC neurons of both sham- and IONL-operated rats at all survival periods. Reactive astrocytes in the ipsilateral TSC also displayed CX3CL1-IF from POD3 to POD14. At POD1 and POD3, microglial cells showed high levels of CX3CR1-IF, which decreased by POD7 and POD14. Conversely, CX3CR1 was increased in TSC neurons and reactive astrocytes at POD7 and POD14, which coincided with high levels of CX3CL1-IF and ADAM17-IF. This indicates that CX3CL1/CX3CR1 may be involved in reciprocal signaling between TSC neurons and reactive astrocytes. The level of CatS-IF in microglial cells suggests that soluble CX3CL1 may be involved in neuron-microglial cell signaling at POD3 and POD7, while ADAM17 allows this release at all studied time points. These results indicate an extended CX3CL1/CX3CR1 signaling axis and its role in the crosstalk between TSC neurons and glial cells during the development of trigeminal neuropathic pain.

• Klíčová slova
• chemokine receptors, chemokines, image analysis, immunohistochemistry, microglial cells, neurons, reactive astroglia,
• MeSH
• astrocyty metabolismus   MeSH
• chemokin CX3CL1 * metabolismus   MeSH
• CX3C chemokinový receptor 1 * metabolismus   genetika   MeSH
• krysa rodu Rattus MeSH
• mikroglie metabolismus   MeSH
• neuralgie trigeminu metabolismus   patologie   MeSH
• neuralgie metabolismus   patologie   MeSH
• neurony metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chemokin CX3CL1 * MeSH
• CX3C chemokinový receptor 1 * MeSH
• Cx3cl1 protein, rat MeSH Prohlížeč
• CX3CR1 protein, rat MeSH Prohlížeč

In this brief report, we demonstrate that the Cav3.3 T-type voltage-gated calcium channel subtype is involved in our FRICT-ION model of chronic trigeminal neuropathic pain. We first showed that the Cacna1i gene encoding Cav3.3 is significantly upregulated in whole trigeminal ganglia of FRICT-ION mice compared to controls at week 10 post-injury. We confirmed protein upregulation of Cav3.3 compared to controls using Western blot analysis of whole trigeminal ganglia tissues. Finally, we demonstrated that intraperitoneal injection of a selective TAT-based Cav3.3 blocking peptide in FRICT-ION mice significantly reduces Cav3.3 protein expression at the peak anti-allodynic effect (4 hrs post-injection) of the attenuated neuropathic pain behavior. We also suggest that blockade of Cav3.3 may be more effective in attenuating trigeminal neuropathic pain in female than male FRICT-ION mice. Therefore, blocking or attenuating Cav3.3 function may be an effective strategy for the treatment of trigeminal neuropathic pain.

• Klíčová slova
• Cav3.3, Neuropathic pain, calcium channels, therapeutics, trigeminal nerve injury,
• MeSH
• blokátory kalciových kanálů farmakologie   MeSH
• ganglion trigeminale * metabolismus   MeSH
• myši MeSH
• neuralgie trigeminu * metabolismus   genetika   farmakoterapie   MeSH
• neuralgie metabolismus   genetika   farmakoterapie   MeSH
• vápníkové kanály - typ T * metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• blokátory kalciových kanálů MeSH
• Cacna1i protein, mouse MeSH Prohlížeč
• vápníkové kanály - typ T * MeSH