The ketogenic diet ameliorates behavioral abnormalities in a PTZ-induced zebrafish larvae model via modulating neurotransmitter balance.

Despite decades of study, pain is still one of the major challenges in both clinical and scientific terms. Chronic pain affects a substantial proportion of the adult population and is associated with considerable personal, social, and healthcare burdens (, ). Importantly, chronic pain is no longer regarded only as a symptom secondary to tissue injury or disease, but is considered rather as a complex condition that may involve persistent maladaptive changes in nociceptive processing, affective regulation, and behavior (). Although substantial progress has been made in defining nociceptive processes and pain neuroanatomy, effective treatment is still limited by the heterogeneous nature and poor understanding of the mechanisms behind the onset, maintenance, modulation, and remission of pain experience. In this regard, the Research Topic “Insights into Pain Mechanisms - 2024/2025” has been created to provide recent advances in pain neurobiology, particularly focusing on molecular pathways, neuroimmune interactions, brain circuits, translational approaches, and innovative technologies that can be useful in mechanism-based and personalized pain management. The five articles featured within this Research Topic represent the range of current research into mechanisms of pain. Together, they move across levels of analysis, from intracellular stress signaling and transcriptomic responses to descending brainstem modulation, multidimensional clinical phenotyping, and artificial intelligence (AI)-supported approaches with potential relevance to precision pain management. Such an integrative approach is especially appropriate in light of the fact that recent advances in the field of pain emphasize the importance of a multimodal approach which addresses biological mechanisms as well as brain-behavioral aspects of pain perception and disability (). The importance of studying mechanisms of pain is not only relevant to developing drugs, but non-pharmacological interventions as well. examined the relationship between pain measures of various dimensions and balance control in community-dwelling older adults. By integrating pressure pain threshold, pain intensity, pain catastrophizing, posturographic parameters, and functional reach performance, their study showed that not only the sensory but also cognitive-affective aspects of pain are independent predictors of postural instability. Chronic pain was linked to reduced functional reach, and longer pain duration predicted greater sway area. These findings take pain mechanism studies beyond the study of sensory processing alone and highlight how persistent pain can affect motor control, risk of falls, and functional independence in older adults.