To research the role of the CXCL12/CXCR4 signaling pathway in inflammation and pain associated with chronic pancreatitis (CP), aiming to provide new therapeutic targets for the disease.

A total of 72 SD rats were randomly divided into 4 groups (18 rats in each group): control group (saline treatment); CP model group (TNBS induced); CP model+solvent treatment group; CP model+AMD3100 treatment group. CP was induced by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Von Frey filaments were used to assess the pancreatic hyperalgesia in rats. The expression levels of CXCL12 and CXCR4 in the rat pancreas were analyzed using Western blot and PCR. HE staining was used to observe the histopathology of pancreatic tissue, and the expressions of substance P (SP) and calcitonin gene-related peptide (CGRP) was detected via immunohistochemistry.

Three weeks after TNBS injection, the expressions of CXCL12 and CXCR4 in the rat pancreas significantly increased, with CXCL12 mRNA levels doubling (P<0.05) and CXCL12 protein expression also significantly rising (P<0.05). HE staining revealed that TNBS injection exacerbated pancreatic edema, inflammation, and necrosis. Immunohistochemical findings indicated that the expression of SP and CGRP significantly increased after TNBS treatment (P<0.05). DIL labeling techniques confirmed that CXCR4, as the receptor for CXCL12, was expressed on specific dorsal root ganglion (DRG) neurons in the pancreas. When the CXCL12 signaling pathway was inhibited using CXCR4 antagonist AMD3100, the pain sensitivity in rats significantly decreased, as shown by a marked reduction in the frequency of positive responses to von Frey filament stimuli (P<0.05). Additionally, after AMD3100 treatment, the expression of SP and CGRP in the pancreas notably declined (P<0.05), and the pathological damage to the pancreatic tissue was clearly mitigated, characterized by a decrease in inflammatory cell infiltration and the restoration of acinar structure.

The CXCL12/CXCR4 signaling pathway plays an important role in the inflammation and pain of chronic pancreatitis (CP). By inhibiting the CXCL12 signaling pathway, the use of the CXCR4 antagonist AMD3100 can effectively alleviate pancreatic inflammation, reduce pain sensitivity, and improve the pathological damage of the pancreatic tissue. The CXCL12/CXCR4 signaling pathway may serve as a potential therapeutic target for chronic pancreatitis, offering a scientific foundation for further research and clinical application.