OBJECTIVE: Osteoarthritis (OA) is a painful degenerative joint disease. To assess joint nociceptor activation indirectly, we used a novel in vitro knee joint preparation and determined the release of calcitonin gene-related peptide (CGRP) and prostaglandin E2 (PGE2) in osteoarthritic mice. METHODS: We studied STR/1N mice, which spontaneously develop OA, along with CD-1 mice as controls and C57/Bl6 mice with unilateral collagenase-induced OA and C57/Bl6 control mice. The release of CGRP and PGE2 from tibial and femoral joint preparations was determined separately in vitro with enzyme immunoassays; we investigated both basal release and release induced by stimulation with capsaicin (CAP, 1 microM) or bradykinin (BK, 10 microM). RESULTS: Basal PGE2 release from femoral and tibial preparations increased by 79% and 97%, respectively, in STR/1N mice between 6 and 18 weeks of age when they developed OA, while age-matched CD-1 mice exhibited only a weak increase (23%). BK-evoked PGE2 release was significantly higher in 18-week-old STR/1N mice (931 +/- 98 pg/ml and 759 +/- 82 pg/ml from femoral and tibial preparations, respectively) than in age-matched CD-1 controls (236 +/- 38 pg/ml and 246 +/- 34 pg/ml). CAP stimulation induced a significant CGRP release, which, however, did not correlate with the temporal development of OA in STR/1N mice. Tibial but not femoral joint preparations from mice with collagenase-induced OA exhibited a significantly enhanced release upon BK stimulation compared to sham controls, while CAP-induced CGRP release did not reveal such difference. CONCLUSION: Basal and evoked PGE2 release from knee joint preparations rose while osteoarthritic alterations developed, whereas CGRP release remained unaltered. The increased PGE2 release may contribute to enhanced nociceptor sensitivity underlying chronic OA pain.
OBJECTIVE:Osteoarthritis (OA) is a painful degenerative joint disease. To assess joint nociceptor activation indirectly, we used a novel in vitro knee joint preparation and determined the release of calcitonin gene-related peptide (CGRP) and prostaglandin E2 (PGE2) in osteoarthritic mice. METHODS: We studied STR/1N mice, which spontaneously develop OA, along with CD-1 mice as controls and C57/Bl6 mice with unilateral collagenase-induced OA and C57/Bl6 control mice. The release of CGRP and PGE2 from tibial and femoral joint preparations was determined separately in vitro with enzyme immunoassays; we investigated both basal release and release induced by stimulation with capsaicin (CAP, 1 microM) or bradykinin (BK, 10 microM). RESULTS: Basal PGE2 release from femoral and tibial preparations increased by 79% and 97%, respectively, in STR/1N mice between 6 and 18 weeks of age when they developed OA, while age-matched CD-1 mice exhibited only a weak increase (23%). BK-evoked PGE2 release was significantly higher in 18-week-old STR/1N mice (931 +/- 98 pg/ml and 759 +/- 82 pg/ml from femoral and tibial preparations, respectively) than in age-matched CD-1 controls (236 +/- 38 pg/ml and 246 +/- 34 pg/ml). CAP stimulation induced a significant CGRP release, which, however, did not correlate with the temporal development of OA in STR/1N mice. Tibial but not femoral joint preparations from mice with collagenase-induced OA exhibited a significantly enhanced release upon BK stimulation compared to sham controls, while CAP-induced CGRP release did not reveal such difference. CONCLUSION: Basal and evoked PGE2 release from knee joint preparations rose while osteoarthritic alterations developed, whereas CGRP release remained unaltered. The increased PGE2 release may contribute to enhanced nociceptor sensitivity underlying chronic OA pain.