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

J Headache Pain. 2016:17:40. doi: 10.1186/s10194-016-0624-y. Epub 2016 Apr 19.

Abstract

Background: This research sought to further validate the rat nitroglycerin (NTG) migraine model by comparing the effects of single versus recurrent NTG episodes on behavioral endpoints that mirror ICHD-3 diagnostic criteria for migraine, and to determine if the altered behavioral endpoints are reduced after administration of sumatriptan.

Methods: Separate cohorts of rats were administered NTG (10 mg/kg/2 ml) or saline (Experiment 1: single injection; Experiment 2: repeated injections; Experiment 3: repeated injections with sumatriptan [0.0, 0.3 and 1.0 mg/kg/ml] rescue. Behavioral endpoints were assessed 2 h after final NTG administration and included time in light/dark chambers for photophobia and activity, pain facial ratings, and cool (5 °C) and warm (46 °C) tail dip.

Results: The first two experiments demonstrated that repeated (n = 5) but not single NTG injections produced photophobia, decreased activity, and yielded less weight gain than saline injections. Experiment 3 showed that sumatriptan attenuated hypoactivity, reduced facial expressions of pain, and reversed weight alterations in a dose-dependent manner.

Conclusions: These findings identify numerous clinical homologies of a recurrent NTG rat migraine model that may be useful for screening novel pharmacotherapies.

Keywords: Animal models; Headache; Migraine; Nitroglycerin; Translational research.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Disease Models, Animal
  • Male
  • Migraine Disorders / chemically induced
  • Migraine Disorders / diagnosis*
  • Migraine Disorders / drug therapy
  • Motor Activity / drug effects*
  • Nitroglycerin*
  • Photophobia / chemically induced
  • Photophobia / diagnosis
  • Photophobia / drug therapy
  • Rats
  • Serotonin 5-HT1 Receptor Agonists / pharmacology
  • Serotonin 5-HT1 Receptor Agonists / therapeutic use
  • Sumatriptan / pharmacology
  • Sumatriptan / therapeutic use
  • Treatment Outcome
  • Vasodilator Agents*

Substances

  • Serotonin 5-HT1 Receptor Agonists
  • Vasodilator Agents
  • Sumatriptan
  • Nitroglycerin