Ohsawa Masahiro, Miyata Shigeo, Carlsson Anna, Kamei Junzo
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-Chome, Shinagawa-Ku, Tokyo, 142-8501, Japan.
Eur J Pharmacol. 2008 Jul 7;588(2-3):213-6. doi: 10.1016/j.ejphar.2008.04.029. Epub 2008 May 24.
Hypoalgesia is one of the serious complications in diabetes. Since there are few therapeutic treatments for this diabetic hypoalgesia, the present study was designed to examine the effect of acetyl-L-carnitine (ALC) on the changes of nociceptive threshold in diabetic mice. For prophylactic study, ALC was administered once daily from 1 day after the streptozotocin treatment. Diabetic mice showed shorter tail-flick latency at 1-4 weeks after the streptozotocin treatment and longer tail-flick latency at 6-9 weeks after the streptozotocin treatment. The shortened tail-flick latency in early stage of diabetic mice was not affected by prophylactic treatment with ALC. On the other hand, ALC dose-dependently improved the hypoalgesia in diabetic mice. For therapeutic study, ALC was administered once daily from 7 weeks after the streptozotocin treatment, when tail-flick latency was already prolonged. The therapeutic treatment with ALC also ameliorated the prolonged tail-flick latency in diabetic mice. Both prophylactic and therapeutic treatment with ALC did not affect the tail-flick latency in non-diabetic mice, indicating ALC did not affect the general nociceptive transmission. These results provide evidence of the prophylactic and therapeutic potential of ALC on the progressive diabetic neuropathy.
痛觉减退是糖尿病的严重并发症之一。由于针对这种糖尿病性痛觉减退的治疗方法很少，本研究旨在研究乙酰左旋肉碱（ALC）对糖尿病小鼠痛觉阈值变化的影响。在预防性研究中，从链脲佐菌素治疗后第1天开始每天给药一次ALC。糖尿病小鼠在链脲佐菌素治疗后1至4周表现出较短的甩尾潜伏期，而在链脲佐菌素治疗后6至9周表现出较长的甩尾潜伏期。糖尿病小鼠早期缩短的甩尾潜伏期不受ALC预防性治疗的影响。另一方面，ALC剂量依赖性地改善了糖尿病小鼠的痛觉减退。在治疗性研究中，从链脲佐菌素治疗7周后开始每天给药一次ALC，此时甩尾潜伏期已经延长。ALC的治疗性治疗也改善了糖尿病小鼠延长的甩尾潜伏期。ALC的预防性和治疗性治疗均未影响非糖尿病小鼠的甩尾潜伏期，表示ALC不影响一般的痛觉传递。这些结果提供了ALC对进行性糖尿病性神经病变的预防和治疗潜力的证据。
