key: cord-0903411-ghciiggo
authors: nan
title: Gleich und doch verschieden – Personalisierte Schmerzmedizin
date: 2020-10-15
journal: Schmerz
DOI: 10.1007/s00482-020-00499-1
sha: 8ebf9cf41b717d16e891ed6dcbe5f7b8e58b2938
doc_id: 903411
cord_uid: ghciiggo

nan

Jeder Mensch hat potente körpereigene Schmerzhemmsysteme, die in absteigende und rein supraspinale Systeme unterteilt werden können. Eine Dysfunktion der endogenen Schmerzhemmung wird mit der Entwicklung und Aufrechterhaltung chronischer Schmerzen sowie mit der Stärke akuter Schmerzen in Verbindung gebracht. Außerdem stellt die endogene Schmerzhemmung ein Target für die innovative, nichtmedikamentöse Therapie von Schmerzen dar. Wichtig für die Schmerztherapie ist auch die Beeinflussung der endogenen Schmerzhemmung durch psychologische Faktoren, die die endogene Schmerzhemmung zur entscheidenden Schnittstelle zwischen Psyche und nozizeptiver Verarbeitung macht. Neben der Schmerzhemmung gibt es auch fazilitierende Systeme, beide werden als "endogene Schmerzmodulation" zusammengefasst. Für die Anwendung dieser Konzepte in der klinischen Praxis ist das Verständnis der zugrundeliegenden Mechanismen ebenso essenziell wie Daten zur Aktivität und Bedeutung der absteigenden Schmerzhemmung bei Patienten. Dieses Symposium wird die verschiedenen Aspekte der endogenen Schmerzhemmung beleuchten und zusammenführen. Zunächst werden Mechanismen und Ansatzpunkte der Aktivierung der absteigenden im Vergleich zur supraspinalen Schmerzhemmung beim Gesunden diskutiert [1, 2] , dann die Rolle der endogenen Schmerzhemmung bei der Migräne dargestellt, die als Erkrankung mit zyklischem Verlauf einen interessanten Sonderfall darstellt [3, 4] . Schließlich wird beleuchtet, inwiefern die Aktivität der endogenen Schmerzhemmung klinische Schmerzen vorhersagen oder auch beeinflussen kann, sowie untersucht, inwiefern Ähnliches für die dem Schmerz verwandte Empfindung des Juckens gilt. Das Symposium bringt psychologische und medizinische experimentelle Forschung zusammen mit Versorgungsforschung im Bereich der spezialisierten (SAPV) und allgemeinen ambulanten Palliativversorgung (AAPV). In einer Hinführung wird das im Bereich der Schmerzmedizin so spannende Thema der Placebo-wie auch Noceboforschung auch für die Palliativmedizin betrachtet. Im G-BA-Innovationsfondsprojekt AP-VEL wurden in Zusammenarbeit mit der AOK Sekundärdaten von fast 1 Mio. Patienten in deren letztem Lebensjahr analysiert und in Verbindung gebracht mit einer parallelen prospektiven Patientenbefragung unter zahlreichen AAPV-wie auch SAPV-Teams in Nordrhein. Der Beitrag fasst den aktuellen Status der SAPV zusammen und zeigt Forderungen für eine Optimierung auf. Ein weiterer Beitrag beleuchtet das so nah an der Schmerzmedizin liegende Thema Jucken -diesmal im Kontext der Palliativversorgung -leitliniengestützt und mit praktischen Beispielen. Das Symposium wird interaktiv und mit Praxisrelevanz drei aktuelle Bereiche der Palliativversorgung für eine multiprofessionelle Zielgruppe beleuchten. Zielgruppe: Das Symposium richtet sich an alle in der Palliativmedizin tätigen Berufsgruppen (Medizin, Pflege, Psychologie, Physiotherapie, Seelsorge u. a.) Background: An early screening of psychosocial risk factors to offer patients an individualized therapy for chronic back pain is recommended. Even though a multidisciplinary approach from medical, physiotherapeutic, and psychological fields in the rehabilitation ambulatory care in Germany is implemented, broad utilization is still missing [1] . In order to conceive a comprehensive individualized treatment and rehabilitation for chronic back pain patients, interdisciplinary programs including alternatives for patients living far away from clinical centers are needed. Aim: The purpose of this pilot study was to test whether it is possible to integrate an individualized and home-based aftercare program into the rehabilitation offer of the German Pension Insurance (feasibility). In addition, we aimed to investigate whether patients accept and adhere to such a program (acceptance and compliance) and whether the first results about the pain development are promising for the upcoming main study. Methods: Adult patients (n = 41) with chronic low back pain were included in this pilot randomized controlled study (RCT). The randomization followed a ratio of 2:1 into an intervention versus a control group within a 12-week program. The intervention group included two programs: unimodal (home-based aftercare sensorimotor training) and multimodal (home-based aftercare sensorimotor training and behavioral therapy module consisting of cognitive distraction, patient education, and body scan); a control group participated in the regular aftercare routine IRENA (Intensified Rehabilitätion Aftercare). Classification into the unimodal or multimodal group followed the risk screening index (RSI), which characterizes low-(unimodal) versus high-risk (multimodal) patients. Subjective pain disability and characteristic pain intensity was measured by the chronic pain grade (CPG) questionnaire. In addition, we assessed acceptance, compliance, and feasibility of the programs with individual questions. Results: The first exploratory analysis showed a significant reduction of the subjective pain disability score after 12 weeks in both intervention groups (p = 0.01 and p = 0.02). Apparently, there was a reduction concerning characteristic pain intensity for both interventions, but without statistical significance. Beyond patient acceptance, compliance and feasibility of the intervention programs were adequate. lery (GHG)-part of the HRM in the valley-combines several treatment factors such as low-level radon exposure, high humidity, and mild hyperthermia in a moderate altitude above sea level. Marked clinical effects in a variety of diseases and domains (e. g., symptoms, reduction of medication, physical functioning, and quality of life) are reported regularly by the patients. Our objective was to report the treatment effects in a patient suffering from small fiber polyneuropathy (SFPN). Methods: A 27-year-old male patient took eight one-hour sessions (at 37°, 75 % humidity, and radon radiation of 44kBq/m3) in the GHG over two weeks. He was encouraged to increase his physical activities (walking, hiking) on the days free of a gallery session. He had been suffering from SFPN (positive intraepidermal nerve fiber density test) for two years with burning pain and red skin (erythromelalgia) on his feet, legs, hands, and face and abdominal pain, severe constipation, and postural orthostatic tachycardia syndrome. During the course of his disease, he tried several medications including antiepileptics (i. e., gabapentin), antidepressants (i. e., duloxetine), opioids (i. e., tilidine), and ketamine with no noteworthy effects on his symptoms. The patient was assessed with pain items (visual analogue scale, VAS), pain distribution (sum of 24 bodily regions; each region rated on a Likert scale (0-5)), and questionnaires (fibromyalgia impact questionnaire revised (FIQ-R), perceived stress scale (PSS)) at predefined intervals before and after the gallery sessions (before/directly after/4 weeks/16 weeks). Background: Nonspecific low back pain (NLBP) causes an enormous burden to patients and tremendous costs for healthcare systems worldwide. Treatments frequently are not oriented to guidelines and about 65 % of patients with acute or subacute NLBP still report pain after 12 months. The cluster-randomized controlled Rise-uP trial aims to establish a general practitioner (GP) centered back pain treatment that includes four digital elements: (i) electronic case report form (eCRF), (ii) a treatment algorithm for guideline-based clinical decision making of GPs, (iii) teleconsultation between GPs and pain specialists for patients at risk for development chronic back pain, and (iv) the multidisciplinary Kaia back pain app. After the superiority of the Rise-uP concept compared to standard of care had shown in a three months follow-up, the long-term results of the Rise-uP trial (6 and 12 months follow-up) are reported here. Methods: Throughout Bavaria, 111 GPs were randomized either to the Rise-uP intervention group (IG) or the control group (CG). Rise-uP patients were treated according to the guideline-oriented Rise-uP treatment algorithm. Standard of care was applied to the CG patients with consideration given to the "National guideline for the treatment of non-specific back pain. " Pain ratings (primary outcome) as well as psychological measures (anxiety, depression, stress), functional ability, and physical and mental wellbeing (secondary outcomes) were assessed at the beginning of the treatment and at a 3, 6 and 12 months follow-up. Results: In total, 1245 patients (IG: 933; CG: 312) with NLBP were included in the study. The Rise-uP group showed significantly stronger pain reduction compared to the control group after 3 months (IG: M = -33 % vs. CG: M = -14 %), 6 months (IG: -39 % vs. CG: -21 %) and after 12 months (IG: -46 % vs. CG: -24 %). The Rise-uP group was also superior in secondary outcomes (stress, anxiety, depression, functional ability, and wellbeing). Interestingly, patients with a high risk of developing chronic pain who received a teleconsultation had a substantially stronger pain reduction (-48 %) compared to high-risk patients who did not receive a teleconsultation (-34 %) after 12 months. This effect seems to be mediated by a higher Kaia usage in patients who had received a teleconsultation compared to those who did not.

Our results show superiority of the innovative digital treatment algorithm realized in Rise-uP in a long-term observation period of one year, even though the CG also had received relevant active treatment by their GPs. We further show the importance of early risk determination. High-risk patients for chronic pain who receive a teleconsultation and show enhanced app usage especially benefit from the Rise-uP approach. This provides clear evidence that digital treatment may be a promising tool to sustainably improve the outcome of NLBP treatment and offers potential to bridge treatment in times of social distancing. Background and aims: Spatial summation of pain (SSp) occurs when subthreshold inputs from different sites induce action potentials in afferent neurons. In pain, SSp might explain why pain increases when the stimulated area is increased (area-based SSp) or when the distance between two stimulated sites is increased (distance-based SSp). SSp reflects how pain is facilitated and integrated in the central nervous system but little is known about factors influencing the magnitude of SSp and-despite years of investigation-the reliability of SSp has never been assessed. The aim of this study is therefore to investigate the effect of the stimulus intensity on the magnitude and reliability of SSp. Methods: Healthy participants were recruited and assessed in terms of area-and distance-based SSp using electrocutaneous stimuli. Five electrodes were attached to the ulnar side of the nondominant hand. SSp was determined for both SSp types, i. e., area-and distance-based SSp, using individually calibrated stimulus intensities inducing pain at the levels of 30, 50, and 70 out of 100 on a 0-100 visual analogue scale (VAS). In the areabased paradigm, participants received stimuli applied to a single electrode or sum of maximum five electrodes. In the distance-based paradigm a single electrode was activated or two electrodes with distances of 0, 1, 2, or 3 cm. After each stimulus, participants rated the intensity of pain using the same VAS scale. For each intensity level, participants received five stimuli repeated three times. They were not informed about the intensity level used in a given trial. Area-and distance-based SSp were assessed twice during the first day and once during the second day to determine the reliability.

Preliminary results indicate that SSp might be effectively induced using electrocutaneous stimuli in both paradigms but the slope for the SSp is slightly higher for area-based (m = 11.71) compared to distance-based SSp (m = 8.66). The effect of the intensity on the magnitude and reliability will be presented at the IASP congress. Conclusions: Spatial summation of pain can be effectively induced using electrocutaneous stimuli, however, a more pronounced effect seems to be elicited by the area-based paradigm. Relevance for patients: Spatial summation of pain is a test paradigm for assessing pain facilitation in humans. It can be used to ensure a valid diagnosis, prediction, and treatment response in different pain states, however reliability and validity of this remains to be evaluated. Background and study aim: Spatial summation of pain (SSp) refers to the increase in pain when the stimulated area is increased while the stimulation intensity remains constant (area-based SSp). A summation of pain also occurs when the distance between two stimuli increases (distancebased SSp). Although these two paradigms are well established and of high clinical relevance, the current understanding of the underlying mechanisms is insufficient. Furthermore, a knowledge gap in the SSp literature concerns mainly the reliability of SSp, which has never been assessed. For this reason, this thesis is dedicated to answering the question as to whether different paradigms of SSp are reliable. Methods: Twenty-four healthy subjects were included in the study and evaluated on two consecutive days with respect to the area-and distancebased SSp. Electrocutaneous stimuli were used, which were applied to the outer side of the nondominant hand via five electrodes. Stimuli of mild, moderate, and strong intensity were used to induce area-based and distance-based SSp. For the area-based paradigm, participants received stimuli by using a single electrode or up to five electrodes. For the distancebased paradigm the same electrode placements were used but the distance between two electrodes (activated at the same time) was manipulated. Either a single electrode or two electrodes separated by 0, 1, 2, or 3 cm were used. Pain induced by each stimulus type was evaluated by the subjects on a 0 to 100 numerical rating scale (NRS). To test the within-day reliability, two sessions were performed on the first day (15' interval) . To test the between-day reliability, a third session on the second day was performed (24 h interval). The reliability was quantified using the intraclass correlation coefficient (ICC), the standard error of measurement (SEM), and the smallest detectable difference (SDD). Results: It is apparent that the between-day reliability of SSp (ICC(2,3) from 0.50 to 0.80) is higher than within-day reliability (ICC(2,3) from 0.28 to 0.75). Comparing the two paradigms showed that the distance-based SSp is more reliable (ICC(2,3) from 0.39 to 0.80) than the area-based SSp (ICC(2,3) from 0.28 to 0.79). When SSp was induced by stimuli eliciting strong pain (NRS 70/100) the highest reliability was found (ICC(2,3) from 0.57 to 0.79).

