Verbascoside administered intrathecally attenuates hyperalgesia via activating mu-opioid receptors in a rat chronic constriction injury model.
Verbascoside administered intrathecally attenuates hyperalgesia via activating mu-opioid receptors in a rat chronic constriction injury model.
复制标题
在大鼠慢性缩窄性损伤模型中，鞘内注射毛蕊花苷可通过激活 mu-阿片受体来减轻痛觉过敏。
DOI：
10.1002/ejp.1952
复制
发表时间：
2022
影响因子：
3.6
通讯作者：
Terada T
中科院分区：
文献类型：
--
作者：
Hara K;Haranishi Y;Terada T
背景马鞭草苷是一种具有代表性的苯乙醇糖苷，广泛存在于植物体内，具有多种有益于人类健康的活性。尽管全身应用马鞭草皂苷具有抗伤害性作用，但人们对其活性部位和作用机制知之甚少。本研究的目的是确定马鞭草皂苷是否能减轻脊髓神经病理性疼痛，以及哪些疼痛调节系统参与其中。采用电子von Frey法和冷板法分别观察鞘内注射马鞭草皂苷及其成分(咖啡酸和羟基酪醇)对机械性痛敏和冷痛敏的影响。鞘内注射几种脊髓痛处理受体拮抗剂，以评价它们对马鞭草皂苷抗痛敏作用的影响。结果马鞭草苷可剂量依赖性地减轻机械性痛觉过敏和冷痛敏，并影响运动功能。咖啡酸仅在高剂量时抑制痛觉过敏，而羟基酪醇不影响痛觉过敏。马鞭草皂苷对痛觉过敏和运动协调的抑制作用可被阿片受体拮抗剂纳洛酮逆转。结论马鞭草皂苷通过激活脊髓内的阿片受体发挥抗痛觉作用，其作用不受咖啡酸和羟酪醇的单独作用。Verbascoside显示出治疗神经病理性疼痛的前景。意义目前可用的神经病理性疼痛治疗方法对大多数患者的疗效有限。一些天然产品具有长期服用的良好生物活性，如抗氧化和神经保护作用。Verbascoside抑制脊髓伤害性传递，没有严重的副作用，程度与治疗神经性疼痛的一线药物加巴喷丁相同。天然产品可能是神经病理性疼痛的新疗法的有希望的候选者。
BackgroundVerbascoside, a representative phenylethanoid glycoside, is widely distributed in plants and has various activities beneficial for human health. Although systemically administered verbascoside has an antinociceptive effect, little is known about the site and mechanism of its activity. The aim of the present study was to determine whether verbascoside attenuates neuropathic pain in the spinal cord and which pain regulatory systems are involved.MethodsChronic constriction injury of the sciatic nerve was introduced to male Sprague Dawley rats. The effects of intrathecal administration of verbascoside and its components (caffeic acid and hydroxytyrosol) on mechanical hyperalgesia and cold hyperalgesia were examined using the electronic von Frey test and cold‐plate test, respectively. Several antagonists of spinal pain processing receptors were administered intrathecally to evaluate their effects on the antihyperalgesic action of verbascoside. A rotarod test was performed to assess the effects on motor coordination.ResultsVerbascoside attenuated mechanical and cold hyperalgesia and affected motor performance in a dose‐dependent manner. Caffeic acid suppressed hyperalgesia only at high doses, whereas hydroxytyrosol did not affect hyperalgesia. The inhibitory effects of verbascoside on hyperalgesia and motor coordination were reversed by naloxone, a µ‐opioid receptor antagonist.ConclusionsThese findings imply that verbascoside exerts an antihyperalgesic effect by activating µ‐opioid receptors in the spinal cord, and that neither caffeic acid nor hydroxytyrosol alone mediates its activity. Verbascoside shows promise for the treatment of neuropathic pain.SignificanceCurrently available treatments for neuropathic pain have limited efficacy in most patients. Some natural products have favourable biological activities for long‐term administration such as antioxidative and neuroprotective effects. Verbascoside inhibits spinal nociceptive transmission without serious side effects to the same degree as gabapentin, a first‐line remedy for neuropathic pain. Natural products may be promising candidates for novel treatments of neuropathic pain.