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-/-) mice and wild-type counterparts (TRPV1+/+). In TRPV1+/+ 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-/- 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
HOE-140 [D-arginyl-L-arginyl-L-prolyl-trans-4-hydroxy-L-prolylglycyl-3-(2-thyenyl)-L-alanyl-L-seryl-D-1,2,2,4-tetrahydro-3-isoquinolinecarbonyl-L-(2a,3b,7ab)-octahydro-1H-
indole-2-carbonyl-
L-arginine], or the B1 receptor antagonist desArgHOE-140 [D-arginyl-L-arginyl-L-prolyl-trans-4-hydroxy-L-prolylglycyl-3-(2-thyenyl)-L-alanyl-L-seryl-D-1,2,2,4-tetrahydro-3-isoquinolinecarbonyl-L-(2a,3b,7ab)-octahydro-1H-
indole-2-carbonyl] was performed to reveal what mediators might activate TRPV1. NDGA significantly inhibited
edema,
hyperalgesia, and
arthritis score in TRPV1+/+, but not in TRPV1-/- mice. The effect of
indomethacin was markedly smaller in knockouts. In TRPV1+/+ animals,
HOE-140, but not desArgHOE-140, inhibited
arthritis, whereas in TRPV1-/- mice,
HOE-140 produced limited effect. Thus, whereas
bradykinin and
lipoxygenase products seem to act exclusively via TRPV1 activation,
prostanoids do not, or at least only partially, to enhance murine
experimental arthritis and related
hyperalgesia.