Animal Models for the Study of Female Sexual Dysfunction

Abstract

Introduction: Significant progress has been made in elucidating the physiological and pharmacological mechanisms of female sexual function through preclinical animal research. The continued development of animal models is vital for the understanding and treatment of the many diverse disorders that occur in women.

Aim: To provide an updated review of the experimental models evaluating female sexual function that may be useful for clinical translation.

Methods: Review of English written, peer-reviewed literature, primarily from 2000 to 2012, that described studies on female sexual behavior related to motivation, arousal, physiological monitoring of genital function and urogenital pain.

Main outcomes measures: Analysis of supporting evidence for the suitability of the animal model to provide measurable indices related to desire, arousal, reward, orgasm, and pelvic pain.

Results: The development of female animal models has provided important insights in the peripheral and central processes regulating sexual function. Behavioral models of sexual desire, motivation, and reward are well developed. Central arousal and orgasmic responses are less well understood, compared with the physiological changes associated with genital arousal. Models of nociception are useful for replicating symptoms and identifying the neurobiological pathways involved. While in some cases translation to women correlates with the findings in animals, the requirement of circulating hormones for sexual receptivity in rodents and the multifactorial nature of women's sexual function requires better designed studies and careful analysis. The current models have studied sexual dysfunction or pelvic pain in isolation; combining these aspects would help to elucidate interactions of the pathophysiology of pain and sexual dysfunction.

Conclusions: Basic research in animals has been vital for understanding the anatomy, neurobiology, and physiological mechanisms underlying sexual function and urogenital pain. These models are important for understanding the etiology of female sexual function and for future development of pharmacological treatments for sexual dysfunctions with or without pain. Marson L, Giamberardino MA, Costantini R, Czakanski P, and Wesselmann U. Animal models for the study of female sexual dysfunction. Sex Med Rev 2013;1:108-122.

Keywords: Arousal; Copulatory Behavior; Desire; Neural Pathways; Orgasm; Pain.

Figure 1

Female sexual behavior comprises desire, arousal, orgasm, and reward. Multiple factors activate and inhibit each stage of the sex cycle. Cognitive activation of hypothalamic and limbic brain regions can result in increased desire and arousal; while activation of brain inhibitory sites (cortex, hypothalamus, limbic system, and midbrain) either by stress, anxiety, or postorgasm (with satiety) can lead to inhibition or cessation of sexual behavior. Sensory cues, such as pleasing visual sexual images or desirable odors (pheromones), can enhance desire and arousal. In contrast, frightening visual or auditory stimuli, or loss of attention or focus can inhibit sexual behavior. Peripheral stimulation may lead to localized genital arousal alone or may produce central arousal and desire depending of the integrity and balance of excitatory (dopamine, oxytocin, noradrenaline, and melanocortin) and inhibitory (opioids, serotonin and endocannabinoids) neurotransmission from the peripheral nerves through the spinal cord to the brain. Androgens (testosterone and estradiol), present at normal levels, act both peripherally and centrally to enhance sexual function, while stress hormones (e.g., cortisol) inhibit sexual interest. Hormones such as oxytocin and progesterone are released into the circulation with orgasm. Pain arising from the genitals or reproductive organs can lead to sexual dysfunction. Peripheral pain activates inhibitory central spinal and brain pathways that may lead to aversion to sexual activity or a decrease in desire and arousal. As a result, an increased focus on activating the excitatory pathways of arousal and reward is required for sexual activity. + indicates activation or facilitation, - indicates inhibition or reduction.

Figure 2

Schematic drawing showing the innervation of the urogenital and rectal area in females. Although this diagram attempts to show the innervation in humans, much of the anatomical information is derived from animal data (see text). CEL, celiac plexus; DRG, dorsal root ganglion; HGP, hypogastric nerve; IHP, inferior hypogastric plexus; PSN, pelvic splanchnic nerve; PUD, pudendal nerve; SA, short adrenergic projections; SAC, sacral plexus; SCG, sympathetic chain ganglion; SHP, superior hypogastric plexus; vag, vagina. This figure has been reproduced with permission of the International Association for the Study of Pain^R (IASP) from reference [98]. The figure may not be reproduced for any other purpose without permission.