Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France.
Phenotype Expertise, 5 Boulevard du Maréchal Koenig, 13009 Marseille, France.
Sci Rep. 2017 Feb 27;7:43493. doi: 10.1038/srep43493.
Primary sensory neurons are heterogeneous by myriad of molecular criteria. However, the functional significance of this remarkable heterogeneity is just emerging. We precedently described the GINIP neurons as a new subpopulation of non peptidergic C-fibers encompassing the free nerve ending cutaneous MRGPRD neurons and C-LTMRs. Using our recently generated ginip mouse model, we have been able to selectively ablate the GINIP neurons and assess their functional role in the somatosensation. We found that ablation of GINIP neurons affected neither the molecular contents nor the central projections of the spared neurons. GINIP-DTR mice exhibited impaired sensation to gentle mechanical stimuli applied to their hairy skin and had normal responses to noxious mechanical stimuli applied to their glabrous skin, under acute and injury-induced conditions. Importantly, loss of GINIP neurons significantly altered formalin-evoked first pain and drastically suppressed the second pain response. Given that MRGPRD neurons have been shown to be dispensable for formalin-evoked pain, our study suggest that C-LTMRs play a critical role in the modulation of formalin-evoked pain.
初级感觉神经元在众多分子标准上是异质的。然而，这种显著的异质性的功能意义才刚刚显现出来。我们之前描述了 GINIP 神经元是一种新的非肽能 C 纤维亚群，包括游离神经末梢皮肤 MRGPRD 神经元和 C-LTMRs。使用我们最近生成的 ginip 小鼠模型，我们能够选择性地去除 GINIP 神经元，并评估它们在躯体感觉中的功能作用。我们发现，去除 GINIP 神经元既不影响保留神经元的分子含量，也不影响其中枢投射。在急性和损伤诱导条件下，GINIP-DTR 小鼠对其毛茸茸皮肤施加的轻柔机械刺激的感觉受损，而对其无毛皮肤施加的有害机械刺激的反应正常。重要的是，GINIP 神经元的缺失显著改变了福尔马林诱发的第一疼痛，并极大地抑制了第二疼痛反应。鉴于已经表明 MRGPRD 神经元对于福尔马林诱发的疼痛是可有可无的，我们的研究表明 C-LTMRs 在调节福尔马林诱发的疼痛中起着关键作用。
