Nerve growth factor: an update on the science and therapy

Abstract

SUMMARY Objective Nerve growth factor (NGF) is a key regulator of nociceptive pain and thus appears to be an interesting target molecule for an innovative class of analgesic medication. We set out to review the principles of neurogenic inflammation and results of anti-NGF regimens in animal studies as well as clinical trials with patients with back pain and osteoarthritis (OA). Design We searched using Google Scholar Search and Pubmed as well as through conference reports for articles and abstracts related to NGF and clinical trials using anti-NGF regimens. We report on efficacy findings and adverse events (AEs) related to these agents in this review. Results We identified five full articles and eight abstract reports relating to anti-NGF agents studied for use in back pain and in OA. Conclusions Anti-NGF agents either alone or in combination with non-steroidal anti-inflammatory agents (NSAIDs) were more efficacious for the treatment of pain in a number of trials of knee and hip pain compared to NSAIDs alone. However, adverse effects that included rapidly progressive OA and joint replacement were more common in patients treated with anti-NGF and NSAIDs than either treatment alone. Anti-NGF treatment related neurologic symptoms including paresthesias, and potentially other types of adverse effects were usually transient but warrant additional investigation.

NGF Blockade at Early Times during Bone Cancer Development Attenuates Bone Destruction and Increases Limb Use

“…However, within this group a small but significant number of patients receiving the highest dose of anti-NGF and naproxen required earlier-than-expected joint replacement. Whether this earlier-than-expected joint replacement was caused by overuse of the arthritic joints due to the robust pain relief provided by anti-NGF, or was a direct effect of blocking NGF on the maintenance and formation of adult bone remains unknown (10). However, in patients with CMB, fracture of the tumor-bearing bone is a highly undesirable event as active tumor-induced bone destruction makes stabilization and repair of the fractured bone problematic.…”

“…Bisphosphonates and the RANK ligand inhibitor, Denosumab, have been approved for treatment of both pain and preventing bone fracture (6, 7). A therapy showing promise in blocking pain induced by CMB and non-malignant skeletal pain is inhibition of nerve growth factor (NGF) and its primary receptor, tyrosine kinase receptor type 1 (TrkA) (8-10). In breast, sarcoma, and prostate mouse models of CMB, anti-NGF significantly attenuates bone cancer pain (11-15).…”

Osteoarthritis joint pain: The cytokine connection

“…NGF has itself been implicated as a key pain regulator in a variety of models acting primarily through transactivation of TRPV1 [28], further illustrating the complexity of interactions that may occur in the inflammatory environment. Clinical trials testing the effectiveness of anti-NGF in treating osteoarthritis pain are currently ongoing (for review, see [29]).…”

Transmission pathways and mediators as the basis for clinical pharmacology of pain

“…Significantly, NGF accumulation in OA and acceleration of bone damage can occur in the absence of joint pain [137]. In a review that combined the findings of several studies the authors noted that, despite its promise as a potential analgesic, NGF-targeting agents increase the risk of both OA and potential joint replacement [138]. Interestingly, this paper observed the bone destructive effects of NGF to be more significant when paired with NSAIDs [138].…”