Mark O. Urban 1, Yangmiao Zhang 1, Matia Ciklic 1, Christopher Conrad 2, Sarah A. Woller 2,
Smriti Iyengar 2, Taleen Hanania 1
1 PsychoGenics Inc., Paramus, NJ, 07652, 2 Division of Translational Research, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Rockville, MD 20852
Headache disorders including tension-type headache and migraine affect 40-50% of the
global population and represent a leading cause of years lived with disability. The National
Institutes of Health Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative,
Preclinical Screening Platform for Pain (PSPP) program aims to accelerate the discovery of
novel pain therapeutics for pain disorders including headache and migraine.
The identification of translatable preclinical models is an important part of the drug
discovery process to establish initial target validation. Translatable preclinical models of
headache and migraine include administration of nitric oxide (NO) donors, since these
compounds produce facial allodynia in rodents and headache and migraine in human
subjects. Isosorbide dinitrate (ISDN) is a NO donor that is unique in that it is largely
peripherally restricted and soluble in saline vehicle. Here, we characterize the behavioral
pain phenotype and pharmacology of the ISDN model in rats to determine the utility of this
model to evaluate novel mechanisms for the treatment of headache and migraine disorders.