Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models.
Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models.
复制标题
Bullatine A 刺激脊髓小胶质细胞强啡肽 A 表达，在多种大鼠疼痛模型中产生抗过敏作用
DOI：
10.1186/s12974-016-0696-2
复制
发表时间：
2016-08-30
影响因子：
9.3
通讯作者：
Wang YX
中科院分区：
文献类型：
--
作者：
Huang Q;Mao XF;Wu HY;Li TF;Sun ML;Liu H;Wang YX
研究背景血伤益智号（学名：Acupuncture brachypodiRadix）是一种治疗慢性疼痛、关节炎和创伤性损伤的药物。布拉亭A为C20-二萜生物碱，是其主要有效成分之一。本研究旨在探讨布拉亭A在多种大鼠疼痛模型中的抗过敏作用及其作用机制。方法采用大鼠神经病理性疼痛、炎症性疼痛、糖尿病性神经病理性疼痛和骨癌性疼痛模型。在脊髓和培养的原代小胶质细胞中测定强啡肽A和促炎细胞因子。结果皮下和鞘内注射布拉汀A剂量依赖性地减弱脊神经结扎、完全弗洛伊德佐剂、糖尿病和骨癌诱导的机械性异常性疼痛和热痛觉过敏，抑制率为45- 70%，皮下注射的半数有效剂量为0.9- 1.9mg/kg。但在正常情况下，布拉亭A对急性伤害性反应无阻断作用。Bullatine A特异性刺激体内脊髓小胶质细胞和体外培养的原代小胶质细胞中强啡肽A的表达;小胶质细胞抑制剂米诺环素可完全抑制该刺激作用。相反，布拉汀A对周围神经损伤或脂多糖诱导的促炎细胞因子表达没有抑制作用。脊髓抗异常性疼痛的影响，bullatine A被完全阻断由鞘内注射米诺环素，特异性强啡肽A抗血清，和选择性K-阿片受体拮抗剂。ConclusionsWe，第一次，证明bullatine A特异性减弱疼痛超敏反应，无论疼痛模型。结果还表明，刺激脊髓小胶质细胞强啡肽A的表达介导的布拉汀A在疼痛超敏反应条件下的抗伤害感受。
BackgroundAconiti brachypodiRadix (Xue-shang-yi-zhi-hao) has been prescribed to manage chronic pain, arthritis, and traumatic injuries. Bullatine A, a C20-diterpenoid alkaloid, is one of its principle effective compounds. This study aimed to investigate the anti-hypersensitivity of bullatine A in a variety of rat pain models and explore its mechanisms of action.MethodsRat neuropathic pain, inflammatory pain, diabetic neuropathic pain, and bone cancer pain models were used. Dynorphin A and pro-inflammatory cytokines were measured in the spinal cord and cultured primary microglia. Double immunofluorescence staining of dynorphin A and glial and neuronal cellular markers was also measured in the spinal cord.ResultsSubcutaneous and intrathecal injection of bullatine A dose-dependently attenuated spinal nerve ligation-, complete Freud’s adjuvant-, diabetes-, and bone cancer-induced mechanical allodynia and thermal hyperalgesia, with the efficacies of 45–70 % inhibition, and half-effective doses of 0.9–1.9 mg/kg for subcutaneous injection. However, bullatine A was not effective in blocking acute nociceptive response in the normal condition. Bullatine A specifically stimulated dynorphin A expression in microglia in the spinal cord in vivo and cultured primary microglia in vitro; the stimulatory effects were completely inhibited by the microglial inhibitor minocycline. In contrast, bullatine A did not have an inhibitory effect on peripheral nerve injury- or lipopolysaccharide-induced pro-inflammatory cytokine expression. The spinal anti-allodynic effects of bullatine A were entirely blocked by intrathecal injection of minocycline, the specific dynorphin A antiserum, and the selective k-opioid receptor antagonist.ConclusionsWe, for the first time, demonstrate that bullatine A specifically attenuates pain hypersensitivity, regardless of the pain models employed. The results also suggest that stimulation of spinal microglial dynorphin A expression mediates bullatine A anti-nociception in pain hypersensitivity conditions.
登录
查看更多内容
影响因子：
6
作者：
Jha MK;Jeon S;Suk K
通讯作者：
Suk K
影响因子：
7.4
作者：
Ledeboer, A;Sloane, EM;Watkins, LR
通讯作者：
Watkins, LR
脊髓 D-氨基酸氧化酶对骨癌疼痛的作用
影响因子：
3.5
作者：
Huang, Jin-Lu;Chen, Xiao-Ling;Wang, Yong-Xiang
通讯作者：
Wang, Yong-Xiang
影响因子：
2.5
作者：
Ju, Jin;Shin, Dong Jin;Yoon, Myung Ha
通讯作者：
Yoon, Myung Ha
影响因子：
1.1
作者：
Huang WC;Qiao Y;Xu L;Kacimi R;Sun X;Giffard RG;Yenari MA
通讯作者：
Yenari MA