investigating-migraine-like-behavior-using-light-aversion-in-mice

Investigating Migraine-Like Behavior Using Light Aversion in Mice

Migraine is a complex neurological disorder characterized by headache and sensory abnormalities, such as hypersensitivity to light, observed as ...

dural-stimulation-periorbital-von-frey-testing-mice-as-preclinical

Dural Stimulation and Periorbital von Frey Testing in Mice As a Preclinical Model of Headache

The cranial meninges, comprised of the dura mater, arachnoid, and pia mater, are thought to primarily serve structural functions for the nervous system.  ...

University of Texas at Dallas

Migraine is one of the most disabling disorders worldwide but the underlying mechanisms are poorly understood. Stress is consistently reported as a common trigger of migraine attacks. Here, we show that repeated stress in mice causes migraine-like behaviors that are responsive to a migraine therapeutic. Adult female and male mice were exposed to 2 hours of restraint stress for 3 consecutive days, after which they demonstrated facial mechanical hypersensitivity and facial grimace responses that were resolved by 14 days after stress. Hypersensitivity or grimace was not observed in either control animals or those stressed for only 1 day. After return to baseline, the nitric oxide donor sodium nitroprusside (SNP; 0.1 mg/kg) elicited mechanical hypersensitivity in stressed but not in control animals, demonstrating the presence of hyperalgesic priming. This suggests the presence of a migraine-like state, because nitric oxide donors are reliable triggers of attacks in migraine patients but not controls. The stress paradigm also caused priming responses to dural pH 7.0 treatment. The presence of this primed state after stress is not permanent because it was no longer present at 35 days after stress. Finally, mice received either the calcitonin gene-related peptide monoclonal antibody ALD405 (10 mg/kg) 24 hours before SNP or a coinjection of sumatriptan (0.6 mg/kg). ALD405, but not sumatriptan, blocked the facial hypersensitivity due to SNP. This stress paradigm in mice and the subsequent primed state caused by stress allow further preclinical investigation of mechanisms contributing to migraine, particularly those caused by common triggers of attacks.

Repetitive stress in mice causes migraine-like behaviors and calcitonin gene-related peptide-dependent hyperalgesic priming to a migraine trigger.

Calcitonin gene-related peptide is recognized as a key player in migraine, yet the mechanisms and sites of calcitonin gene-related peptide action remain unknown. The efficacy of calcitonin gene-related peptide-blocking antibodies as preventative migraine drugs supports a peripheral site of action, such as the trigeminovasculature. Given the apparent disconnect between the importance of vasodilatory peptides in migraine and the prevailing opinion that vasodilation is an epiphenomenon, the goal of this study was to test whether vasodilation plays a role in calcitonin gene-related peptide-induced light aversive behavior in mice.

Vascular actions of peripheral CGRP in migraine-like photophobia in mice.

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.

Meningeal CGRP-Prolactin Interaction Evokes Female-Specific Migraine Behavior.

Circadian patterns of migraine attacks have been reported by patients but remain understudied. In animal models, circadian phases are generally not taken into consideration. In particular, rodents are nocturnal animals, yet they are most often tested during their inactive phase during the day. This study aims to test the validity of CGRP-induced behavioral changes in mice by comparing responses during the active and inactive phases.

Bianca N. Mason

School of Behavioral and Brain Sciences,
School of Brain and Behavioral Sciences and Center for Advanced Pain Studies

University of Texas at Dallas

Investigating Migraine-Like Behavior Using Light Aversion in Mice

Dural Stimulation and Periorbital von Frey Testing in Mice As a Preclinical Model of Headache

Bianca N. Mason

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}School of Behavioral and Brain Sciences,School of Brain and Behavioral Sciences and Center for Advanced Pain Studies

University of Texas at Dallas

Investigating Migraine-Like Behavior Using Light Aversion in Mice

Dural Stimulation and Periorbital von Frey Testing in Mice As a Preclinical Model of Headache

School of Behavioral and Brain Sciences,
School of Brain and Behavioral Sciences and Center for Advanced Pain Studies