Abstract:

Objective： The ionotropic glutamate receptorantagonists include two types： MK-801， anta-gonist of N-methyl-D-asparticacid (NMDA) receptor, and NBQX, antagonist of non-NMDA receptor.The above-mentioned ionotropic antagonists can block the glutamate and its corresponding receptor binding to produce analgesic effect. The objective of this research was to study two antagonists in analgesic effect on rat behavior，as well as to investigate the down-regulation and up-regulation of cyclooxygenase-2 (COX-2) and Janus-activated kinase (Jak3) in collagen-induced arthritis (CIA) rat serum and tissue fluid after the application of these antagonists, that is, the effect on molecular biology. Methods： This study used the ionotropic glutamate receptors as the target and established CIA rat model. Vivo studies were used to observe changes in behavior and molecular biology of the CIA rat.Behavioral assessment includedmechanical allodynia and joint swelling in the CIA rat，where themechanical allodynia was measured using the paw-withdrawal threshold (PWT) with VonFrey filaments according to the “Up-Down” method，and the drainage volume was used to assess joint swelling. Then the blood samples taken from the heart of the rat and the tissue homogenate were collected to detect the down-regulation and up-regulation of COX-2 and Jak3 in the serum and tissue fluid after the antagonists wereused. Results： Using MK-801, NBQX alone or using the combination of these two antagonists，these three methods all could alleviate pain(P＜0.01).The analgesic effect lasted more than 24 h.Both antagonists reached the peak of analgesia at the end of 4 hours post-injection.NBQX had stronger analgesic effect than MK-801 (P＜0.05).Whether alone or combined use of these two antagonists，could not change the CIA rats’ swelling of the joint (P＞0.05). MK -801 could decrease the expression of COX-2 (P＜0.01).At the same time, NBQX did not have this effect (P＞0.05). Using MK-801, NBQX alone or combination of these two antagonists could not affect the increased expression of Jak3 caused by the CIA (P＞0.05). Conclusion: MK-801 and NBQX could both alleviate pain, NBQX was much better than MK-801. Neither MK-801 nor NBQX had the effect on the swelling of the joint. NMDA receptor and COX-2 inflammatory pathways had certain interactions. For Jak3, it could not be found to have cross-function with ionotropic glutamate signaling pathways by this experiment.

Key words: Arthritis, rheumatoid, Glutamic acid, Receptor, Inflammation, Pain