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Vasopressin 1A and 1B receptor-mediated antinociception in a mouse model of cortical spreading depolarization.

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Τίτλος: Vasopressin 1A and 1B receptor-mediated antinociception in a mouse model of cortical spreading depolarization.
Συγγραφείς: Kwamo T; Boston University, Boston, MA, United States., Hancock M; Boston University, Boston, MA, United States., Kaya MZ; Neurovascular Research Unit, Massachusetts General Hospital, Boston, MA, United States., Olagundoye F; Boston University, Boston, MA, United States., Harriott AM; Neurovascular Research Unit, Massachusetts General Hospital, Boston, MA, United States.
Πηγή: Pain [Pain] 2026 Sep 01; Vol. 167 (9), pp. 2062-2072. Date of Electronic Publication: 2026 Jun 22.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 7508686 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-6623 (Electronic) Linking ISSN: 03043959 NLM ISO Abbreviation: Pain Subsets: MEDLINE
Imprint Name(s): Publication: 2015- : Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: Amsterdam, Elsevier/North-Holland.
Ιατρικοί όροι (MeSH): Receptors, Vasopressin*/metabolism , Cortical Spreading Depression*/drug effects , Cortical Spreading Depression*/physiology , Migraine Disorders*/drug therapy, Pyrrolidines/pharmacology ; Pyrrolidines/therapeutic use ; Antidiuretic Hormone Receptor Antagonists/pharmacology ; Hyperalgesia/drug therapy ; Animals ; Male ; Mice ; Disease Models, Animal ; Female ; Mice, Inbred C57BL ; Mice, Transgenic ; Indoles
Περίληψη: Abstract: The purpose of this study is to elucidate the role of vasopressin 1 receptors (V1Rs) in migraine with aura. Cortical spreading depolarization (SD) is a slow depolarizing wave that underlies migraine with aura, activates trigeminal nociceptors, and causes periorbital mechanical allodynia. Spreading depolarization increases fos expression in the hypothalamic paraventricular nucleus (PVN). The PVN contains oxytocin and vasopressin neurons, which bind vasopressin receptors. We examined the effect of selective vasopressin 1A receptor antagonist relcovaptan and vasopressin 1B receptor antagonist nelivaptan on SD-induced migraine-relevant behavior. Single optogenetic SD (opto-SD) was induced in male and female Thy1-ChR2-YFP adult mice that received either (10 mg/kg, i.p.) relcovaptan, nelivaptan, or vehicle immediately after SD. One hour later, periorbital mechanical thresholds were tested with von Frey monofilaments. Spontaneous pain was tested with face grimace and photosensitivity with grimace to increasing light exposure. Open field was used to test anxiety-like behavior and locomotion at 4 hours. Opto-SD decreased periorbital thresholds, which recovered by 4 hours. Opto-SD also increased grimace and resulted in an upward shift in the grimace-light intensity curve. Opto-SD produced modest reductions in distance traveled related to increased immobility episodes. These impairments were accompanied by an SD-mediated increase in activation of PVN neurons, of which subpopulations stained positive for vasopressin or oxytocin. Relcovaptan prevented recovery from opto-SD-induced periorbital allodynia. Similarly, nelivaptan also prevented recovery from opto-SD-induced periorbital allodynia. However, there was no effect of either drug on opto-SD-induced grimace, photosensitivity, or locomotion. These data are consistent with an analgesic effect of endogenous vasopressinergic receptor activation in a mouse model of migraine.
(Copyright © 2026 International Association for the Study of Pain.)
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Grant Information: 5K08NS124991 United States NS NINDS NIH HHS
Contributed Indexing: Keywords: Cortical spreading depolarization; Migraine with aura; Vasopressin receptor 1
Substance Nomenclature: 0 (Receptors, Vasopressin)
0 (Pyrrolidines)
0 (Antidiuretic Hormone Receptor Antagonists)
C1GL8G6G0O (relcovaptan)
0 (Indoles)
Entry Date(s): Date Created: 20260625 Date Completed: 20260819 Latest Revision: 20260825
Update Code: 20260825
DOI: 10.1097/j.pain.0000000000004025
PMID: 42350316
Βάση Δεδομένων: MEDLINE
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  Label: MeSH Terms
  Group: Su
  Data: <searchLink fieldCode="MM" term="%22Receptors%2C+Vasopressin%22">Receptors, Vasopressin*</searchLink>/<searchLink fieldCode="MM" term="%22Receptors%2C+Vasopressin+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Cortical+Spreading+Depression%22">Cortical Spreading Depression*</searchLink>/<searchLink fieldCode="MM" term="%22Cortical+Spreading+Depression+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Cortical+Spreading+Depression%22">Cortical Spreading Depression*</searchLink>/<searchLink fieldCode="MM" term="%22Cortical+Spreading+Depression+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Migraine+Disorders%22">Migraine Disorders*</searchLink>/<searchLink fieldCode="MM" term="%22Migraine+Disorders+drug+therapy%22">drug therapy</searchLink><br /><searchLink fieldCode="MH" term="%22Pyrrolidines%22">Pyrrolidines</searchLink>/<searchLink fieldCode="MH" term="%22Pyrrolidines+pharmacology%22">pharmacology</searchLink> ; <searchLink fieldCode="MH" term="%22Pyrrolidines%22">Pyrrolidines</searchLink>/<searchLink fieldCode="MH" term="%22Pyrrolidines+therapeutic+use%22">therapeutic