Animal models of migraine and experimental techniques used to examine trigeminal sensory processing

Andrea M Harriott,Philip R Holland,Marta Vila-Pueyo,Lauren C Strother

doi:10.1186/s10194-019-1043-7

Andrea M Harriott, Philip R Holland + Show 2 more

Open Access

https://doi.org/10.1186/s10194-019-1043-7

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Abstract

BackgroundMigraine is a common debilitating condition whose main attributes are severe recurrent headaches with accompanying sensitivity to light and sound, nausea and vomiting. Migraine-related pain is a major cause of its accompanying disability and can encumber almost every aspect of daily life.Main bodyAdvancements in our understanding of the neurobiology of migraine headache have come in large from basic science research utilizing small animal models of migraine-related pain. In this current review, we aim to describe several commonly utilized preclinical models of migraine. We will discuss the diverse array of methodologies for triggering and measuring migraine-related pain phenotypes and highlight briefly specific advantages and limitations therein. Finally, we will address potential future challenges/opportunities to refine existing and develop novel preclinical models of migraine that move beyond migraine-related pain and expand into alternate migraine-related phenotypes.ConclusionSeveral well validated animal models of pain relevant for headache exist, the researcher should consider the advantages and limitations of each model before selecting the most appropriate to answer the specific research question. Further, we should continually strive to refine existing and generate new animal and non-animal models that have the ability to advance our understanding of head pain as well as non-pain symptoms of primary headache disorders.

Highlights

ConclusionSeveral well validated animal models of pain relevant for headache exist, the researcher should consider the advantages and limitations of each model before selecting the most appropriate to answer the specific research question
Migraine is a common debilitating condition whose main attributes are severe recurrent headaches with accompanying sensitivity to light and sound, nausea and vomiting
It has been reported that 70% of migraineurs experience cephalic allodynia: referred pain or sensitization around the head that is induced by the activation of the trigeminal system during an attack [153]; extracephalic allodynia in the arms and legs is reported in more severe and chronic cases [154, 155] and is likely attributed to sensitization of third order trigeminal neurons in the thalamus [153, 156]

Summary

Conclusion

Our understanding of migraine-related pain processing and the development of novel therapeutics for its modulation has evolved via key translational research streams in humans and experimental animals. We have largely focused on the most commonly used preclinical models of migraine-related pain; despite significant success, there remains a major unmet need to generate novel knowledge on the underlying mechanisms of migraine initiation, associated symptoms and attack cessation. Future preclinical research is a necessity to achieve this goal, and while alternate readouts that can help to reduce the use of animals in research are encouraged, for the whole animal is the only model that can accurately examine the complex interactions between the peripheral and central nervous systems. It is essential that researchers continue to refine existing and develop novel models to enable studies that explore the diverse symptomatology of migraine, while continuing to achieve significant translational success in terms of novel disease modifying therapies

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