title: NRG1-ErbB signalling promotes microglia activation contributing to incision-induced mechanical allodynia.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiang
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: F
authors.initials: F
authors.lastname: Gao
authors.forename: H
authors.initials: H
authors.lastname: Xiang
authors.forename: A
authors.initials: A
authors.lastname: Manyande
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.forename: X
authors.initials: X
authors.lastname: Tian
mesh_terms: D000818:Animals; D018409:Foot Injuries / Q000503:physiopathology; D006930:Hyperalgesia / Q000503:physiopathology*; D007278:Injections, Spinal; D008262:Macrophage Activation / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia; D020890:Neuregulin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D018739:Oncogene Proteins v-erbB / Q000037:antagonists & inhibitors* / Q000235:genetics*; D010149:Postoperative Pain / Q000503:physiopathology*; D010812:Physical Stimulation; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013489:Suppression, Genetic; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D018739:Oncogene Proteins v-erbB; C509204:PD168393; D011799:Quinazolines; D034741:RNA, Small Interfering