We previously developed a spatial summation model and demonstrated that spatial summation of pain involves the activation of both excitatory and inhibitory systems. The aim of this study was to determine whether the endogenous pain inhibitory systems recruited by the spatial summation model are opioid-mediated by verifying if they could be blocked by the opioid antagonist naloxone. Twenty healthy volunteers (10 men, 10 women) participated in a randomized, four-session, cross-over study. Each session consisted of pain perception ratings (visual analog scale) taken during the immersion of different surfaces of the arm in circulating noxious cold water (12 degrees C). The arm was arbitrarily divided into eight segments from fingertips to shoulder. Two sessions were increasing (from fingertips to shoulder) and two sessions were decreasing (from shoulder to fingertips). All sessions consisted of eight consecutive 2-min immersions separated by 5-min resting periods. Intravenous injections of naloxone hydrochloride (0.14 mg/kg) or saline (NaCl, 0.9%) were administered under double-blind conditions. We found that during the control session (saline injection) there was a significant difference in pain intensity ratings between the increasing and decreasing sessions. The decreasing session resulted in lower pain intensity. As previously demonstrated, this lowering of the perception curve seems to be due to a large recruitment of inhibitory systems at the beginning of the decreasing session as opposed to a gradual recruitment during the increasing session. However, during the opioid inhibition session (naloxone injection) no differences were found between the increasing and decreasing sessions. Naloxone inhibited the endogenous pain inhibitory systems activated by the spatial summation model, suggesting that these systems have an opioid-mediated component, as previously reported for diffuse noxious inhibitory controls.