The aim of this study was to further the understanding of mechanisms that underlie the pruritic and antipruritic effects of kappa opioid receptor drugs. The kappa opioid receptor (KOR) has been studied for its potential therapeutic benefits. It has been previously shown that the kappa opioid receptor antagonist, 5’-guanidinonaltrindole (GNTI), causes compulsive, hind-leg scratching in mice, while the kappa opioid receptor agonist, nalfurafine, inhibits this pruritic effect. There are applications for this antipruritic effect in medicine, to counteract symptoms in kidney-failure patients. By learning more about the mechanisms of this anti-pruritic effect, better drugs can be developed in the future with increased specificity and decreased side effects. We pre-treated male C57/BL6 mice with either saline or nalfurafine (0.05mg/kg, s.c. flank), and challenged them 20 minutes later with 5’-GNTI (0.03mg/kg, s.c. behind the neck) or saline. The number of hind-leg scratches in the 30 minutes following GNTI injection were counted as the measure of itch. We compared the results between kappa opioid receptor (KOR) knock-out mice, mu opioid receptor (MOR) knock-out mice, and wild-type mice, to determine the role of KOR and MOR in GNTI-induced itch and nalfurafine inhibition of itch. We concluded that while the pruritic effects of 5’-GNTI are not mediated by KOR or MOR, the antipruritic effects of nalfurafine was KOR dependent.