Role of Transient Receptor Potential Vanilloid 1 Receptors in Adjuvant-Induced Chronic Arthritis: In Vivo Study Using Gene-Deficient Mice

Abstract

The transient receptor potential vanilloid 1 (TRPV1) receptor is a nonselective cation channel localized on a subset of primary sensory neurons and can be activated by a wide range of stimuli. The present study investigated the role of this receptor in chronic arthritis evoked by complete Freund's adjuvant (CFA) using TRPV1 receptor gene-deleted (TRPV1 Ϫ/Ϫ ) mice and wildtype counterparts (TRPV1 ϩ/ϩ ). In TRPV1 ϩ/ϩ mice, CFA injected intraplantarly into the left hindpaw and the root of the tail induced swelling of the injected and contralateral paws up to 130 and 28%, respectively, measured by plethysmometry throughout 18 days. Mechanonociceptive threshold measured with dynamic plantar aesthesiometry was decreased by 50 and 18% on the injected and contralateral paws, respectively. Histological examination and scoring of the tibiotarsal joints revealed marked arthritic changes in wild-type mice. In TRPV1 Ϫ/Ϫ animals edema, histological score and mechanical allodynia were significantly smaller. Daily treatment with the lipoxygenase inhibitor nordihydroguaretic acid (NDGA), the cyclooxygenase inhibitor indomethacin, the bradykinin B2 receptor antagonist

TRPV1 Gates Tissue Access and Sustains Pathogenicity in Autoimmune Encephalitis

“…Abnormal TRPV1 activity can alter the severity and progression of peripheral inflammatory conditions dramatically, including type 1 diabetes (T1D), colitis and arthritis, through mechanisms largely mediated by its local efferent secretory function: too little in T1D, too much in colitis and arthritis (14)(15)(16).…”

Mechanisms of Prolonged Presynaptic Ca2+Signaling and Glutamate Release Induced by TRPV1 Activation in Rat Sensory Neurons

“…This includes noxious heat, protons, lipid-derived endovanilloids, and inflammatory mediators (Caterina and Julius, 2001;De Petrocellis and Di Marzo, 2005). Behavioral studies using TRPV1 knock-out mice or selective TRPV1 antagonists have indicated that the receptor is involved in the development of various chronic pain conditions, including those associated with cancer, arthritis, irritable bowel syndrome, and migraine (Caterina et al, 2000;Davis et al, 2000;Akerman et al, 2004;Ghilardi et al, 2005;Jones et al, 2005;Szabo et al, 2005). Accordingly, TRPV1 presents an attractive target for analgesics, and several TRPV1 antagonists are currently under preclinical investigation or clinical trials (Immke and Gavva, 2006;Szallasi et al, 2007).…”

The endocannabinoid system in pain and inflammation: Its relevance to rheumatic disease

“…The importance of these receptors in arthritis is highlighted in TRPV1-/-knockout animals that demonstrate elevations in pain threshold and an associated reduction in joint inflammation (46). In addition to enhanced neurotransmitter release, stimulation of TRPV1 is associated with increases in inflammatory mediators contributing to joint inflammation (47).…”