Quantitative sensory testing (QST). English version.

Quantitative sensory testing (QST) is a standardized and formalized clinical sensitivity test. Testing describes a subjective (psychophysical) method that entails a cooperation of the person to be examined. Within its framework, calibrated stimuli are applied to capture perception and pain thresholds, thus providing information on the presence of sensory plus or minus signs. The presented QST battery imitates natural thermal or mechanical stimuli. The aim is to acquire symptom patterns of sensory loss (for the functioning of the thick and thin nerve fibers) as well as a gain of function (hyperalgesia, allodynia, hyperpathia) with a simultaneous detection of cutaneous and deep tissue sensibility. Most of the tested QST parameters are normally distributed only after a logarithmic transformation (secondary normal distribution)-except the number of paradoxical heat sensations, of cold and heat pain thresholds, and vibration detection thresholds. A complete QST profile can be measured within 1 h. QST is suitable not only for clinical trials but also in practice as a diagnostic method to characterize the function of the somatosensory system-from the peripheral nerve fiber receptor to the projection pathways to the brain.

[Pain management in rare diseases]. / Schmerztherapie bei seltenen Erkrankungen.

In this article we address the relevance of rare diseases and their peculiarities with respect to pain therapy. Towards this end, four rare diseases (hemophilia, Morbus Fabry, dermatomyositis, and facioscapulohumeral dystrophy (FSHD)) will be presented and fundamental aspects of their pain therapies described. The diseases were chosen to showcase a pain therapy based on the WHO-step-by-step plan (hemophilia), a complex but established pain therapy (M. Fabry), and two less well established, individually adapted pain therapies (dermatomyositis, FSHD).

Matrix stimulation in cancer pain: Methodology, safety and effectiveness.

BACKGROUND: This feasibility study addresses the applicability of matrix electrodes for the reduction of ongoing pain in cancer patients via low-frequency electrical stimulation (LFS). METHODS: Low-frequency matrix stimulation (4 Hz) was applied to the skin within the 'Head's zones' referring to the tumour localization of cancer pain patients. Pain at baseline was compared to a 3-day treatment interval consisting of 5 min of matrix stimulation in the morning and evening followed by a 3-day follow-up period without therapy. Main outcome parameters included numeric rating scale values (rating scale 0-100), painDETECT, HADS, and German pain questionnaire, as well as the opioid intake, calculated as the oral morphine equivalent (OME). RESULTS: Twenty patients with cancer pain (aged 64.4 ± 10.3; 9 women) were examined. In the majority of patients, the pain was classified as nociceptive. The mean pain reduction achieved by matrix therapy was 30%, under stable daily controlled-release opioid doses between 177 and 184 mg/day (OME). Seventeen patients (85%) were responders, defined by a pain reduction of at least 30%, while four responders experienced a pain reduction of over 50%. The only side effect was short-term erythema. CONCLUSION: Findings are consistent with the concept of synaptic long-term depression in cancer pain induced after conditioning LFS. Despite the short, but well-tolerated, treatment duration of 2 × 5 min/day, effects persisted throughout the 3-day follow-up. SIGNIFICANCE: Cutaneous neuromodulation using LFS via a matrix electrode has been shown to be a safe intervention for effectively reducing cancer pain in palliative care patients.

[Neuromodulation using matrix stimulation : A treatment for acute pain?] / Neuromodulation mittels Matrixstimulation : Ein Therapieansatz für akute Schmerzen?

BACKGROUND: There is currently a lack of studies that evaluate the effects of matrix electrode neuromodulation on acute pain. In this prospective and randomized cross-over study, we investigated the efficacy of 4 Hz-matrix stimulation on venipuncture-induced pain in 30 healthy subjects. METHODS: We compared two conditions of neurostimulation: in EC1 (experimental condition 1), we performed venipuncture during stimulation, with 2.5 min of prestimulation with 600 stimuli; in EC2 (experimental condition 2), the length of stimulation was 5 min, at 1200 stimuli, with subsequent venipuncture. A group with no stimulation was used as control condition. RESULTS: The EC2 group did not only show a 77% reduction in puncture pain when compared to the control group (p < 0.001; effect size [ES] d = 1.45), but also had a significant effect compared with EC1 (p < 0.001; ES d = 1.33). EC1, on the other hand, did not demonstrate a significant difference to the control group. The status of the veins was evaluated based on visibility and did not differ significantly between the conditions. CONCLUSION: The results of this study showed for the first time that pre-emptive matrix stimulation could be an effective way to reduce acute pain. The duration of stimulation seems to play a key role in the effectiveness of the neurophysiological mechanism of action. Matrix stimulation is a therapeutic intervention with very few side effects, which could, in the future, expand our pain-management options for the treatment of acute pain.

