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Sex influences the progression of cephalic mechanical and light hypersensitivities in a mouse model of chronic migraine.

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Title: Sex influences the progression of cephalic mechanical and light hypersensitivities in a mouse model of chronic migraine.
Authors: Raquin, Marie (AUTHOR), Mrad, Yara (AUTHOR), Zkim, Mohamed A. (AUTHOR), Dallel, Radhouane (AUTHOR), Ranchon‐Cole, Isabelle (AUTHOR), Alba‐Delgado, Cristina (AUTHOR)
Source: Headache: The Journal of Head & Face Pain. Oct2025, Vol. 65 Issue 9, p1603-1616. 14p.
Subjects: Propranolol, Sensory defensiveness, Light, Sumatriptan, Intraperitoneal injections, T-test (Statistics), Data analysis, Research funding, Sex distribution, Touch, Brain, Two-way analysis of variance, Allergies, Descriptive statistics, Chronic diseases, Mice, Experimental design, Animal experimentation, Drug efficacy, Statistics, Data analysis software, Disease progression, Migraine, Allodynia, Evaluation
Abstract: Objectives/Background: Our aim was to compare the temporal dynamics of light and cephalic mechanical sensitivities in male and female mice as they relate to migraine chronicization. Cutaneous and light hypersensitivities are among the most common features of migraine, with greater severity observed in females. In 3% of patients, episodic migraine progresses to a chronic form, and sensory hypersensitivity becomes persistent. The pathophysiology underlying this transformation is complex and not fully understood. Moreover, studies comparing the evolution of sensory hypersensitivity between sexes are scarce. Methods: Systemic administration of isosorbide dinitrate (ISDN, 10 mg/kg) was used to induce migraine‐like behaviors in C57BL/6 mice. Cephalic sensitivity was assessed using periorbital von Frey testing. Light sensitivity was evaluated using the elevated plus maze and light/dark box paradigms. The effectiveness of current migraine treatments, sumatriptan (1 mg/kg) and propranolol (20 mg/kg), was also evaluated. Results: A single ISDN injection induced transient cephalic mechanical hypersensitivity in both males and females, with no sex differences observed. Acute treatment with sumatriptan effectively blocked this hypersensitivity, showing similar efficacy in both sexes. Notably, light hypersensitivity was induced exclusively in acute ISDN‐treated females, developing earlier, and persisting longer than cephalic mechanical hypersensitivity. Repeated ISDN administration resulted in persistent and dose‐dependent sensory hypersensitivity in both sexes. Interestingly, the chronicization patterns were sex‐specific; ISDN‐treated females developed persistent light and cephalic mechanical hypersensitivities simultaneously, whereas ISDN‐treated males showed delayed light aversion. Prophylactic treatment with propranolol prevented the chronicity of cephalic mechanical hypersensitivity in both sexes, and partially attenuated acute ISDN‐induced mechanical and light hypersensitivities. Conclusion: The progression from acute to chronic ISDN‐induced cephalic mechanical and light hypersensitivities has sex‐specific characteristics that mimic the clinical features of migraine. These findings support the involvement of distinct underlying mechanisms and highlight the need for tailored treatment strategies to optimize migraine management in both male and female populations. Plain Language Summary: This study examines how sensory sensitivity symptoms changed over time in a migraine‐like mouse model. Female mice developed sensitivity to touch and light more quickly and intensely than male mice. These findings underscore the importance of considering sex differences in future migraine research. [ABSTRACT FROM AUTHOR]
Copyright of Headache: The Journal of Head & Face Pain is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
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  Label: Title
  Group: Ti
  Data: Sex influences the progression of cephalic mechanical and light hypersensitivities in a mouse model of chronic migraine.
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  Label: Authors
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  Data: <searchLink fieldCode="AR" term="%22Raquin%2C+Marie%22">Raquin, Marie</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mrad%2C+Yara%22">Mrad, Yara</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zkim%2C+Mohamed+A%2E%22">Zkim, Mohamed A.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dallel%2C+Radhouane%22">Dallel, Radhouane</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ranchon‐Cole%2C+Isabelle%22">Ranchon‐Cole, Isabelle</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Alba‐Delgado%2C+Cristina%22">Alba‐Delgado, Cristina</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Headache%3A+The+Journal+of+Head+%26+Face+Pain%22">Headache: The Journal of Head & Face Pain</searchLink>. Oct2025, Vol. 65 Issue 9, p1603-1616. 14p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Propranolol%22">Propranolol</searchLink><br /><searchLink fieldCode="DE" term="%22Sensory+defensiveness%22">Sensory defensiveness</searchLink><br /><searchLink fieldCode="DE" term="%22Light%22">Light</searchLink><br /><searchLink fieldCode="DE" term="%22Sumatriptan%22">Sumatriptan</searchLink><br /><searchLink fieldCode="DE" term="%22Intraperitoneal+injections%22">Intraperitoneal injections</searchLink><br /><searchLink fieldCode="DE" term="%22T-test+%28Statistics%29%22">T-test (Statistics)</searchLink><br /><searchLink fieldCode="DE" term="%22Data+analysis%22">Data analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Research+funding%22">Research funding</searchLink><br /><searchLink fieldCode="DE" term="%22Sex+distribution%22">Sex distribution</searchLink><br /><searchLink fieldCode="DE" term="%22Touch%22">Touch</searchLink><br /><searchLink fieldCode="DE" term="%22Brain%22">Brain</searchLink><br /><searchLink fieldCode="DE" term="%22Two-way+analysis+of+variance%22">Two-way analysis of variance</searchLink><br /><searchLink fieldCode="DE" term="%22Allergies%22">Allergies</searchLink><br /><searchLink fieldCode="DE" term="%22Descriptive+statistics%22">Descriptive statistics</searchLink><br /><searchLink fieldCode="DE" term="%22Chronic+diseases%22">Chronic diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Mice%22">Mice</searchLink><br /><searchLink fieldCode="DE" term="%22Experimental+design%22">Experimental design</searchLink><br /><searchLink fieldCode="DE" term="%22Animal+experimentation%22">Animal experimentation</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+efficacy%22">Drug efficacy</searchLink><br /><searchLink fieldCode="DE" term="%22Statistics%22">Statistics</searchLink><br /><searchLink fieldCode="DE" term="%22Data+analysis+software%22">Data analysis software</searchLink><br /><searchLink fieldCode="DE" term="%22Disease+progression%22">Disease progression</searchLink><br /><searchLink fieldCode="DE" term="%22Migraine%22">Migraine</searchLink><br /><searchLink fieldCode="DE" term="%22Allodynia%22">Allodynia</searchLink><br /><searchLink fieldCode="DE" term="%22Evaluation%22">Evaluation</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Objectives/Background: Our aim was to compare the temporal dynamics of light and cephalic mechanical sensitivities in male and female mice as they relate to migraine chronicization. Cutaneous and light hypersensitivities are among the most common features of migraine, with greater severity observed in females. In 3% of patients, episodic migraine progresses to a chronic form, and sensory hypersensitivity becomes persistent. The pathophysiology underlying this transformation is complex and not fully understood. Moreover, studies comparing the evolution of sensory hypersensitivity between sexes are scarce. Methods: Systemic administration of isosorbide dinitrate (ISDN, 10 mg/kg) was used to induce migraine‐like behaviors in C57BL/6 mice. Cephalic sensitivity was assessed using periorbital von Frey testing. Light sensitivity was evaluated using the elevated plus maze and light/dark box paradigms. The effectiveness of current migraine treatments, sumatriptan (1 mg/kg) and propranolol (20 mg/kg), was also evaluated. Results: A single ISDN injection induced transient cephalic mechanical hypersensitivity in both males and females, with no sex differences observed. Acute treatment with sumatriptan effectively blocked this hypersensitivity, showing similar efficacy in both sexes. Notably, light hypersensitivity was induced exclusively in acute ISDN‐treated females, developing earlier, and persisting longer than cephalic mechanical hypersensitivity. Repeated ISDN administration resulted in persistent and dose‐dependent sensory hypersensitivity in both sexes. Interestingly, the chronicization patterns were sex‐specific; ISDN‐treated females developed persistent light and cephalic mechanical hypersensitivities simultaneously, whereas ISDN‐treated males showed delayed light aversion. Prophylactic treatment with propranolol prevented the chronicity of cephalic mechanical hypersensitivity in both sexes, and partially attenuated acute ISDN‐induced mechanical and light hypersensitivities. Conclusion: The progression from acute to chronic ISDN‐induced cephalic mechanical and light hypersensitivities has sex‐specific characteristics that mimic the clinical features of migraine. These findings support the involvement of distinct underlying mechanisms and highlight the need for tailored treatment strategies to optimize migraine management in both male and female populations. Plain Language Summary: This study examines how sensory sensitivity symptoms changed over time in a migraine‐like mouse model. Female mice developed sensitivity to touch and light more quickly and intensely than male mice. These findings underscore the importance of considering sex differences in future migraine research. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Headache: The Journal of Head & Face Pain is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=188480392
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1111/head.15015
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 14
        StartPage: 1603
    Subjects:
      – SubjectFull: Propranolol
        Type: general
      – SubjectFull: Sensory defensiveness
        Type: general
      – SubjectFull: Light
        Type: general
      – SubjectFull: Sumatriptan
        Type: general
      – SubjectFull: Intraperitoneal injections
        Type: general
      – SubjectFull: T-test (Statistics)
        Type: general
      – SubjectFull: Data analysis
        Type: general
      – SubjectFull: Research funding
        Type: general
      – SubjectFull: Sex distribution
        Type: general
      – SubjectFull: Touch
        Type: general
      – SubjectFull: Brain
        Type: general
      – SubjectFull: Two-way analysis of variance
        Type: general
      – SubjectFull: Allergies
        Type: general
      – SubjectFull: Descriptive statistics
        Type: general
      – SubjectFull: Chronic diseases
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Experimental design
        Type: general
      – SubjectFull: Animal experimentation
        Type: general
      – SubjectFull: Drug efficacy
        Type: general
      – SubjectFull: Statistics
        Type: general
      – SubjectFull: Data analysis software
        Type: general
      – SubjectFull: Disease progression
        Type: general
      – SubjectFull: Migraine
        Type: general
      – SubjectFull: Allodynia
        Type: general
      – SubjectFull: Evaluation
        Type: general
    Titles:
      – TitleFull: Sex influences the progression of cephalic mechanical and light hypersensitivities in a mouse model of chronic migraine.
        Type: main
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            NameFull: Raquin, Marie
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            NameFull: Mrad, Yara
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            NameFull: Zkim, Mohamed A.
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            NameFull: Dallel, Radhouane
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            NameFull: Ranchon‐Cole, Isabelle
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          Dates:
            – D: 01
              M: 10
              Text: Oct2025
              Type: published
              Y: 2025
          Identifiers:
            – Type: issn-print
              Value: 00178748
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              Value: 65
            – Type: issue
              Value: 9
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