Title Ben, Velasco Enrique, Engelmayer Nurit, Rayi Prudhvi Raj, Yanai Roy, Hart Shmuel, Katz Ben, Lev Shaya, Yarom Yosef, Binshtok Alexander M
Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel.
The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Sci Adv. 2025 Jun 20;11(25):eadr3467. doi: 10.1126/sciadv.adr3467.
Pain hypersensitivity is associated with increased activity of peripheral and central neurons along the pain neuroaxis. We show that at the peak of acute inflammatory pain, superficial medullary dorsal horn projection neurons (PNs) that relay nociceptive information to the parabrachial nucleus reduce their intrinsic excitability and, consequently, action potential firing. When pain resolves, the excitability of these neurons returns to baseline. Using electrophysiological and computational approaches, we found that an increase in potassium A-current () underlies the decrease in the excitability of medullary dorsal horn PNs in acute pain conditions. In chronic pain conditions, no changes of were observed, and medullary dorsal horn PNs exhibit increased intrinsic excitability and firing. Our results reveal a differential modulation of the excitability of medullary dorsal horn projection neurons in acute and chronic pain conditions, suggesting a regulatory mechanism that, in acute pain conditions, tunes the output of the dorsal horn and, if lacking, could facilitate pain chronification.
疼痛超敏与沿疼痛神经轴的外周和中枢神经元活动增加有关。我们发现，在急性炎症性疼痛的高峰期，将伤害性信息传递至臂旁核的浅表延髓背角投射神经元（PNs）会降低其内在兴奋性，从而导致动作电位发放减少。当疼痛缓解时，这些神经元的兴奋性会恢复到基线水平。通过电生理和计算方法，我们发现急性疼痛状态下，钾离子A电流（）增加是延髓背角PNs兴奋性降低的基础。在慢性疼痛状态下，未观察到的变化，且延髓背角PNs表现出内在兴奋性和发放增加。我们的研究结果揭示了急性和慢性疼痛状态下延髓背角投射神经元兴奋性的差异调节，提示了一种调节机制，即在急性疼痛状态下，该机制可调节背角的输出，若缺乏该机制，则可能促进疼痛慢性化。
