Pregabalin in the treatment of post-traumatic peripheral neuropathic pain: a randomized double-blind trial.

BACKGROUND: Pregabalin is effective in the treatment of peripheral and central neuropathic pain. This study evaluated pregabalin in the treatment of post-traumatic peripheral neuropathic pain (including post-surgical). METHODS: Patients with a pain score >or=4 (0-10 scale) were randomized and treated with either flexible-dose pregabalin 150-600 mg/day (n = 127) or placebo (n = 127) in an 8-week double-blind treatment period preceded by a 2-week placebo run-in. RESULTS: Pregabalin was associated with a significantly greater improvement in the mean end-point pain score vs. placebo; mean treatment difference was -0.62 (95% CI -1.09 to -0.15) (P = 0.01). The average pregabalin dose at end-point was approximately 326 mg/day. Pregabalin was also associated with significant improvements from baseline in pain-related sleep interference, and the Medical Outcomes Study sleep scale sleep problems index and sleep disturbance subscale (all P < 0.001). In the all-patient group (ITT), pregabalin was associated with a statistically significant improvement in the Hospital Anxiety and Depression Scale anxiety subscale (P < 0.05). In total, 29% of patients had moderate/severe baseline anxiety; treatment with pregabalin in this subset did not significantly improve anxiety. More patients reported global improvement at end-point with pregabalin than with placebo (68% vs. 43%; overall P < 0.01). Adverse events led to discontinuation of 20% of patients from pregabalin and 7% from placebo. Mild or moderate dizziness and somnolence were the most common adverse events in the pregabalin group. CONCLUSION: Flexible-dose pregabalin 150-600 mg/day was effective in relieving neuropathic pain, improving disturbed sleep, improving overall patient status, and was generally well tolerated in patients with post-traumatic peripheral neuropathic pain.

Linguistic validation of the DN4 for use in international studies.

OBJECTIVES: Traditionally, pain is divided into two main groups: nociceptive pain due to an excess of nociception and neuropathic pain associated with an injury or dysfunction of the central or peripheral nervous system. The French neuropathic pain group has developed a specific questionnaire, the DN4, to help clinicians in the differential diagnosis of neuropathic and non-neuropathic pain. In order to allow this questionnaire to be used in international studies, it has been translated and linguistically validated into Dutch, German, Greek and Hungarian, using a well-established procedure. METHODS: The same method was used for each country and involved four stages: (1) two forward translations followed by comparison and reconciliation of the translations, (2) one backward translation, (3) review by an expert clinician, and (4) cognitive testing of the first seven items on patients. RESULTS: The translation work produced three types of situations. Either the original wording could be translated literally or semantic issues were discussed as the original wording was not always sufficiently clear and had to be clarified by adding an explanation, or, in the case of idiomatic phrases such as "pins and needles", it was necessary to use different expressions, the challenge being to retain the original concept while doing so. The versions proposed to patients and experts were well understood. CONCLUSION: The DN4 items were linguistically validated in each of the target languages, thus providing the means for standardising the diagnosis of neuropathic pain and pooling the data collected during clinical research in the different countries involved.

Comparison of TTS-fentanyl with sustained-release oral morphine in the treatment of patients not using opioids for mild-to-moderate pain.

OBJECTIVE: This randomised, multicentre, direct open comparative trial evaluated the efficacy, treatment convenience, tolerability and safety aspects of transdermal therapeutic system (TTS)-fentanyl and sustained-release oral morphine (SRM) in both opioid-naïve patients with moderate-to-severe cancer-related pain and in patients who had already been using opioids for mild-to-moderate pain. The two treatment groups were run in parallel. Special attention was paid to constipation, nausea/vomiting, drowsiness and respiratory depression. PATIENTS AND METHODS: The 131 enrolled patients started the 4-week treatment at low doses of opioid (25 microg/h TTS-fentanyl for 3 days or 30 mg SRM every 12 h) and were individually titrated. Tolerability, efficacy and safety were assessed throughout the study period. Frequency of constipation was the primary study variable and accordingly the study was powered for this. Both patients and investigators made a global treatment evaluation. RESULTS: TTS-fentanyl and SRM were shown to be equally effective. Pain control and sleep quality improved with both treatments. None of the patients developed respiratory depression. Statistically significantly more patients in the SRM treatment group discontinued the trial prematurely (59% vs 27%; p < 0.001), particularly due to adverse events (36% vs 4%; p < 0.001). Fewer patients in the TTS-fentanyl than in the SRM treatment group reported constipation during the trial. This finding was statistically significant after 1 week of treatment (27% vs 57%; p = 0.003). The favourable tolerability profile of TTS-fentanyl was also reflected in both the patient and the investigator global evaluation of the treatment. Patient assessment favoured TTS-fentanyl treatment in terms of a significantly lower rate of troublesome side-effects ('quite a bit' to 'very much' troublesome side-effects in 14% vs 36% of patients; p = 0.003) and less interruption of daily activities (absence of any interruption of daily activities in 88% vs 63% of patients; p = 0.012). Investigators scored TTS-fentanyl as significantly better with respect to 'side-effects' (p = 0.039) and 'overall impression' (p = 0.013). Sub-analyses of opioid-naïve users gave similar results. CONCLUSION: These data indicate that TTS-fentanyl, when used as an opioid of first choice in the treatment of cancer-related pain, is as effective as, but better tolerated than, SRM, including in opioid-naïve patients.