[High-intensity focused ultrasound (HIFU) for tumor pain relief in inoperable pancreatic cancer : Evaluation with the pain sensation scale (SES)]. / Hochintensiver fokussierter Ultraschall (HIFU) zur Linderung tumorbedingter Schmerzen bei inoperablem Pankreaskarzinom : Evaluation anhand der Schmerzempfindungsskala (SES).

BACKGROUND: High-intensity focused ultrasound (HIFU) in combination with palliative standard therapy is an innovative and effective treatment option for pain reduction in patients with inoperable pancreatic cancer. OBJECTIVE: Evaluation of the effects of additive ultrasound (US)-guided HIFU treatment in inoperable pancreatic cancer on the sensory and affective pain perception using validated questionnaries. MATERIAL AND METHODS: In this study 20 patients with locally advanced inoperable pancreatic cancer and tumor-related pain were treated by US-guided HIFU (6 stage III, 12 stage IV according to UICC and 2 with local recurrence after surgery). Ablation was performed using the JC HIFU system (HAIFU, Chongqing, China) with an ultrasonic device for real-time imaging. Clinical assessment included evaluation of pain severity using validated questionnaires with particular attention to the pain sensation scale (SES) with its affective and sensory component and the numeric rating scale (NRS). RESULTS: The average pain reduction after HIFU was 2.87 points on the NRS scale and 57.3 % compared to the mean baseline score (n = 15, 75 %) in 19 of 20 treated patients. Four patients did not report pain relief, however, the previous opioid medication could be stopped (n = 2) or the analgesic dosage could be reduced (n = 2). No pain reduction was achieved in one patient. Furthermore, after HIFU emotional as well as sensory pain aspects were significantly reduced (before vs. 1 week after HIFU, p < 0.05 for all pain scales). CONCLUSION: US-guided HIFU can be used for effective and early pain relief and reduction of emotional and sensory pain sensation in patients with locally advanced pancreatic cancer.

[Update palliative pain therapy]. / Update palliative Schmerztherapie.

Cancer pain and pain associated with non-neoplastic diseases can be associated with pain mechanisms, such as a peripheral or central sensitization or deafferentation. The clarification allows indirect conclusions about the underlying mechanisms based on clinical signs, such as allodynia or hyperalgesia. Non-opioid analgesics are the basis of cancer pain therapy according to the World Health Organization (WHO) pain ladder. In the case of severe cancer pain, treatment can be escalated directly from level 1 to level 3. Opioids are highly effective for the treatment of cancer pain even with a neuropathic component, which can occur in up to 40 % of cases as amixed pain syndrome. Coanalgesics represent a valuable therapeutic adjunct for better pain control and can address treatment of comorbidities, such as anxiety, depression and sleep disorders. When liver and/or renal function is reduced, the dosage of many drugs has to be adapted. Treatment of multimorbid or critically ill patients with opioids and antidepressants/anticonvulsants requires consideration of numerous possible pharmacodynamic and pharmacokinetic interactions.

Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer.

PURPOSE: Evaluation of ultrasound-guided high-intensity focused ultrasound (HIFU) used for the first time in Germany in patients with inoperable pancreatic cancer for reduction of tumor volume and relief of tumor-associated pain. MATERIALS AND METHODS: 15 patients with locally advanced inoperable pancreatic cancer and tumor-related pain symptoms were treated by HIFU (n = 6 UICC stage III, n = 9 UICC stage IV). 13 patients underwent simultaneous standard chemotherapy. Ablation was performed using the JC HIFU system (Chongqing, China HAIFU Company) with an ultrasonic device for real-time imaging. Imaging follow-up (US, CT, MRI) and clinical assessment using validated questionnaires (NRS, BPI) was performed before and up to 15 months after HIFU. RESULTS: Despite biliary or duodenal stents (4/15) and encasement of visceral vessels (15/15), HIFU treatment was performed successfully in all patients. Treatment time and sonication time were 111 min and 1103 s, respectively. The applied total energy was 386 768 J. After HIFU ablation, contrast-enhanced imaging showed devascularization of treated tumor regions with a significant average volume reduction of 63.8 % after 3 months. Considerable pain relief was achieved in 12 patients after HIFU (complete or partial pain reduction in 6 patients). CONCLUSION: US-guided HIFU with a suitable acoustic pathway can be used for local tumor control and relief of tumor-associated pain in patients with locally advanced pancreatic cancer. KEY POINTS: • US-guided HIFU allows an additive treatment of unresectable pancreatic cancer.• HIFU can be used for tumor volume reduction.• Using HIFU, a significant reduction of cancer-related pain was achieved.• HIFU provides clinical benefit in patients with pancreatic cancer. Citation Format: • Strunk HM, Henseler J, Rauch M et al. Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer. Fortschr Röntgenstr 2016; 188: 662 - 670.

