Among the numerous models proposed as in vivo systems for testing novel antimigraine drug candidates, the most widely studied and accepted one is the nitroglycerin (NTG)-induced model of migraine. Creative Biolabs offers drug efficacy testing services of novel antimigraine drugs in both rat and mice nitroglycerin fusion models. Moreover, a comprehensive battery of assessment tools is employed, allowing us to offer customized protocols and study designs.
Introduction of NTG Model of Migraine
NGT infusion is the most widely used and trustworthy method to provoke migraine-like headaches in humans as well as in animals. The infusion of the nitric oxide donor NTG results in upregulation of proinflammatory mediators, macrophage activation, edema formation, and mast cell degranulation by its direct action on meningeal tissues and produces plasma protein extravasations (PPE).
NGT is metabolized to nitric oxide (NO) by a combination of glutathione-S-transferase, cytochrome P450, and thiol reactions. Type II nitric oxide synthase (NOS) is expressed by macrophages and can be activated by NGT. After some hours of NGT infusion, iNOS generates NO at 100-1000 fold than its constitutive counterparts and promotes inflammation and the development of migraine. NGT activates second-order nociceptors, NF-ĸB, and increases the expression of c-fos, neuronal nitric oxide synthase (nNOS), and calmodulin-dependent protein kinase II in the trigeminal nucleus caudalis. Increased production of NO has been reported to upregulate COX, TNF-a, and matrix metalloprotease-9 (MMP-9).
Fig.1 Effect of URB937 during the plantar formalin test. URB937 significantly inhibited nocifensive behavior induced by formalin injection in Phase II and it also significantly reduced NTG-induced hyperalgesia. (Greco et al. 2015)
Features of NTG Model of Migraine
Assessments
Creative Biolabs conducts a comprehensive battery of assessments for efficacy evaluation of putative antimigraine drugs. For instance, cranial blood perfusion can be measured by laser Doppler flowmetry technique. Level of inflammatory mediators like TNF-α and mRNA and protein expression for c-fos is analyzed in the trigeminal vascular system at various time points using ELISA, RT-PCR, and immunohistochemistry. Hypersensitivity to pain either on the paw/tail or in the facial (trigeminal) region is measured by behavioral responses to chemical, mechanical or thermal stimuli. Briefly, the assessments provided by Creative Biolabs include:
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The neurological platform of Creative Biolabs provides an extensive range of neurological disease models. If you are interested, click the following links for more detailed description of each model:
Supported by PhD-level scientists, state-of-the-art facilities, and abundant project management experience, Creative Biolabs is capable of providing and delivering robust preclinical in vivo contract drug discovery and development services. Contact us for more information on these models or if you would like to customize a model.
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