Upregulation of P2Y1 in neonatal nociceptors regulates heat and mechanical sensitization during cutaneous inflammation.
Upregulation of P2Y1 in neonatal nociceptors regulates heat and mechanical sensitization during cutaneous inflammation.
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DOI：
10.1177/1744806917730255
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发表时间：
2017-01
期刊：
影响因子：
3.3
通讯作者：
Jankowski MP
中科院分区：
文献类型：
--
作者：
Lu P;Hudgins RC;Liu X;Ford ZK;Hofmann MC;Queme LF;Jankowski MP
传统上与来自外周的感觉转导相关的各种通道和受体的上调与初级传入神经的特定亚群在不同年龄对皮肤的机械和热刺激的响应性的变化紧密对应。先前的成人报告表明，嘌呤能二磷酸腺苷受体P2 Y1可以特异性调节感觉神经元对热刺激的反应，以及皮肤炎症期间初级传入神经的神经化学改变。为了确定在出生后第7天（P7）开始皮肤炎症的新生小鼠背根神经节中发现的P2 Y1的上调是否是导致在更快的传导中发现的热敏感性的特异性改变的原因，（“A”纤维）伤害感受器，我们使用离体有毛后爪皮肤-隐神经-背根神经节评估皮肤传入的反应特性，脊髓制备结合神经靶向敲除P2 Y1。我们发现，在新生儿皮肤炎症过程中P2 Y1敲低足以降低“A”纤维伤害感受器对热刺激的敏感性。令人惊讶的是，我们还发现，神经特异性下调P2 Y1可以减少观察到的这些传入亚型的皮肤机械变形的敏感性。背根神经节的免疫细胞化学分析表明，P2 Y1可能通过调节损伤诱导的瞬时受体电位香草酸1型受体的增加来介导其作用。这表明，在生命早期外周炎症过程中，皮肤伤害感受器中P2 Y1的上调可以调节有髓鞘伤害感受器对机械和热刺激的敏感性，可能是通过调节瞬时受体电位香草酸1型表达。
The upregulation of various channels and receptors classically linked to sensory transduction from the periphery tightly correspond with changes in the responsiveness of specific subpopulations of primary afferents to mechanical and heat stimulation of the skin at different ages. Previous reports in adults have suggested that the purinergic adenosine diphosphate receptor, P2Y1 can specifically regulate sensory neuron responsiveness to heat stimuli in addition to neurochemical alterations in primary afferents during cutaneous inflammation. To determine if the upregulation of P2Y1 found in the dorsal root ganglia of neonatal mice with cutaneous inflammation initiated at postnatal day 7 (P7) was responsible for the specific alteration in heat sensitivity found in faster conducting (“A”-fiber) nociceptors, we assessed the response properties of cutaneous afferents using an ex vivo hairy hindpaw skin-saphenous nerve-dorsal root ganglion-spinal cord preparation in conjunction with nerve-targeted knockdown of P2Y1. We found that P2Y1 knockdown during neonatal cutaneous inflammation was sufficient to reduce the sensitization of “A”-fiber nociceptors to heat stimuli. Surprisingly, we also found that nerve-specific downregulation of P2Y1 could reduce the observed sensitization of these afferent subtypes to mechanical deformation of the skin. Immunocytochemical analysis of dorsal root ganglia showed that P2Y1 may mediate its effects through modulation of the injury-induced increase of transient receptor potential vanilloid type 1 receptor. This suggests that the upregulation of P2Y1 in cutaneous nociceptors during early life peripheral inflammation can regulate the sensitization of myelinated nociceptors to both mechanical and heat stimuli possibly through modulation of transient receptor potential vanilloid type 1 expression.
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DOI：
10.1523/jneurosci.3148-12.2012
发表时间：
2012-12-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Jankowski MP;Soneji DJ;Ekmann KM;Anderson CE;Koerber HR
通讯作者：
Koerber HR
影响因子：
5.3
作者：
Davidson, TJ;Harel, S;Troy, CM
通讯作者：
Troy, CM
DOI：
10.1523/jneurosci.2195-10.2010
发表时间：
2010-12-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Jankowski MP;Rau KK;Soneji DJ;Anderson CE;Koerber HR
通讯作者：
Koerber HR
影响因子：
5.3
作者：
Albers, KM;Woodbury, CJ;Koerber, HR
通讯作者：
Koerber, HR
影响因子：
3.6
作者：
Barragan-Iglesias, Paulino;Mendoza-Garces, Luis;Isaac Rocha-Gonzalez, Hector
通讯作者：
Isaac Rocha-Gonzalez, Hector