Rodent Animal Models of Endometriosis-Associated Pain: Unmet Needs and Resources Available for Improving Translational Research in Endometriosis

Chronic pain induced by endometriosis is a maladaptive pain experienced by half of women with this disease. The lack of pharmacological treatments suitable for long-term relief of endometriosis-associated pain, without impact on fertility, remains an urgent unmet need. Progress has been slowed by the absence of a reproducible rodent endometriosis model which fully replicates human physiopathological characteristics including pain symptoms. Although pain assessment in rodents is a complicated task requiring qualified researchers, the choice of behavioural test is no less important, since selecting inappropriate tests can cause erroneous data. Pain is usually measured with reflex tests in which hypersensitivity is evaluated by applying a noxious stimulus, yet this ignores the associated emotional component which could be evaluated via non-reflex tests. We conducted a systematic review of endometriosis models used in rodents and how many of them studied pain. Type of behavioural test used was also analysed and classified according to reflex and non-reflex tests. Finally, we determined the most used reflex tests for the study of endometriosis-induced pain, and the main non-reflex behavioural tests utilized in visceral pain that can be extrapolated to the study of endometriosis and complement traditional reflex tests.