Mechanism and therapeutic effectiveness of nerve growth factor in osteoarthritis pain

Figures & data

Figure 1 Molecular mechanisms of NGF function leading to pain.

Notes: (A) The NGF–TrkA complex evokes sustained density and increased activity in peripheral and central neurons through the pain receptor TRPV1. Once opened, TRPV1 facilitates Ca²⁺ influx and increased expression of CGRP and SP, leading to central sensitization. (B) NGF stimulates mast cells to express histamine, serotonin/5-HT, protons, and NGF. (C) The NGF–TrkA complex is endocytosed and retrogradely transported to neuronal cell bodies, where it modulates the expression of bradykinin receptors, acid-sensing ion channel 2/3, voltage-gated sodium channels, and TRPV1, resulting in peripheral sensitization and pain hypersensitivity.
Abbreviations: 5-HT, 5-hydroxytryptamine; ASIC, acid-sensing ion channel; CGRP, calcitonin gene-related peptide; NGF, nerve growth factor; SP, substance P; TrkA, tropomyosin receptor kinase A; TRPV1, transient receptor potential vanilloid receptor 1.

Table 1 The four categories of drugs that have been applied to relieve OA pain

Category	Target	Mechanism	References
1	NGF	NGF-capturing agents	^Citation18, ^Citation37
2	NGF	Antagonists at the NGF-binding site	^Citation44^–^Citation46
3	TrkA	Antagonists of TrkA function	^Citation47^–^Citation49
4	TRPV1	Antagonists of TRPV1	^Citation52, ^Citation53

Abbreviations: NGF, nerve growth factor; OA, osteoarthritis; TrkA, tropomyosin receptor kinase A; TRPV1, transient receptor potential vanilloid receptor 1.

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