OX2 receptors mediate the inhibitory effects of orexin-A on potassium chloride-induced increases in intracellular calcium ion levels in neurons derived from rat dorsal root ganglion in a chronic pain model.
OX2 receptors mediate the inhibitory effects of orexin-A on potassium chloride-induced increases in intracellular calcium ion levels in neurons derived from rat dorsal root ganglion in a chronic pain model.
复制标题
在慢性疼痛模型中，OX2 受体介导食欲素 A 对氯化钾诱导的大鼠背根神经节来源的神经元细胞内钙离子水平增加的抑制作用。
DOI：
10.1002/npr2.12094
复制
发表时间：
2020
影响因子：
2.5
通讯作者：
Saigusa T
中科院分区：
文献类型：
--
作者：
Yamaguchi M;Ishikawa M;Aono Y;Saigusa T
已知Orexin-A在慢性疼痛的动物模型中诱导抗伤害性作用。我们发现，食欲素A抑制KCl负荷诱导的大鼠C纤维样神经元细胞内钙离子水平（[Ca 2 +]i）的增加，表现出炎症伤害性行为。在这里，我们研究了食欲素A对来自另一种类型的慢性疼痛（即神经性疼痛）大鼠模型的C纤维样神经元去极化的影响。因此，我们分析了orexin-A对KCl诱导的增加[Ca 2 +]iin C-纤维样神经元的大鼠坐骨神经ligation.MethodsPaw撤回和阈值力触觉刺激的影响进行了评估，使用冯弗雷丝。假手术大鼠作为对照。[Ca2+]iin神经元用钙荧光探针显示。[Ca 2 +] i的变化进行了评估，使用相对荧光intensity.Results7天后坐骨神经结扎，缩足和触觉刺激的阈值力分别增加和减少。对来自坐骨神经结扎或对照大鼠的神经元的KCl负载增加了相对荧光强度。在坐骨神经结扎大鼠中，KCl诱导的相对荧光强度增加可被食欲素A抑制，而对照大鼠则无此作用。OX 1和OX 2受体拮抗剂MK-4305和OX 2受体拮抗剂EMPA，但不包括OX 1受体拮抗剂SB 334867，结论本研究结果构成神经药理学证据，表明OX 2而不是OX 1受体介导食欲素A对KCl诱导的[Ca 2 +]增加的抑制作用。在坐骨神经结扎引起痛觉过敏的大鼠C纤维样神经元中。
AimsOrexin‐A is known to induce anti‐nociceptive effects in animal models of chronic pain. We have found that orexin‐A inhibits KCl loading‐induced increases in the intracellular calcium ion levels ([Ca2+]i) in C‐fiber‐like neurons of rats showing inflammatory nociceptive behavior. Here, we examined the effects of orexin‐A on the depolarization of C‐fiber‐like neurons derived from a rat model for another type of chronic pain, namely neuropathic pain. Thus, we analyzed the effects of orexin‐A on KCl‐induced increases in [Ca2+]iin C‐fiber‐like neurons of rats with sciatic nerve ligation.MethodsPaw withdrawal and threshold force in response to tactile stimuli were evaluated using von Frey filaments. Sham‐operated rats served as controls. [Ca2+]iin neurons were visualized by calcium fluorescent probe. Changes in [Ca2+]iwere assessed using relative fluorescence intensity.ResultsSeven days after sciatic nerve ligation, paw withdrawal and threshold force for tactile stimuli were increased and reduced, respectively. KCl loading to neurons from either sciatic nerve‐ligated or control rats increased relative fluorescence intensity. The KCl‐induced increase in relative fluorescence intensity in sciatic nerve‐ligated, but not that of control, rats was inhibited by orexin‐A. The OX1and OX2receptor antagonist MK‐4305 and OX2receptor antagonist EMPA, but not the OX1receptor antagonist SB 334867, each counteracted orexin‐A‐induced inhibition of KCl‐provoked increases in relative fluorescence intensity.ConclusionThe present findings constitute neuropharmacological evidence that OX2but not OX1receptors mediate the inhibitory effects of orexin‐A on KCl‐induced increases in [Ca2+]iin C‐fiber‐like neurons of rats showing hyperalgesia provoked by sciatic nerve ligation.