The A118G polymorphism in the opioid receptor mu 1 gene (OPRM1) is associated with decreased opioid receptor availability, altered emotion, and increased pain. Given that emotions modulate pain (positive emotions inhibit pain, negative emotions enhance pain), we predicted that G allele carriers would experience impaired emotional modulation of pain compared to non-G allele carriers. Emotional pictures (ie, erotica, neutral, attack) from the International Affective Picture System were used by permission from the authors to experimentally manipulate emotions in 64 adult participants while painful electrocutaneous stimulations were delivered in a cross-sectional study. Ratings of arousal and valence/pleasure were made in response to pictures, and pain ratings and a physiological measure of spinal nociception (ie, nociceptive flexion reflex, NFR) were collected in response to painful stimulations. Secondary analyses were conducted to examine the relationship between the A118G polymorphism and emotional modulation of pain/NFR. Exposure to emotional pictures elicited similar changes in valence, but G-carriers rated erotic pictures as more arousing. In non-carriers, pain was facilitated by attack pictures and pain and NFR were inhibited by erotic pictures relative to neutral pictures. Among G-carriers, pain was facilitated by negative emotional pictures but there was no pain or NFR inhibition by positive emotional pictures. The altered response to pleasant stimuli further supports the role of opioids in appetitive behavior and describes how the A118G polymorphism may prevent carriers from inhibiting pain during pleasure.