Jabbari Sajjad, Bananej Maryam, Zarei Mohammad, Komaki Alireza, Hajikhani Ramin
Department of Biology, Faculty of Sciences, Islamic Azad University, Tehran North Branch, Tehran, Iran.
Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Res Pharm Sci. 2021 Mar 5;16(2):203-216. doi: 10.4103/1735-5362.310527. eCollection 2021 Apr.
Kaempferol (KM), a flavonoid, has an anti-inflammatory and anticancer effect and prevents many metabolic diseases. Nonetheless, very few studies have been done on the antinociceptive effects of KM. This research aimed at assessing the involvement of opioids, gamma-aminobutyric acid (GABA) receptors, and inflammatory mediators in the antinociceptive effects of KM in male Wistar rats.
The intracerebroventricular and/or intrathecal administration of the compounds was done for examining their central impacts on the thermal and chemical pain by the tail-flick and formalin paw tests. For assessing the role of opioid and GABA receptors in the possible antinociceptive effects of KM, several antagonists were used. Also, a rotarod test was carried out for assessing motor performance.
FINDINGS/RESULTS: The intracerebroventricular and/or intrathecal microinjections of KM (40 μg/rat) had partially antinociceptive effects in the tail-flick test in rats ( < 0.05). In the formalin paw model, the intrathecal microinjection of KM had antinociceptive effects in phase 1 (20 and 40 μg/rat; < 0.05 and < 0.01, respectively) and phase 2 (20 and 40 μg/rat; < 0.01 and < 0.001, respectively). Using naloxonazine and/or bicuculline approved the involvement of opioid and GABA receptors in the central antinociceptive effects of KM, respectively. Moreover, KM reduced the expression levels of caspase 6, interleukin-1β, tumor necrosis factor-α, and interleukin-6. The antinociceptive effects of KM were not linked to variations in the locomotor activity.
It can be concluded that KM has remarkable antinociceptive effects at a spinal level, which is associated with the presence of the inflammatory state. These impacts were undetectable following injections in the lateral ventricle. The possible mechanisms of KM antinociception are possibly linked to various modulatory pathways, including opioid and GABA receptors.
山奈酚（KM）是一种黄酮类化合物，具有抗炎和抗癌作用，并能预防多种代谢性疾病。然而，关于KM的抗伤害感受作用的研究却很少。本研究旨在评估阿片类物质、γ-氨基丁酸（GABA）受体和炎症介质在雄性Wistar大鼠中KM抗伤害感受作用中的参与情况。
通过侧脑室和/或鞘内注射化合物，利用甩尾试验和福尔马林足试验来检测它们对热痛和化学痛的中枢影响。为了评估阿片类和GABA受体在KM可能的抗伤害感受作用中的作用，使用了几种拮抗剂。此外，还进行了转棒试验以评估运动性能。
在大鼠甩尾试验中，侧脑室和/或鞘内微量注射KM（40μg/只）具有部分抗伤害感受作用（P<0.05）。在福尔马林足模型中，鞘内微量注射KM在第1期（20和40μg/只；分别为P<0.05和P<0.01）和第2期（20和40μg/只；分别为P<0.01和P<0.001）具有抗伤害感受作用。使用纳洛酮嗪和/或荷包牡丹碱分别证实了阿片类和GABA受体参与了KM的中枢抗伤害感受作用。此外，KM降低了半胱天冬酶6、白细胞介素-1β、肿瘤坏死因子-α和白细胞介素-6的表达水平。KM的抗伤害感受作用与运动活动的变化无关。
可以得出结论，KM在脊髓水平具有显著的抗伤害感受作用，这与炎症状态的存在有关。在侧脑室注射后未检测到这些影响。KM抗伤害感受的可能机制可能与多种调节途径有关，包括阿片类和GABA受体。
