Modelling headache and migraine and its pharmacological manipulation.

Area of Science:

• Neuroscience
• Pharmacology
• Translational Medicine

Background:

• Laboratory animals share anatomical and physiological similarities with humans in cephalic nociceptive pathways.
• These similarities have enabled the development of successful headache and anti-migraine drug models.
• However, modeling primary headache disorders like migraine remains challenging due to limitations in human hypothesis testing.

Purpose of the Study:

• To review commonly used headache and migraine models.
• To emphasize recent developments in animal modeling for headache and migraine research.
• To highlight the translational gap and how new techniques are bridging it.

Main Methods:

• Review of existing literature on animal models of headache and migraine.
• Emphasis on recent advancements such as imaging techniques, cortical spreading depolarization (CSD) studies, and optogenetics.
• Discussion of behavioral assessments in intact animals and induction of headache/migraine-like episodes (e.g., using glyceryltrinitrate and CGRP).

Main Results:

• Cortical spreading depolarization (CSD) in patients has spurred renewed interest in CSD-based animal models.
• CSD-based models, including transgenics and optogenetics, offer more realistic simulations of migraine pain originating in the brain.
• Quantitative assessment of behavioral correlates of headache and photophobia in animals allows for direct study without anesthetics.
• Induction of headache/migraine-like episodes and parallel changes in rodents mirror human responses, facilitating translational research.

Conclusions:

• Animal models, despite species differences and controversies, are crucial for advancing our understanding of headache and migraine.
• Recent developments in modeling, particularly CSD-based approaches and behavioral assessments, hold significant promise for future research and therapeutic development.
• Continued refinement of models and addressing model-specific observations are key to overcoming challenges in clinical trials and improving patient outcomes.