Clinically relevant behavioral endpoints in a recurrent nitroglycerin migraine model in rats

Sufka, Kenneth J.; Staszko, Stephanie M.; Johnson, Ainslee; Davis, Morgan E.; Davis, Rachel; Smitherman, Todd A.

doi:10.1186/s10194-016-0624-y

Cited by 70 publications

(60 citation statements)

References 27 publications

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“…We have tested the effects of chronic NTG in a warm water tail immersion assay (46-48°C) (Pradhan, Smith, Zyuzin, et al, 2014), and we see similar changes in pain sensitivity. In addition, others have reported that acute and chronic NTG can produce light aversion, which models the photophobia associated with migraine (Farajdokht, Babri, Karimi, & Mohaddes, 2016; Markovics et al, 2012; Sufka et al, 2016). Taken together, multiple lines of evidence indicate that NTG administration in rodents can be used to effectively model migraine-associated behaviors.…”

Section: Commentarymentioning

confidence: 99%

Animal Model of Chronic Migraine‐Associated Pain

Moye

Pradhan

2017

CP Neuroscience

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Migraine is a debilitating condition that affects hundreds of millions of people worldwide. A subset of these patients experience chronic migraine, resulting in long-term disability and a severely lowered quality of life. The development of novel migraine therapies has been slow, partially due to the small number of predictive animal models. We have recently developed a novel model of chronic migraine-associated pain, using the known human migraine trigger, nitroglycerin. Injection of nitroglycerin evokes an acute mechanical hyperalgesia, which is sensitive to the acute migraine therapy sumatriptan. In addition, chronic administration of nitroglycerin produces a progressive and sustained decrease in basal mechanical responses; and this hypersensitivity is blocked by migraine preventatives such as topiramate. This mouse model of chronic migraine can be used to study the mechanisms underlying progression of migraine from an episodic to a chronic disorder, and for identifying and screening novel acute and preventive migraine therapies.

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Section: Commentarymentioning

confidence: 99%

Animal Model of Chronic Migraine‐Associated Pain

Moye

Pradhan

2017

CP Neuroscience

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“…A number of studies have used depression of activity (e.g., locomotor activity, feeding, rearing) to assess pain resulting from headache in humans [18] and rodents [7, 9, 17, 20, 28]. The problem with these studies is that assessment was limited to 60 min or less making it impossible to quantify the full duration and magnitude of the migraine.…”

Section: Introductionmentioning

confidence: 99%

Depression of home cage wheel running: a reliable and clinically relevant method to assess migraine pain in rats

2017

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BackgroundThe development of new anti-migraine treatments is limited by the difficulty inassessing migraine pain in laboratory animals. Depression of activity is one of the few diagnostic criteria formigraine that can be mimicked in rats. The goal of the present study was to test the hypothesis thatdepression of home cage wheel running is a reliable and clinically relevant method to assess migraine painin rats.MethodsAdult female rats were implanted with a cannula to inject allyl isothiocyanate (AITC) onto the dura to induce migraine pain, as has been shown before. Rats recovered from implantation surgery for 8 days in cages containing a running wheel. Home cage wheel running was recorded 23 h a day. AITC and the migraine medication sumatriptan were administered in the hour prior to onset of the dark phase.ResultsAdministration of AITC caused a concentration-dependent decrease in wheel running that lasted 3 h. The duration and magnitude of AITC-induced depression of wheel running was consistent following three repeated injections spaced 48 h apart. Administration of sumatriptan attenuated AITC-induced depressionof wheel running when a large dose (1 mg/kg) was administered immediately following AITC administration. Wheel running patterns did not change when sumatriptan was given to naïve rats.ConclusionsThese data indicate that home cage wheel running is a sensitive, reliable, and clinically relevant method to assess migraine pain in the rat.

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“…CADASIL and FASP animals received serial NTG injections on Days 0, 2, 4, 6, and 8 (the day of the gastrointestinal motility procedure), similar to prior reports in mice 43 and rats, 44,45 with the intent to maximize the effects of pretreatment with NTG. CADASIL and FASP animals received serial NTG injections on Days 0, 2, 4, 6, and 8 (the day of the gastrointestinal motility procedure), similar to prior reports in mice 43 and rats, 44,45 with the intent to maximize the effects of pretreatment with NTG.…”

Section: Methodsmentioning

confidence: 99%

No Gastrointestinal Dysmotility in Transgenic Mouse Models of Migraine

et al. 2019

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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.Abbreviations: CADASIL cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, FASP familial advanced sleep phase, FHM familial hemiplegic migraine, IBS irritable bowel syndrome, IG idiopathic gastroparesis, NTG nitroglycerin (Headache 2020;60:396-404) Headache

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Clinically relevant behavioral endpoints in a recurrent nitroglycerin migraine model in rats

Cited by 70 publications

References 27 publications

Animal Model of Chronic Migraine‐Associated Pain

Animal Model of Chronic Migraine‐Associated Pain

Depression of home cage wheel running: a reliable and clinically relevant method to assess migraine pain in rats

No Gastrointestinal Dysmotility in Transgenic Mouse Models of Migraine

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