IntroductionIn dyspareunia—a somatically unexplained vulvovaginal pain associated with sexual intercourse—learned pain-related fear and inhibited sexual arousal are supposed to play a pivotal role. Based on research findings indicating that enhanced pain conditioning is involved in the etiology and maintenance of chronic pain, in the present study it was hypothesized that enhanced pain conditioning also might be involved in dyspareunia. AimTo test whether learned associations between pain and sex negatively affect sexual response; whether women with dyspareunia show stronger aversive learning; and whether psychological distress, pain-related anxiety, vigilance, catastrophizing, and sexual excitation and inhibition were associated with conditioning effects. MethodsWomen with dyspareunia (n = 36) and healthy controls (n = 35) completed a differential conditioning experiment, with one erotic picture (the CS+) paired with a painful unconditional stimulus and one erotic picture never paired with pain (the CS−). Main Outcome MeasuresGenital sexual response was measured by vaginal photoplethysmography, and ratings of affective value and sexual arousal in response to the CS+ and CS− were obtained. Psychological distress, pain cognitions, and sexual excitation and inhibition were assessed by validated questionnaires. ResultsThe two groups showed stronger negative affect and weaker subjective sexual arousal to the CS+ during the extinction phase, but, contrary to expectations, women with dyspareunia showed weaker differential responding. Controls showed more prominent lower genital response to the CS+ during acquisition than women with dyspareunia. In addition, women with dyspareunia showed stronger expectancy for the unconditional stimulus in response to the safe CS−. Higher levels of pain-related fear, pain catastrophizing, and sexual inhibition were associated with weaker differential conditioning effects. ConclusionsPairing of sex with pain negatively affects sexual response. The results indicate that a learned association of sex with pain and possibly deficient safety learning play a role in dyspareunia.Both S, Brauer M, Weijenborg P, Laan E. Effects of Aversive Classical Conditioning on Sexual Response in Women With Dyspareunia and Sexually Functional Controls. J Sex Med 2017;14:687–701.