Low doses ketamine: antihyperalgesic drug, non-analgesic

• Published in: Annales françaises d'anesthésie et de réanimation 2005-11, Vol.24 (11-12), p.1349
• Main Authors: Richebé, P, Rivat, C, Rivalan, B, Maurette, P, Simonnet, G
• Format: Article
• Language: fre
• Subjects: Analgesics, Opioid - administration & dosage; Analgesics, Opioid - therapeutic use; Anesthetics, Dissociative - pharmacology; Anesthetics, Dissociative - therapeutic use; Animals; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Amino Acid Antagonists - therapeutic use; Humans; Hyperalgesia - chemically induced; Ketamine - pharmacology; Ketamine - therapeutic use; Nociceptors - drug effects; Pain - physiopathology; Pain, Postoperative - drug therapy; Receptors, N-Methyl-D-Aspartate - drug effects
• ISSN: 0750-7658
• DOI: 10.1016/j.annfar.2005.07.069

Recent data in animal experiments as in clinical trials have clearly reported that pain modulation is related to an equilibrium between antinociceptive and pronociceptive systems. Therefore, the apparent pain level could not only be a consequence of a nociceptive input increase but could also result from a pain sensitization process. Glutamate, via NMDA receptors, plays a major role in the development of such a neuronal plasticity in the central nervous system, leading to a pain hypersensitivity that could facilitate chronic pain development. By an action on NMDA receptors opioids also induce, in a dose dependent manner, an enhancement of this postoperative hypersensitivity. "Antihyperalgesic" doses of ketamine, an NMDA receptor antagonist, were able to decrease this central sensitization not only in painful animal but also in human volunteers exposed to different pain models, or in the postoperative period. Many studies have reported that ketamine effects are elicited when this drug is administered the following manner: peroperative bolus (0.1 to 0.5 mg/kg), followed by a constant infusion rate (1 to 2 microg/kg per min) during the peroperative period and for 48 to 72 hours after anaesthesia. Those ketamine doses improved postoperative pain management by reducing hyperalgesia due to both surgical trauma and high peroperative opioid doses. This antihyperalgesic action of ketamine also limited the postoperative morphine tolerance leading to a decrease in analgesic consumption and an increase in the analgesia quality.