It is unanimously accepted that there is an unmet need for pain medications that 
are both effective and safe. Unfortunately, no really novel analgesics have been 
approved over the past three decades. In view of both experimental and clinical 
evidence of a major role for nerve growth factor (NGF) in the generation and 
maintenance of a wide range of pain states, drug discovery efforts focusing on 
the development of anti-NGF agents have aroused particular interest. Several 
humanized anti-NGF monoclonal antibodies (mAbs) have entered clinical trials as 
potential analgesics. In this respect, tanezumab is at an advanced stage of 
clinical development while fulranumab, fasinumab and ABT-110, previously known 
as PG110, are in early phases of clinical development. This Current Opinion 
article aims at describing the rationale for targeting NGF for pain, reviewing 
the analgesic efficacy and safety of anti-NGF agents based on data from fully 
published studies, conference abstracts, and the US Food and Drug Administration 
(FDA) website, and discussing the possible future of these agents in managing 
chronic pain. Anti-NGF mAbs produced significant pain relief and functional 
improvement in patients with osteoarthritis of the knee and/or hip. Conversely, 
studies in non-specific lower back pain generated mixed results; overall, this 
condition appeared to be less responsive to anti-NGF agents than osteoarthritis. 
Finally, there was no conclusive evidence of the effectiveness of anti-NGF mAbs 
in some types of chronic visceral or neuropathic pain. Furthermore, these 
studies raised safety concerns about anti-NGF mAbs. As a class, these drugs may 
cause or worsen peripheral neuropathies. But the most problematic issue-which 
prompted the FDA to place studies of these compounds on clinical hold in 
2010-was rapid joint destruction leading to joint replacement surgery. The 
aetiologies of these side effects have been much debated and their 
pathophysiology is poorly understood. After an Arthritis Advisory Committee 
meeting held in March 2012, pharmaceutical companies negotiated with the FDA on 
the conditions for restarting clinical studies. Although the FDA lifted its 
clinical hold, there remain many unresolved issues about the long-term efficacy 
and safety of anti-NGF mAbs. While acknowledging that the future of these drugs 
is unforeseeable, it appears that they may not be the safe and effective 
painkillers that have been awaited for decades.