Upregulation of neuregulin-1 reverses signs of neuropathic pain in rats

International Journal of Clinical and Experimental Pathology

Guojun Wang¹  Lei Yuan¹  Aijun Zhang¹  Youming Lu¹  Pengqi Zhang¹  Xin Chen¹  Dawei Dai¹ 

关键词: Neuregulin-1;    GABA;    spinal dorsal horn;    neuropathic pain;    dorsal root ganglion;    gate control;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

Background: Peripheral nerve injury can result in neuropathic pain, a chronic condition of unclear cause often poorly responsive to current treatments. One possibility is that nerve injury disrupts large A-fiber-mediated inhibition of C-fiber-evoked responses in spinal dorsal horn neurons, leading to central sensitization. A recent study provided a potential molecular mechanism; large dorsal root ganglion (DRG) neurons secrete neuregulin-1 (NRG1), which binds to erbB4 receptors on interneurons and promotes GABA release to inhibit C-fiber-evoked nociceptive transmission. Thus, reduced NRG1 expression following nerve injury could induce chronic pain by disinhibition. We examined if DRG expression of NRG1 is in fact reduced in a rat model of neuropathic pain and if exogenous NRG1 alleviates behavioral signs of this condition. Methods: Three neuropathic pain models were established in rats: spared nerve injury of the tibial and common peroneal nerves (SNI model), intraplantar injection of complete Freund’s adjuvant (CFA model), and subcutaneous formalin injection. NRG1 expression was assessed by immunofluorescent staining, hyperalgesia by paw withdrawal threshold to von Frey filament stimulation, and pain-like behavior by spontaneous flinching. Results: NRG1 protein immunoreactivity was reduced in the rat DRG after SNI. Intrathecal administration of neuregulin-1beta 1 (NRG1-1), a 62 amino acid NRG1 mimetic, transiently increased paw withdrawal threshold in SNI model and reduced flinching in the formalin injection model. Conclusion: Our results are consistent with a model of neuropathic pain whereby peripheral nerve injury reduces NRG1-mediated inhibition of nociceptive signaling. Modulating NRG1 may have therapeutic potential for treating neuropathic pain.

【 授权许可】

Unknown