[Dose-finding for treatment with a transdermal fentanyl patch : Titration with oral transmucosal fentanyl citrate and morphine sulfate]. / Dosisfindung zur Behandlung mit transdermalem Fentanylpflaster : Titration mit oralem, transmukosalem Fentanylcitrat und Morphinsulfat.

To date, no studies investigating titration with oral transmucosal fentanyl for the dose-finding of transdermal fentanyl treatment have been published. In an open randomized study 60 patients with chronic malignant (n = 39) or nonmalignant pain (n = 21), who required opioid therapy according to step three of the guidelines of the World Health Organization (WHO), were investigated. In two groups of 30 patients each titration with immediate release morphine (IRM) or oral transmucosal fentanyl citrate (OTFC) was undertaken. For measurement purposes the Brief Pain Inventory (BPI) and Minimal Documentation System (MIDOS) were used. After a 24-h titration phase, in which patients documented the intensity of pain, nausea, and tiredness, treatment with transdermal fentanyl was evaluated over a 10-day period by means of the necessary dose adaptation (responder ≤ 1 dose adaptation; conversion formula 1:1 [OTFC group] vs 100:1 [IRM group]).The pain reduction over the first 24 h (titration phase) did not differ significantly between the groups. The number of responders (17 OTFC vs. 21 IRM) over the 10-day period did not show any difference either. In both groups there was a significant reduction in pain intensity (p < 0.001). Over the course of the study, there were significantly more drop-outs because of adverse effects in the OTFC group than in the IRM group (8 vs 1, p = 0.028).Oral transmucosal fentanyl citrate can be applied for the titration of transdermal fentanyl, but it does not show any clinically relevant advantage. For example, the risk of side effects-induced drop-outs was greater in the present study. Whether the unnecessary opioid switching to treat chronic pain and breakthrough pain is advantageous with regard to minimizing conversion errors cannot be definitively answered within the scope of this study.

[Dyspnea, itching and depression in palliative medicine]. / Luftnot, Jucken und Depression in der Palliativmedizin.

Palliative medicine focuses on relieving burdening symptoms to improve quality of life. The most common symptoms are physical weakness, pain, loss of appetite, nausea as well as dyspnea, itching and depression. Frequently, good symptom control can be achieved using the most effective drug combination therapy or non-medicinal interventions. This article specifically addresses the physical symptoms dyspnea, itching and the psychological symptom depression.

[Cannabinoids in palliative care: Systematic review and meta-analysis of efficacy, tolerability and safety]. / Cannabinoide in der palliativen Versorgung : Systematische Übersicht und Metaanalyse der Wirksamkeit, Verträglichkeit und Sicherheit.

