Nerve growth factor (NGF) as a target for the treatment of neuropathic pain

Neuropathic pain (NP) is defined by the International Association for the Study of Pain (IASP) as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system either at peripheral or central level." NP can persist long after an injury has healed, and be excruciating in the absence of observable pathology. It can arise from nerve injury, disease processes, or chemotherapy, chronic inflammatory conditions (e.g., osteoarthritis or rheumatoid arthritis), or idiopathic pain conditions (e.g., inflammatory bowel disease, fibromyalgia, migraine headache, or urologic and pelvic pain syndromes). The heterogeneous clinical manifestations of NP likely reflect heterogeneous underlying mechanisms that involve various neuropeptides, inflammatory mediators, cytokines and trophic factors. First-line treatments include tricyclic antidepressants, dual serotonin / norepinephrine reuptake inhibitors, anticonvulsant calcium channel blockers and topical lidocaine. Second-line drugs include opioids and tramadol. However, these drugs do not always provide satisfactory pain relief, and each is associated with potentially serious adverse effects or abuse. Moreover, it is generally believed that better efficacy would be achieved by more selective targeting of relevant biochemical factors. One such factor that has recently gained attention is nerve growth factor (NGF). We review the rationale and current status of NGF-related approaches to analgesia.