Department of Pharmacology and Neuroscience, UNT Health Science Center, Fort Worth, USA.
Department of Medical Education, Texas Christian University and UNT Health Science Center School of Medicine (Applicant for LCME accreditation), Fort Worth, USA.
Pharmacol Rep. 2018 Apr;70(2):316-321. doi: 10.1016/j.pharep.2017.11.002. Epub 2017 Nov 11.
The objective of this study was to evaluate creatine as an anti-nociceptive compound in an animal model of thermal and inflammatory pain. Creatine has the structural potential to interact with acid-sensing ion channels (ASIC), which have been involved in pain sensation modulation. The hypothesis evaluated in this study was that creatine will interact with ASICs leading to decreased nociception.
Male and female C57BL/6J mice were fed with either a control diet or the control diet supplemented with creatine (6.25 g/kg diet). After one week on the diet, the mice were tested for thermal hyperalgesia and inflammatory pain response.
The latency to withdraw the tail during the thermal hyperalgesia test was unaffected by sex or diet. During the formalin test, males and females responded differently to the stimulus, and the female mice supplemented with creatine seemed to recover faster than the controls. To determine whether ASICs mediate the action of creatine, GMQ, an ASIC3 agonist, was injected in one paw and pain response was quantified. Females responded more strongly to GMQ injections, and all mice fed creatine had a decreased response to GMQ.
These preliminary data suggest a potential effect of creatine on inflammation-based nociception that may be mediated via ASIC3. While preliminary, this study warrants further research on the potential of creatine as an analgesic and can serve as a stepping stone for the development of ASIC-based therapeutics.
本研究旨在评估肌酸作为一种抗伤害性化合物在热和炎症性疼痛动物模型中的作用。肌酸具有与酸敏离子通道（ASIC）相互作用的结构潜力，ASIC 参与疼痛感觉的调节。本研究评估的假设是肌酸将与 ASIC 相互作用，导致伤害性降低。
雄性和雌性 C57BL/6J 小鼠分别喂食对照饮食或对照饮食补充肌酸（6.25g/kg 饮食）。饮食一周后，对小鼠进行热痛觉过敏和炎症性疼痛反应测试。
在热痛觉过敏测试中，尾巴撤回的潜伏期不受性别或饮食的影响。在福马林测试中，雄性和雌性对刺激的反应不同，补充肌酸的雌性小鼠似乎比对照组恢复得更快。为了确定 ASIC 是否介导肌酸的作用，在一只爪子中注射 GMQ（ASIC3 激动剂），并量化疼痛反应。雌性对 GMQ 注射的反应更强，所有喂食肌酸的小鼠对 GMQ 的反应都减弱。
这些初步数据表明肌酸对基于炎症的伤害性感受可能具有潜在的影响，这种影响可能是通过 ASIC3 介导的。虽然这是初步研究，但本研究证明了肌酸作为一种镇痛剂的潜力，并为基于 ASIC 的治疗方法的发展提供了一个起点。
