[Experimental knee pain model in rats and analgesic effect of sodium hyaluronate (SPH)].
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.
Gotoh
S
S
Tokyo Research Institute, Seikagaku Kogyo Co., Ltd., Japan.
Miyazaki
K
K
Onaya
J
J
Sakamoto
T
T
Tokuyasu
K
K
Namiki
O
O
D000700:Analgesics / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D001920:Bradykinin; D015232:Dinoprostone / Q000494:pharmacology; D004195:Disease Models, Animal; D006820:Hyaluronic Acid / Q000378:metabolism / Q000627:therapeutic use*; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage; D007719:Knee Joint; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D013582:Synovial Fluid / Q000502:physiology
D000700:Analgesics; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase; D015232:Dinoprostone; D001920:Bradykinin