• peptidergic afferent;
  • sympathetic postganglionic neuron;
  • sympathetically mediated pain

(Headache 2010;50:442-450)

Objective.— We examined the distribution of artemin and its receptor, glial cell line-derived neurotrophic factor family receptor α3 (GFRα3), 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, GFRα3, 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 GFRα3 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. GFRα3-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 GFRα3-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.