Uterine cervical afferents in thoracolumbar dorsal root ganglia express transient receptor potential vanilloid type 1 channel and calcitonin gene-related peptide, but not P2X3 receptor and somatostatin.
BACKGROUND
Little is known regarding the phenotype of afferents that innervate the uterine cervix. Chronic estrogen sensitizes uterine cervical afferents to mechanical distension, but whether this reflects changes in afferent neurotransmitter or excitatory ion channel expression is unknown. The authors used immunocytochemistry to characterize uterine cervical afferents and the effects of estrogen on them.


METHODS
Fluorogold was injected into the uterine cervix of intact rats (n = 7) and those with ovariectomy alone (n = 9) or with estrogen supplementation (n = 8). Bilateral dorsal root ganglia at T12-L2 were removed and immunostained for transient receptor potential vanilloid type 1 (TRPV1), P2X3 receptor, calcitonin gene-related peptide, and somatostatin. The proportion of fluorogold-traced dorsal root ganglion neurons expressing each of these markers was compared with untraced neurons.


RESULTS
Most fluorogold-traced cells were found at L1 (> 55%) and were of small diameter (24 microm). TRPV1 expression was similar between traced and untraced cells, except the estrogen treatment increased TRPV1 expression in traced cells. Calcitonin gene-related peptide expression was greater in traced than in untraced cells, with no effect of experimental treatment. No traced cells expressed the P2X3 receptor or somatostatin, although each of these was present in untraced cells.


CONCLUSIONS
Uterine cervical afferents in the hypogastric nerve express TRPV1, an important nociceptive channel, which may play a role in estrogen-induced sensitization of cervical afferents. High expression of calcitonin gene-related peptide suggests a sensory and efferent role for this peptide. In contrast to other viscera, these afferents do not express somatostatin or P2X3 receptor, indicating a unique phenotype of these C fibers.
Department of Anesthesiology and Pain Mechanisms Laboratory, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. ctong@wfubmc.edu
Chuanyao
C
Tong
Dawn
D
Conklin
Brittany B
BB
Clyne
Jennifer D
JD
Stanislaus
James C
JC
Eisenach
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis*; D002584:Cervix Uteri / Q000294:innervation*; D004967:Estrogens / Q000502:physiology; D005260:Female; D005727:Ganglia, Spinal / Q000737:chemistry*; D007150:Immunohistochemistry; D009475:Neurons, Afferent / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000032:analysis*; D058477:Receptors, Purinergic P2X3; D013004:Somatostatin / Q000032:analysis*; D050916:TRPV Cation Channels / Q000032:analysis*
D004967:Estrogens; C546410:P2rx3 protein, rat; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide