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Neuropathic pain sometimes needs invasive pain therapy. We present the case of a patient with cancer-related neuropathic pain untreatable with conventional pain therapy after tumour-embolization. The patient was treated successfully with intrathecal (i.t.) administration of S(+)-ketamine, in addition to morphine. Plasma concentrations of S(+)-ketamine were measured regularly throughout the treatment. Continuous i.t. administration of S(+)-ketamine over a period of 3 months demonstrated low plasma levels and no unwanted side-effects.

Implications: Our report describes for the first time the continuous long-term intrathecal application of S(+)-ketamine in a patient with chronic pain and morphine tolerance. Intrathecally applied S(+)-ketamine led to a significant pain reduction and consecutively reduced the doses of intrathecal morphine required for pain relief even several weeks after the cessation of the 24-day period of intrathecal S(+)-ketamine administration.

Although ketamine has been in clinical use for 3 decades, the neuropharmacological basis of its analgesic, anaesthetic, sympathomimetic, and psychotomimetic effects is still a subject of controversial discussion and intensive investigational efforts. In recent years, however, new experimental approaches to its effects on the cellular and molecular level and the availability of pure ketamine enantiomers contributed substantially to the understanding of its complex neuropharmacology. This article reviews the current knowledge of ketamine effects on ligand-operated and voltage-operated transmembrane ion channels, G-protein-coupled receptors, transmitter uptake, and the NO-cGMP system in neurons. With regard to its potential clinical relevance and supposed relative role among the complex mechanisms involved in pain perception, analgesia, anaesthesia, and psychotomimesis, the contributions of recent experimental and clinical findings to the identification of major target sites of ketamine are summarised. In contrast to the uncertainty surrounding the potential role of opioid receptors, there is now considerable evidence that NMDA antagonism is a central mechanism that contributes to the amnesic, analgesic, anaesthetic, and psychotomimetic as well as the neuroprotective actions of ketamine. Moreover, the involvement of non-NMDA glutamate receptors, muscarinic and nicotinic cholinergic transmission, interactions with 5-HT receptors, and L-Type Ca2+ channels may account for some of its anaesthetic and neuroprotective properties.

In recent years, much interest has focused on NMDA- and opiate-receptor-mediated actions of ketamine, whereas the search for other potential neuronal effects of this phencyclidine derivative has not attracted comparable attention. Nevertheless, the superfamily of voltage-operated membrane channels (VOC), ligand-operated ion channels (LOC) stimulated by acetylcholine and GABA, the non-NMDA subtypes of glutamate-activated LOC (kainate and AMPA receptor channels) and the closely related re-uptake processes of the monoamines noradrenaline, dopamine and serotonin should be considered potential targets of ketamine within the nervous system. Therefore, this review article summarizes our current knowledge of ketamine effects on these transmembrane ion channels and carrier mechanisms in the neuron. Unlike the NMDA-insensitive glutamate receptors for kainate and AMPA, the LOC activated by acetylcholine and the principal inhibitory amino acid GABA (gamma-aminobutyric acid) were both sensitive to clinical concentrations of ketamine, although in different ways. The relevance of these findings for the generation of the anaesthetic state, however, still remains to be established. Moreover, all VOC tested so far were reversibly inhibited at supra-clinical concentrations of ketamine (> 100 microM). Whereas no direct relevance to the state of general anaesthesia emerges from these data, local anaesthesia produced by comparably high concentrations of ketamine can be explained on the basis of its more or less unspecific inhibitory actions on VOC. Finally, the excellent antinociceptive activity of ketamine at the spinal and supra-spinal level may result at least in part from its inhibitory effects on the neuronal uptake of the monoamines noradrenaline, dopamine and serotonin.