Mindfulness-based processes can enhance attention and produce analgesia, making them effective for pain interventions. This review introduces the concept of mindfulness and its components as relevant to pain mechanisms, noting that differences in definitions, study design, and attention direction strategies must be considered when synthesizing findings. A dynamic process model of mindfulness-based analgesia is proposed: early effects stem from improved cognitive regulation, while later effects involve reduced interference between cognitive and affective factors. With practice, mechanisms shift, as neural activation changes from increased activity in the ACC and aINS in beginners to increased pINS and reduced lPFC activity in experts.
Ketamine produces rapid antidepressant effects by both blocking NMDA receptors and increasing serotonin levels through inhibition of the serotonin transporter (SERT). A cryogenic electron microscopy structure shows ketamine binding to SERT's central site. The elevated serotonin activates vasoactive intestinal peptide (VIP)-expressing interneurons, a cell type essential for ketamine's rapid effects. Inhibiting these neurons blocks the antidepressant actions, identifying a specific neural pathway. This dual mechanism offers potential strategies for developing rapidly acting antidepressants.