Netrin-1 Contributes to Myelinated Afferent Fiber Sprouting and Neuropathic Ache.
Mol Neurobiol. 2016 Oct;53(eight):5640-51
Authors: Wu CH, Yuan XC, Gao F, Li HP, Cao J, Liu YS, Yu W, Tian B, Meng XF, Shi J, Pan HL, Li M
Netrin-1 is a neuronal steering molecule implicated within the growth of spinal wire neurons and cortical neurons. Within the grownup spinal wire, UNC5H (repulsive receptor of netrin-1), however not deleted in colorectal most cancers (DCC) (enticing receptor of netrin-1), constitutes a serious mode of netrin-1 sign transduction, which can be concerned in axon repulsion and inhibits neurite outgrowth. Irregular sprouting of myelinated afferent fibers within the spinal dorsal horn could cause mechanical allodynia related to postherpetic neuralgia (PHN, Shingles) and different neuropathic pains. Nevertheless, whether or not netrin-1 participates in sprouting of myelinated afferent fibers and mechanical allodynia stays unknown. In an ultropotent TRPV1 agonist resiniferatoxin (RTX)-induced PHN-like mannequin, RTX remedy for six weeks elevated netrin-1 expression in dorsal horn neurons, together with NK-1-positive projection neurons. In human neuroblastoma SH-SY5Y cells, we discovered that TRPV1 antagonist capsazepine antagonized RTX-induced upregulation of netrin-1. After RTX remedy, UNC5H2 expression was progressively decreased, whereas DCC expression was considerably elevated. Silencing netrin-1 within the spinal dorsal horn considerably attenuated RTX-induced mechanical allodynia and sprouting of myelinated fibers into the spinal lamina II. Our outcomes recommend that RTX remedy upregulates netrin-1 expression via activation of TRPV1 receptors and alter UNC5H2-rich spinal dorsal horn right into a growth-permissive atmosphere by growing DCC expression, thus enhancing the sprouting of myelinated afferent nerves. Netrin-1 could also be focused for lowering major afferent sprouting and mechanical allodynia in PHN and different neuropathic ache circumstances.
PMID: 26482371 [PubMed – indexed for MEDLINE]