Distribution of artemin and GFRalpha3 labeled nerve fibers in the dura mater of rat: artemin and GFRalpha3 in the dura.
OBJECTIVE
We examined the distribution of artemin and its receptor, glial cell line-derived neurotrophic factor family receptor alpha3 (GFRalpha3), in the dura mater of rats.


BACKGROUND
Artemin, a member of the glial cell line-derived neurotrophic factor family, is a vasculature-derived growth factor shown to regulate migration of sympathetic neuroblasts and targeting of sympathetic innervation. The artemin receptor, GFRalpha3, is present in both sympathetic efferents and a subpopulation of nociceptive afferents. Recent evidence has shown that artemin may contribute to inflammatory hyperalgesia. The extent to which artemin is present in the dural vasculature and its relationship to GFRalpha3 containing fibers have yet to be investigated.


METHODS
We used retrograde labeling, double and triple labeling with immunohistochemistry on the dura mater and trigeminal ganglia of female Sprague-Dawley rats.


RESULTS
Artemin-like immunoreactivity (-LI) was detected in the smooth muscle of dural vasculature. GFRalpha3-LI was present in nerve fibers that closely associated with tyrosine hydroxylase or calcitonin gene-related peptide (CGRP). CGRP-LI and transient receptor potential ion channel 1 (TRPV1)-LI were present in all GFRalpha3-positive dural afferents, which constituted 22% of the total population of dural afferents.


CONCLUSIONS
These anatomical results support the hypothesis that artemin contributes to dural afferent activity, and possibly migraine pain, through modulation of both primary afferent and sympathetic systems.
Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA.
Lisa A
LA
McIlvried
Kathryn
K
Albers
Michael S
MS
Gold
D000344:Afferent Pathways / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D004388:Dura Mater / Q000098:blood supply* / Q000503:physiopathology; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008576:Meningeal Arteries / Q000294:innervation* / Q000503:physiopathology; D008881:Migraine Disorders / Q000378:metabolism* / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000294:innervation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism
C490887:Artn protein, rat; D009419:Nerve Tissue Proteins; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D015740:Calcitonin Gene-Related Peptide