Physiology Department, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
Biomolecules. 2024 Aug 26;14(9):1065. doi: 10.3390/biom14091065.
L. (CSL) extract has pain-relieving potential due to its cannabinoid content, so the effects of two CSL extracts on alleviating neuropathic pain were investigated in vivo. Methods and groups: Male Wistar rats (n = 130) were divided into groups and received vincristine (0.1 mg/kg) and gabapentin (60 mg/kg) to induce and relieve neuropathic pain or CSL extracts (D and B). The mRNA and protein expression of the cannabinoid receptors type 1 and 2 (CB1R, CB2R) were evaluated in the cerebral cortex, hippocampus, and lymphocytes. Behavioural tests (Tail-Flick and von Frey) were performed on all animals.
VK-induced neuropathic pain was accompanied by decreased CB1R protein level and CB2R mRNA expression in the cortex. Gabapentin relieved pain and increased CB1R protein levels in the hippocampus compared to the vincristine group. Hippocampus CB1R protein expression increased with the administration of extract D (10 mg/kg, 40 mg/kg) and extract B (7.5 mg/kg, 10 mg/kg) compared to VK group. In the cerebral cortex CSL decreased CB1R protein expression (10 mg/kg, 20 mg/kg, 40 mg/kg of extract B) and mRNA level (5 mg/kg, 7.5 mg/kg of extract B; 20 mg/kg of extract D) compared to the VK-group.CB2R protein expression increased in the hippocampus after treatment with extract B (7.5 mg/kg) compared to the VK-group. In the cerebral cortex extract B (10 mg/kg, 20 mg/kg) increased CB2R protein expression compared to VK-group.
Alterations in cannabinoid receptor expression do not fully account for the observed behavioural changes in rats. Therefore, additional signalling pathways may contribute to the initiation and transmission of neuropathic pain. The extracts tested demonstrated antinociceptive effects comparable to gabapentin, highlighting the antinociceptive properties of extracts for human use.
L.(CSL)提取物由于其大麻素含量具有止痛潜力,因此研究了两种 CSL 提取物对缓解神经病理性疼痛的体内作用。方法和分组:雄性 Wistar 大鼠(n=130)分为几组,给予长春新碱(0.1mg/kg)和加巴喷丁(60mg/kg)诱导和缓解神经病理性疼痛,或给予 CSL 提取物(D 和 B)。评估大麻素受体 1 和 2(CB1R、CB2R)的 mRNA 和蛋白表达在大脑皮层、海马体和淋巴细胞中。对所有动物进行行为测试(尾巴闪烁和 von Frey)。
VK 诱导的神经病理性疼痛伴随着皮质中 CB1R 蛋白水平和 CB2R mRNA 表达的降低。与 vincristine 组相比,gabapentin 缓解疼痛并增加海马体中的 CB1R 蛋白水平。与 VK 组相比,D 提取物(10mg/kg、40mg/kg)和 B 提取物(7.5mg/kg、10mg/kg)给药后,海马体中 CB1R 蛋白表达增加。与 VK 组相比,CSL 降低了大脑皮层中 CB1R 蛋白表达(10mg/kg、20mg/kg、40mg/kg 的 B 提取物)和 mRNA 水平(5mg/kg、7.5mg/kg 的 B 提取物;20mg/kg 的 D 提取物)。与 VK 组相比,海马体中 CB2R 蛋白表达在 B 提取物(7.5mg/kg)治疗后增加。与 VK 组相比,大脑皮层中 B 提取物(10mg/kg、20mg/kg)增加了 CB2R 蛋白表达。
大麻素受体表达的改变不能完全解释大鼠观察到的行为变化。因此,其他信号通路可能有助于神经病理性疼痛的发生和传递。测试的提取物表现出与加巴喷丁相当的镇痛作用,突出了提取物对人类使用的镇痛特性。