Zhou Shudi, Yin Yuexi, Sheets Patrick L
Medical Neurosciences Graduate Program, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Neurobiol Pain. 2023 Feb 13;13:100121. doi: 10.1016/j.ynpai.2023.100121. eCollection 2023 Jan-Jul.
The medial prefrontal cortex (mPFC) consists of a heterogeneous population of neurons that respond to painful stimuli, and our understanding of how different pain models alter these specific mPFC cell types remains incomplete. A distinct subpopulation of mPFC neurons express prodynorphin (Pdyn), the endogenous peptide agonist for kappa opioid receptors (KORs). Here, we used whole cell patch clamp for studying excitability changes to Pdyn expressing neurons in the prelimbic region of the mPFC (PL neurons) in mouse models of surgical and neuropathic pain. Our recordings revealed that PL neurons consist of both pyramidal and inhibitory cell types. We find that the plantar incision model (PIM) of surgical pain increases intrinsic excitability only in pyramidal PL neurons one day after incision. Following recovery from incision, excitability of pyramidal PL neurons did not differ between male PIM and sham mice, but was decreased in PIM female mice. Moreover, the excitability of inhibitory PL neurons was increased in male PIM mice, but was with no difference between female sham and PIM mice. In the spared nerve injury model (SNI), pyramidal PL neurons were hyperexcitable at both 3 days and 14 days after SNI. However, inhibitory PL neurons were hypoexcitable at 3 days but hyperexcitable at 14 days after SNI. Our findings suggest different subtypes of PL neurons manifest distinct alterations in the development of different pain modalities and are regulated by surgical pain in a sex-specific manner. Our study provides information on a specific neuronal population that is affected by surgical and neuropathic pain.
内侧前额叶皮质（mPFC）由对疼痛刺激有反应的异质性神经元群体组成，而我们对于不同疼痛模型如何改变这些特定的mPFC细胞类型的理解仍不完整。mPFC神经元的一个独特亚群表达前强啡肽（Pdyn），它是κ阿片受体（KORs）的内源性肽激动剂。在此，我们使用全细胞膜片钳技术，研究手术和神经性疼痛小鼠模型中，mPFC前边缘区表达Pdyn的神经元（PL神经元）的兴奋性变化。我们的记录显示，PL神经元包括锥体神经元和抑制性细胞类型。我们发现，手术疼痛的足底切口模型（PIM）在切口后一天仅增加锥体PL神经元的内在兴奋性。切口恢复后，雄性PIM小鼠和假手术小鼠的锥体PL神经元兴奋性没有差异，但PIM雌性小鼠的兴奋性降低。此外，雄性PIM小鼠的抑制性PL神经元兴奋性增加，但雌性假手术小鼠和PIM小鼠之间没有差异。在 spared nerve injury模型（SNI）中，锥体PL神经元在SNI后3天和14天都表现为兴奋性过高。然而，抑制性PL神经元在SNI后3天兴奋性过低，但在14天时兴奋性过高。我们的研究结果表明，PL神经元的不同亚型在不同疼痛模式的发展中表现出明显的变化，并以性别特异性方式受手术疼痛调节。我们的研究提供了关于受手术和神经性疼痛影响的特定神经元群体的信息。
