Analgesic potency of intrathecally administered punicalagin in rat neuropathic and inflammatory pain models

Analgesic potency of intrathecally administered punicalagin in rat neuropathic and inflammatory pain models
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DOI:
10.1007/s11418-021-01576-0
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发表时间:
2021-10-13
影响因子:
3.3
通讯作者:
Terada, Tadanori
Terada, Tadanori
中科院分区:
医学3区
文献类型:
--
作者:
Haranishi, Yasunori;Hara, Koji;Terada, Tadanori

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石榴皮苷是一种天然多酚类化合物,属于鞣花单宁,是石榴(Punica granatum L.)的主要成分。石榴皮苷具有有效的抗氧化和抗炎作用。虽然已报道了口服石榴提取物的抗伤害性作用,但关于安石榴苷对中枢神经系统伤害性传递的作用知之甚少。我们研究安石榴苷是否能改善脊髓中的神经性疼痛和炎性疼痛。使雄性Sprague-Dawley大鼠经受坐骨神经的慢性压迫性损伤(CCI),并植入鞘内导管用于药物施用。CCI大鼠采用电刺激von Frey试验和冷板试验评价神经病理性痛的机械痛敏和冷痛敏,正常大鼠采用福尔马林试验评价急性和持续性炎性痛。进行旷场试验以探索安石榴苷是否影响CCI大鼠的自发活动。Punicalagin鞘内给药衰减机械和冷痛觉过敏的程度与加巴喷丁在CCI大鼠和福尔马林注射大鼠的早期和晚期疼痛相关的行为减少相同。Punicalagin不影响运动功能。这些结果表明,安石榴苷在没有运动缺陷的脊髓中发挥抗伤害性作用,从而显示出对神经性疼痛和炎性疼痛的治疗潜力。
Punicalagin, a natural polyphenolic compound classified as an ellagitannin, is a major ingredient of pomegranate (Punica granatum L.). Punicalagin has potent antioxidant and anti-inflammatory effects. Although the antinociceptive effects of orally administered pomegranate extracts have been reported, little is known about the effect of punicalagin on nociceptive transmission in the central nervous system. We examined whether punicalagin ameliorates neuropathic pain and inflammatory pain in the spinal cord. Male Sprague-Dawley rats were subjected to chronic constriction injury (CCI) of the sciatic nerve, and an intrathecal catheter was implanted for drug administration. The electronic von Frey test and cold-plate test were performed in CCI rats to evaluate mechanical and cold hyperalgesia in neuropathic pain, and the formalin test was performed in normal rats to evaluate acute and persistent inflammatory pain. An open-field test was conducted to explore whether punicalagin affects locomotor activity in CCI rats. Punicalagin administered intrathecally attenuated mechanical and cold hyperalgesia to the same degree as gabapentin in CCI rats and reduced pain-related behaviors in both the early and late phases in formalin-injected rats. Punicalagin did not affect motor function. These results suggest that punicalagin exerts an antinociceptive effect in the spinal cord without motor deficit, thus showing therapeutic potential for neuropathic pain and inflammatory pain.