School of Biological Sciences, Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand.
Callaghan Innovation, Lower Hutt, New Zealand.
Eur J Pain. 2020 Nov;24(10):1990-1998. doi: 10.1002/ejp.1641. Epub 2020 Sep 18.
N-docosahexaenoyl ethanolamine (DHEA; also known as synaptamide) binds to both the cannabinoid-1 and 2 (CB1 and CB2) cannabinoid receptors and has anti-inflammatory properties in vitro. However, the in vivo effects of DHEA remain unknown. Therefore, this study was designed to understand the effects of DHEA in models of pain and inflammation in mice.
The intraplantar formaldehyde assay, hot water tail withdrawal assay and hotplate model were used to assess the antinociceptive properties of DHEA in mice. The mechanism of action was studied by antagonising the cannabinoid receptors, transient receptor potential vanilloid 1 (TRPV1) ion channel, peroxisome proliferator-activated receptors (PPARs) and G-protein receptor 55 (GPR55).
N-docosahexaenoyl ethanolamine (2-10 mg/kg) reduced the levels of nociceptive and inflammatory pain-related behaviour over 60 min in the intraplantar formaldehyde assay via both intraperitoneal and local intraplantar administration. The area under the curve analysis showed the overall antinociceptive effects of DHEA (10 mg/kg) were not modulated by pre-treatment with antagonists for the cannabinoid receptors, TRPV1ion channel, PPARα, PPARγ or GPR55. However, the time-course analysis showed that within the early inflammatory phase, antagonism of the CB2 receptor, PPARα and PPARγ led to a partial reversal of the antinociceptive effects of DHEA. In the hot water tail withdrawal and hotplate models of thermal nociception, DHEA (2-10 mg/kg) did not have any antinociceptive effects.
N-docosahexaenoyl ethanolamine reduced the level of formaldehyde-induced nociceptive and inflammatory pain-related behaviour; however, was not active in thermal nociceptive models. This study highlights the potential of DHEA for the treatment of acute inflammatory pain.
This study shows that both intraperitoneal and intraplantar administration of DHEA reduces the level of formaldehyde-induced nociceptive and inflammatory pain.
二十二碳六烯酰乙醇胺（DHEA；也称为神经酰胺）与大麻素-1 和 2（CB1 和 CB2）大麻素受体结合，并且在体外具有抗炎特性。然而，DHEA 的体内作用尚不清楚。因此，本研究旨在了解 DHEA 在小鼠疼痛和炎症模型中的作用。
采用足底注射甲醛法、热板法和热水尾缩法评估 DHEA 在小鼠中的镇痛作用。通过拮抗大麻素受体、瞬时受体电位香草醛 1（TRPV1）离子通道、过氧化物酶体增殖物激活受体（PPARs）和 G 蛋白受体 55（GPR55）来研究其作用机制。
DHEA（2-10mg/kg）通过腹腔内和局部足底内给药，在 60 分钟内降低了足底注射甲醛引起的痛觉和炎症性疼痛相关行为的水平。曲线下面积分析显示，DHEA（10mg/kg）的整体镇痛作用不受大麻素受体、TRPV1 离子通道、PPARα、PPARγ 或 GPR55 拮抗剂预处理的调节。然而，时间进程分析显示，在早期炎症期，CB2 受体、PPARα 和 PPARγ 的拮抗作用导致 DHEA 的镇痛作用部分逆转。在热板法和热水尾缩法的热痛觉模型中，DHEA（2-10mg/kg）没有任何镇痛作用。
二十二碳六烯酰乙醇胺降低了甲醛诱导的痛觉和炎症性疼痛相关行为的水平；然而，在热痛觉模型中没有活性。本研究强调了 DHEA 治疗急性炎症性疼痛的潜力。
本研究表明，DHEA 无论是腹腔内还是足底内给药，均可降低甲醛诱导的痛觉和炎症性疼痛的水平。
