Progesterone distribution in the trigeminal system and its role to modulate sensory neurotransmission: influence of sex
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Progesterone distribution in the trigeminal system and its role to modulate sensory neurotransmission : influence of sex. / Maddahi, Aida; Warfvinge, Karin; Holm, Anja; Edvinsson, Jacob C.A.; Reducha, Philip Victor; Kazantzi, Spyridoula; Haanes, Kristian A.; Edvinsson, Lars.
In: Journal of Headache and Pain, Vol. 24, No. 1, 154, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Progesterone distribution in the trigeminal system and its role to modulate sensory neurotransmission
T2 - influence of sex
AU - Maddahi, Aida
AU - Warfvinge, Karin
AU - Holm, Anja
AU - Edvinsson, Jacob C.A.
AU - Reducha, Philip Victor
AU - Kazantzi, Spyridoula
AU - Haanes, Kristian A.
AU - Edvinsson, Lars
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Background: Women are disproportionately affected by migraine, representing up to 75% of all migraine cases. This discrepancy has been proposed to be influenced by differences in hormone levels between the sexes. One such hormone is progesterone. Calcitonin gene-related peptide (CGRP) system is an important factor in migraine pathophysiology and could be influenced by circulating hormones. The purpose of this study was to investigate the distribution of progesterone and its receptor (PR) in the trigeminovascular system, and to examine the role of progesterone to modulate sensory neurotransmission. Methods: Trigeminal ganglion (TG), hypothalamus, dura mater, and the basilar artery from male and female rats were carefully dissected. Expression of progesterone and PR proteins, and mRNA levels from TG and hypothalamus were analyzed by immunohistochemistry and real-time quantitative PCR. CGRP release from TG and dura mater were measured using an enzyme-linked immunosorbent assay. In addition, the vasomotor effect of progesterone on male and female basilar artery segments was investigated with myography. Results: Progesterone and progesterone receptor -A (PR-A) immunoreactivity were found in TG. Progesterone was located predominantly in cell membranes and in Aδ-fibers, and PR-A was found in neuronal cytoplasm and nucleus, and in satellite glial cells. The number of positive progesterone immunoreactive cells in the TG was higher in female compared to male rats. The PR mRNA was expressed in both hypothalamus and TG; however, the PR expression level was significantly higher in the hypothalamus. Progesterone did not induce a significant change neither in basal level nor upon stimulated release of CGRP from dura mater or TG in male or female rats when compared to the vehicle control. However, pre-treated with 10 µM progesterone weakly enhanced capsaicin induced CGRP release observed in the dura mater of male rats. Similarly, in male basilar arteries, progesterone significantly amplified the dilation in response to capsaicin. Conclusions: In conclusion, these results highlight the potential for progesterone to modulate sensory neurotransmission and vascular responses in a complex manner, with effects varying by sex, tissue type, and the nature of the stimulus. Further investigations are needed to elucidate the underlying mechanisms and physiological implications of these findings. Graphical Abstract: [Figure not available: see fulltext.].
AB - Background: Women are disproportionately affected by migraine, representing up to 75% of all migraine cases. This discrepancy has been proposed to be influenced by differences in hormone levels between the sexes. One such hormone is progesterone. Calcitonin gene-related peptide (CGRP) system is an important factor in migraine pathophysiology and could be influenced by circulating hormones. The purpose of this study was to investigate the distribution of progesterone and its receptor (PR) in the trigeminovascular system, and to examine the role of progesterone to modulate sensory neurotransmission. Methods: Trigeminal ganglion (TG), hypothalamus, dura mater, and the basilar artery from male and female rats were carefully dissected. Expression of progesterone and PR proteins, and mRNA levels from TG and hypothalamus were analyzed by immunohistochemistry and real-time quantitative PCR. CGRP release from TG and dura mater were measured using an enzyme-linked immunosorbent assay. In addition, the vasomotor effect of progesterone on male and female basilar artery segments was investigated with myography. Results: Progesterone and progesterone receptor -A (PR-A) immunoreactivity were found in TG. Progesterone was located predominantly in cell membranes and in Aδ-fibers, and PR-A was found in neuronal cytoplasm and nucleus, and in satellite glial cells. The number of positive progesterone immunoreactive cells in the TG was higher in female compared to male rats. The PR mRNA was expressed in both hypothalamus and TG; however, the PR expression level was significantly higher in the hypothalamus. Progesterone did not induce a significant change neither in basal level nor upon stimulated release of CGRP from dura mater or TG in male or female rats when compared to the vehicle control. However, pre-treated with 10 µM progesterone weakly enhanced capsaicin induced CGRP release observed in the dura mater of male rats. Similarly, in male basilar arteries, progesterone significantly amplified the dilation in response to capsaicin. Conclusions: In conclusion, these results highlight the potential for progesterone to modulate sensory neurotransmission and vascular responses in a complex manner, with effects varying by sex, tissue type, and the nature of the stimulus. Further investigations are needed to elucidate the underlying mechanisms and physiological implications of these findings. Graphical Abstract: [Figure not available: see fulltext.].
KW - CGRP
KW - Dura matter
KW - Migraine
KW - Progesterone
KW - Progesterone receptor
KW - Trigeminal ganglion
U2 - 10.1186/s10194-023-01687-x
DO - 10.1186/s10194-023-01687-x
M3 - Journal article
C2 - 37957603
AN - SCOPUS:85176456812
VL - 24
JO - Journal of Headache and Pain
JF - Journal of Headache and Pain
SN - 1129-2369
IS - 1
M1 - 154
ER -
ID: 373661011