Student Research Committee.
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah.
Behav Pharmacol. 2021 Dec 1;32(8):607-614. doi: 10.1097/FBP.0000000000000655.
One of the main functions of the sensory system in our body is to maintain somatosensory homeostasis. Recent reports have led to a significant advance in our understanding of pain signaling mechanisms; however, the exact mechanisms of pain transmission have remained unclear. There is an urgent need to reveal the precise signaling mediators of pain to provide alternative therapeutic agents with more efficacy and fewer side effects. Accordingly, although the anti-inflammatory, antioxidative and anti-neuropathic effects of astaxanthin (AST) have been previously highlighted, its peripheral antinociceptive mechanisms are not fully understood. In this line, considering the engagement of l-arginine/nitric oxide (NO)/cyclic GMP (cGMP)/potassium channel (KATP) signaling pathway in the antinociceptive responses, the present study evaluated its associated role in the antinociceptive activity of AST. Male mice were intraperitoneally (i.p.) injected with l-arginine (100 mg/kg), SNAP (1 mg/kg), L-NAME (30 mg/kg), sildenafil (5 mg/kg), and glibenclamide (10 mg/kg) alone and prior to the most effective dose of AST. Following AST administration, intraplantarly (i.pl) injection of formalin was done, and pain responses were evaluated in mice during the primary (acute) and secondary (inflammatory) phases of formalin test. The results highlighted that 10 mg/kg i.p. dose of AST showed the greatest antinociceptive effect. Besides, while L-NAME and glibenclamide reduced the antinociceptive effect of AST, it was significantly increased by l-arginine, SNAP and sildenafil during both the primary and secondary phases of formalin test. These data suggest that the antinociceptive activity of AST is passing through the l-arginine/NO/cGMP/KATP pathway.
人体感觉系统的主要功能之一是维持躯体感觉稳态。最近的报告使我们对疼痛信号机制的理解有了重大进展；然而，疼痛传递的确切机制仍不清楚。迫切需要揭示疼痛的精确信号转导介质，为具有更高疗效和更少副作用的替代治疗剂提供依据。因此，尽管虾青素（AST）的抗炎、抗氧化和抗神经病变作用以前已经被强调，但其外周镇痛机制尚未完全阐明。考虑到 l-精氨酸/一氧化氮（NO）/环鸟苷酸（cGMP）/钾通道（KATP）信号通路在镇痛反应中的参与，本研究评估了其在 AST 镇痛活性中的相关作用。雄性小鼠腹膜内（i.p.）注射 l-精氨酸（100 mg/kg）、SNAP（1 mg/kg）、L-NAME（30 mg/kg）、西地那非（5 mg/kg）和格列本脲（10 mg/kg）单独注射和 AST 最有效剂量之前。AST 给药后，对小鼠进行足底内（i.pl）注射福尔马林，并在福尔马林试验的原发性（急性）和继发性（炎症）阶段评估小鼠的疼痛反应。结果表明，AST 的 10 mg/kg i.p.剂量显示出最大的镇痛作用。此外，L-NAME 和格列本脲降低了 AST 的镇痛作用，而 l-精氨酸、SNAP 和西地那非在福尔马林试验的原发性和继发性阶段均显著增加了 AST 的镇痛作用。这些数据表明，AST 的镇痛活性是通过 l-精氨酸/NO/cGMP/KATP 途径实现的。