Conclusion: This study demonstrated that not only the used paradigm but especially the intensity of pain has an influence on the reliability of SSp.

Poor reliability of small intensity paradigms might explain negative results of previous case-control studies. More reliable effects were found when testing the paradigms and intensities on two consecutive days than within the same day. Since no reliability study on SSp has been conducted so far, this is the first study that proves SSp to be a reliable paradigm depending on its type and intensity used. Neuronale Gb3-Ablagerungen wurden markiert und anschließend analysiert. Zusätzlich wurden Calcium-Imaging-Versuche zur Untersuchung der zellulären Aktivität durchgeführt. Ergebnisse: Wir konnten patienteneigene iPSC von beiden FD Patienten und der Kontrolle herstellen und daraus periphere sensible Neurone gewinnen. Gb3 konnten wir in Patienten-iPSC und -Neuronen nachweisen. Durch In-vitro-Enzymsubstitution reduzierten sich die Ablagerungen deutlich. Es zeigte sich auch, dass die Ablagerungen nicht nur exklusiv in den Neuronsomata zu finden sind, sondern auch proximal in den Neuriten vorkommen. Mittels Calcium-Imaging konnten wir nachweisen, dass die neuronale Aktivität in FD-Neuronen bei erhöhter Temperatur in vitro höher ist als bei Kontrollen. Schlussfolgerung: Unsere patienteneigenen Neurone imitieren den zellulären FD-Phänotyp, können mittels Enzymersatz "behandelt" werden und reagieren auf einen typischen FD-Schmerzstimulus mit erhöhter Aktivität. Somit haben wir die solide Basis für künftige In-vitro-Experimente geschaffen, um den Pathomechanismus von Schmerz bei FD zu entschlüsseln. Context: Neck, shoulder, and low back pain are common and mostly due to tight and cramped muscles. For the treatment of such pain conditions, topical application of heat is a widely established practice. Through a local increase in blood flow and skin temperature, heat therapy leads to relaxation of the muscles and relief of pain [1] [2] [3] . The objective of this study was to investigate the tolerability, safety, and therapeutic benefit of a topical heat patch in the treatment of local muscular or joint pain in patients with back pain. Methods: Prospective, multicenter postmarket clinical follow-up (PMCF) study in accordance with medical device legislation with a heat patch* intended for the relief of muscle and joint pain. The treatment period was three consecutive days (the planned application time per heat patch was 12 hours per day) with a two to three day followup period without treatment. Tolerability assessments were performed on visit 2 and safety and efficacy evaluations on visits 2 and 3. Additionally, a diary was kept by the patients. At the end of treatment (visit 2), global efficacy was rated as "excellent, " "very good, " or "good" for 78.5 % of the patients by the investigator and with 84.1 % by the patients themselves.

With respect to product acceptance, a high proportion of patients would buy (79.5 %) and recommend (84.1 %) the heat patch. Due to the flexibility of the patch, 93.2 % agree that it provides superior wearing comfort and allows continued movement. Due to the spiral heat design, 84.1 % agree that the test product provides an effective heat transmission and even distribution of warmth. Global local tolerability was assessed as "very good" or "good" for 86.2 % of the patients by the investigators and with 90.0 % by the patients themselves at the end of treatment. No serious and only a small number of nonserious adverse events occurred during the course of the study. Conclusion: In this study a good local tolerability and therapeutic benefit of the heat patch in the treatment of back pain after local application was shown. The results lead to the conclusion that the transmitted warmth contributes to long-lasting pain relief, reduced muscle stiffness, and an overall improvement in flexibility. Overall, the results of this PMCF study show that the use of Spiral Heat* is a safe and effective treatment for back, neck or shoulder pain. * Hansaplast/Elastoplast/Thermaplast Spiral Heat pharmacological intervention (exercise, physiotherapy, behavioral therapy, stress-reduction programs, etc.), and trials that report at least one stress biomarker. Studies published in English, German, and Spanish from the last 20 years were included. Additional studies were included though manual search of identified original articles and reviews reference lists.

No study included mediation analysis of any biomarker on the effectiveness of nonpharmacological interventions in chronic back pain, after the identification of 10 records. Further, there is some evidence of the change on specific biomarkers (tumor necrosis factor, superoxide dismutase, catalase and glutathione peroxidase, noradrenaline, matrix metalloproteinase-2, beta-endorphin, serotonin, and active anti-inflammatory cytokine TGF-b1) among individuals with chronic back pain after receiving a non-pharmacological intervention. Background: Stress is a critical factor in the development of chronic back pain (1). Furthermore, different types of psychological stress as social and work-related stress influence in an individualized way the development of pain intensity and disability in low back pain (2) . Likewise, the use of objective measures such as stress biomarkers allows a broader comprehension of the role of stress on the development of chronic back pain (3, 4) . Further, it is hypothesized that stress biomarkers are helpful to analyze the mechanism of action (mediation analysis) of chronic back pain therapies. Mediation analysis helps us understand the relationship between the intervention with the mediation variables, as well as to inform if those intermediate variables are associated with the target pain outcomes (3). Various randomized controlled trials of psychosocial interventions on low back pain show mostly small effects on pain disability. For this reason, research on the specific mechanisms of effectiveness is essential (5) .

