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Melior Pharmaceuticals

melior melior melior discovery melior pharmaceuticals preclinical services pre-clinical services in vivo pharmacology in vivo efficacy efficacy models pharmacokinetics indications discovery specialized animal models bioanalytical services theratrace exton pennsylvania cro contract research drug discovery drug development metabolic disease alzheimer’s alzheimers diabetes reprofiling

Melior Discovery pain/neuropathic

Migraine Model
Headache disorders consistently rank as one of the most prevalent neurological conditions globally, with migraine being one of the most disabling disorders.  Though the mechanism of migraine is complex and unresolved, one hypothesis states repeated activation of the trigeminal vascular system leads to long-term physiological changes.  Clinical symptoms include trigeminal allodynia and sensitivity to nitrates, both resulting in pain. 

                       

After four weeks of prostaglandin infusions directly onto the dura, rats exhibit chronic periorbital allodynia and nitrate sensitivity measured by mechanical von Frey fibers.  Following infusion, rats are challenged with vehicle-only, glycerol trinitrate (GTN) and vehicle, or GTN and sumatriptan (potent vasoconstrictor). 

 

The figure shows the proportional effects on periorbital von Frey thresholds relative to an individuals’ pretreatment baseline (proportional change in threshold; mean ± SEM). The periorbital thresholds of rats dosed with GTN and vehicle were significantly reduced compared to baseline thresholds at the 1.5 and 2.5 hour marks, confirming GTN sensitivity. Periorbital thresholds were significantly increased in animals dosed with GTN and sumatriptan, demonstrating that sensitivity to GTN was successfully blocked by administration of sumatriptan. No significant change was recorded in animals given vehicle. Data are mean ± SEM; *p<0.05, ***p<0.001 compared to baseline.

 

If you are interested in learning more about Migraine Validation, please contact models@meliordiscovery.com to start the conversation today.