Gotoh S, Miyazaki K, Onaya J, Sakamoto T, Tokuyasu K, Namiki O
Tokyo Research Institute, Seikagaku Kogyo Co., Ltd., Japan.
Nihon Yakurigaku Zasshi. 1988 Jul;92(1):17-27. doi: 10.1254/fpj.92.17.
Using the model of knee pain reaction induced by intra-articular injection of endogenous pain substances, especially bradykinin (BK) in rats, the mechanism of the analgesic effect of sodium hyaluronate (SPH) was investigated. The simultaneous administration of prostaglandin E2 with BK or hyaluronidase digestion of endogenous hyaluronic acid (HA) in our experiments brought remarkable hyperalgesia on BK-induced knee pain. These results suggest that higher sensitivity to the pain reaction is induced in a diseased joint (higher prostaglandin content, lower concentration and molecular size of HA in synovial fluid) than in a normal one. SPH definitely decreased BK-induced pain, and its analgesic effect was observed for a longer period, depending on its dose in pre-treatment and the degree of its distribution in synovial tissues. As the analgesic effect of SPH was observed in the hyaluronidase-treated joint as well, it is suggested that the increasing viscosity of synovial fluid caused by increasing HA concentration can decrease the pain even without normalizing molecular size of HA in the joint. HA oligomer and other compounds with similar viscosity or with similar polyanionic character as SPH showed no analgesic effect. From these results, it seems that the characteristic steric configurations of higher molecular HA are needed for the manifestation of the analgesic effect. SPH seems to show its analgesic effect by covering pain receptors in synovial tissues and holding endogenous pain substances in its molecule.
利用关节腔内注射内源性疼痛物质（尤其是缓激肽，BK）诱导大鼠膝关节疼痛反应的模型，研究了透明质酸钠（SPH）的镇痛作用机制。在我们的实验中，将前列腺素E2与BK同时给药，或对内源性透明质酸（HA）进行透明质酸酶消化，均会使BK诱导的膝关节疼痛出现显著的痛觉过敏。这些结果表明，与正常关节相比，患病关节（前列腺素含量较高、滑液中HA浓度较低且分子大小较小）对疼痛反应的敏感性更高。SPH确实能减轻BK诱导的疼痛，且根据其预处理剂量及其在滑膜组织中的分布程度，其镇痛作用持续时间更长。由于在经透明质酸酶处理的关节中也观察到了SPH的镇痛作用，因此表明，即使关节内HA分子大小未恢复正常，HA浓度增加导致的滑液粘度增加也能减轻疼痛。HA寡聚物以及其他具有与SPH相似粘度或相似聚阴离子特性的化合物均未显示出镇痛作用。从这些结果来看，似乎需要较高分子HA的特征性空间构型才能表现出镇痛作用。SPH似乎是通过覆盖滑膜组织中的疼痛感受器并在其分子中保留内源性疼痛物质来发挥其镇痛作用的。
