실험적으로 유발한 흰쥐 관절염 모델에서 COX 억제제, NMDA 수용체 길항제와 capsaicin이 척수 뒤뿔의 c-fos 단백질과 척수신경절의 substance P, CGRP에 미치는 영향

Abstract

Arthritis is the most common disease of joint in old age and almost all the old human are suffering from arthritis. Arthritis gives so severe pain hard to endure that it can devastate human. But we still do not know where the arthritic pain comes from and the generation mechanism of it.

For the study of effects of anti-inflammatory drugs on the c-fos immunoreactive neurons, substance P-and CGRP-immunoreactive neurons in dorsal horn and DRG, cyclooxygenase (COX) inhibitors indomethacin (0.5 ㎎/㎏), piroxicam (0.5 ㎎/㎏), NMDA receptor antagonist MK 801 (2 ㎎/㎏), and capsaicin (50 ㎎/㎏) were administered to the experimental arthritis model. Male Sprague-Dawley rats were used for this study. Arthritis was induced by injection of 4% kaolin followed by 2% carrageenan into the articular capsule of left knee. Two hours, 24 hours and 7 days after injection, animals were sacrificed and processed for immunohistochemical staining for c-fos in spinal dorsal houn, for substance P (SP) and CGRP in DRG.

The results were as follows; 1. The number of c-fos immunoreactive neurons were significantly decreased at 2 h after piroxicam and MK-801 administration and 1 week after indomethacin, MK-801 and capsaicin treatement in the inflamed side of dorsal horn. 2. there were the significant decrease of SP-and CGRP-immunoreactive area 2 h after indomethacin administration and 1 week after capsaicin treatment in the inflamed side of dorsal horn. 3. The number of SP- and CGRP-immunoreactive neurons in DRG were decreased after drugs administration and no difference is in the degree of effectiveness between drugs.

Indomethacin and piroxicam which is an inhibitors of COX, significantly reduced the expression of c-fos proteins and desensitized nociceptive primary afterents at the early time, and capsaicin, a pungent algesic substance, decreased the level of c-fos protein, SP and CGRP over a wider time in dorsal horn and DRG.