Y Xiang1, T Liu, H Yang, F Gao, H Xiang, A Manyande, Y Tian, X Tian. 1. Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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.
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.
Authors: David J Clarke; Tariq W Chohan; Mustafa S Kassem; Kristie L Smith; Rose Chesworth; Tim Karl; Michael P Kuligowski; Sandra Y Fok; Maxwell R Bennett; Jonathon C Arnold Journal: Schizophr Bull Date: 2019-03-07 Impact factor: 9.306