Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5830075 | European Journal of Pharmacology | 2011 | 6 Pages |
Persistent pain associated with inflammatory arthritis is an aggravating factor that decreases patients' quality of life. Current therapies for joint pain have limited effectiveness and produce unwanted negative side effects. Although the involvement of substance P and its cognate tachykinin receptor, NK1, in joint inflammation has been extensively documented through animal experiments, the development of oral tachykinin NK1 receptor antagonists against arthritis-induced pain has been unsuccessful in humans to date. To explore the possibility of using tachykinin NK1 receptor antagonists as local therapeutic agents for inflammatory arthritis, we examined the effects of tachykinin NK1 receptor antagonists administered into the rat ankle joint on hyperalgesia in complete Freund's adjuvant (CFA)-induced inflammatory monoarthritis. Administration of the tachykinin NK1 receptor antagonist WIN 51708 or GR 82334 into the affected ankle joint at day 3 following intra-articular CFA injection reduced the mechanical hyperalgesia 12Â h after the tachykinin NK1 receptor antagonist injection and their analgesic effects persisted for at least 2Â days. Histological examinations revealed that intra-articular WIN 51708 reduced the CFA-induced destructive changes in the cartilage. These findings suggest that intra-articular injection of tachykinin NK1 receptor antagonists is a promising strategy for relieving the hyperalgesia that occurs in inflammatory arthritis.