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

AbstractBackgroundSpinal 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.MethodsExpressions 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.ResultsNRG1‐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.ConclusionIncision‐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.