Development of nociceptive synaptic inputs to the neonatal rat dorsal horn: glutamate release by capsaicin and menthol
Development of nociceptive synaptic inputs to the neonatal rat dorsal horn: glutamate release by capsaicin and menthol
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DOI：
10.1113/jphysiol.2003.040451
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发表时间：
2003-05-15
影响因子：
5.5
通讯作者：
Fitzgerald, M
中科院分区：
文献类型：
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作者：
Baccei, ML;Bardoni, R;Fitzgerald, M
为了研究新生大鼠脊髓背角浅层伤害性突触传入的生后发育，我们观察了辣椒素和薄荷醇对生后（P）0-1、P5-6和P9-11脊髓薄片中辣椒素能mEPSCs的影响。辣椒素（100 nM至2 μ M）在所有测试年龄段均以浓度依赖性方式增加mEPSC频率，在P5和P10之间的作用显著增强。这种作用对香草酸受体（VR）拮抗剂敏感。mEPSC频率的升高发生在辣椒素浓度（100 nM），不改变mEPSC振幅的分布，并取消了背根切断术，表明辣椒素通过突触前VR 1受体定位于初级传入。menopause显着增加mEPSC频率与辣椒素类似的发展模式，而不一贯影响mEPSC振幅。辣椒素后mEPSC频率的增加不依赖于跨膜钙内流，因为它持续在零[Ca（2+）]（o）。辣椒素促进自发性谷氨酸释放足以引起新生儿背角神经元的动作电位，但伴随着电刺激背根引起的EPSC阻滞。这些结果表明，VR 1表达伤害性初级传入，形成功能性突触连接在浅背角从出生和VR 1受体的激活增加自发谷氨酸释放通过一个未确定的机制。此外，这些数据表明，未成熟的初级传入表达功能性薄荷醇受体，能够调节递质的释放。这些结果对婴儿疼痛处理具有重要的功能意义。
To study the postnatal development of nociceptive synaptic inputs in the superficial dorsal horn of the neonatal rat spinal cord, we examined the effect of capsaicin and menthol on glutamatergic mEPSCs in postnatal day (P) 0-1, P5-6 and P9-11 slices of spinal cord. Capsaicin (100 nM to 2 muM) increased the mEPSC frequency in a concentration-dependent manner at all ages tested, with a significant enhancement of the effect between P5 and P10. This effect was sensitive to vanilloid receptor (VR) antagonists. The elevation in mEPSC frequency occurred at concentrations of capsaicin (100 nM) that did not alter the distribution of mEPSC amplitudes and was abolished by a dorsal rhizotomy, demonstrating that capsaicin acts via presynaptic VR1 receptors localized on primary afferents. Menthol significantly increased the mEPSC frequency with a similar developmental pattern to capsaicin without consistently affecting mEPSC amplitude. The increase in mEPSC frequency following capsaicin did not depend on transmembrane calcium influx since it persisted in zero [Ca(2+)](o). The facilitation of spontaneous glutamate release by capsaicin was sufficient to evoke action potentials in neonatal dorsal horn neurons but was accompanied by a block of EPSCs evoked by electrical stimulation of the dorsal root. These results indicate that VR1-expressing nociceptive primary afferents; form functional synaptic connections in the superficial dorsal horn from birth and that activation of the VR1 receptor increases spontaneous glutamate release via an undetermined mechanism. In addition, the data suggest that immature primary afferents express functional menthol receptors that are capable of modulating transmitter release. These results have important functional implications for infant pain processing.