Summary: New research suggests that an antibiotic-induced shift in gut amino acid concentrations may be a causal mechanism for reduced inflammatory pain.
Source: University of New England
Glenn Stevenson, Ph.D., professor of psychology in the School of Social and Behavioral Sciences at the University of New England, recently published a study investigating how modulation of the gut microbiome influences inflammatory pain.
The article, titled “Effects of vancomycin on persistent pain-stimulated and pain-depressed behaviors in female Fischer rats with or without voluntary access to running wheels,” appears in The Journal of Pain and focuses on how the narrow-spectrum antibiotic vancomycin alters gut microbiota composition, gut amino acid profiles, and related pain behaviors.
Stevenson’s team examined the effects of oral vancomycin on inflammatory pain modeled by dilute formalin injection and measured both pain-stimulated behaviors and pain-depressed behaviors such as voluntary wheel running. The research specifically evaluated whether changes in the gut microbiome produced by antibiotic treatment could influence inflammatory pain occurring distant from the gut, such as in the limbs.
According to Stevenson, this study is the first to use the behavioral procedures developed in his laboratory to assess how antibiotic-driven shifts in the gut microbiota affect distal inflammatory pain. The research spanned four years and combined behavioral testing with microbiome and metabolite analyses to explore potential causal mechanisms.
Key findings indicate that two weeks of oral vancomycin reduced pain-related behaviors in the formalin model. Vancomycin attenuated Phase II formalin-induced pain-stimulated behavior and prevented the decline in voluntary wheel running that typically follows formalin injection. Microbiome analysis showed that vancomycin depleted major gut phyla including Firmicutes and Bacteroidetes while partially sparing Lactobacillus species and some Clostridiales.
Importantly, metabolomic profiling of the gut revealed an altered amino acid profile associated with vancomycin treatment: increases in arginine, glycine, alanine, proline, valine, and leucine, along with decreases in tyrosine and methionine. The authors propose that these antibiotic-induced shifts in gut amino acid concentrations may contribute to reductions in inflammatory pain amplitude, suggesting a plausible causal link between gut metabolites and peripheral pain signaling.
Fecal microbiota transplantation in the study produced a trend toward reversing the vancomycin effect on pain-stimulated behavior, though this change did not reach statistical significance. Together, the behavioral, microbiome, and metabolite results indicate that targeted manipulation of the gut microbiota could represent a novel strategy to modulate persistent inflammatory pain that occurs outside the gastrointestinal tract.
Stevenson highlighted the collaborative nature of the work: “This publication represents a highly interdisciplinary research team with expertise in genomics, proteomics, metabolomics, pharmacology, psychology, neuroscience, microbiology, and virology. When you put all these disciplines together to solve a single problem, you end up doing innovative, creative, and significant work.” He noted that core ideas for the project emerged from meetings with colleagues Meghan May and Tamara King and expanded through partnerships with researchers at Penn and Children’s Hospital.
Stevenson also emphasized the role of undergraduate students in the project: “This is another example of the high-quality, high-impact research that our UNE undergraduate students are engaged in daily. These co-authorships go a long way toward securing post-graduate positions for our students.”
About this pain research news
Author: Press Office, University of New England
Source: University of New England
Contact: Press Office – University of New England
Image: The image is in the public domain
Original Research: Closed access. “Effects of Vancomycin on Persistent Pain-Stimulated and Pain-Depressed Behaviors in Female Fischer Rats With or Without Voluntary Access to Running Wheels” by Glenn Stevenson et al., Journal of Pain.
Abstract
Effects of Vancomycin on Persistent Pain-Stimulated and Pain-Depressed Behaviors in Female Fischer Rats With or Without Voluntary Access to Running Wheels
These experiments evaluated the effects of the narrow-spectrum antibiotic vancomycin on inflammatory pain-stimulated and pain-depressed behaviors in a rat model. Persistent inflammatory pain was induced with dilute formalin (0.5%). Two weeks of oral vancomycin administered in drinking water attenuated Phase II formalin pain-stimulated behavior and prevented formalin-induced reductions in wheel running. Fecal microbiota transplantation produced a non-significant trend toward reversing the vancomycin effect on pain-stimulated behavior.
Microbiome analysis demonstrated depletion of Firmicutes and Bacteroidetes with partial sparing of Lactobacillus species and some Clostridiales following vancomycin treatment. Metabolomic profiling revealed altered gut amino acid concentrations—specifically increases in arginine, glycine, alanine, proline, valine, and leucine, and decreases in tyrosine and methionine—associated with the antibiotic effect. These findings suggest that vancomycin may exert therapeutic effects on persistent inflammatory pain that is distal to the gut, and that modulation of the gut microbiome and its metabolite profile may offer a pathway for attenuating inflammatory pain amplitude.
Perspective: The narrow-spectrum antibiotic vancomycin reduces pain-related behaviors in the formalin model of inflammatory pain. These data support the concept that manipulating the gut microbiome and its metabolic outputs could be a viable approach to lessen persistent inflammatory pain.