Emodin attenuates CFA-induced inflammatory pain in association with suppression of the Cx3cl1/Cx3cr1/p38 MAPK signaling axis
Year: 2026
Type: article
Abstract: Objectives To investigate the analgesic effect of emodin on Complete Freund’s Adjuvant (CFA)-induced inflammatory pain and to clarify the underlying molecular mechanism. Methods Emodin was administered intraperitoneally or prophylactically to attenuate CFA-induced inflammatory pain. RNA-seq was performed to identify the biological functions of differentially expressed genes in mouse dorsal root ganglion (DRG) tissues. The expression levels of Cx3cl1/Cx3cr1 were evaluated by RT-qPCR, Western blotting, and immunofluorescence. Pharmacological and genetic approaches were employed to block Cx3cr1 and assess its effect on pain thresholds in CFA-treated mice. Hematoxylin and eosin (H&E) staining was used to examine the infiltration of immune and inflammatory cells in dorsal root ganglion (DRG) tissues before and after emodin treatment. Following emodin treatment, the levels of p-p38/p38 in DRG tissues were determined by Western blotting, and the mRNA levels of the pro-inflammatory cytokines Tnf-α , Il-1β , and Il-6 in DRG tissues were measured by RT-qPCR. Results Both therapeutic and prophylactic administration of emodin effectively alleviated CFA-induced mechanical and thermal hypersensitivity. Emodin treatment suppressed the CFA-induced upregulation of Cx3cl1/Cx3cr1 mRNA and protein levels in the DRG. Pharmacological and genetic blockade of Cx3cr1 effectively attenuated CFA-induced hyperalgesia. In addition, emodin markedly inhibited p-p38/p38 protein expression in the DRG of mice with CFA-induced inflammatory pain, reduced immune cell infiltration in DRG tissues, and downregulated the levels of the pro-inflammatory cytokines Tnf-α , Il-1β , and Il-6 . Conclusion Emodin attenuated CFA-induced inflammatory pain in mice, an effect associated with reduced Cx3cl1/Cx3cr1 signaling, decreased p38 MAPK activation, diminished immune-cell infiltration in the DRG, and lower expression of the proinflammatory cytokines Tnf-α , Il-1β , and Il-6 in DRG tissue.
Source: Frontiers in Pharmacology
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7221774504