use</searchLink> ; <searchLink fieldCode="MH" term="%22Antidiuretic+Hormone+Receptor+Antagonists%22">Antidiuretic Hormone Receptor Antagonists</searchLink>/<searchLink fieldCode="MH" term="%22Antidiuretic+Hormone+Receptor+Antagonists+pharmacology%22">pharmacology</searchLink> ; <searchLink fieldCode="MH" term="%22Hyperalgesia%22">Hyperalgesia</searchLink>/<searchLink fieldCode="MH" term="%22Hyperalgesia+drug+therapy%22">drug therapy</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Disease+Models%2C+Animal%22">Disease Models, Animal</searchLink> ; <searchLink fieldCode="MH" term="%22Female%22">Female</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%2C+Inbred+C57BL%22">Mice, Inbred C57BL</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%2C+Transgenic%22">Mice, Transgenic</searchLink> ; <searchLink fieldCode="MH" term="%22Indoles%22">Indoles</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Abstract: The purpose of this study is to elucidate the role of vasopressin 1 receptors (V1Rs) in migraine with aura. Cortical spreading depolarization (SD) is a slow depolarizing wave that underlies migraine with aura, activates trigeminal nociceptors, and causes periorbital mechanical allodynia. Spreading depolarization increases fos expression in the hypothalamic paraventricular nucleus (PVN). The PVN contains oxytocin and vasopressin neurons, which bind vasopressin receptors. We examined the effect of selective vasopressin 1A receptor antagonist relcovaptan and vasopressin 1B receptor antagonist nelivaptan on SD-induced migraine-relevant behavior. Single optogenetic SD (opto-SD) was induced in male and female Thy1-ChR2-YFP adult mice that received either (10 mg/kg, i.p.) relcovaptan, nelivaptan, or vehicle immediately after SD. One hour later, periorbital mechanical thresholds were tested with von Frey monofilaments. Spontaneous pain was tested with face grimace and photosensitivity with grimace to increasing light exposure. Open field was used to test anxiety-like behavior and locomotion at 4 hours. Opto-SD decreased periorbital thresholds, which recovered by 4 hours. Opto-SD also increased grimace and resulted in an upward shift in the grimace-light intensity curve. Opto-SD produced modest reductions in distance traveled related to increased immobility episodes. These impairments were accompanied by an SD-mediated increase in activation of PVN neurons, of which subpopulations stained positive for vasopressin or oxytocin. Relcovaptan prevented recovery from opto-SD-induced periorbital allodynia. Similarly, nelivaptan also prevented recovery from opto-SD-induced periorbital allodynia. However, there was no effect of either drug on opto-SD-induced grimace, photosensitivity, or locomotion. These data are consistent with an analgesic effect of endogenous vasopressinergic receptor activation in a mouse model of migraine.<br /> (Copyright © 2026 International Association for the Study of Pain.)
– Name: Ref
  Label: References
  Group: RefInfo
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– Name: GrantInfo
  Label: Grant Information
  Group: Grant
  Data: 5K08NS124991 United States NS NINDS NIH HHS
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>Cortical spreading depolarization; Migraine with aura; Vasopressin receptor 1
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Receptors, Vasopressin)<br />0 (Pyrrolidines)<br />0 (Antidiuretic Hormone Receptor Antagonists)<br />C1GL8G6G0O (relcovaptan)<br />0 (Indoles)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20260625 <i>Date Completed: </i>20260819 <i>Latest Revision: </i>20260825
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260825
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1097/j.pain.0000000000004025
– Name: AN
  Label: PMID
  Group: ID
  Data: 42350316
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42350316
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1097/j.pain.0000000000004025
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 2062
    Subjects:
      – SubjectFull: Pyrrolidines pharmacology
        Type: general
      – SubjectFull: Pyrrolidines therapeutic use
        Type: general
      – SubjectFull: Antidiuretic Hormone Receptor Antagonists pharmacology
        Type: general
      – SubjectFull: Hyperalgesia drug therapy
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Male
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Disease Models, Animal
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Mice, Inbred C57BL
        Type: general
      – SubjectFull: Mice, Transgenic
        Type: general
      – SubjectFull: Indoles
        Type: general
      – SubjectFull: Receptors, Vasopressin metabolism
        Type: general
      – SubjectFull: Cortical Spreading Depression drug effects
        Type: general
      – SubjectFull: Cortical Spreading Depression physiology
        Type: general
      – SubjectFull: Migraine Disorders drug therapy
        Type: general
    Titles:
      – TitleFull: Vasopressin 1A and 1B receptor-mediated antinociception in a mouse model of cortical spreading depolarization.
        Type: main
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              Text: 2026 Sep 01
              Type: published
              Y: 2026
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