Journal of Pain Research (May 2022)
Z-Guggulsterone Relieves Neuropathic Pain by Inhibiting the Expression of Astrocytes and Proinflammatory Cytokines in the Spinal Dorsal Horn
Abstract
Sha-Jie Dang,1,2,* Wen-Bo Wei,3,* Rui-Li Li,4,* Can-Xu Song,5 Jin Xu1 1The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 2Department of Anesthesiology, Shaanxi Provincial Cancer Hospital, Xi’an, 710061, People’s Republic of China; 3Department of Orthopedics, Shaanxi Provincial People’s Hospital, Xi’an, 710068, People’s Republic of China; 4Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China; 5Department of Ultrasound, Shaanxi Provincial Cancer Hospital, Xi’an, 710061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jin Xu, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China, Email [email protected]: The study objective was to investigate whether Z-guggulsterone can relieve neuropathic pain in sciatic nerve chronic constriction injury (CCI) mice by inhibiting the expression of astrocytes and proinflammatory cytokines in the spinal dorsal horn.Methods: Neuropathic pain was induced and assessed in CCI mice. Z-guggulsterone was administered multiple times via intraperitoneal injection. Pain behaviour assessments were made by conducting paw withdrawal mechanical threshold (PWMT) and thermal withdrawal latency (TWL) tests. The expression level of the glial fibrillary acidic protein (GFAP) in the spinal dorsal horn was observed by immunofluorescence. The levels of the proinflammatory cytokines, IL-1β, IL-6 and TNF-α in the spinal cord were measured by ELISA. Data were analysed using one-way ANOVA or two-way ANOVA.Results: The PWMT and TWL were higher on the 5th, 7th, 10th and 14th days after CCI, the expression level of GFAP in the spinal dorsal horn was lower, and the levels of IL-1β, IL-6 and TNF-α in the spinal cord were lower in the CCI+Z-GS-L, CCI+Z-GS-M and CCI+Z-GS-H groups than in the CCI+Veh group in a dose-dependent manner (P < 0.05).Conclusion: Z-guggulsterone can relieve neurological pain in CCI mice, which may be related to the inhibition of astrocytes and proinflammatory cytokines in the spinal dorsal horn.Keywords: neuropathic pain, Z-guggulsterone, spinal dorsal horn, astrocytes, proinflammatory cytokines