Ketamine for neuropathic pain: Animal and human studies

This chapter examines the potential of ketamine as a treatment for neuropathic pain, drawing comparisons between animal studies and human evidence. Neuropathic pain, affecting up to 8% of the population in Europe and North America, remains challenging to treat, with current therapies providing limited relief for only 30%–50% of patients. Animal studies highlight neuropathic pain as an inflammatory condition of the central nervous system, marked by NMDA receptor RNA upregulation, activation of microglial cells and astrocytes, and elevated neuroinflammatory biomarkers. These findings reinforce the NMDA receptor and neuroinflammation as key therapeutic targets. Ketamine, with its NMDA receptor antagonism, mu-opioid receptor activity, and antiinflammatory effects, shows promise in preclinical models, where prolonged relatively low-dose administration produces sustained pain relief. However, randomized controlled trials in humans offer limited support, particularly for single-dose or short-duration treatments. In contrast, real-world data suggest greater efficacy, likely due to flexible, patient-centered dosing regimens. Two key insights from animal studies may guide clinical practice: prolonged administration protocols and low-dose strategies to balance efficacy and tolerability. Further research is needed to optimize ketamine's therapeutic potential and bridge the gap between animal data, real-world findings, and randomized trials to better address the unmet needs of neuropathic pain management.