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Mitragynine, bioactive alkaloid of kratom, reduces chemotherapy-induced neuropathic pain in rats through α-adrenoceptor mechanism.
Drug and Alcohol Dependence ( IF 4.2 ) Pub Date : 2020-02-27 , DOI: 10.1016/j.drugalcdep.2020.107946
Jeffery D Foss 1 , Sunil U Nayak 1 , Christopher S Tallarida 2 , Daniel J Farkas 1 , Sara J Ward 3 , Scott M Rawls 3
Affiliation  

Background and Purpose

Kratom is a coffee-like plant containing compounds that cause opioid and stimulant effects. The most prevalent bioactive alkaloid of kratom is mitragynine (MG). Opioid effects of MG are apparent (e.g. antinociception and nanomolar affinity for µ, κ and δ opioid receptors), but effects encompassing interactions with additional systems, such as adrenergic and dopaminergic, remain undefined. Given that enhanced adrenergic transmission is a mechanism common to most first-line neuropathic pain medications, we tested the hypothesis that MG reduces chemotherapy-induced neuropathic pain through a mechanism involving α-adrenoceptor activation.

Methods

Rats were injected once with oxaliplatin (6 mg/kg IP) to induce allodynia and then treated with MG (0, 1, 5, 10 mg/kg IP) for 5-7 days. To investigate receptor mechanisms, a fixed dose of MG (5 mg/kg IP) was injected with yohimbine (5 mg/kg IP, α2-adrenoceptor antagonist), prazosin (5 mg/kg IP, α1-adrenoceptor antagonist), or naltrexone (5 mg/kg IP, opioid antagonist).

Key Results

MG (5, 10 mg/kg) dose-dependently reduced mechanical sensitivity in oxaliplatin-injected rats. Anti-allodynic effects of MG were completely inhibited by yohimbine, and significantly reduced by prazosin and naltrexone. MG produced modest hyperlocomotion but only at a dose (30 mg/kg) higher than those required to reduce allodynia.

Conclusion and Implication

The finding that MG reduced neuropathic pain through a mechanism requiring active α-adrenoceptors indicates that the pharmacological profile of MG includes activation of adrenergic, as well as opioid, systems.



中文翻译:

桔小素是kratom的生物活性生物碱,可通过α-肾上腺素能受体机制减轻化疗引起的大鼠神经性疼痛。

背景和目的

Kratom是一种类似咖啡的植物,其中含有会引起阿片类物质和刺激作用的化合物。kratom最流行的生物活性生物碱是米特拉吉宁(MG)。MG的阿片类药物作用是显而易见的(例如,对u,κ和δ类阿片受体的抗伤害感受和纳摩尔亲和力),但还不清楚与其他系统(例如肾上腺素能和多巴胺能)相互作用的作用。鉴于增强的肾上腺素传递是大多数一线神经性止痛药物共有的机制,我们测试了以下假设:MG通过一种涉及α-肾上腺素受体激活的机制减轻了化疗引起的神经性痛。

方法

给大鼠注射一次奥沙利铂(6 mg / kg IP)诱导异常性疼痛,然后用MG(0、1、5、10 mg / kg IP)治疗5-7天。为了研究受体机制,MG的固定剂量(5毫克/千克IP)用育亨宾注射(5mg / kg的IP,α 2 -肾上腺素能受体拮抗剂),哌唑嗪(5mg / kg的IP,α 1 -肾上腺素能受体拮抗剂),或纳曲酮(5 mg / kg IP,阿片类药物拮抗剂)。

关键结果

MG(5,10 mg / kg)剂量依赖性地降低了奥沙利铂注射大鼠的机械敏感性。育亨宾完全抑制了MG的抗痛觉过敏作用,而吡唑嗪和纳曲酮则显着降低了其抗痛觉过敏作用。MG产生了适度的运动过快,但仅以比减轻异常性疼痛所需的剂量高的剂量(30 mg / kg)。

结论与启示

MG通过需要活性α-肾上腺素受体的机制减轻神经性疼痛的发现表明,MG的药理学特征包括肾上腺素及阿片样物质系统的激活。

更新日期:2020-02-28
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