R. Sabatowski

Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial

&NA; This study was designed to assess the efficacy and safety of pregabalin—a novel &agr;2‐&dgr; ligand with analgesic, anxiolytic, and anticonvulsant activity—for treating neuropathic pain in patients with post‐herpetic neuralgia (PHN). Two hundred and thirty‐eight patients were randomised into this multicentre, doubleblind, placebo‐controlled trial to receive 150 (n=81), 300 mg/day (n=76) pregabalin, or placebo (n=81) for 8 weeks. Among the exclusion criteria was failure to respond to previous treatment for PHN with gabapentin at doses ≥1200 mg/day. Endpoint mean pain scores were significantly reduced in patients receiving 150 or 300 mg/day pregabalin compared with placebo. Efficacy was observed as early as week 1 and was maintained throughout the study. Significantly more patients in both pregabalin groups (150 mg, 26%; 300 mg, 28%) were responders (≥50% decrease in mean pain score from baseline to endpoint) than in the placebo group (10%). Additionally, by week 1 and for the studys duration, 150 and 300 mg/day pregabalin significantly reduced weekly mean sleep interference scores. More pregabalin‐treated patients than placebo‐treated patients reported that they were ‘much improved’ or ‘very much improved’. Health‐related quality‐of‐life (HRQoL) measurements using the SF‐36 Health Survey demonstrated improvement in the mental health domain for both pregabalin dosages, and bodily pain and vitality domains were improved in the 300 mg/day group. The most frequent adverse events were dizziness, somnolence, peripheral oedema, headache, and dry mouth. Pregabalin efficaciously treated the neuropathic pain of PHN. Additionally, pregabalin was associated with decreased sleep interference and significant improvements in HRQoL measures.

Validation of the German version of the Brief Pain Inventory.

The Brief Pain Inventory is a comprehensive instrument for pain assessment and has been validated in several languages. A validated German version was not available until now. From March to May 1995 all outpatients of the pain clinic of the Department of Anesthesiology completed a questionnaire with the German versions of the Brief Pain Inventory (BPI) and the SF-36 quality-of-life questionnaire. The BPI was repeated after the consultation. The physician assessed the performance status score of the Eastern Cooperative Oncology Group (ECOG). The questionnaire was completed by 151 patients. Forty-two patients were excluded from evaluation for methodological reasons, so 109 patients were evaluated. As in the original version of the BPI, factor analysis showed a common factor for pain intensity and a second factor for pain-related interference with function. The comparative fit index of 0.86 confirmed this model. Responses before and after consultation correlated closely for the sum scores of the pain intensity items (Perarson correlation r = 0.976) as well as for the interference with function items (r = 0.974). Pain intensity in the BPI correlated with bodily pain in the SF-36 (r = 0.585). Sum scores of the pain interference items were higher in patients with deteriorated ECOG performance status, whereas sum scores of the intensity items were not changed. Validity and reliability of the German BPI were comparable to the original version. The BPI may be advantageous for palliative care patients, as it places only a small burden on the patient and offers easy criteria for evaluation. However, further research is needed to differentiate the impact of pain-related and disease-related interference with function on the BPI, and to find an algorithm for the evaluation of the BPI when values are missing.

Assessment and treatment of neuropathic cancer pain following WHO guidelines

Neuropathic pain syndromes are one of the major problems of cancer pain treatment. The present study surveys 593 cancer patients treated by a pain service following the WHO guidelines for relief of cancer pain. Of these, 380 presented with nociceptive, 32 with neuropathic and 181 with mixed (nociceptive and neuropathic) pain. In patients with nociceptive, mixed and neuropathic pain, the average duration of evaluated pain treatment was 51, 53 and 38 days, respectively. Non-opioid or opioid analgesics were given to 99%, 96% and 79%, antidepressants to 8%, 25% and 19%, anticonvulsants to 2%, 22% and 38% and corticosteroids to 26%, 35% and 22% of patients, respectively. Systemic analgesia was supported by palliative antineoplastic treatment (48%, 56% and 38% of patients), nerve blocks (3%, 6% and 6%), psychotherapy (3%, 7% and 3%), physiotherapy (6%, 12% and 13%) and transcutaneous electric nerve stimulation (1%, 6% and 6%). Analgesic treatment resulted in a significant pain relief in all groups of patients, as the mean pain intensity (NRS) decreased from 66 (nociceptive), 65 (mixed) and 70 (neuropathic) on admission to 26, 30 and 28 after 3 days and 18, 17 and 21 at the end of survey. The total outcome of pain treatment was not predicted by the designation to nociceptive, mixed or neuropathic pain. In conclusion, neuropathic cancer pain is not intractable and can be relieved in the majority of patients by treatment following the WHO guidelines.