In view of the critical role of stress and the need of mediation analysis on low back pain interventions, the focus of this systematic review is the mediation effect of stress biomarkers on the effectiveness of non-pharmacological interventions in chronic back pain. Methods: This systematic review used four electronic databases: PubMed, Medline (platform Web of Science), PsycINFO (platform EBSCO), and the Cochrane Central Register of Controlled Trials. The key search terms were "biomarkers, " "non-pharmacological interventions, " "pain, " and "mediation". The type of studies included interventional. The study eligibility criteria were adult patients with chronic back pain receiving any non- Background: Strong opioids are the mainstay of analgesic therapy in treating moderate to severe cancer-related pain [1] . Opioid induced constipation (OIC) is observed in up to 87 % of patients with cancer who are under treatment with opioids [2] . One of the characteristics of OIC is its persistence throughout the opioid treatment period compared to other adverse effects related to opioids use that resolve over time [3] . OIC is difficult to treat, as treatment based on dietary measures and laxatives are not effective in many patients [4] . Naloxegol is a peripherally acting µ-opioid receptor antagonist (PAMO-RA) indicated for the treatment of OIC in adults with an inadequate response to laxatives (LIR). To date, no data is available on the long-term use of naloxegol in patients with cancer. This is the first study to analyze the efficacy, quality of life (QOL), and safety of naloxegol for the treatment of OIC in patients with cancer in a realworld setting with a one-year follow-up. Methods: Patients over 18 years with active oncological disease (Karnofsky index ≥ 50), who were under treatment with opioids were recruited for the study in 16 Spanish centers. OIC with LIR was the main inclusion criteria. All the patients were treated with naloxegol. Efficacy was measured by the response rate and alleviation of symptoms using the patient assessment of constipation symptoms questionnaire (PAC-SYM) [5] ; pain intensity with a 0-to 10-point visual analog scale (VAS); OIC related QOL and global QOL with the patient assessment of constipation quality of life questionnaire (PAC-QOL) and the EuroQoL-5D-5L questionnaire, respectively [6, 7] . Results: A total of 126 patients were included (58.7 % male; mean age of 61.5 years (34-89)). Pain intensity on the VAS was reduced compared to baseline values (baseline-12 months: 4.6 to 3.6, p < 0.001). At 12 months, by inadequate blood plasma levels as a consequence of lower release rates due to ongoing emptying of the patch. If this is the case and EDFs occur subsequently to insufficient release, we might expect a relation to low residual contents or high variability in fentanyl uptake from the TPs. Therefore, we investigated the residual fentanyl content of different marketed matrix patches after application to pain patients under real-life conditions. Materials and methods: In total, 256 patches from 17 different patients (4 patients applied two patches simultaneously, marked as (a) and (b)) were collected by the pain department of the University Medicine Greifswald ( UMG) after use and were stored at -40 °C until analysis. In general, five different membrane patches and eight different matrix patches were used. Patient data, including time and duration of TP application, were provided by the UMG after residual content analyses were finished. During evaluation of patient data, all four patients (2, 7, 16, and 17) who used membrane patches as well as patients 4, 9, and 14 were excluded from the study due to reported irregularities during the test period. For the residual 10 patients, the mean residual fentanyl content (% of the declared drug load) and standard deviations (SDs) were calculated. For extraction, patches were attached on a bent stainless-steel wire to prevent sticking to the wall of the Erlenmeyer flasks and incubated for 12 h in 100 mL of methanol. Continuous mixing of the extraction medium was ensured by placing the sealed Erlenmeyer flasks in a shaking water bath with a constant temperature of 25 °C. Single extraction proved to be exhausting with fresh unused patches, as less than 0.5 % of the declared fentanyl could be recovered by a second extraction. Quantification of fentanyl was carried out using a Shimadzu HPLC equipped with a diode array detector. The calibration curve was prepared using 1 mL ampoules with a standard solution of 1 mg/mL fentanyl obtained from Cerilliant®. Results and discussion: Mean residual fentanyl contents were found to be between 39.1 and 70.8 % of the declared initial content with high interpatient variability between all patients, which is in line with the values reported in the literature. These high residual opioid contents led to certain recommendations for the handling and disposal of used patches. As the transdermal fentanyl uptake depends on various factors, e. g., site of application, skin temperature and blood circulation, the observed variability was not surprising (2) . Interestingly, the results showed that patch size and, as for matrix patches the nominal release rate is directly proportional to patch size, release rate doesn't seem to influence the percent remaining quantity of fentanyl in the TP. The evaluation of the clinical reports revealed that patients 1, 8, and 13 suffered from EDFs. Setting this in relation with the results of the residual fentanyl determination, it's interesting that patient 1 and 13 did not only obtain the lowest residual fentanyl content in used patches but also showed the highest variability in fentanyl uptake, with relative standard deviations of 8.4 % for patient 1, and 12.5 % in the case of patient 13. Knowing that even the rate of fentanyl released from the patch isn't constant over the application time (3), a low and inconsistent residual drug content might lead to unsteady plasma concentrations as an explanation for EDFs. Also, patient 8, who reported EDF as well, showed a negative deviation to the theoretical residual content, albeit with lower fluctuations. Taking a look at the results of this small case study in general, EDFs seem to be aided, but aren't necessarily caused, by a high and irregular fentanyl uptake from TPs, leading to low residual drug content and thus a lower concentration gradient between the matrix and skin. Conclusion: EDFs, as the main objective of this study, were reported for 3 of 10 patients. Indications for a connection between low, fluctuating residual fentanyl content in the patches and EDF were found. Whereas residual drug content in used fentanyl patches showed overall high interpatient variability, intrapatient variability differed essentially between patients. Interestingly, two of the three patients who reported EDFs were the ones with the lowest residual percentage drug content and highest variability in fentanyl uptake. However, to state the hypothesis that EDFs are caused by variations in fentanyl uptake, the patient individual totality of variables affecting fentanyl uptake might have to be taken into a more detailed account to understand the occurrence of EDFs. Nevertheless, the Background: Fentanyl, an opioid 100 times more potent than morphine, is widely used for the treatment of severe pain. Due to this high analgesic potency and its highly lipophilic characteristics as well as small molecule size, fentanyl is well suited for both membrane-and matrix-based transdermal patches (TPs). Both systems require a high concentration gradient between drug reservoir and skin during the entire therapy to ensure a continuous fentanyl delivery into the systemic circulation. Therefore, a high residual content of fentanyl in used patches is unavoidable. However, some patients experience end-of-dose failure ( EDF) during opioid therapy with TPs (1). This phenomenon expresses itself by insufficient pain relief and is mostly faced by dose escalation in combination with opioid rotation, multimodal therapy, and nonpharmacological interventions. ) and pain documentation (RR = 0.87, CI = 0.80-0.85) also had a positive effect on the WfmPT. All these effects were highly significant (p < 0.01). Discussion: WfmPT shows clinically expectable associations with other factors. Further, patient involvement has a large impact here. In today's medicine, a patient-oriented approach is often regarded as a higher standard and the simple question if patients wish for more treatment allows them more influence in the process of care. There was a strong association between WfmPT and worst pain ratings. WfmPT is a comprehensible and easily obtainable outcome, which might be of value in daily routine and clinical studies.

