Spinal cord dorsal horn inhibition is critical to the processing of sensory inputs, and its impairment leads to mechanical allodynia. How this decreased inhibition occurs and whether its restoration alleviates allodynic pain are poorly understood. Here, we show that a critical step in the loss of inhibitory tone is the change in the firing pattern of inhibitory parvalbumin (PV)-expressing neurons (PVNs). Our results show that PV, a calcium-binding protein, controls the firing activity of PVNs by enabling them to sustain high-frequency tonic firing patterns. Upon nerve injury, PVNs transition to adaptive firing and decrease their PV expression. Interestingly, decreased PV is necessary and sufficient for the development of mechanical allodynia and the transition of PVNs to adaptive firing. This transition of the firing pattern is due to the recruitment of calcium-activated potassium (SK) channels, and blocking them during chronic pain restores normal tonic firing and alleviates chronic pain. Our findings indicate that PV is essential for controlling the firing pattern of PVNs and for preventing allodynia. Developing approaches to manipulate these mechanisms may lead to different strategies for chronic pain relief.

中文翻译：

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小白蛋白通过调节抑制性神经元的放电模式来控制慢性疼痛


脊髓背角抑制对于感觉输入的处理至关重要，其损伤会导致机械性异常性疼痛。这种抑制作用的减弱是如何发生的，以及它的恢复是否能减轻异常性疼痛，人们知之甚少。在这里，我们表明抑制性张力丧失的关键步骤是表达抑制性小清蛋白（PV）的神经元（PVN）的放电模式的变化。我们的结果表明，PV（一种钙结合蛋白）通过使 PVN 维持高频强直放电模式来控制 PVN 的放电活动。神经损伤后，PVN 转变为适应性放电并降低其 PV 表达。有趣的是，PV 的减少对于机械性异常性疼痛的发生以及 PVN 向适应性放电的转变是必要且充分的。这种放电模式的转变是由于钙激活钾（SK）通道的募集，在慢性疼痛期间阻断它们可以恢复正常的强直放电并减轻慢性疼痛。我们的研究结果表明，PV 对于控制 PVN 的放电模式和预防异常性疼痛至关重要。开发操纵这些机制的方法可能会导致缓解慢性疼痛的不同策略。