Several studies have suggested that systemic tramadol, an opioid, can represent a valuable treatment in severe pain conditions because of their effects on central pain pathways. However, there are not enough studies supporting that tramadol is efficacious when administered locally. Therefore, we studied the potential local analgesic effects of tramadol in peripheral nociception. In addition, we tested the antinociceptive effects of tramadol-CaCl2 or naloxone combinations after subcutaneous intraplantar injection in a validated rat model of acute thermal nociception. Local analgesic effects of tramadol were compared with those of lidocaine. The effects of tramadol on thermal paw withdrawal latencies were monitored using the plantar test. The antinociceptive potency of tramadol is higher and long-lasting than that of lidocaine. Naloxone was unable to inhibit the increased antinociceptive response produced by tramadol. Ca2+ modified the effect of tramadol. When Ca2+ dose was increased in the solution, thermal antinociceptive potency of tramadol, but not lidocaine was prolonged. Thermal nociceptive responses were not affected in the non-injected paws, indicating a lack of systemic effects with doses of tramadol and lidocame that elicited local analgesia. These results suggest that intraplantar tramadol administration can produce local analgesic effect with a different action mechanism than that of lidocaine. In addition, extracellular Ca2+ may play an important role in the local analgesic action of tramadol. (c) 2006 Elsevier B.V. All rights reserved.