results of this small case study indicate that a constant drug release from TPs is crucial for effective pain relief. Results: In bivariate analyses, all variables were significantly related in hypothesized directions (p<.05). In mediation analyses with 10,000 bootstrapped samples, total effects of gratitude, self-compassion, and self-forgiveness were significant (GQ: t = -5.29, p<.0001; SC: t = -7.59, p<.0001; SF: t = -6.87, p<.0001), and direct effects were nonsignificant when stress, pain, and fatigue were added (GQ: t = -1.01, p = .31; SC: t = .34, p = .73; SF: t = -.74, p = .46). Each model accounted for 37 % of indirect effect variance (R2 = .37, p<.0001) and all indirect effects were significant. Conclusion: Supporting hypotheses, gratitude, self-compassion, and selfforgiveness were linked to less stress, pain, and fatigue and, in turn, to better functionality. Therapeutic promotion of positive psychological characteristics (e. g., mindfulness meditation; gratitude diaries) and reduction of stress (e. g., progressive muscle relaxation), pain (e. g., cognitive behavioral therapy), and fatigue (e. g., sleep diaries) may improve functional status in persons with chronic pain. Context: Chronic visceral pain is highly prevalent with a major psychological and socioeconomic burden; effective long-term treatments are still not available. Systemic inflammatory processes and an altered neuroimmune communication are discussed to contribute to the pathophysiology of chronic visceral pain syndromes. Furthermore, inflammatory processes pose a potential risk factor for mood disorders, especially of the depressive spectrum, and clinical studies demonstrate a complex and reciprocal connection between chronic pain and negative emotions. While these data support a close relationship between inflammation and negative mood in the context of visceral pain, a deeper understanding of the underlying psycho-neuro-biological processes is still needed. Thus, we conducted a randomized controlled study in healthy volunteers, and experimentally induced a transient low-grade systemic inflammation as well as a negative, depression-like mood to investigate the effects of inflammation and mood on visceral pain sensitivity. Methods: In this ongoing randomized, double-blind, placebo-controlled crossover fMRI study, healthy volunteers (N = 37; 16 female) received lowdose endotoxin (lipopolysaccharide; inflammation condition) or saline (placebo condition) on two otherwise identical study days. In both conditions, sad and neutral emotional states were induced using the established Velten paradigm. Immediately after mood induction, individualized painful rectal distensions were applied. Subjective ratings of mood, pain intensity, and unpleasantness were obtained, and blood oxygen level-dependent (BOLD) responses were analyzed using fMRI. Blood samples were repeatedly collected to analyze proinflammatory plasma cytokines. Results: Endotoxin application led to transient increases in proinflammatory serum cytokine concentrations, indicating low-grade inflammation. Participants' ratings of sadness were significantly increased in the negative mood condition compared to the neutral mood condition. During systemic inflammation, perceived intensity and unpleasantness of visceral pain stimuli were significantly increased. However, no effects of negative mood or the interaction of inflammation and negative mood on visceral pain sensitivity were found. Statistical analysis of fMRI data is ongoing to address neural mechanisms of inflammation-induced visceral hyperalgesia.

The present interim analysis shows that endotoxin application led to a systemic inflammatory response. While greater sadness ratings were observed in the negative mood condition, supporting the efficacy of the mood induction paradigm, no effects of negative mood on visceral pain sensitivity were found. However, inflammation significantly increased perceived intensity and unpleasantness of visceral pain. These findings from a carefully controlled experimental study can help to disentangle the complex interactions between inflammation, negative mood, and visceral pain. 

