Increased expression of CGRP in sensory afferents of arthritic mice--effect of genetic deletion of the vanilloid receptor TRPV1.
The neuropeptide calcitonin gene-related peptide (CGRP), expressed by nociceptive sensory afferents in joints, is an important mediator in the pathogenesis of arthritis. Capsaicin causes neurons in the dorsal root ganglia (DRG) to release CGRP from their central and/or peripheral axons, suggesting a functional link between CGRP and the capsaicin receptor TRPV1. The expression of both TRPV1 and CGRP have been reported to increase in several models of arthritis but the specific involvement of TRPV1-expressing articular afferents that can release CGRP remains unclear. We here wanted to ascertain whether the increase in the number of CGRP-positive primary afferents during arthritis may be affected by genetic deletion of TRPV1. For this, we quantified the expression of CGRP in primary afferent neurons in DRG in wild type mice (WT) vs. TRPV1-KO mice with adjuvant-induced arthritis (AIA), using immunohistochemistry. We found that the fraction of DRG neurons that were immunopositive for CGRP (1) was higher in naïve TRPV1-KO mice than in naïve WT mice, (2) increased progressively 3-21 days after induction of AIA, and (3) this increase was bilateral but significantly greater on the complete Freund's adjuvant-injected side than on the incomplete Freund's adjuvant-injected side in TRPV1-KO mice. The increased expression of CGRP in AIA may reflect a phenotypic switch of primary afferents from non-peptidergic to peptidergic and the larger increase in TRPV1-KO mice may represent a plastic change to compensate for the missing receptor in a major sensory circuit.
Chen
Yong
Y
Department of Cell and Developmental Biology, University of North Carolina, CB# 7090, Chapel Hill, NC 27599, USA.
Willcockson
Helen H
HH
Valtschanoff
Juli G
JG
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism
D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D015740:Calcitonin Gene-Related Peptide
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