NSAIDs are the drugs most commonly used to alleviate pain. Despite being a heterogeneous group of compounds, all of them share a mechanism of action based on blockade of COXs enzymes, which confers them anti-inflammatory and analgesic properties. Diclofenac is a NSAID with preferred activity on COX-2 isozymes, but additionally, other targets may be implicated in its analgesic activity. Among them, diclofenac may facilitate the activity of K_v7 channels, that have been previously recognized as potential therapeutic targets in analgesia. In this study, the antinociceptive actions of diclofenac acting at the spinal level and the role of K_v7 channels in its effects were evaluated. Electrophysiological recordings of spinal reflexes and responses of dorsal horn neurons were obtained using in vitro spinal cord preparations from neonatal mice. Diclofenac, applied at clinically relevant concentrations to the entire preparation, depressed wind-up of spinal reflexes with a pattern similar to that of flupirtine, an analgesic with activity as K_v7 channel opener. Depressant actions of both compounds were strongly reduced after K_v7 channel blockade with XE-991, indicating the implication of these channels in the observed effects. Flupirtine, but not diclofenac, also reduced action potential firing of dorsal horn neurons in response to electrical activation of nociceptive afferents, suggesting differences in the actions of both compounds on K_v7 channel configurations present in sensory areas of the cord. Results demonstrate previously unknown central actions of diclofenac on K_v7 channels located in spinal circuits, expanding the knowledge about its pharmacological actions.

NSAID是最常用于减轻疼痛的药物。尽管是一组异质化合物，但它们均基于阻断COXs酶而具有共同的作用机制，这赋予了它们抗炎和止痛的特性。双氯芬酸是一种对COX-2同工酶具有优选活性的NSAID，但此外，其他靶标也可能与其镇痛活性有关。其中，双氯芬酸可促进K _v 7通道的活性，该通道先前已被认为是镇痛的潜在治疗靶标。在这项研究中，评估了双氯芬酸在脊髓水平的抗伤害作用以及K _v 7通道在其作用中的作用。使用以下方法获得脊神经反射和背角神经元反应的电生理记录新生小鼠的体外脊髓制剂。双氯芬酸以临床相关浓度应用于整个制剂，可抑制脊柱反射的发卷，其模式类似于氟吡汀，后者的镇痛作用为K _v 7通道开放剂。用XE-991阻断K _v 7通道后，两种化合物的镇静作用均大大降低，表明这些通道对观察到的效果有影​​响。氟吡汀（而非双氯芬酸）还降低了伤害性传入神经的电激活，从而刺激了背角神经元的动作电位放电，提示这两种化合物对K _v的作用存在差异电线的感应区域中存在7个通道配置。结果证明了双氯芬酸对位于脊髓回路中K _v 7通道上的未知中央作用，从而扩大了其药理作用的知识。