PMID- 33749851
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20240211
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 89
IP  - 6
DP  - 2021 Jun
TI  - Meningeal CGRP-Prolactin Interaction Evokes Female-Specific Migraine Behavior.
PG  - 1129-1144
LID - 10.1002/ana.26070 [doi]
AB  - OBJECTIVE: Migraine is three times more common in women. CGRP plays a critical 
      role in migraine pathology and causes female-specific behavioral responses upon 
      meningeal application. These effects are likely mediated through interactions of 
      CGRP with signaling systems specific to females. Prolactin (PRL) levels have been 
      correlated with migraine attacks. Here, we explore a potential interaction 
      between CGRP and PRL in the meninges. METHODS: Prolactin, CGRP, and receptor 
      antagonists CGRP8-37 or Delta1-9-G129R-hPRL were administered onto the dura of 
      rodents followed by behavioral testing. Immunohistochemistry was used to examine 
      PRL, CGRP and Prolactin receptor (Prlr) expression within the dura. 
      Electrophysiology on cultured and back-labeled trigeminal ganglia (TG) neurons 
      was used to assess PRL-induced excitability. Finally, the effects of PRL on 
      evoked CGRP release from ex vivo dura were measured. RESULTS: We found that dural 
      PRL produced sustained and long-lasting migraine-like behavior in cycling and 
      ovariectomized female, but not male rodents. Prlr was expressed on dural afferent 
      nerves in females with little-to-no presence in males. Consistent with this, PRL 
      increased excitability only in female TG neurons innervating the dura and 
      selectively sensitized CGRP release from female ex vivo dura. We demonstrate 
      crosstalk between PRL and CGRP systems as CGRP8-37 decreases migraine-like 
      responses to dural PRL. Reciprocally, Delta1-9-G129R-hPRL attenuates dural 
      CGRP-induced migraine behaviors. Similarly, Prlr deletion from sensory neurons 
      significantly reduced migraine-like responses to dural CGRP. INTERPRETATION: This 
      CGRP-PRL interaction in the meninges is a mechanism by which these peptides could 
      produce female-selective responses and increase the prevalence of migraine in 
      women. ANN NEUROL 2021;89:1129-1144.
CI  - (c) 2021 American Neurological Association.
FAU - Avona, Amanda
AU  - Avona A
AUID- ORCID: 0000-0003-4155-8484
AD  - Department of Neuroscience, Center for Advanced Pain Studies, University of Texas 
      at Dallas, Richardson, TX.
FAU - Mason, Bianca N
AU  - Mason BN
AD  - Department of Neuroscience, Center for Advanced Pain Studies, University of Texas 
      at Dallas, Richardson, TX.
FAU - Burgos-Vega, Carolina
AU  - Burgos-Vega C
AD  - Department of Neuroscience, Center for Advanced Pain Studies, University of Texas 
      at Dallas, Richardson, TX.
FAU - Hovhannisyan, Anahit H
AU  - Hovhannisyan AH
AD  - Department of Endodontics, University of Texas Health Science Center at San 
      Antonio, San Antonio, TX.
FAU - Belugin, Sergei N
AU  - Belugin SN
AD  - Department of Endodontics, University of Texas Health Science Center at San 
      Antonio, San Antonio, TX.
FAU - Mecklenburg, Jennifer
AU  - Mecklenburg J
AD  - Department of Endodontics, University of Texas Health Science Center at San 
      Antonio, San Antonio, TX.
FAU - Goffin, Vincent
AU  - Goffin V
AD  - Inserm U1151, Universite Paris Descartes, Paris, France.
FAU - Wajahat, Naureen
AU  - Wajahat N
AUID- ORCID: 0000-0001-6623-7893
AD  - Department of Neuroscience, Center for Advanced Pain Studies, University of Texas 
      at Dallas, Richardson, TX.
FAU - Price, Theodore J
AU  - Price TJ
AD  - Department of Neuroscience, Center for Advanced Pain Studies, University of Texas 
      at Dallas, Richardson, TX.
FAU - Akopian, Armen N
AU  - Akopian AN
AD  - Department of Endodontics, University of Texas Health Science Center at San 
      Antonio, San Antonio, TX.
FAU - Dussor, Gregory
AU  - Dussor G
AD  - Department of Neuroscience, Center for Advanced Pain Studies, University of Texas 
      at Dallas, Richardson, TX.
LA  - eng
GR  - R01 NS065926/NS/NINDS NIH HHS/United States
GR  - R01 NS072204/NS/NINDS NIH HHS/United States
GR  - R01 NS102161/NS/NINDS NIH HHS/United States
GR  - R01 NS104200/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210422
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 9002-62-4 (Prolactin)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
SB  - IM
CIN - Nat Rev Neurol. 2021 May;17(5):261. PMID: 33828293
MH  - Animals
MH  - Calcitonin Gene-Related Peptide/*metabolism
MH  - Female
MH  - Male
MH  - Meninges/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred ICR
MH  - Migraine Disorders/*metabolism
MH  - Prolactin/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sex Characteristics
PMC - PMC8195469
MID - NIHMS1703764
COIS- Potential Conflicts of Interest Nothing to report.
EDAT- 2021/03/23 06:00
MHDA- 2021/08/03 06:00
PMCR- 2022/06/01
CRDT- 2021/03/22 12:51
PHST- 2021/03/18 00:00 [revised]
PHST- 2020/07/22 00:00 [received]
PHST- 2021/03/19 00:00 [accepted]
PHST- 2021/03/23 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2021/03/22 12:51 [entrez]
PHST- 2022/06/01 00:00 [pmc-release]
AID - 10.1002/ana.26070 [doi]
PST - ppublish
SO  - Ann Neurol. 2021 Jun;89(6):1129-1144. doi: 10.1002/ana.26070. Epub 2021 Apr 22.