8 The NMDA-antagonist ketamine for prevention and treatment of acute and chronic post-operative pain

Abstract

Summary The data reviewed here show that ketamine in sub-anaesthetic doses has analgesic properties that is related to the blockade of central NMDA receptors. Ketamine may become an effective pre-emptive analgesic by reducing the central sensitization to pain caused by increased activity in nociceptive primary afferents. Central sensitization to pain is dependent on the activation of NMDA receptors, and the action of ketamine is related to the blockade of central NMDA receptors. Psychotomimetic side effects is a major disadvantage with ketamine. Therefore, the compound should be co-administered with other drugs that may have additive effects so that the dose of ketamine can be reduced, like opioids or local anaesthetics, or drugs that reduce the psychotomimetic side effects, like benzodiazepines. Ketamine also reduces the different components associated with chronic pathological pain, including continuous, intermittent and evoked pain. Chronic pathological pain is dependent on altered functional activity in central nociceptive pathways, including neuronal hyperexcitability and hyperactivity. In these patients the central sensitization to pain has not been reversed in the normal way after an acute trauma. Evidence is given that ketamine may down-regulate this neuronal hyperactivity and thereby relieve pathological pain. However, a major objection against ketamine is the frequency of side effects. Therefore, the role of NMDA-receptor antagonists in the treatment of chronic pain, is dependent on the development of new and more selective NMDA-receptor blockers with few side effects. Furthermore, the co-administration of NMDA-receptor antagonists with other neurochemicals such as opioids, neuropeptides, and possibly local anaesthetics, might increase the analgesic efficacy.