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Dynamic changes in intestinal microbiota mediate mechanical hyperalgesia in surgical menopause model: a potential
Ying Zhao1, Ninger Gong2, Shichao Wang3
1Department of Anesthesiology and Perioperative Medicine, Zhengzhou University People's Hospital; Zhengzhou University, Zhengzhou, Henan, China; Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
The role of the intestinal microbiota in hyperalgesia in ovariectomized mice remains unclear. This study aimed to investigate pain behavior and dynamic changes in the intestinal microbiota and the levels of related metabolites in a model of surgical menopause and to verify the hypothesis that the intestinal microbiota mediates the occurrence and persistence of hyperalgesia through neuroinflammation. An ovariectomy (OVX) model was constructed to assess the intestinal microbiota composition, the levels of related metabolites, and inflammation levels in the spinal dorsal root ganglion (DRG). Fecal microbiota transplantation (FMT) was used to alter the intestinal microbiota, and its impact on pain-related behaviors and the level of inflammation in the DRG was evaluated. The mechanical pain threshold was significantly lower in the OVX group compared with the sham group at 4-8 w after surgery, and the thermal pain threshold was greater at 5 and 8 w after surgery. A decrease in the mechanical pain threshold was observed in the OVX group 5, and 7-9 weeks after FMT, indicating hyperalgesia. PCoA and OPLS-DA revealed differences in the composition of the microbiota and the abundance of related metabolites between the OVX and sham groups. Correlation analysis revealed an association between pain thresholds and the levels and metabolites of certain bacterial genera. The expression of C/EBPβ and IL-1β in the OVX group was greater than that in the sham group, and the expression of IL-6, IL-1β, and TRPV1 in the sham group was greater than that in the OVX group after FMT. In conclusion, the dynamic changes in the intestinal microbiota in female mice induced by surgical menopause result in hyperalgesia, possibly due to an increase in the severity of inflammation in the spinal DRG.
Insights
Surgical menopause in mice causes hyperalgesia by altering gut microbiota and increasing spinal cord inflammation. Fecal microbiota transplantation reversed some pain behaviors, suggesting microbiota
Area of Science:
- Neuroscience
- Microbiology
- Immunology
Background:
- The connection between the gut microbiota and pain perception, particularly in the context of surgical menopause (ovariectomy), is not well understood.
- Surgical menopause can lead to various physiological changes, including potential alterations in pain signaling pathways.
Purpose of the Study:
- To investigate the impact of ovariectomy (OVX) on pain behavior, gut microbiota composition, and related metabolites in mice.
- To examine the role of the intestinal microbiota in mediating hyperalgesia following surgical menopause.
- To explore the relationship between gut microbiota changes, neuroinflammation in the spinal dorsal root ganglion (DRG), and pain.
Main Methods:
- Established an ovariectomy (OVX) mouse model to simulate surgical menopause.
- Analyzed fecal microbiota composition and metabolite levels using PCoA and OPLS-DA.
- Utilized fecal microbiota transplantation (FMT) to modulate the gut microbiota and assess its effect on pain behavior and DRG inflammation.
- Measured mechanical and thermal pain thresholds, and quantified inflammatory markers (C/EBPβ, IL-1β, IL-6, TRPV1) in the DRG.
Main Results:
- OVX mice exhibited significantly reduced mechanical pain thresholds and altered thermal pain thresholds, indicating hyperalgesia.
- Fecal microbiota transplantation (FMT) in OVX mice led to a decrease in mechanical pain thresholds weeks after transplantation.
- Significant differences in gut microbiota composition and metabolite profiles were observed between OVX and sham groups.
- Correlation analysis linked specific bacterial genera and their metabolites to pain thresholds.
- OVX increased the expression of C/EBPβ and IL-1β in the DRG; FMT altered IL-6, IL-1β, and TRPV1 expression.
Conclusions:
- Dynamic changes in the intestinal microbiota induced by surgical menopause contribute to the development of hyperalgesia in mice.
- Neuroinflammation in the spinal dorsal root ganglion (DRG) is implicated in the occurrence and persistence of hyperalgesia.
- The gut microbiota plays a mediating role in the relationship between surgical menopause and hyperalgesia.
