ErbB4 in Spinal PV Interneurons Regulates Mechanical Allodynia in Neuropathic Pain via Modulation of Glycinergic Inhibitory Tone

Yingying Yu, Guohua Wei, Qi Zhou, Huanhuan Sha Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of ChinaCorrespondence: Huanhuan ShaDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of ChinaTel/Fax +86-25-8371-4511Email shasha_1985@126.comBackground: Mechanical allodynia is the most common and challenging symptom associated with neuropathic pain; however, the underlying mechanisms are still unclear. The aim of this study was to investigate whether ErbB4, a receptor for neuregulin-1 (NRG1), participates in the modulation of mechanical allodynia.Methods: Radiant heat and von Frey filaments were applied to assess nociceptive behaviors. Real-time quantitative polymerase chain reaction, Western blotting, immunofluorescence, and small interfering RNA were used to identify the likely mechanisms.Results: ErbB4 was rapidly and persistently activated in spinal parvalbumin (PV) interneurons after chronic constriction injury (CCI) in mice. Knockdown of ErbB4 in the spinal cord prevented and reversed CCI-induced mechanical allodynia, and activation of ErbB4 by spinal application of NRG1 induced mechanical allodynia in naïve mice. Furthermore, we found that activation of ErbB4 decreased the glycine concentration in the spinal cord, contributing to modulation of mechanical allodynia.Conclusion: ErbB4 in spinal PV interneurons gates mechanical allodynia in neuropathic pain via regulation of glycinergic inhibitory tone, suggesting that a possible ErbB4-mediated process participates in the development of neuropathic pain.Keywords: Erb4, mechanical allodynia, parvalbumin interneuron, glycin