Baccei Mark L, Bardoni Rita, Fitzgerald Maria
Department of Anatomy and Developmental Biology, University College London, UK.
J Physiol. 2003 May 15;549(Pt 1):231-42. doi: 10.1113/jphysiol.2003.040451. Epub 2003 Apr 4.
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 microM) 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 [Ca2+]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.
为了研究新生大鼠脊髓浅层背角伤害性突触输入的出生后发育情况，我们检测了辣椒素和薄荷醇对出生后第（P）0 - 1天、P5 - 6天和P9 - 11天脊髓切片中谷氨酸能微小兴奋性突触后电流（mEPSCs）的影响。辣椒素（100 nM至2 μM）在所有测试年龄段均以浓度依赖性方式增加mEPSC频率，在P5至P10之间效果显著增强。这种效应对香草酸受体（VR）拮抗剂敏感。mEPSC频率的升高发生在辣椒素浓度（100 nM）下，该浓度并未改变mEPSC幅度的分布，并且被背根切断术所消除，表明辣椒素通过位于初级传入纤维上的突触前VR1受体起作用。薄荷醇显著增加mEPSC频率，其发育模式与辣椒素相似，且未持续影响mEPSC幅度。辣椒素引起的mEPSC频率增加不依赖于跨膜钙内流，因为在零[Ca2+]o时这种增加仍持续存在。辣椒素对自发性谷氨酸释放的促进作用足以在新生背角神经元中诱发动作电位，但同时伴随着对背根电刺激诱发的兴奋性突触后电流（EPSCs）的阻断。这些结果表明，表达VR1的伤害性初级传入纤维从出生起就在浅层背角形成功能性突触连接，并且VR1受体的激活通过一种未确定的机制增加自发性谷氨酸释放。此外，数据表明未成熟的初级传入纤维表达能够调节递质释放的功能性薄荷醇受体。这些结果对婴儿疼痛处理具有重要的功能意义。
