Xiangnan Li1, Haiqin Yang2, Qing Ouyang2, Fangting Liu2, Jian Li2, Zhenghua Xiang3, Hongbin Yuan4. 1. *Department of Anesthesiology, Changzheng Hospital, the Second Military Medical University, Shanghai, 200003, China; Department of Anesthesiology, the Third People's Hospital of Yancheng, Yancheng, 224001, China; 2. *Department of Anesthesiology, Changzheng Hospital, the Second Military Medical University, Shanghai, 200003, China; 3. Department of Neurobiology, Key Laboratory of Molecular Neurobiology, Ministry of Education, Second Military Medical University, Shanghai, 200433, China. 4. *Department of Anesthesiology, Changzheng Hospital, the Second Military Medical University, Shanghai, 200003, China; jfjczyy@aliyun.com zhxiang@hotmail.com.
Abstract
OBJECTIVE: There is some evidence implicating receptor for advanced glycation end products (RAGE) signaling in the pathogenesis of neuropathic pain (NP). The objective was to investigate whether RAGE signaling in the dorsal root ganglion (DRG) might contribute to NP following peripheral nerve injury. DESIGN: Experimental study before and after spinal nerve ligation (SNL) surgery. SETTING: Caged in a controlled environment. SUBJECTS: Male Sprague-Dawley rats. METHODS: A SNL rat model of NP was used. Mechanical hyperalgesia was measured by the paw withdrawal threshold (PWT) to mechanical stimuli (1.4-15 g). Protein expressions of RAGE (immunofluorescence and western blotting), glial fibrillary acidic protein (GFAP; satellite glial cell [SGC] activation marker), IL-1β (ELISA), TNF-α (ELISA), and NF-κB (western blotting) in the DRG were determined. RAGE signaling was inhibited by intrathecal injection of anti-RAGE antibody. RESULTS: After 7 days, SNL surgery reduced the PWT and upregulated the protein expression of RAGE, GFAP, NF-κB, TNF-α, and IL-1β. Intrathecal injection of RAGE-neutralizing antibody attenuated the SNL-induced mechanical hyperalgesia, activation of SGCs, and upregulation of NF-κB, TNF-α, and IL-1β in the DRG. CONCLUSION: RAGE signaling may contribute to the pain hypersensitivity observed in the rat SNL model of NP. Although the precise mechanism remains to be established, NF-κB, TNF-α, and IL-1β likely play a role, together with the activation of SGCs.
OBJECTIVE: There is some evidence implicating receptor for advanced glycation end products (RAGE) signaling in the pathogenesis of neuropathic pain (NP). The objective was to investigate whether RAGE signaling in the dorsal root ganglion (DRG) might contribute to NP following peripheral nerve injury. DESIGN: Experimental study before and after spinal nerve ligation (SNL) surgery. SETTING: Caged in a controlled environment. SUBJECTS: Male Sprague-Dawley rats. METHODS: A SNL rat model of NP was used. Mechanical hyperalgesia was measured by the paw withdrawal threshold (PWT) to mechanical stimuli (1.4-15 g). Protein expressions of RAGE (immunofluorescence and western blotting), glial fibrillary acidic protein (GFAP; satellite glial cell [SGC] activation marker), IL-1β (ELISA), TNF-α (ELISA), and NF-κB (western blotting) in the DRG were determined. RAGE signaling was inhibited by intrathecal injection of anti-RAGE antibody. RESULTS: After 7 days, SNL surgery reduced the PWT and upregulated the protein expression of RAGE, GFAP, NF-κB, TNF-α, and IL-1β. Intrathecal injection of RAGE-neutralizing antibody attenuated the SNL-induced mechanical hyperalgesia, activation of SGCs, and upregulation of NF-κB, TNF-α, and IL-1β in the DRG. CONCLUSION:RAGE signaling may contribute to the painhypersensitivity observed in the rat SNL model of NP. Although the precise mechanism remains to be established, NF-κB, TNF-α, and IL-1β likely play a role, together with the activation of SGCs.
Authors: Doris Lam; Zeinab Momeni; Michael Theaker; Santosh Jagadeeshan; Yasuhiko Yamamoto; Juan P Ianowski; Verónica A Campanucci Journal: PLoS One Date: 2018-02-23 Impact factor: 3.240