NRG1-ErbB signalling promotes microglia activation contributing to incision-induced mechanical allodynia
1Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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.
Insights
Neuregulin-1 (NRG1) and its receptor erythroblastosis oncogene B (ErbB) signaling pathway activation in the spinal cord contributes to incision-induced pain. Targeting this NRG1-ErbB pathway may offer new treatments for post-operative mechanical allodynia.
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Spinal microglia activation is a key factor in post-operative pain following surgical injury.
- Neuregulin-1 (NRG1) and its receptor erythroblastosis oncogene B (ErbB) family are implicated in neuropathic pain via microglia proliferation and chemotaxis.
- The role of NRG1-ErbB signaling in incision-induced mechanical allodynia remains unclear.
Purpose of the Study:
- To investigate the contribution of NRG1-ErbB signaling to incision-induced mechanical allodynia.
- To determine if NRG1-ErbB signaling mediates spinal microglia activation following surgical incision.
Main Methods:
- Utilized a paw plantar incision model to induce mechanical allodynia.
- Measured NRG1, ErbB2 expression, and microglia activation using real-time PCR, Western blot, and immunofluorescence staining.
- Investigated the effects of pharmacological blockade of NRG1-ErbB signaling and siRNA-mediated down-regulation of NRG1 types I and II on pain and microglia activation.
Main Results:
- Incision led to significantly increased expression of NRG1 types I and II in the L5 dorsal root ganglion and spinal cord.
- NRG1-ErbB signaling was found to mediate incision-induced microglia activation and mechanical allodynia.
- Pharmacological inhibition of NRG1-ErbB signaling and siRNA knockdown of NRG1 suppressed microglia activation and alleviated mechanical allodynia.
Conclusions:
- Incision-induced NRG1 expression activates dorsal horn microglia, contributing to mechanical allodynia.
- Targeting the NRG1-ErbB signaling pathway presents a potential therapeutic strategy for managing incision-induced mechanical allodynia.
