The aim of this study was to establish the effect of lidocaine, a local anesthetic, on pain and itch using formalin-induced nociception and kappa opioid antagonist-induced scratching models in mice. We investigated if local intradermal pretreatment (at -10 min) with lidocaine N-ethyl bromide (lidocaine, 2%, 0.1 ml) antagonizes behavioral responses and prevents c-fos expression induced by pain and itch. Male, Swiss Webster mice (25-30 g, n=6-10) were used. Formalin (5%, 20 microl, s.c.) or saline was administered to the right dorsal hindpaw and the time spent licking this paw was recorded at 0-10 min and 20-35 min. For itching, mice were challenged with 5'-guanidinonaltrindole (GNTI, 0.3mg/kg, s.c., behind the neck) or saline and the number of neck-directed scratches with hindpaws was counted for 30 min. C-fos immunohistochemistry was performed in lumbar (for pain) and cervical (for scratching) spinal sections 2h after the respective treatments. We found that lidocaine (a) antagonizes both formalin-induced pain and GNTI-induced scratching and (b) prevents c-fos expression evoked by pain (medial side of the superficial layer and deeper layers of the dorsal horn) and itch (lateral side of the superficial layer of the dorsal horn). Additionally, GNTI caused c-fos activation in mice wearing an Elizabethan collar (to prevent scratching of the neck) suggesting that GNTI provokes c-fos expression by inducing an itch sensation. Our results highlight the antipruritic properties of lidocaine and argue for its comprehensive clinical testing against pruritic states.