AANA April 2026 Journal Course: The Gut-Brain Axis and Chronic Pain: The Emerging Role of Microbiota-The Gut-Brain Axis and Chronic Pain: The Emerging Role of Microbiota

The Gut-Brain Axis and Chronic Pain: The Emerging Role of Microbiota

Pdf Summary

This AANA Journal course reviews growing evidence that the gut microbiome influences chronic pain through bidirectional “gut–brain axis” signaling. Chronic pain is often maintained by central sensitization—heightened excitability and synaptic plasticity in nociceptive pathways—driven by neuroinflammation in both the peripheral and central nervous systems. The gastrointestinal tract hosts most of the body’s microbiota and contributes to immune regulation, barrier function, and production of neurotransmitters and bioactive metabolites that can shape pain processing.<br /><br />Gut dysbiosis (reduced diversity, loss of beneficial taxa, or overgrowth of harmful organisms) can impair intestinal tight junctions, creating “leaky gut.” This allows microbial products (eg, pathogen-associated molecular patterns such as lipopolysaccharide) and inflammatory mediators to enter circulation, amplify peripheral inflammation, and disrupt the blood–brain barrier. In the CNS, these signals activate microglia and astrocytes, increasing proinflammatory cytokines (eg, TNF-α, IL-1β, IL-6, CXCL1), enhancing excitatory glutamatergic transmission and reducing inhibitory GABAergic tone—changes that promote peripheral and central sensitization.<br /><br />The article highlights microbiota-derived metabolites that can worsen or alleviate pain. Harmful mediators include LPS and other bacterial cell wall components that trigger cytokine cascades and nociceptor sensitization. Potentially protective compounds include short-chain fatty acids (notably butyrate), GABA, kynurenic acid (analgesia via GPR35), and secondary bile acids that may reduce pain via TGR5-mediated endogenous opioid release.<br /><br />Preclinical and clinical findings link microbiome patterns to visceral pain/IBS (including effects of antibiotics, probiotics, rifaximin, and fecal microbiota transplant), inflammatory pain (germ-free models show reduced pain), neuropathic pain (chemotherapy-induced neuropathy modulated by microbiota; probiotic signals), migraines (mixed probiotic evidence), and opioid tolerance (opioids promote dysbiosis and barrier disruption; germ-free/antibiotic models attenuate tolerance).<br /><br />For CRNAs, the review emphasizes microbiome-conscious perioperative pain strategies: opioid-sparing multimodal analgesia, regional techniques, antibiotic stewardship, and supportive measures (dietary fiber, fermented foods, selected pre/pro/synbiotics, and investigational FMT), while noting the need for larger human trials and validated microbial biomarkers.

Keywords

gut microbiome

gut–brain axis

chronic pain

central sensitization

gut dysbiosis

intestinal permeability (leaky gut)

neuroinflammation

microglia activation

short-chain fatty acids (butyrate)

opioid tolerance