A new perspective on chronic pain: molecular biological mechanisms and neuroimmune interactions

Chronic pain is not merely a symptom but a complex pathophysiological condition closely associated with nociceptor activation and sensitization, central nervous system reorganization, neuroimmune interactions, and gut microbiota dysbiosis. The limited efficacy of traditional treatments such as medications, surgeries, nerve blocks, and neuroplasticity in many patients can be attributed to their failure to adequately address these molecular, neurological, and immunological pathological mechanisms. This review article thoroughly analyzes the molecular mechanisms underlying the persistence and exacerbation of chronic pain. It particularly focuses on the effects of nociceptor sensitization, central nervous system sensitization, neurogenic inflammation, and gut microbiota dysbiosis on pain chronification. The paper also details how adrenal insufficiency and the weakening of the cholinergic antiinflammatory pathway contribute to the aggravation of chronic pain. A notable finding is that gut microbiota dysbiosis extends beyond gastrointestinal issues, potentially triggering systemic inflammatory responses and pain sensitization. This occurs through visceral-somatic neural connections and neuroimmune interactions, suggesting new therapeutic targets for chronic pain.