Department of Traditional Chinese Medicine, Tangdu Hospital, Air Force Medical University, Xi'an, China.
Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xi'an, China.
Mol Pain. 2022 Apr;18:17448069221121562. doi: 10.1177/17448069221121562.
Neuropathic pain takes a heavy toll on individual well-being, while current therapy is far from desirable. Herein, we assessed the analgesic effect of β-elemene, a chief component in the traditional Chinese medicine Curcuma wenyujin, and explored the underlying mechanisms at the level of spinal dorsal horn (SDH) under neuropathic pain. A spared nerve injury (SNI)-induced neuropathic pain model was established in rats. Intraperitoneal injection (i.p.) of β-elemene was administered for 21 consecutive days. Mechanical allodynia was explored by von Frey filaments. The activation of the mitogen-activated protein kinase (MAPK) family (including ERK, p38, and JNK) in spinal neurons, astrocytes, and microglia was evaluated using immunostaining 29 days after SNI surgery. The expression of GFAP, Iba-1, p-ERK, p-JNK, and p-p38 within the SDH was measured using immunoblotting. The levels of proinflammatory cytokines (including TNF-α, IL-1β, and IL-6) were measured with ELISA. The levels of oxidative stress indicators (including MDA, SOD, and GSH-PX) were detected using biochemical tests. Consecutive i.p. administration of β-elemene relieved SNI-induced mechanical allodynia (with an EC50 of 16.40 mg/kg). SNI significantly increased the expression of p-ERK in spinal astrocytes but not microglia on day 29. β-elemene reversed spinal astrocytic ERK activation and subsequent upregulation of proinflammatory cytokines in SNI rats, with no effect on the expression of p38 and JNK in spinal glia. β-elemene also exerted antioxidative effects by increasing the levels of SOD and GSH-PX and decreasing the level of MDA. Our results suggest that SNI induces robust astrocytic ERK activation within the SDH in the late phase of neuropathic pain. β-elemene exerts remarkable analgesic effects on neuropathic pain, possibly by inhibiting spinal astrocytic ERK activation and subsequent neuroinflammatory processes. Our findings suggest that β-elemene might be a promising analgesic for the treatment of chronic pain.
神经病理性疼痛严重影响个体的幸福感，而目前的治疗方法远不理想。在此，我们评估了中药莪术中的主要成分β-榄香烯在神经病理性疼痛情况下脊髓背角（SDH）水平的镇痛作用及其潜在机制。建立大鼠 spared nerve injury（SNI）诱导的神经病理性疼痛模型。连续 21 天腹腔注射β-榄香烯。使用 von Frey 纤维探测机械性痛觉过敏。SNI 手术后 29 天，通过免疫染色评估丝裂原活化蛋白激酶（MAPK）家族（包括 ERK、p38 和 JNK）在脊髓神经元、星形胶质细胞和小胶质细胞中的激活情况。使用免疫印迹法测量 SDH 中 GFAP、Iba-1、p-ERK、p-JNK 和 p-p38 的表达。通过 ELISA 测量促炎细胞因子（包括 TNF-α、IL-1β 和 IL-6）的水平。通过生化试验检测氧化应激指标（包括 MDA、SOD 和 GSH-PX）的水平。连续腹腔注射β-榄香烯可缓解 SNI 诱导的机械性痛觉过敏（EC50 为 16.40mg/kg）。SNI 在第 29 天显著增加了脊髓星形胶质细胞中 p-ERK 的表达，但对小胶质细胞无影响。β-榄香烯逆转了 SNI 大鼠脊髓星形胶质细胞 ERK 激活及其随后的促炎细胞因子上调，对脊髓胶质细胞中 p38 和 JNK 的表达无影响。β-榄香烯还通过增加 SOD 和 GSH-PX 的水平和降低 MDA 的水平发挥抗氧化作用。我们的结果表明，SNI 在神经病理性疼痛的晚期诱导 SDH 中强烈的星形胶质细胞 ERK 激活。β-榄香烯对神经病理性疼痛具有显著的镇痛作用，可能是通过抑制脊髓星形胶质细胞 ERK 激活及其随后的神经炎症过程。我们的研究结果表明，β-榄香烯可能是治疗慢性疼痛的一种有前途的药物。
