Effects of low-dose intranasal (S)-ketamine in patients with neuropathic pain

Background: NMDA receptors are involved in the development and maintenance of neuropathic pain. We evaluated the efficacy and safety of intranasal (S)-ketamine, one of the most potent clinically available NMDA receptor antagonists. Methods: Sixteen patients with neuropathic pain of various origins were randomized into two treatment groups: (S)-ketamine 0.2 mg/kg (group 1); (S)-ketamine 0.4 mg/kg (group 2). Plasma concentrations of (S)-ketamine and (S)-norketamine were measured over 6 h by High Performance Liquid Chromatography combined with mass spectrometry. Quantitative sensory testing (QST) was conducted before, during and after treatment. Side effects and amount of pain reduction were recorded. Results: Intranasal (S)-ketamine administration lead to peak plasma concentrations of 27.7 +/- 5.9 ng/ml at 10 +/- 6.3 min (group 1) and 34.3 +/- 22.2 ng/ml at 13.8 +/- 4.8 min after application (group 2). Maximal plasma concentrations of (S)-norketamine were 18.3 +/- 14.9 ng/ml at 81 +/- 59 min (group 1) and 34.3 +/- 5.5 ng/ml at 75 +/- 40 min (group 2). Pain scores decreased significantly in both groups with minimal pain at 60 min after drug administration (70 +/- 10% and 61 +/- 13% of initial pain in groups 1 and 2). The time course of pain decrease was significantly correlated with plasma concentrations of (S)-ketamine and (S)-norketamine (partial correlations: (S)-norketamine: -0.90 and -0.86; (S)-ketamine: -0.72 and -0.71 for group 1 and group 2, respectively). Higher dosing elicited significantly more side effects. Intranasal (S)-ketamine had no significant impact on thermal or mechanical detection and pain thresholds in normal or symptomatic skin areas. Conclusions: Intranasal administration of low dose (S)-ketamine rapidly induces adequate plasma concentrations of (S)-ketamine and subsequently of its metabolite (S)-norketamine. The time course of analgesia correlated with plasma concentrations. (C) 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.