NRG1-ErbB signalling promotes microglia activation contributing to incision-induced mechanical allodynia

Xiang, Yan, Liu, T., Yang, Hui, Gao, Feng, Xiang, Hong-Bing, Manyande, Anne, Tian, Yu-Ke and Tian, Xuebi (2015) NRG1-ErbB signalling promotes microglia activation contributing to incision-induced mechanical allodynia. European Journal of Pain, 19 (5). pp. 686-694. ISSN 1090-3801

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Abstract

BACKGROUND:
Spinal microglia activation is one of the pathologic mechanisms involved in post-operative pain, which results from surgical injuries in skin, fascia, muscle and small nerves innervating these tissues. Recent research has shown that neuregulin-1 (NRG1) and its receptor erythroblastosis oncogene B (ErbB) family mediate microglia proliferation and chemotaxis contributing to the development of neuropathic pain. However, it is unclear whether NRG1-ErbB signalling contributes to incision-induced mechanical allodynia.
METHODS:
Expressions of NRG1, ErbB2 and activation of microglia in spinal cord following paw plantar incision in an incision-induced mechanical allodynia model were detected with real-time PCR, Western blot and immunofluorescence staining. Altered mechanical pain and spinal microglia activation were observed by pharmacologically blocking of NRG1-ErbB signalling or down-regulation of NRG1 types I and II via small interfering RNA (siRNA) intervention.
RESULTS:
NRG1-ErbB signalling mediated incision-induced microglia activation and mechanical allodynia. Expressions of types I and II NRG1 in L5 dorsal root ganglion at RNA level and in spinal cord at protein level were dramatically increased after paw incision. Pharmacologically blocking of NRG1-ErbB signalling by ErbB inhibitor and down-regulation, the expression of NRG1 types I and II via siRNA suppressed incision-induced microglia activation and alleviated mechanical allodynia.
CONCLUSION:
Incision-induced NRG1 expression mediated activation of dorsal horn microglia and contributed to the development of mechanical allodynia. Specifically targeting NRG1-ErbB signalling may therefore provide a new therapeutic intervention for relieving incision-induced mechanical allodynia.

Item Type: Article
Subjects: Psychology
Depositing User: Anne Manyande
Date Deposited: 26 Oct 2015 14:44
Last Modified: 09 Oct 2017 09:08
URI: http://repository.uwl.ac.uk/id/eprint/1300

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