The aim of the study is to establish if the putative anticonvulsant SPM 927 has an analgesic effect in human neuropathic pain and to assess its tolerability. This is an open label study of 25 adult human subjects with resistant neuropathic pain. Subjects were treated with SPM 927 in a dose-escalating scheme to 600 mg daily, if tolerated. Treatment was continued for 4 weeks then withdrawn without tapering. Pain scores were recorded using a 11-point Likert score and a categorical pain-rating scale. Laboratory parameters and, electrocardiographs (ECGs) were collected; side effects were noted. Of the 25 enrolled subjects, 12 completed the study according to the protocol. The remaining subjects dropped out due to adverse events (n=12) or withdrawn consent. Mean daily pain scores (Likert score) fell by 0.83 (95% CI -1.77, +0.11) at the end of maintenance and rose by 0.58 (95% CI -0.23, +1.40) after withdrawal of SPM 927. Similar changes were seen in the categorical pain-rating scores. There were decreases in the mean scores for shooting pain, paraesthesia, and allodynia, but much less change in the numbness and burning-pain scores. The most common side effects were nausea, dizziness, leukocytosis, and increased ALT. No consistent changes in ECG recordings or haemodynamic variables were observed. SPM 927 may have an analgesic effect in human neuropathic pain and was reasonably well tolerated in this study. These data support the continued clinical development of SPM 927 for neuropathic pain.