Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation

Julie Keeble, Fiona Russell, Bradley Curtis, Anna Starr, E. Pintér, Susan D. Brain

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

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 IS 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 α (TNFα) was involved in influencing TRPV1 activation was investigated in separate experiments. Results. Increased levels of knee swelling, hyperpermeability, leukocyte accumulation, and TNFα were found in WT mice IS hours after IA CFA treatment compared with saline treatment. Significantly less knee swelling and hyperpermeability were found in TRPV1-/- mice, but leukocyte accumulation and TNFα 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 TNFα. Conclusion. 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.

Original languageEnglish
Pages (from-to)3248-3256
Number of pages9
JournalArthritis and Rheumatism
Volume52
Issue number10
DOIs
Publication statusPublished - Oct 2005

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Blood Vessels
Joints
Inflammation
Knee
Tumor Necrosis Factor-alpha
Knee Joint
Leukocytes
Hot Temperature
vanilloid receptor subtype 1
Intra-Articular Injections
Freund's Adjuvant
Synovial Fluid
Hyperalgesia
Knockout Mice
Peroxidase
Albumins
Neutrophils
Therapeutics
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation. / Keeble, Julie; Russell, Fiona; Curtis, Bradley; Starr, Anna; Pintér, E.; Brain, Susan D.

In: Arthritis and Rheumatism, Vol. 52, No. 10, 10.2005, p. 3248-3256.

Research output: Contribution to journalArticle

Keeble, Julie ; Russell, Fiona ; Curtis, Bradley ; Starr, Anna ; Pintér, E. ; Brain, Susan D. / Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation. In: Arthritis and Rheumatism. 2005 ; Vol. 52, No. 10. pp. 3248-3256.
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