Nencini Sara, Morgan Michael, Thai Jenny, Jobling Andrew I, Mazzone Stuart B, Ivanusic Jason J
Department of Anatomy and Physiology, University of Melbourne, Melbourne, VIC, Australia.
Front Physiol. 2021 Jul 15;12:644929. doi: 10.3389/fphys.2021.644929. eCollection 2021.
Piezo2 is a mechanically gated ion-channel that has a well-defined role in innocuous mechanical sensitivity, but recently has also been suggested to play a role in mechanically induced pain. Here we have explored a role for Piezo2 in mechanically evoked bone nociception in Sprague Dawley rats. We have used an electrophysiological bone-nerve preparation to record the activity of single Aδ bone afferent neurons in response to noxious mechanical stimulation, after Piezo2 knockdown in the dorsal root ganglia with intrathecal injections of Piezo2 antisense oligodeoxynucleotides, or in control animals that received mismatch oligodeoxynucleotides. There were no differences in the number of Aδ bone afferent neurons responding to the mechanical stimulus, or their threshold for mechanical activation, in Piezo2 knockdown animals compared to mismatch control animals. However, bone afferent neurons in Piezo2 knockdown animals had reduced discharge frequencies and took longer to recover from stimulus-evoked fatigue than those in mismatch control animals. Piezo2 knockdown also prevented nerve growth factor (NGF)-induced sensitization of bone afferent neurons, and retrograde labeled bone afferent neurons that expressed Piezo2 co-expressed TrkA, the high affinity receptor for NGF. Our findings demonstrate that Piezo2 contributes to the response of bone afferent neurons to noxious mechanical stimulation, and plays a role in processes that sensitize them to mechanical stimulation.
Piezo2是一种机械门控离子通道，在无害机械敏感性方面具有明确作用，但最近也有人提出它在机械性诱发疼痛中发挥作用。在此，我们探讨了Piezo2在Sprague Dawley大鼠机械诱发的骨伤害感受中的作用。我们使用了一种电生理骨神经标本，在鞘内注射Piezo2反义寡脱氧核苷酸使背根神经节中的Piezo2基因敲低后，或在接受错配寡脱氧核苷酸的对照动物中，记录单个Aδ骨传入神经元对有害机械刺激的反应活性。与错配对照动物相比，Piezo2基因敲低动物中对机械刺激有反应的Aδ骨传入神经元数量及其机械激活阈值没有差异。然而，Piezo2基因敲低动物中的骨传入神经元放电频率降低，从刺激诱发的疲劳中恢复所需的时间比错配对照动物中的神经元更长。Piezo2基因敲低还可防止神经生长因子（NGF）诱导的骨传入神经元敏化，并且逆行标记的表达Piezo2的骨传入神经元共表达TrkA，即NGF的高亲和力受体。我们的研究结果表明，Piezo2有助于骨传入神经元对有害机械刺激的反应，并在使它们对机械刺激敏感的过程中发挥作用。
