The anesthetic ketamine is used to treat chronic pain syndromes, especially those with a neuropathic component. Low-dose ketamine produces strong analgesia, likely by blocking the N-methyl-D-aspartate receptor, though other mechanisms such as enhanced descending inhibition and anti-inflammatory effects may contribute. Short-term infusions provide pain relief only during administration, while prolonged infusions of 4–14 days can yield analgesic effects lasting up to three months. Side effects include psychedelic symptoms, nausea, vomiting, somnolence, cardiovascular stimulation, and occasional hepatotoxicity.
Low-dose S(+)-ketamine alters the brain's intrinsic large-scale functional connectivity, as measured by resting-state fMRI. In twelve healthy men, ketamine increased connectivity in the cerebellum and visual cortex while decreasing connectivity in auditory and somatosensory networks, including regions involved in pain sensing and affective processing such as the amygdala, insula, and anterior cingulate cortex. Pain-related connectivity changes occurred in areas responsible for descending pain inhibition, including the anterior cingulate cortex, insula, orbitofrontal cortex, and brainstem. These connectivity changes correspond to ketamine's known effects on analgesia, psychedelic experiences, and other side effects.