PDF(Pubmed)
Abstract：
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.
摘要：
脊髓背角抑制对感觉输入的处理至关重要，其损害导致机械性异常性疼痛。这种减少的抑制作用是如何发生的，以及它的恢复是否减轻了异常疼痛，人们知之甚少。这里,我们表明，抑制性音调丧失的关键步骤是抑制性小白蛋白（PV）表达神经元（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能够维持高频补音放电模式来控制PVN的放电活动。神经损伤后,PVN过渡到适应性放电并降低其PV表达。有趣的是,降低PV对于机械性异常疼痛的发展和PVN向适应性放电的过渡是必要和充分的。放电模式的这种转变是由于钙激活钾（SK）通道的募集，并在慢性疼痛期间阻断它们恢复正常的滋补放电并缓解慢性疼痛。我们的发现表明，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。
