No Gastrointestinal Dysmotility in Transgenic Mouse Models of Migraine

Headache. 2020 Feb;60(2):396-404. doi: 10.1111/head.13724. Epub 2019 Dec 26.

Abstract

Objective: To determine whether transgenic mouse models of migraine exhibit upper gastrointestinal dysmotility comparable to those observed in migraine patients.

Background: There is considerable evidence supporting the comorbidity of gastrointestinal dysmotility and migraine. Gastrointestinal motility, however, has never been investigated in transgenic mouse models of migraine.

Methods: Three transgenic mouse strains that express pathogenic gene mutations linked to monogenic migraine-relevant phenotypes were studied: CADASIL (Notch3-Tg88), FASP (CSNK1D-T44A), and FHM1 (CACNA1A-S218L). Upper gastrointestinal motility was quantified by measuring gastric emptying and small intestinal transit in mutant and control animals. Gastrointestinal motility was measured at baseline and after pretreatment with 10 mg/kg nitroglycerin (NTG).

Results: No significant differences were observed for gastric emptying or small intestinal transit at baseline for any of the 3 transgenic strains when compared to appropriate controls or after pretreatment with NTG when compared to vehicle.

Conclusions: We detected no evidence of upper gastrointestinal dysmotility in mice that express mutations in genes linked to monogenic migraine-relevant phenotypes. Future studies seeking to understand why humans with migraine experience delayed gastric emptying may benefit from pursuing other modifiers of gastrointestinal motility, such as epigenetic or microbiome-related factors.

Keywords: gastrointestinal motility; gastroparesis; headache; migraine.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Female
  • Gastrointestinal Diseases* / etiology
  • Gastrointestinal Motility*
  • Male
  • Mice
  • Mice, Transgenic
  • Migraine Disorders* / complications
  • Migraine Disorders* / genetics