Pearls and pitfalls in experimental in vivo models of headache: Conscious behavioral research

Background: Physiological studies have been determinant for the understanding of migraine pathophysiology and the screening of novel therapeutics. At present, there is no animal model that translates fully the clinical symptoms of migraine, and generally these studies are conducted on anesthetized animals. Methodology: Pain as well as non-painful symptoms such as photophobia, need to have a conscious individual to be experienced; therefore, the new development and adaptation of behavioral assays assessing pain and other non-painful symptomatology in conscious animals represents a great opportunity for headache research and it is exciting that more and more researchers are using behavioral paradigms. Summary: This review will describe the different behavioral models for the study of headache that are performed in non-anesthetized conscious animals. The pearls and challenges for measuring hypersensitivity in rodents such as the common tests for measuring mechanical allodynia and thermal hyperalgesia have been the landmark for the development of assays that measure hypersensitivity in the craniofacial region. Here we describe the different behavioral assays that measure hypersensitivity in the craniofacial region as well as the established behavioral models of trigeminovascular nociception and non-nociceptive migrainous symptoms.