Gut microbiome profiles in patients with nociceptive pain, neuropathic pain, and pain-free controls: a case-control study

Reg Anesth Pain Med. 2026 Jun 3:rapm-2026-107796. doi: 10.1136/rapm-2026-107796. Online ahead of print.

ABSTRACT

OBJECTIVE: Gut microbiota have been implicated in pain modulation through immune, inflammatory, and neurobiological pathways, yet whether distinct gut microbial signatures differentiate nociceptive from neuropathic low back pain remains unclear.

METHODS AND ANALYSIS: In this longitudinal study, we profiled the gut microbiome of individuals with nociceptive low back pain (n=10), neuropathic low back pain (n=10), and pain-free controls (n=10) at baseline and after 3 months. Pain patients were resampled following standard-of-care treatment, while controls were resampled to capture background temporal variation. Gut microbial profiles were characterized using 16S rRNA gene (V4) sequencing. Alpha diversity was analyzed using mixed-effects models, beta diversity using Bray-Curtis, weighted UniFrac, and centered log-ratio-Euclidean distances, and differential abundance using Analysis of Compositions of Microbiomes with Bias Correction 2 (ANCOM-BC2).

RESULTS: Entropy-based alpha-diversity indices did not differ between groups or over time. Richness-based metrics suggested a possible reduction in the neuropathic-dominant group in pairwise contrasts after rarefaction, although omnibus group effects did not reach conventional statistical significance. Overall microbial community structure did not differ between pain groups and controls, and no population-specific or population-by-time effects were detected at the genus or amplicon sequence variant level.

CONCLUSION: Together, these findings indicate that gut microbiome differences across chronic pain phenotypes are subtle, characterized mainly by changes in low-abundance taxa rather than broad community shifts, underscoring limitations of microbiome-based stratification in chronic pain and the need for larger, integrative studies.

PMID:42236126 | DOI:10.1136/rapm-2026-107796