The effects of intraarticular resiniferatoxin in experimental knee-joint arthritis.
In this study we sought to determine whether an intraarticular administration of a vanilloid agonist resiniferatoxin (RTX) produces an analgesic effect in experimental arthritis. Knee joint inflammation was induced in rats by intraarticular carrageenan (2%, 30 microL). Pain score and left/right hind leg weight distribution ratio were used to assess pain behavior. Changes in knee dimensions were evaluated by measuring external circumference and intraarticular area (ultrasound scanning). The intraarticular administration of RTX (0.0003% or 0.003%, 30 microL) provided a significant analgesic effect. Twenty-four hours after RTX administration, the pain score was reduced from 15.1 +/- 4.7 to 6.9 +/- 4.4 (P < 0.01) with 0.0003% and was abolished (P < 0.0001) with 0.003%. The improvement in weight distribution ratio lasted for several days after the RTX administration. Reduction in knee circumference demonstrated that intraarticular RTX suppressed the carrageenan-induced edema by at least one third. Ultrasound scanning revealed no RTX-induced decrease of the intraarticular area. The experiments demonstrated that intraarticular RTX inhibits pain behavior in knee-joint arthritis and that this effect is dose-dependent. These results suggest a new direction for peripheral analgesia.
Kissin
Eugene Y
EY
*Arthritis Center, Boston University School of Medicine, Boston, Massachusetts and †Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Freitas
Cristina F
CF
Kissin
Igor
I
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D004224:Diterpenes / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007270:Injections, Intra-Articular; D007719:Knee Joint; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000502:physiology
D004224:Diterpenes; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C024353:resiniferatoxin; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium