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

Abstract

Chronic pain induced by endometriosis is a maladaptive pain experienced by half of women with this disease. The lack of pharmacological treatments suitable for the long-term relief of endometriosis-associated pain, without an impact on fertility, remains an urgent unmet need. Progress has been slowed by the absence of a reproducible rodent endometriosis model that fully replicates human physiopathological characteristics, including pain symptoms. Although pain assessment in rodents is a complicated task requiring qualified researchers, the choice of the behavioral 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 that could be evaluated via non-reflex tests. We conducted a systematic review of endometriosis models used in rodents and the number of them that studied pain. The type of behavioral test used was also analyzed 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 behavioral tests utilized in visceral pain that can be extrapolated to the study of endometriosis and complement traditional reflex tests.

The Unmet Needs for Studying Chronic Pelvic/Visceral Pain Using Animal Models

“…What endpoint should be looked for? Many reviews have brought to light the advantages and disadvantages of using spontaneous and induced pain behavior tests [ 139 , 140 ]. The induced pain behavior tests, such as von Frey filament stimulation or the hot plate test, are normally based on the reflexive and conscious withdrawal of body parts submitted to a stimulus [ 139 ].…”

An overview and comprehensive analysis of interdisciplinary clinical research in endometriosis based on trial registry

“… 23 Animal models provide extensive opportunities for biological experiments and translational research, but inherent limitations exist due to the disparities with human physiology. 24 , 25 Clinical evidence guides clinical practice, and well-designed randomized controlled trials (RCTs) play an irreplaceable role in advancing medical interventions and management approaches.…”

Endometriosis – a painful disease

“…It is beyond the scope of this review to comprehensively cover both clinical and preclinical research advances, and therefore, we will limit our discussion to clinical research. However, we wish to acknowledge the importance of preclinical research in advancing our understanding and highlight that although there have been important advances, pain still remains poorly assessed in preclinical models of endometriosis [6,7].…”