Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation.
OBJECTIVE
To investigate the endogenous involvement of transient receptor potential vanilloid 1 (TRPV1) in a model of knee joint inflammation in the mouse.


METHODS
Following characterization of wild-type (WT) and TRPV1-knockout mice, inflammation was induced via intraarticular (IA) injection of Freund's complete adjuvant (CFA). Knee swelling was assessed as diameter, and inflammatory heat hyperalgesia was determined using the Hargreaves technique, for up to 3 weeks. At 18 hours, acute hyperpermeability was measured with 125I-albumin, and cytokines and myeloperoxidase activity, a marker of neutrophils, were assayed in synovial fluid extracts. The possibility that exogenous tumor necrosis factor alpha (TNFalpha) was involved in influencing TRPV1 activation was investigated in separate experiments.


RESULTS
Increased levels of knee swelling, hyperpermeability, leukocyte accumulation, and TNFalpha were found in WT mice 18 hours after IA CFA treatment compared with saline treatment. Significantly less knee swelling and hyperpermeability were found in TRPV1-/- mice, but leukocyte accumulation and TNFalpha levels were similar in WT and TRPV1-/- mice. Knee swelling in response to CFA remained significantly higher for a longer period in WT mice compared with TRPV1-/- mice, with thermal hyperalgesic sensitivity observed at 24 hours and at 1 week in WT, but not TRPV1-/-, mice. Knee swelling was attenuated (P < 0.05) in TRPV1-/- compared with WT mice 4 hours after IA administration of TNFalpha.


CONCLUSIONS
Our findings indicate that TRPV1 has a role in acute and chronic inflammation in the mouse knee joint. Thus, selective antagonism of TRPV1 should be considered as a potential target for treatment of acute and chronic joint inflammation.
Keeble
Julie
J
Cardiovascular Division, New Hunt's House, King's College London, Guy's Campus, London, UK.
Russell
Fiona
F
Curtis
Bradley
B
Starr
Anna
A
Pinter
Erika
E
Brain
Susan D
SD
D000208:Acute Disease; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000503:physiopathology*; D002908:Chronic Disease; D004487:Edema / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000276:immunology / Q000503:physiopathology*; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism*; D007719:Knee Joint / Q000098:blood supply / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D050916:TRPV Cation Channels; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D007473:Ion Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D005620:Freund's Adjuvant