ABSTRACT
Inflammatory orofacial pain, in which substance P (SP) plays an important role, is closely related to the cross-talk between trigeminal ganglion (TG) neurons and satellite glial cells (SGCs). SGC activation is emerging as the key mechanism underlying inflammatory pain through different signalling mechanisms, including glial fibrillary acidic protein (GFAP) activation, phosphorylation of mitogen-activated protein kinase (MAPK) signalling pathways, and cytokine upregulation. However, in the TG, the mechanism underlying SP-mediated orofacial pain generated by SGCs is largely unknown. In this study, we investigated whether SP is involved in inflammatory orofacial pain by upregulating interleukin (IL)-1β and tumour necrosis factor (TNF)-α from SGCs, and we explored whether MAPK signalling pathways mediate the pain process. In the present study, complete Freund's adjuvant (CFA) was injected into the whisker pad of rats to induce an inflammatory model in vivo. SP was administered to SGC cultures in vitro to confirm the effect of SP. Facial expression analysis showed that pre-injection of L703,606 (an NK-1 receptor antagonist), U0126 (an inhibitor of MAPK/extracellular signal-regulated kinase [ERK] kinase [MEK] 1/2), and SB203580 (an inhibitor of P38) into the TG to induce targeted prevention of the activation of the NK-1 receptor and the phosphorylation of MAPKs significantly suppressed CFA-induced inflammatory allodynia. In addition, SP promoted SGC activation, which was proven by increased GFAP, p-MAPKs, IL-1β and TNF-α in SGCs under inflammatory conditions. Moreover, the increase in IL-1β and TNF-α was suppressed by L703, 606, U0126 and SB203580 in vivo and in vitro. These present findings suggested that SP, released from TG neurons, activated SGCs through the ERK1/2 and P38 pathways and promoted the production of IL-1β and TNF-α from SGCs, contributing to inflammatory orofacial pain associated with peripheral sensitization.
ABSTRACT
Objective To investigate the effects of remifentanil on large-conductance Ca2+ -activated potassium channel (BKCa) in human mesenteric arterial smooth muscle cells (MASMCs) and the mechanism of the vasorelaxant effect of remifentanil. Methods Human MASMCs were obtained freshly by the method of enzymolysis. BKCa current (IBKCa) was recorded by the whole-cell patch clamp technique. The changes in IBKC. produced by different concentrations of remifentanil (1.2, 4.8, 19.4, 77.4 and 310.0 nmol/L) with the holding potential of + 80 mV were observed. BKCa activation rate was calculated. Results Remifentanil significantly increased IBKCa,moved Ⅰ-Ⅴ curve upward and had no effect on the threshold of activation for IBKCa . With the increase in the concentration of remifentanil, BKCa activation rate increased gradually (P ＜ 0.01), and it remained stable when the concentration reached 19.4 nmol/L. There was no significant difference in the peak time of IBKCa after different concentrations of remifentanil were given (P ＞ 0.05). Logarithmic curve was found to suit the relationship between the concentration of remifentanil and BKCa activation rate and the IC50 concentration was (118 ± 7) nmol/L. Conclusion Remifentanil results in vasorelaxation by activating BKCa in MASMCs in a concentration-dependent manner.
ABSTRACT
Objective To explore the influence of gentamycin on murine cochlea spiral ganglion neurons' electrophysiological properties and its significance.Methods Using whole-cell voltage clamp technique, we studied gentamycin's influence on the peak currents of the potassium and sodium ion channels on cell membranes of acutely dissociated murine spiral ganglion neurons,the relationship to gentamycin's concentration in extracellular fluid, and the currents' recovery after gentamycin being washed out.Results Gentamycin could inhibit voltage-dependent potassium channels, but it couldn't inhibit voltage-dependent sodium channels. Gentamycin's inhibitation on potassium currents had dose-dependence with gentamycin's concerntration in extracellular fluid and the currents recoverd incompletely after gentamycin being washed out.Conclusion This research explained the ototoxic mechanism of gentamycin through its action on keeping from spiral ganglion neurons' potassium ion channels from the electrophysiological aspect, and set a foundation for further research.