Vázquez López José Luis, Schild Lorenz, Günther Thomas, Schulz Stefan, Neurath Hartmud, Becker Axel
Otto-von-Guericke University, Faculty of Medicine, Institute of Pharmacology and Toxicology, Leipziger Str. 44, 39120 Magdeburg, Germany.
Otto-von-Guericke-University, Faculty of Medicine, Department of Pathobiochemistry, Leipziger Strasse 44, 39120 Magdeburg, Germany.
J Ethnopharmacol. 2017 Jun 9;205:178-185. doi: 10.1016/j.jep.2017.05.008. Epub 2017 May 10.
Mitragyna speciosa and its extracts are called kratom (dried leaves, extract). They contain several alkaloids with an affinity for different opioid receptors. They are used in traditional medicine for the treatment of different diseases, as a substitute by opiate addicts, and to mitigate opioid withdrawal symptoms. Apart from their medical properties, they are used to enhance physical endurance and as a means of overcoming stress.
The aim of this study was to determine the mechanisms underlying the effects of kratom on restraint-stress-induced analgesia which occurs during or following exposure to a stressful or fearful stimulus.
To gain further insights into the action of kratom on stress, we conducted experiments using restraint stress as a test system and stress-induced analgesia as a test parameter. Using transgenic mu opioid-receptor (MOR) deficient mice, we studied the involvement of this receptor type. We used nor-binaltorphimine (BNT), an antagonist at kappa opioid receptors (KOR), to study functions of this type of receptor. Membrane potential assay was also employed to measure the intrinsic activity of kratom in comparison to U50,488, a highly selective kappa agonist.
Treatment with kratom diminished stress-induced analgesia in wildtype and MOR knockout animals. Pretreatment of MOR deficient mice with BNT resulted in similar effects. In comparison to U50,488, kratom exhibited negligible intrinsic activity at KOR alone.
The results suggest that the use of kratom as a pharmacological tool to mitigate withdrawal symptoms is related to its action on KOR.
帽柱木及其提取物被称为 kratom（干叶、提取物）。它们含有几种对不同阿片受体有亲和力的生物碱。它们在传统医学中用于治疗各种疾病，被阿片类药物成瘾者用作替代品，并用于减轻阿片类药物戒断症状。除了其医学特性外，它们还被用于增强身体耐力和作为克服压力的一种手段。
本研究的目的是确定 kratom 对束缚应激诱导的镇痛作用的潜在机制，这种镇痛作用发生在暴露于应激或恐惧刺激期间或之后。
为了进一步深入了解 kratom 对压力的作用，我们使用束缚应激作为测试系统，应激诱导的镇痛作为测试参数进行了实验。使用转基因μ阿片受体（MOR）缺陷小鼠，我们研究了这种受体类型的参与情况。我们使用κ阿片受体（KOR）拮抗剂 nor-binaltorphimine（BNT）来研究这种受体类型的功能。还采用膜电位测定法来测量 kratom 与高度选择性κ激动剂 U50,488 相比的内在活性。
用 kratom 处理可减轻野生型和 MOR 基因敲除动物的应激诱导镇痛作用。用 BNT 预处理 MOR 缺陷小鼠产生了类似的效果。与 U50,488 相比，kratom 单独在 KOR 上表现出可忽略不计的内在活性。
结果表明，kratom 作为减轻戒断症状的药理学工具的用途与其对 KOR 的作用有关。
