Nerve Growth Factor has two faces, if not more. Most people know it as a protein supporting regeneration. However, it is also a compound enhancing pain and inflammation.
The role of NGF in inflammation and pain has been firmly established, as well as its presence in inflammatory chronic diseases such as asthma, inflammatory bowel disorders and related disorders.
Recently, in a sophisticated article, titled “Presence of NGF and its receptor TrkA in degenerative lumbar facet joint specimens” it was found that NGF and its specific receptor Trka, is present in in peri/articular tissues from lumbar facet joints in patients suffering from chronic low back pain. The TrkA receptor is expressed on many nociceptors and is activated by NGF. The relevance of NGF for analgesia is already long known (e.g. Lewin 1993)
Prostaglandins, bradykinin, serotonin, histamine, hydrogen ions and NGF can all lead to the sensitization of nociceptors. Most of these compound are secreted by activated mast cells. Mast cells also secrete NGF. TrkA receptors are also known to be expressed by both sympathetic postganglionic neurons and by mast cells. So a vicious circle of activation, a positive feedback loop can come into existence, leading to chronic pain states.
This adds to older data, were a close interaction between mast cells and nerve cells have been demonstrated:
“Since intimate contacts between mast cells and neuronal membranes were seen by electron microscopy, we assume that the events at the mast cell/nerve cell surface involve recognition of neuronal membrane proteins or surface-associated molecules.” (Blennerhassett, 1991).
In chronic back pain, mast cells, NGF, cytokines and their mutual interactions all play a role in the pathological process of chronic pain. Regarding NGF, mRNA and protein levels have seen to increase in ipsilateral DRGs starting day 5 after constriction injury of the sciatic nerve (Herzberg et al., 1997). Application of anti-serum to NGF at the site of constriction injury delays hyperalgesia. Expression of NGF is also increased in rat DRGs 3 days after lumbar disc herniation (Obata, 2002; Zhou et al., 1996).
PEA counteracts the increasing pain state
The ALIAmide palmitoylethanolamide can counteract the overactivity induced by NGF and the activation of the TrkA receptor, a hypothesis put forward by Levi-Montalcini already in 1993.
The Surace (2009) paper supports the further exploration and use of palmitoylethanolamide in chronic low back pain, and helps us understand the patho-mechanism behind chronic back pain.
M. F. Surace, D. Prestamburgo, M. Campagnolo, A. Fagetti, L. Murena. Presence of NGF and its receptor TrkA in degenerative lumbar facet joint specimens Eur Spine J (2009) 18 (Suppl 1):S122–S125
G.R. Lewin, A.M. Ritter, L.M. Mendell Nerve growth factor-induced hyperalgesia in the neonatal and adult rat J. Neurosci., 13 (1993), pp. 2136–2148
Zhou, X.F., Rush, R.A., Mclachlan, E.M., 1996. Differential expression of the p75 nerve
growth factor receptor in glia and neurons of the rat dorsal root ganglia after
peripheral nerve transection. J. Neurosci. 16, 2901–2911.
M.G. Blennerhassett, M. Tomioka, and J. Bienenstock. Formation of contacts between mast cells and sympathetic neurons in vitro, Cell Tissue Res (1991)265:121-128
Herzberg, U., Eliav, E., Dorsey, J.M., Gracely, R.H., Kopin, I.J., 1997. NGF involvement in
pain induced by chronic constriction injury of the rat sciatic nerve. Neuroreport 8,
Obata, K., Tsujino, H., Yamanaka, H., Yi, D., Fukuoka, T., Hashimoto, N., Yonenobu, K., Yoshikawa, H., Noguchi, K., 2002. Expression of neurotrophic factors in the dorsal root ganglion in a rat model of lumbar disc herniation. Pain 99, 121–132.