Abstract Background/aims Pain is a common problem which significantly impacts on quality of life. Clinical pain is complicated to study due to numerous confounding variables. Normal volunteer models use standardised painful stimuli with resulting reduced phenotype variability. Current studies suggest an association between genetic variability and pain sensitivity. Methods Data from 50 healthy volunteers in three studies of multi-modal, multi-tissue experimental pain stimulation were included. Skin heat, muscle cuff pressure and visceral pressure were analysed. Genetic variants in the genes coding for the mu, delta and kappa opioid receptors (OPRM, OPRD and OPRK) were studied using multivariate regression modelling to investigate association with pain sensitivity. Results Reproducibility of baseline data for skin heat, muscle cuff pressure and visceral pressure between studies was confirmed (Cronbach’s α > 0.8). Gender differences in pain sensitivity were seen. Females were more sensitive to skin heat and muscle pressure (P =0.006 and 0.02 respectively). Genetic associations were also found. OPRK was associated with both skin heat pain (P =0.009) and muscle cuff pain (P =0.003). Visceral pressure pain was not associated with either gender or genotype. Conclusion Genetic variations in the kappa opioid receptor appear to mediate different pain modalities. Gender remains an independent predictor of pain sensitivity.