The study of the pain mechanisms using rat dorsal root ganglia

背根神经节(DRG)神经元和相关的初级传入神经向脊髓背角传递不同的感觉方式，包括伤害性感觉。在初级传入神经元上发现了许多类型的神经细胞，无论是在其中枢或外周突起上，还是在DRG细胞的胞体上，并已有报道存在几种GPCRs，包括P物质、M受体、5-HT2受体和增食欲素受体。因此，背根神经节被用于研究伤害性感受。确定这些受体上的药物作用是有意义的，我们研究了谷氨酸受体在DRG中的作用以及麻醉剂对非洲爪哇卵母细胞表达的mGluR1和mGluR5功能的影响。采用全细胞电压钳技术，研究了氟烷、异氟醚、安氟醚、乙醚和乙醇对非洲爪哇卵母细胞SPR介导的SP诱发电流的影响。所有受试的挥发性麻醉剂和乙醇都能抑制Spr诱导的Ca(2+…更多)-激活的氯(-)电流在药理上相关的浓度。神经类固醇Alphaxone抑制非洲爪哇卵母细胞表达的M(1)和M(3)受体的乙酰胆碱(Ach)介导的反应，而DHEA不抑制。此外，我们还考察了右旋美托咪定在该体系中的作用。右旋美托咪定不影响5-HT2c-、P物质或增食欲素A诱导的表达相应受体的卵母细胞的氯离子电流。该化合物对乙酰胆碱(Ach，1μM)诱导的表达M_1受体的非洲爪哇卵母细胞钙激活的C_1~-电流也无明显影响。相反，右旋美托咪定可抑制表达M3受体的非洲爪哇卵母细胞Ach诱导的电流。选择性蛋白激酶C抑制剂GF109203X处理后，右美托咪定可降低Ach诱导的C_1~-电流。此外，该化合物还以浓度依赖的方式抑制M受体介导的培养的DRG细胞内[Ca~(2+)]~(2+)的升高。这些结果表明，谷氨酸受体可能在DRG的痛觉传递中起重要作用。较少

The dorsal root ganglion (DRG) neurons and associated primary afferent nerves transmit different sensory modalities, including nociception, to the spinal dorsal horn. Many types of neuronal cell have been found on primary afferent neurons, either on their central or peripheral processes or on the cell bodies of DRG cells and the presence of several GPCRs has been reported, including substance P, muscarinic, 5-HT_2 and orexin receptors. Consequently, the DRG has been used to study nociception. It is of interest to determine drug actions on these receptors, and we investigated the role of the glutamate receptor in DRG and the effects of anesthetics on the function of mGluR1 and mGluR5 expressed in Xenopus laevis oocytes. We examined the effects of halothane, isoflurane, enflurane, diethyl ether, and ethanol on SP-induced currents mediated by SPR expressed in Xenopus oocytes, by using a whole-cell voltage clamp. All the volatile anesthetics tested, and ethanol, inhibited SPR-induced Ca(2+ … More )-activated Cl(-) currents at pharmacologically relevant concentrations. Neurosteroid, alphaxalone, inhibited the acetylcholine (Ach)-mediated responses of M(1) and M(3) receptors expressed in Xenopus oocytes, whereas DHEA did not. Moreover, we examined the the effects of Dexmedetomidine in this systems. Dexmedetomidine did not affect the 5-HT_2c-, substance P-, or orexin A-induced Cl^- currents in oocytes expressing the respective receptors. The compound also had little effect on the acetylcholine (Ach, 1μM)-induced Ca^<2+>-activated C1^- currents in Xenopus oocytes expressing M_1 receptors. In contrast, dexmedetomidine inhibited the Ach-induced currents in Xenopus oocytes expressing M_3 receptors. Dexmedetomidine reduced the Ach-induced C1^- currents after treatment with the selective protein kinase C inhibitor GF109203X. Moreover, the compound inhibited the muscarinic receptor-mediated increases in [Ca^<2+>; in cultured DRG cells in a concentration-dependent manner. From these results, the glutamate receptors may play the important role in pain transmission in DRG. Less