Department of Anesthesia, Division of Pain Management, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 6016, Cincinnati, OH 45229, USA.
Mol Pain. 2014 Jun 7;10:34. doi: 10.1186/1744-8069-10-34.
It is well-documented that neonates can experience pain after injury. However, the contribution of individual populations of sensory neurons to neonatal pain is not clearly understood. Here we characterized the functional response properties and neurochemical phenotypes of single primary afferents after injection of carrageenan into the hairy hindpaw skin using a neonatal ex vivo recording preparation.
During normal development, we found that individual afferent response properties are generally unaltered. However, at the time period in which some sensory neurons switch their neurotrophic factor responsiveness, we observe a functional switch in slowly conducting, broad spiking fibers ("C"-fiber nociceptors) from mechanically sensitive and thermally insensitive (CM) to polymodal (CPM). Cutaneous inflammation induced prior to this switch (postnatal day 7) specifically altered mechanical and heat responsiveness, and heat thresholds in fast conducting, broad spiking ("A"-fiber) afferents. Furthermore, hairy skin inflammation at P7 transiently delayed the functional shift from CM to CPM. Conversely, induction of cutaneous inflammation after the functional switch (at P14) caused an increase in mechanical and thermal responsiveness exclusively in the CM and CPM neurons. Immunocytochemical analysis showed that inflammation at either time point induced TRPV1 expression in normally non-TRPV1 expressing CPMs. Realtime PCR and western blotting analyses revealed that specific receptors/channels involved in sensory transduction were differentially altered in the DRGs depending on whether inflammation was induced prior to or after the functional changes in afferent prevalence.
These data suggest that the mechanisms of neonatal pain development may be generated by different afferent subtypes and receptors/channels in an age-related manner.
有大量文献证明，新生儿在受伤后会感到疼痛。然而，对于感觉神经元群体对新生儿疼痛的贡献，我们仍知之甚少。在这里，我们使用新生体外记录制备方法，对爪蟾后足皮肤角叉菜胶注射后的单个初级传入纤维，对其功能反应特性和神经化学表型进行了描述。
在正常发育过程中，我们发现单个传入纤维的反应特性通常没有改变。然而，在某些感觉神经元改变其神经营养因子反应性的时期，我们观察到慢传导、宽峰纤维（“C”纤维伤害感受器）从机械敏感和热不敏感（CM）到多模态（CPM）的功能转换。在这种转换之前（出生后第 7 天）诱导的皮肤炎症特异性地改变了快速传导、宽峰（“A”纤维）传入纤维的机械和热反应性以及热阈值。此外，P7 时的毛发皮肤炎症短暂延迟了从 CM 到 CPM 的功能转变。相反，在功能转换后（P14）诱导的皮肤炎症仅在 CM 和 CPM 神经元中引起机械和热反应性的增加。免疫细胞化学分析显示，在两个时间点的炎症均诱导了正常不表达 TRPV1 的 CPM 中 TRPV1 的表达。实时 PCR 和 Western blot 分析显示，根据炎症是在传入纤维出现之前还是之后诱导的，感觉转导中涉及的特定受体/通道在 DRG 中会发生不同的改变。
这些数据表明，新生儿疼痛发展的机制可能是通过不同的传入纤维亚型和受体/通道以年龄相关的方式产生的。