High-Dose Tramadol in Comparison to Low-Dose Morphine for Cancer Pain Relief

Cancer pain treatment following the World Health Organization guidelines is effective and feasible. However, the evidence supporting the use of opioids for mild to moderate pain on the second step of the analgesic ladder is widely discussed. The present evaluation compares the efficacy and safety of high doses of oral tramadol (> or = 300 mg/d) with low doses of oral morphine (< or = 60 mg/d). Patients were included in this nonblinded and nonrandomized study if the combination of a nonopioid analgesic and up to 250 mg/d of oral tramadol was inadequate. 810 patients received oral tramadol for a total of 23,497 days, and 848 patients received oral morphine for a total of 24,695 days. The average dose of tramadol was 428 +/- 101 mg/d (range 300-600 mg/d); the average dose of morphine was 42 +/- 13 mg/d (range 10-60 mg/d). Additional nonopioid analgesics were given on more than 95% of days. Antiemetics, laxatives, neuroleptics, and steroids were prescribed significantly more frequently in the morphine group; the use of other adjuvants was similar in both groups. The mean pain intensity on a 0-100 numerical rating scale (NRS) was 27 +/- 21 (95% CI 26-29) in the tramadol and 26 +/- 20 (95% CI 24-27) in the morphine group (NS). The analgesic efficacy was good in 74% and 78%, satisfactory in 10% and 7%, and inadequate in 16% and 15% of patients receiving tramadol and morphine, respectively (NS). Constipation, neuropsychological symptoms, and pruritus were observed significantly more frequently with low-dose morphine; other symptoms had similar frequencies in both groups. These data suggest that tramadol can be used for the treatment of cancer pain, when nonopioids alone are not effective. High doses of tramadol are effective and safe.

Driving Ability Under Long-Term Treatment with Transdermal Fentanyl

Clinical experience shows that neuropsychological side effects due to opioid therapy usually decrease during the first weeks of therapy. However, the effect of long-term treatment with transdermal fentanyl on complex activities, such as driving, is not yet clear. In a prospective trial, patients with continuous noncancer pain, who had received stable doses of transdermal fentanyl for at least 2 weeks, completed a series of computerized tests to measure attention, reaction, visual orientation, motor coordination and vigilance. Data from 90 healthy volunteers were matched to 30 patients; 9 patients were excluded from the per-protocol analysis because they took additional drugs in violation of the protocol. None of the performance measures for the 21 remaining fentanyl patients was significantly inferior to the controls. We conclude that stable doses of transdermal fentanyl for the treatment of chronic non-cancer pain are not associated with significant impairments in psychomotor and cognitive performance. The threshold for fitness to drive as defined by German law did not differ significantly between the groups.

