Targeting nerve growth factor for pain relief: pros and cons

Abstract

Nerve growth factor (NGF) is a neurotrophic protein that has crucial roles in survival, growth and differentiation. It is expressed in neuronal and non-neuronal tissues. NGF exerts its effects via two types of receptors including the high affinity receptor, tropomyosin receptor kinase A and the low affinity receptor p75 neurotrophin receptor highlighting the complex signaling pathways that underlie the roles of NGF. In pain perception and transmission, multiple studies shed light on the effects of NGF on different types of pain including inflammatory, neuropathic, cancer and visceral pain. Also, the binding of NGF to its receptors increases the availability of many nociceptive receptors such as transient receptor potential vanilloid 1, transient receptor potential ankyrin 1, N-methyl-D-aspartic acid, and P2X purinoceptor 3 as well as nociceptive transmitters such as substance P and calcitonin gene-related peptide. The role of NGF in pain has been documented in pre-clinical and clinical studies. This review aims to shed light on the role of NGF and its signaling in different types of pain.

Keywords: Acute Disease; Chronic Disease; Inflammation; Low Back Pain; Musculoskeletal; Neoplasms; Nerve Growth Factor; Neuropathic Pain; Orofacial Pain; Osteoarthritis; Pain.

Fig. 1

Signaling pathways of NGF in pain. NGF: nerve growth factor, EP: prostaglandin E2 receptor, NMDA: N-methyl-D-aspartic acid, TrkA: tropomyosin receptor kinase A, P2X3: P2X purinoceptor 3, DRG: dorsal root ganglion, TRPV1: transient receptor potential vanilloid 1, SP: substance P, CGRP: calcitonin gene-related peptide, NK1: neurokinin-1.