Systemic Injection of Thalidomide Prevent and Attenuate Neuropathic Pain and Alleviate Neuroinflammatory Response in the Spinal Dorsal Horn

Abstract

Hao Xu,1,2,* Sha-Jie Dang,3,4,* Yuan-Yuan Cui,1 Zhen-Yu Wu,1 Jun-Feng Zhang,2 Xiao-Peng Mei,5 Yu-Peng Feng,1 Yun-Qing Li1 1Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi’an, Shaan Xi, People’s Republic of China; 2Institution of Basic Medical Science, Xi’an Medical University, Xi’an, Shaan Xi, People’s Republic of China; 3Department of Anesthesiology, Shaanxi Provincial Cancer Hospital, Xi’an, Shaan Xi, People’s Republic of China; 4The Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaan Xi, People’s Republic of China; 5Department of Anesthesiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaan Xi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun-Qing Li; Yu-Peng FengDepartment of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi’an, Shaan Xi, People’s Republic of ChinaEmail [email protected]; [email protected] and objective: Thalidomide (Tha) has been shown to exert immunomodulatory and anti-inflammatory properties. Whether Tha can alleviate spinal nerve ligation (SNL)-induced neuropathic pain (NP) is still unclear. This study aimed to investigate the therapeutic effect of Tha on the SNL-induced NP and further explore the potential analgesic mechanisms of Tha.Methods: The effects of Tha on SNL-induced mechanical allodynia were assessed by pain behavioral testing. The expressions of the astrocyte marker glial fibrillary acidic protein (GFAP) and the microglia marker Iba1 in the spinal dorsal horn were evaluated by immunofluorescence histochemistry. Protein expressions of the tumor necrosis factor alpha (TNF-α) in the spinal dorsal horn were tested by Western blot assay. Data were analyzed using one-way ANOVA or two-way ANOVA.Results: By the pretreatment with a single intraperitoneal injection, the PWMT in SNL+Tha group was significantly increased from day 1 to day 2 after SNL (P < 0.05 compared with SNL+Veh group). By the posttreatment with a single intraperitoneal injection, the PWMT in SNL+Tha group was also significantly increased from day 3 to day 4 after SNL (P < 0.05 compared with SNL+Veh group). By the posttreatment with multiple intraperitoneal injection, both the PWMT and the PWTL in SNL+Tha group were similarly significantly increased from day 3 to day 14 after SNL (P < 0.05 compared with SNL+Veh group). Furthermore, the GFAP and Iba1 expressions and TNF-α levels of the ipsilateral spinal dorsal horn in SNL+Tha group were significantly weaker from day 3 to day 14 after SNL than those in SNL+Veh group (P < 0.05).Conclusion: Tha can significantly alleviate NP induced by SNL. The analgesic mechanism may be related to inhibition of astrocyte and microglia activation as well as down-regulation of TNF-α levels in the spinal dorsal horn.Keywords: Tha, neuropathic pain, Glia, TNF-α, spinal nerve ligation

Keywords

• tha
• neuropathic pain
• glia
• tnf-α
• spinal nerve ligation