Acutely, nerve growth factor (NGF) exerts profound effects on nociceptive transmission and produces pain and hyperalgesia. In the present study, we sought to determine the tissue levels and role of NGF after a plantar incision. A substantial increase in NGF protein expression occurred in skin 4-h, 1-day and 2-days and 5-days after incision comparing contralateral uninjured skin. Plantar incision did not change NGF levels in the tibial nerve and L4-L6 dorsal root ganglia. The therapeutic effect of a monoclonal antibody against endogenous NGF was evaluated by intraperitoneal administration of a single preoperative dose of anti-NGF. Of three different doses of anti-NGF used, the highest dose 2.8 mg/kg anti-NGF attenuated or almost abolished guarding pain scores at 4-h, 1-day (>80% decrease) and 2-days after incision. This effect is dose dependent in that lower doses (1, 0.1 mg/kg) were effective only at 1-day after incision. Anti-NGF also attenuated heat hyperalgesia at 1-day and 2-days after incision when the highest dose was used. However, treatment by anti-NGF did not affect C-fibers sensitized 1-day after incision in a glabrous skin-tibial nerve in vitro preparation. In conclusion, increased NGF was present in skin after plantar incision. NGF contributes to some incision-induced pain behaviors, guarding and heat hyperalgesia. Anti-NGF did not affect the extent of sensitization of C-fibers observed in vitro.