Ketamine for the treatment of chronic non-cancer pain.
BACKGROUND
Worldwide the number of patients affected by chronic pain is growing and conventional treatment is often insufficient. Recently the importance of the N-methyl-d-aspartate receptor (NMDAR) in the mechanisms and maintenance of chronic pain was established. Ketamine (introduced in the 1960s as an anesthetic) is the most studied NMDAR antagonist in the treatment of various chronic pain syndromes.


METHODS
The pharmacology, safety and toxicology of ketamine are discussed. Further, electronic databases were scanned for prospective, randomized controlled trials that assessed ketamine's analgesic effect in patients with chronic pain. The focus of this review is on trials published after 2008 that applied long-term intravenous infusions.


RESULTS
While most studies on intravenous ketamine show acute analgesic effects, three recent trials on long-term ketamine treatment (days to weeks) demonstrate the effectiveness of ketamine in causing long-term (months) relief of chronic pain. Despite these positive results, further studies are needed on safety/toxicity issues. Other administration modes are less effective in causing long-term pain relief.


CONCLUSIONS
There is now evidence form a limited number of studies that pain relief lasting for months is observed after long-term intravenous ketamine infusion, suggesting a modulatory effect of ketamine in the process of chronic pain, possibly via blockade of upregulated NMDAR.
Noppers
Ingeborg
I
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Niesters
Marieke
M
Aarts
Leon
L
Smith
Terry
T
Sarton
Elise
E
Dahan
Albert
A
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D000700:Analgesics; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine