Abstract
Nerve growth factor (NGF) is central to the development and functional regulation of sensory neurons that signal the first events that lead to pain. These sensory neurons, called nociceptors, require NGF in the early embryo to survive and also for their functional maturation. The long road from the discovery of NGF and its roles during development to the realization that NGF plays a major role in the pathophysiology of inflammatory pain will be reviewed. In particular, we will discuss the various signaling events initiated by NGF that lead to long-lasting thermal and mechanical hyperalgesia in animals and in man. It has been realized relatively recently that humanized function blocking antibodies directed against NGF show remarkably analgesic potency in human clinical trials for painful conditions as varied as osteoarthritis, lower back pain, and interstitial cystitis. Thus, anti-NGF medication has the potential to make a major impact on day-to-day chronic pain treatment in the near future. It is therefore all the more important to understand the precise pathways and mechanisms that are controlled by NGF to both initiate and sustain mechanical and thermal hyperalgesia. Recent work suggests that NGF-dependent regulation of the mechanosensory properties of sensory neurons that signal mechanical pain may open new mechanistic avenues to refine and exploit relevant molecular targets for novel analgesics.
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Acknowledgments
The authors’ work was supported by grants from the Deutsche Forschungsgemeinshaft collaborative research centers 665 and 958 and a senior European Research Council grant. EStJS was supported by fellowship from the Alexander von Humboldt foundation.
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Lewin, G.R., Lechner, S.G., Smith, E.S.J. (2014). Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy. In: Lewin, G., Carter, B. (eds) Neurotrophic Factors. Handbook of Experimental Pharmacology, vol 220. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45106-5_10
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