title: Intra-articular administration of tachykinin NK₁ receptor antagonists reduces hyperalgesia and cartilage destruction in the inflammatory joint in rats with adjuvant-induced arthritis.
abstract: 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, NK(1), in joint inflammation has been extensively documented through animal experiments, the development of oral tachykinin NK(1) receptor antagonists against arthritis-induced pain has been unsuccessful in humans to date. To explore the possibility of using tachykinin NK(1) receptor antagonists as local therapeutic agents for inflammatory arthritis, we examined the effects of tachykinin NK(1) receptor antagonists administered into the rat ankle joint on hyperalgesia in complete Freund's adjuvant (CFA)-induced inflammatory monoarthritis. Administration of the tachykinin NK(1) receptor antagonist WIN 51708 or GR 82334 into the affected ankle joint at day 3 following intra-articular CFA injection reduced the mechanical hyperalgesia 12 h after the tachykinin NK(1) receptor antagonist injection and their analgesic effects persisted for at least 2 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 NK(1) receptor antagonists is a promising strategy for relieving the hyperalgesia that occurs in inflammatory arthritis.
authors.affiliation: Department of Orthopedics, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. s7013@nms.ac.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Uematsu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakai
authors.forename: Hiromoto
authors.initials: H
authors.lastname: Ito
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000731:Androstanes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000843:Ankle Joint; D001169:Arthritis, Experimental / Q000150:complications*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002356:Cartilage / Q000187:drug effects* / Q000473:pathology; D005620:Freund's Adjuvant / Q000009:adverse effects; D006930:Hyperalgesia / Q000150:complications* / Q000188:drug therapy*; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007279:Injections, Subcutaneous; D008297:Male; D010803:Physalaemin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*
chemical_list: D000700:Analgesics; D000731:Androstanes; D001562:Benzimidazoles; D018039:Receptors, Tachykinin; C086111:WIN 51708; C079014:GR 82334; D010803:Physalaemin; D005620:Freund's Adjuvant; D007213:Indomethacin