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NRG 1‐ ErbB signalling promotes microglia activation contributing to incision‐induced mechanical allodynia
Author(s) -
Xiang Y.,
Liu T.,
Yang H.,
Gao F.,
Xiang H.,
Manyande A.,
Tian Y.,
Tian X.
Publication year - 2015
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.590
Subject(s) - microglia , erbb , neuropathic pain , medicine , neuregulin 1 , allodynia , spinal cord , nociception , anesthesia , receptor , inflammation , immunology , hyperalgesia , psychiatry
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 ( NRG 1) 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 NRG 1‐ ErbB signalling contributes to incision‐induced mechanical allodynia. Methods Expressions of NRG 1, ErbB 2 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 NRG 1‐ ErbB signalling or down‐regulation of NRG 1 types I and II via small interfering RNA ( siRNA ) intervention. Results NRG 1‐ ErbB signalling mediated incision‐induced microglia activation and mechanical allodynia. Expressions of types I and II NRG 1 in L 5 dorsal root ganglion at RNA level and in spinal cord at protein level were dramatically increased after paw incision. Pharmacologically blocking of NRG 1‐ ErbB signalling by ErbB inhibitor and down‐regulation, the expression of NRG 1 types I and II via siRNA suppressed incision‐induced microglia activation and alleviated mechanical allodynia. Conclusion Incision‐induced NRG 1 expression mediated activation of dorsal horn microglia and contributed to the development of mechanical allodynia. Specifically targeting NRG 1‐ ErbB signalling may therefore provide a new therapeutic intervention for relieving incision‐induced mechanical allodynia.