| Abstract [eng] |
Chronic pain is a significant public health problem, affecting approximately 20% of the population and imposing a substantial social and economic burden. Despite scientific advances, its pathophysiology remains complex and not yet fully understood. The aim of this extended literature review is to synthesize current knowledge on the pathophysiological mechanisms underlying the transition from acute to chronic pain. First the classification of chronic pain based on underlying mechanisms was reviewed and the physiological foundations of nociception were discussed. Then, the key peripheral and central mechanisms contributing to pain chronification were analyzed. The literature review was conducted using the PubMed database, including articles published between 2015 and 2026. MeSH terms were applied to ensure accuracy and relevance of the search results. In addition, terminology from the International Association for the Study of Pain (IASP) and major textbooks of physiology and pain were used. The pathophysiology of chronic pain is multidimensional and involves a complex interplay between peripheral and central mechanisms. A key mechanism is sensitization, characterized by increased neuronal responsiveness to normal stimuli and the emergence of responses to subthreshold stimuli. At the peripheral level, nociceptive neuron sensitization, neuroactive mediators (released by neuronal, immune, and non-immune cells), and structural remodeling of nerve fibers play a major role. At the central level, central sensitization is crucial and is associated with synaptic plasticity, reduced inhibition, NMDA receptor activation, and neuroinflammation. In addition, dysfunction of descending modulatory systems and reorganization of brain structures contribute to altered pain perception. These processes are dynamic and highly interconnected. Due to the complex interplay of these mechanisms, achieving effective management of chronic pain remains challenging. Despite significant progress, a mismatch between experimental and clinical research persists, limiting the implementation of new therapeutic strategies into practice. To improve treatment outcomes, it is essential to advance longitudinal human studies, standardize assessment methods, and develop mechanism-based, individualized treatment approaches. |
