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Review
. 2019 Oct;160(10):2210-2220.
doi: 10.1097/j.pain.0000000000001625.

Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: mechanism of action in the context of efficacy and safety

Martin Schmelz  1 , Patrick Mantyh  2 , Anne-Marie Malfait  3 , John Farrar  4 , Tony Yaksh  5 , Leslie Tive  6 , Lars Viktrup  7
Affiliations
Review

Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: mechanism of action in the context of efficacy and safety

Martin Schmelz et al. Pain. 2019 Oct.

Abstract

Chronic pain continues to be a significant global burden despite the availability of a variety of nonpharmacologic and pharmacologic treatment options. Thus, there is a need for new analgesics with novel mechanisms of action. In this regard, antibodies directed against nerve growth factor (NGF-Abs) are a new class of agents in development for the treatment of chronic pain conditions such as osteoarthritis and chronic low-back pain. This comprehensive narrative review summarizes evidence supporting pronociceptive functions for NGF that include contributing to peripheral and central sensitization through tropomyosin receptor kinase A activation and stimulation of local neuronal sprouting. The potential role of NGF in osteoarthritis and chronic low-back pain signaling is also examined to provide a mechanistic basis for the observed efficacy of NGF-Abs in clinical trials of these particular pain states. Finally, the safety profile of NGF-Abs in terms of common adverse events, joint safety, and nerve structure/function is discussed.

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Conflict of interest statement

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

Figure 1.
Figure 1.
Pronociceptive actions of NGF. 5-HT, 5-hydroxytryptamine; ASIC, acid-sensing ion channels; BDNF, brain-derived neurotrophic factor; BK, bradykinin; Ca, calcium; CGRP, calcitonin gene–related peptide; DRG, dorsal root ganglion; K, potassium; Na, sodium; NGF, nerve growth factor; PGE2, prostaglandin E2; SubP, substance P; TrkA, tropomyosin receptor kinase A; TRPV1, transient receptor potential cation channel subfamily V member 1.
Figure 2.
Figure 2.
Nociceptive components of osteoarthritic knee pain. DAMPS, damage-associated molecular patterns; ECM, extracellular matrix; EGF, epidermal growth factor; FGF-2, fibroblast growth factor–2; NGF, nerve growth factor; OA, osteoarthritis; PGE2, prostaglandin E2; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.
Figure 3.
Figure 3.
Potential neuropathic and nociceptive components of chronic low-back pain.
See this image and copyright information in PMC

Comment in

References

    1. Allegri M, Montella S, Salici F, Valente A, Marchesini M, Compagnone C, Baciarello M, Manferdini ME, Fanelli G. Mechanisms of low back pain: a guide for diagnosis and therapy. F1000Res 2016;5:1530. - PMC - PubMed
    1. Andreev NYu, Dimitrieva N, Koltzenburg M, McMahon SB. Peripheral administration of nerve growth factor in the adult rat produces a thermal hyperalgesia that requires the presence of sympathetic post-ganglionic neurones. PAIN 1995;63:109–15. - PubMed
    1. Apfel SC. Nerve growth factor for the treatment of diabetic neuropathy: what went wrong, what went right, and what does the future hold? Int Rev Neurobiol 2002;50:393–413. - PubMed
    1. Ashraf S, Bouhana KS, Pheneger J, Andrews SW, Walsh DA. Selective inhibition of tropomyosin-receptor-kinase A (TrkA) reduces pain and joint damage in two rat models of inflammatory arthritis. Arthritis Res Ther 2016;18:97. - PMC - PubMed
    1. Averill S, McMahon SB, Clary DO, Reichardt LF, Priestley JV. Immunocytochemical localization of trkA receptors in chemically identified subgroups of adult rat sensory neurons. Eur J Neurosci 1995;7:1484–94. - PMC - PubMed

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