Validation of the German version of the brief fatigue inventory

Sedation and tiredness are among the most frequent symptoms among cancer patients. A detailed assessment of these symptoms is necessary to evaluate therapeutic effects, such as the use of methylphenidate or comparison of different opioids. The Brief Fatigue Inventory (BFI) has been validated as a short and comprehensive instrument to assess severity of fatigue and fatigue-related impairment in cancer patients. We validated the German version of the BFI in patients with chronic cancer-related and noncancer-related pain treated in a tertiary pain center. Patients treated in the Pain Clinic of the Department of Anesthesiology completed the BFI, the minimal documentation system (MIDOS) and the short form SF-36 quality-of-life questionnaire (SF-36). Test-retest reliability was assessed with a second BFI immediately after the consultation and in a subgroup of patients after 3 to 7 days. Nineteen percent of the 117 patients were treated for cancer-related pain (C); the other patients suffered from chronic severe pain of nonmalignant origin (NC). Patients reported mean values for average fatigue of 3.9 (C) and 4.9 (NC), and for worst fatigue of 5.5 (C) and 6.2 (NC). The mean score of the 6 impairment items was 4.3 in both groups. Factor analysis led to a solution with one common factor for all nine items. Fatigue on the BFI correlated highly with feeling tired in the SF-36 and with sedation in MIDOS, and less with being worn out in SF-36 and weakness in MIDOS. Internal consistency was high, as was test-retest reliability, with a correlation of the intensity, mean scores of 0.93 and the impairment mean scores of 0.87. In conclusion, we found the German version of the BFI to be reliable and valid for cancer and noncancer patients. Minor differences were seen in the validation compared to the original version.

Assessing cognition and psychomotor function under long-term treatment with controlled release oxycodone in non-cancer pain patients

Background:u2002 The therapeutic use of opioids can be associated with altered cognition and impaired psychomotor function. Several studies have demonstrated the impact of opioid therapy on psychomotor performance and cognition, but no data exist about the effect of long‐term treatment with controlled release oxycodone (CRO) on driving ability.

Tumorschmerztherapie in Deutschland

ZusammenfassungMit dem 1. Februar 1998 trat die zehnte Novelle der Betäubungsmittel-Verschreibungsverordnung (BtMVV) in Kraft. Damit wurden die Verordnung von Betäubungsmitteln und der Umgang mit den Betäubungsmittelrezepten erheblich erleichtert. Im Rahmen einer bundesweiten Anwendungsbeobachtung zu Fentanyl-TTS wurden zusätzlich Daten zum Stellenwert der WHO-Empfehlungen im Behandlungskonzept von Tumorschmerzpatienten und zur Einstellung zur BtMVV erhoben. Nur 9% der befragten Ärzte beantworteten die Fragebögen. Obwohl ein großer Teil dieser Ärzte angab, das WHO-Stufenschema zu kennen (93%), traten weiterhin bestehende Defizite zu Tage. Bei 15% der dokumentierten Patienten wies ein negativer Pain Management Index auf eine insuffiziente Schmerztherapie hin. Eine Zusatzmedikation zur Behandlung von Schmerzspitzen wurde in der Mehrzahl der Fälle (84%) nicht verordnet. Die Versorgung von Tumorschmerzpatienten kann nicht allein durch eine Vereinfachung der BtMVV und Erleichterungen bei der Verordnung von Opioid-Analgetika verbessert werden. Weitreichende Fort- und Ausbildungsprogramme sind in Zukunft erforderlich, um die nach wie vor bestehenden Defizite zu beseitigen.AbstractThe German regulations for opioid prescriptions have been changed in February 1998. The regulations have been made much more easier and should therefore have improved the pain management in Germany. We investigated the knowledge of the WHO analgesic ladder and how they have been followed in a nation-wide survey among physicians not specialised in pain management. Only 9% of the questionnaires were returned. Although the majority of the physicians (93%) reported knowledge about the WHO recommendations for the treatment of cancer pain, more than 15% of the participating physicians rated transdermal fentanyl as a weak opioid or even as a non-opioid. A negative pain management index in 15% of the patients gave evidence of poor quality in pain management. The majority of patients (84%) did not receive immediate release analgesics for the treatment of breakthrough pain.Continuous medical education is still necessary before a further alleviation of regulations will help to reduce the undertreatment of patients suffering from cancer pain in Germany.

