Special Issue: Neurobiology of Pain
Pro-neurotrophins, sortilin, and nociception
Article first published online: 4 FEB 2014
© 2014 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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European Journal of Neuroscience
Special Issue: NEUROBIOLOGY OF PAIN
Volume 39, Issue 3, pages 363–374, February 2014
How to Cite
Lewin, G. R. and Nykjaer, A. (2014), Pro-neurotrophins, sortilin, and nociception. European Journal of Neuroscience, 39: 363–374. doi: 10.1111/ejn.12466
- Issue published online: 4 FEB 2014
- Article first published online: 4 FEB 2014
- Manuscript Accepted: 28 NOV 2013
- Manuscript Revised: 13 NOV 2013
- Manuscript Received: 26 SEP 2013
- Deutsche Forschungsgemeinshaft
- Lundbeck Foundation
- European Research Council
- mechanical hyperalgesia;
- neuropathic pain and inflammation;
- NGF ;
Nerve growth factor (NGF) signaling is important in the development and functional maintenance of nociceptors, but it also plays a central role in initiating and sustaining heat and mechanical hyperalgesia following inflammation. NGF signaling in pain has traditionally been thought of as primarily engaging the classic high-affinity receptor tyrosine kinase receptor TrkA to initiate sensitization events. However, the discovery that secreted proforms of nerve NGF have biological functions distinct from the processed mature factors raised the possibility that these proneurotrophins (proNTs) may have distinct function in painful conditions. ProNTs engage a novel receptor system that is distinct from that of mature neurotrophins, consisting of sortilin, a type I membrane protein belonging to the VPS10p family, and its co-receptor, the classic low-affinity neurotrophin receptor p75NTR. Here, we review how this new receptor system may itself function with or independently of the classic TrkA system in regulating inflammatory or neuropathic pain.