Chemokine CCL7 mediates trigeminal neuropathic pain via CCR2/CCR3-ERK pathway in the trigeminal ganglion of mice.

BACKGROUND: Chemokine-mediated neuroinflammation plays an important role in the pathogenesis of neuropathic pain. The chemokine CC motif ligand 7 (CCL7) and its receptor CCR2 have been reported to contribute to neuropathic pain via astrocyte-microglial interaction in the spinal cord. Whether CCL7 in the trigeminal ganglion (TG) involves in trigeminal neuropathic pain and the involved mechanism remain largely unknown. METHODS: The partial infraorbital nerve transection (pIONT) was used to induce trigeminal neuropathic pain in mice. The expression of Ccl7, Ccr1, Ccr2, and Ccr3 was examined by real-time quantitative polymerase chain reaction. The distribution of CCL7, CCR2, and CCR3 was detected by immunofluorescence double-staining. The activation of extracellular signal-regulated kinase (ERK) was examined by Western blot and immunofluorescence. The effect of CCL7 on neuronal excitability was tested by whole-cell patch clamp recording. The effect of selective antagonists for CCR1, CCR2, and CCR3 on pain hypersensitivity was checked by behavioral testing. RESULTS: Ccl7 was persistently increased in neurons of TG after pIONT, and specific inhibition of CCL7 in the TG effectively relieved pIONT-induced orofacial mechanical allodynia. Intra-TG injection of recombinant CCL7 induced mechanical allodynia and increased the phosphorylation of ERK in the TG. Incubation of CCL7 with TG neurons also dose-dependently enhanced the neuronal excitability. Furthermore, pIONT increased the expression of CCL7 receptors Ccr1, Ccr2, and Ccr3. The intra-TG injection of the specific antagonist of CCR2 or CCR3 but not of CCR1 alleviated pIONT-induced orofacial mechanical allodynia and reduced ERK activation. Immunostaining showed that CCR2 and CCR3 are expressed in TG neurons, and CCL7-induced hyperexcitability of TG neurons was decreased by antagonists of CCR2 or CCR3. CONCLUSION: CCL7 activates ERK in TG neurons via CCR2 and CCR3 to enhance neuronal excitability, which contributes to the maintenance of trigeminal neuropathic pain. CCL7-CCR2/CCR3-ERK pathway may be potential targets for treating trigeminal neuropathic pain.

Cu Nanowires and Nanoporous Ag Matrix Fabricated through Directional Solidification and Selective Dissolution of Ag-Cu Eutectic Alloys.

Cu nanowires and a nanoporous Ag matrix were fabricated through directional solidification and selective dissolution of Ag-Cu eutectic alloys. Ag-39.9at.%Cu eutectic alloys were directionally solidified at growth rates of 14, 25, and 34 µm/s at a temperature gradient of 10 K/cm. The Cu phase in the Ag matrix gradually changed from lamellar to fibrous with an increase in the growth rate. The Ag matrix phase was selectively dissolved, and Cu nanowires of 300-600 nm in diameter and tens of microns in length were prepared in 0.1 M borate buffer with a pH of 9.18 at a constant potential of 0.7 V (vs. SCE). The nanoporous Ag matrix was fabricated through selective dissolution of Cu fiber phase in 0.1 M acetate buffer with a pH of 6.0 at a constant potential of 0.5 V (vs. SCE). The diameter of Ag pores decreased with increasing growth rate. The diameter and depth of Ag pores increased when corrosion time was extended. The depth of the pores was 30 µm after 12 h.

Conformation-controlled emission of AIE luminogen: a tetraphenylethene embedded pillar[5]arene skeleton.

An unprecedented meso-decorated pillar[5]arene derivative, EtP5A-DPE, embedded with a TPE unit was prepared and structurally characterized. In the crystal, the incubation of the guest 1,4-dicyanobutane molecule inside the tetraphenylethene-embedded pillar scaffold induces a significant change in the molecular conformation, shutting down the AIE emission of this compound.