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Inflammatory and injury-induced skeletal pain are common conditions, and both conventional nonselective NSAIDs and the newer cyclo-oxygenase-2-specific inhibitors are widely used as post-traumatic and post-surgical analgesics. However, new research suggests that these drugs, particularly the cyclo-oxygenase-2 inhibitors, have a negative effect on the healing process in fractured bone and within orthopedic surgical sites, thus highlighting a need to develop new approaches for managing skeletal pain. Various experimental studies have revealed that locally upregulated neurotrophic factors, especially nerve growth factor, have a major role in mediating injury-induced or inflammatory pain. Nerve growth factor inhibitors, therefore, might be an effective alternative modality for post-traumatic and post-surgical analgesia, without impairing bone healing.The data for this Review were identified by searching the PubMed database. Only full-text articles published in English from 1990-2008 were considered. The search terms included “fracture”, “inflammatory”, “pain”, and “healing” with “NSAIDs” or “neurotrophic factor”.