A Randomized, Open, Parallel Group, Multicenter Trial to Investigate Analgesic Efficacy and Safety of a New Transdermal Fentanyl Patch Compared to Standard Opioid Treatment in Cancer Pain

A new 72-hour transdermal fentanyl matrix patch has been designed, which has a 35%-50% reduction of the absolute fentanyl content compared with other currently available transdermal fentanyl patches that are using the matrix technology. The new patch has previously been shown to be pharmacokinetically bioequivalent to the marketed fentanyl patch. To determine noninferiority in efficacy in cancer patients and to compare safety, a clinical trial comparing the new fentanyl patch with standard oral or transdermal opioid treatment was planned. The design was an open, parallel group, multicenter trial, in which 220 patients were randomized to receive either the fentanyl patch or standard opioid treatment for 30 days. The primary efficacy variable, pain intensity (PI) on a 0-10-point numerical rating scale, was recorded once daily. The primary endpoint was the relative area under the curve of PI expressed as a percentage of the maximum possible PI area under the curve. Any adverse events were recorded; four tolerability endpoints, constipation, nausea, daytime drowsiness, and sleeping disturbances, were assessed daily. Noninferiority was shown; the upper 95% confidence interval limits of the mean difference in relative PI area under the curve between the fentanyl patch and standard opioid treatment were less than 10% for both the intention-to-treat and per-protocol populations. Scores for the tolerability endpoints were similar in the treatment groups. The new fentanyl matrix patch with a lower drug load was found noninferior and as safe as established standard oral and transdermal opioid treatment.

Central pain processing in chronic low back pain. Evidence for reduced pain inhibition

ZusammenfassungHintergrundEine vergleichende Untersuchung hatte eine verstärkte zentralnervöse Schmerzverarbeitung bei Patienten mit idiopathischem chronischem Rückenschmerz („chronic low back pain“, LBP) v.xa0a. in den somatosensorischen Kortexarealen (S1, S2) gezeigt. In einer weiteren Analyse untersuchten wir diesen und weitere Unterschiede der neuronalen Aktivierung zwischen LBP und Gesunden im Hinblick auf mögliche zentrale Pathomechanismen.MethodenWährend der fMRT-Experimente waren Druckschmerzstimuli gleicher Schmerzintensität (mäßig intensiv) am linken Daumennagel in einem Blockparadigma verabreicht worden. In einer weiteren Analyse der fMRT-Daten wurden Unterschiede in der schmerzevozierten neuronalen Aktivierung beider Gruppen statistisch verglichen.ErgebnisseSubjektiv gleich schmerzhafte Stimuli lösten bei den Patienten im Bereich des periaquäduktalen Grau (PAG) eine signifikant reduzierte neuronale Aktivierung aus. Dagegen war das Ausmaß der Aktivierung bei LBP in S1, S2 und dem lateralen, orbitofrontalen Kortex (LOFK) signifikant höher als in der Kontrollgruppe.SchlussfolgerungBei Patienten mit LBP könnte eine Funktionsverminderung in den vom PAG kontrollierten absteigenden schmerzinhibierenden Systemen eine mögliche Ursache der klinischen Schmerzsymptomatik sein.AbstractIntroductionA study of patients with low back pain (LBP) had revealed altered central pain processing. At an equal pain level LBP patients had considerably more neuronal activation in the somatosensory cortices than controls. In a new analysis of this dataset, we further investigated the differences in central pain processing between LBP patients and controls, looking for possible pathogenic mechanisms.MethodsCentral pain processing was studied by functional magnetic resonance imaging (fMRI), using equally painful pressure stimuli in a block paradigm. In this study, we reanalyzed the fMRI data to statistically compare pain-elicited neuronal activation of both groups.ResultsEqually painful pressure stimulation resulted in a significantly lower increase of regional cerebral blood flow (rCBF) in the periaqueductal gray (PAG) of the LBP patients. The analysis further revealed a significantly higher increase of rCBF in LBP than in HC in the primary and secondary somatosensory cortex and the lateral orbitofrontal cortex (LOFK), elicited by these same stimuli.ConclusionsThese findings support a dysfunction of the inhibitory systems controlled by the PAG as a possible pathogenic mechanism in chronic low back pain.