From mechanisms to therapy: Targeting the gut-brain axis in chronic gastrointestinal pain

Chronic gastrointestinal pain (CGP) is a common and often difficult-to-manage symptom in disorders of gut-brain interaction (DGBI). Owing to the limited efficacy of current therapeutic approaches in a subset of patients, a better understanding of gut-brain axis (GBA) dysfunction may facilitate the development of improved treatment strategies. This review summarizes the pathophysiological mechanisms underlying CGP, focusing on the contributions of microbial dysbiosis, mucosal immune activation, and neuroendocrine disturbances to peripheral and central nociceptive sensitization. Current therapeutic approaches, including cognitive and behavioral interventions, pharmacological neuromodulation, and microbiome-directed therapies, are critically reviewed with regard to their mechanistic basis and available clinical evidence. In addition, we discuss evidence indicating that plant-derived bioactive compounds have been reported to modulate multiple pathways implicated in CGP, including epithelial barrier dysfunction, visceral hypersensitivity, inflammatory signaling, oxidative stress, and ion channel activity. By integrating advances in psychogastroenterology with emerging findings from natural product research, this review discusses potential complementary strategies for CGP management and the challenges associated with their clinical translation. A deeper understanding of GBA regulation may facilitate the identification of novel therapeutic targets and inform the development of more individualized treatment strategies for CGP, although further preclinical and clinical studies are required to establish their efficacy and safety.