BACKGROUND: Cannabinoids have multiple medical indications in palliative care, such as relief of pain or nausea or increase of appetite and weight stabilisation. The value of cannabinoids for these indications is not resolved sufficiently for palliative patients. A systematic review with meta-analysis of the efficacy, tolerability and safety on the basis of randomised controlled studies (RCT) or randomised open label or crossover studies has not yet been conducted. MATERIALS AND METHODS: An extensive search for RCTs, randomised open label or crossover studies dealing with the underlying question was performed in the databases of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus and Clinicaltrials.gov up to April 2015. Studies with a duration of ≥ 2 weeks and ≥ 10 participants per treatment group were included into analysis. Using a random effects model, pooled estimates of event rates for categorical data and standardized mean differences (SMD) for continuous variables and risk differences (RD) for dichotomous variables were calculated. RESULTS: Out of initially 108 studies 9, with a total of 1561 participants suffering from advanced or end stage diseases, were included. The median study duration of the cancer research was 8 weeks (16 days-11 weeks), of the HIV research 6 weeks (3-12 weeks) and of the study concentrating on Alzheimer's 2 × 6 weeks. The outcome results for cannabis/cannabinoids vs. placebo in patients with cancer were not significant for the 30 % decrease in pain (RD: 0.07; 95 % confidence interval (CI): - 0.01 to 0.16; p = 0.07), caloric intake (SMD: 0.2; 95 % CI: - 0.66 to 1.06; p = 0.65) or sleep problems (SMD: - 0.09; 95 % CI: - 0.62 to 0.43; p = 0.72). In the treatment of HIV cannabinoids were superior to placebo for the outcome of weight change (SMD: 0.57; 95 % CI: 0.22-0.92; p = 0.001). Change in appetite was significant for the treatment of HIV (SMD: 0.57; 95 % CI: 0.11-1.03; p = 0.02), but not for treatment of cancer (SMD: 0.81; 95 % CI: - 1.14 to 2.75; p = 0.42). Nausea/vomiting (SMD: 0.20; 95 % CI: - 0.03 to 0.44; p = 0.09) and health-related quality of life (HRQoL; SMD: 0.00; 95 % CI: - 0.19 to 0.18; p = 0.98) did not show significant differences in the therapy of the two diseases. For the outcomes of tolerability the results were not significant for occurrence of dizziness (RD: 0.03; 95 % CI: - 0.02 to 0.08; p = 0.23) or psychiatric diseases, such as hallucinations or psychosis (RD: - 0.01; 95 % CI: - 0.04 to 0.03; p = 0.69) in the therapy of cancer. The outcome of psychiatric diseases in the treatment of HIV was significant (RD: 0.05; 95 % CI: 0.00-0.11; p = 0.05). The number of withdrawals due to adverse events, as a marker for tolerability, and the reports of serious adverse events as a measure of safety was not significantly different (RD: 1.20; 95 % CI: 0.85-1.71; p = 0.30 and RD: 1.15; 95 % CI: 0.88-1.49; p = 0.30, respectively). Dronabinol vs. megestrol acetate showed a superiority of megestrol in the therapy of cancer-associated anorexia for the endpoints change of appetite (49 vs. 75 %; p = 0.0001), weight gain (3 vs. 11 %; p = 0.02), HRQoL (p = 0.003) and tolerability (p = 0.03). There was no difference in the safety of the therapies (p = 0.12). In the treatment of HIV-associated wasting syndrome megestrol acetate was better than dronabinol for the endpoint of weight gain (p = 0.0001), whereas tolerability and safety did not differ. In the therapy of Alzheimer's dronabinol was better than placebo in the endpoint of weight gain according to one study (n = 15). A difference between herbal cannabis and synthetic cannabinoids, analysed by one study (n = 62) could not be found. CONCLUSION: Cannabinoids can lead to an increase in appetite in patients with HIV wasting syndrome but the therapy with megestrol acetate is superior to treatment with cannabinoids. The included studies were not of sufficient duration to answer questions concerning the long-term efficacy, tolerability and safety of therapy with cannabis or cannabinoids. Due to the sparse amount of data it is not possible to recommend a favoured use of cannabis or cannabinoids at this point.

[Quantitative sensory testing]. / Quantitative sensorische Testung.

Quantitative sensory testing (QST) is a standardized and formalized set of clinical sensitivity tests based on subjective (psychophysical) methods, which depends on the cooperation of the subject being investigated. Calibrated stimuli are used to measure the perception and pain thresholds, which provide information on the presence of sensory plus or minus signs. The QST equipment presented mimics natural thermal or mechanical stimuli. The rationale is to test for patterns of functional sensory loss or gain by simultaneous assessment of both cutaneous and deep pain sensitivity. The majority of QST parameters are normally distributed only after logarithmic transformation (i.e. secondary normalization). With QST a complete somatosensory profile can be obtained within 1 h. The QST is a suitable method for characterizing the function of the somatosensory system in clinical trials and also in clinical practice as a diagnostic procedure.

[Pain management in palliative care. Current aspects of medicinal therapy]. / Palliative Schmerztherapie. Aktuelle Aspekte der Arzneimitteltherapie.

Palliative care patients do not only suffer from cancer pain but also from painful muscle spasticity due to multiple sclerosis, amyotrophic lateral sclerosis, after stroke or due to dementia if damage of the pyramidal motor system is present. Centrally active muscle relaxants can be helpful also when used as coanalgesics for cancer pain. In addition to opioids other coanalgesics, such as tricyclic antidepressants or serotonin/noradrenalin reuptake inhibitors as well as anticonvulsants (sodium channel and calcium channel blockers) can be helpful if neuropathic cancer pain is present. Idiopathic Parkinsonism or multiple system atrophy leads more to a painful rigor and pain control should be supported here by optimal adjustment of L-DOPA or DOPA agonist therapy. However, pain treatment should always address the psychological, social and spiritual demands of the patient.