Premium
Characterization of VR1 within the BMBF‐Leitproject: ‘Molecular Pain Research’
Author(s) -
Jostock R.,
Christoph T.,
Schiene K.,
Behrendt H.J.,
Kurreck J.,
Grünweller A.,
Erdmann V. A.,
Jahnel R.,
Hucho F.,
Gillen C.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.85.s2.4_4.x
Subject(s) - capsazepine , chemistry , neuropathic pain , allodynia , hyperalgesia , trpv1 , anandamide , receptor , pharmacology , nociception , antagonist , transient receptor potential channel , cannabinoid receptor , medicine , biochemistry
The vanilloid receptor VR1 is a ligand, heat and proton gated ion channel, expressed predominantly by primary sensory neurons. We show the molecular characterization of VR1 and its involvement in nociceptive behavior. Biochemical analysis of VR1 showed glycosylation at N604 and the predicted tetrameric structure. Reduced pH potentiated the gating of the receptor by NADA and anandamide in recombinant VR1. Acidification could sensitize VR1 and lead to hyperalgesia. Therefore, the VR1 antagonist capsazepine was tested in several animal models. Capsazepine reduced formalin induced nocifensive behavior and CFA induced mechanical hyperalgesia, and was antiallodynic and antihyperalgesic in animal models of neuropathic pain. VR1 antisense oligonucleotides inhibited VR1 expression in vitro and reduced tactile allodynia in vivo . In conclusion, we could provide evidence for a role of VR1 in inflammatory and neuropathic pain pathways.