Relief from Chronic Neuropathic Pain with Ketamine but Increased Burden of Psychedelic Adverse Effects?

Neuropathic pain (NP) is a frequently undertreated component of chronic pain, posing challenges due to its complexity. This has led to interest in N-methyl-D-aspartate receptor (NMDAR) antagonists like ketamine. NP is linked to maladaptive processes, such as NMDAR-related windup and sensitization. While results from ketamine trials on chronic NP have been inconsistent, perioperative use has shown potential to reduce chronic postsurgical pain and NP. For chronic NP, intravenous racemic ketamine at doses of 0.5–1.5 mg/kg/day for 4–5 days is recommended as an initial hospital-based approach. When effective, this provides pain relief lasting 1–3 months. Non-IV administration with de-escalating doses can then be tailored to individual patients, and infusions may be repeated quarterly if necessary. However, neurocognitive side effects can cause discomfort or treatment discontinuation. Psychological guidance during treatment helps patients remain engaged, and using gamma aminobutyric acid (GABA)-ergic agents beforehand can reduce adverse effects. Despite some challenges, the potential benefits of ketamine in chronic NP management often outweigh the risks. Further high-quality trials are urgently needed to refine ketamine use for NP.