Quality of life research in pain patients

What do the numbers mean? Normative data in chronic pain measures

Die Depressions-Angst-Stress-Skalen. Der DASS -ein Screening-verfahren nicht nur für Schmerzpatienten

Psychologische Schmerzdiagnostik

Klinische Schmerzmessung

Graded chronic pain status: An epidemiological evaluation

Pain measurement in chronic pain management

Updating the definition of pain

Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study

Position Statement On Integrating New Migraine Treatments Into Clinical Practice

A randomized trial of a web-based intervention to improve migraine self-management and coping

A pilot study of cognitive behavioural therapy and relaxation for migraine headache: a randomised controlled trial

Therapie der Migräneattacke und Prophylaxe der Migräne, S1-Leitlinie. Deutsche Gesellschaft für Neurologie (Hrsg.), Leitlinien für Diagnostik und Therapie in der Neurologie

Psychologische Prävention der Migräne

Integrated multidisciplinary care of headache disorders: A narrative review

The International Classification of Headache Disorders

The influence of multimodal behavioral treatment on the consumption of acute migraine drugs: a randomized, controlled study

Multimodal behavioral treatment of migraine: An Internet-administered, randomized, controlled trial

Effect of preventive (β blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial

Whiplash, Headache and Neck Pain: Research Based Directions for Physical Therapies, 1. Aufl

Short-term effectiveness of an online behavioral training in migraine self-management: a randomized controlled trial

Effectiveness of Therapeutic Patient Education for Adults with Migraine. A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Entspannungsverfahren und verhaltenstherapeutische Interventionen zur Behandlung der Migräne. Leitlinie der Deutschen Migräne-und Kopfschmerzgesellschaft

The effect of neuriscience education on pain, disability, anxiety, and stress in chronoc musculoskeletal pain

Behavioral migraine management modifies behavioral and cognitive coping in people with migraine

Dynamics of changes in self-efficacy and locus of control expectancies in the behavioral and drug treatment of severe migraine

Mediumterm effectiveness of online behavioral training in migraine self-management: A randomized trial controlled over 10 months

Follow-up over 20 months confirms gains of online behavioural training in frequent episodic migraine

Therapie und Versorgung bei chronischer Migräne. Expertenempfehlung der Deutschen Migräne-und Kopfschmerzgesellschaft/Deutsche Gesellschaft für Neurologie sowie der Österreichischen Kopfschmerzgesellschaft/Schweizerischen Kopfwehgesellschaft

2019-nCoV epidemic: address mental health care to empower society

Imaging how attention modulates pain in humans using functional MRI

Comorbidity between pain and mental illness -Evidence of a bidirectional relationship

COVID-19 Pandemia and public and global mental health from the perspective of global health security

Evaluating psychosocial contributions to chronic pain outcomes

Anxiety, depression and sleep disorders in patients with diabetic neuropathic pain: a systematic review

Spatial summation of pain and its meaning to patients

Spatial Summation of Pain in Humans Investigated Using Transcutaneous Electrical Stimulation

Cortical Responses to Thermal Pain Depend on Stimulus Size: A Functional MRI Study

Therapeutic Heat. Therapeutic Heat and Cold

Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF

The role of psychosocial stress in the development of chronic musculoskeletal pain disorders: protocol for a systematic review and meta-analysis

Stress and Self-Efficacy as Long-Term Predictors for Chronic Low Back Pain: A Prospective Longitudinal Study

Causal mechanisms of a healthy lifestyle intervention for patients with musculoskeletal pain who are overweight or obese

Biomarkers of stress in behavioural medicine

Applying causal mediation methods to clinical trial data: What can we learn about why our interventions (don't) work?

A prospective study of mechanical physiotherapy for lumbar disk prolapse: five year follow-up and final report

Efficacy of Gabapentin for radiculopathy caused by lumbar spinal stenosis and lumbar disc hernia

The efficacy of gabapentin in the treatment of pain due to far lateral lumbar disc herniations

Avoid operative interventions without interdisciplinary clarification

Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines

Pathophysiology and Management of opioid-induced constipation: European expert consensus statement

Analgesic drugs

Laxatives do not improve symptoms of opioid-induced constipation: Results of a patient survey

Psychometric validation of a constipation symptom assessment questionnaire

Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire

Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L)

Treatment Strategies to Overcome End-of-Dose Failure with Oral and Transdermal Opioids

Inter-and intra-individual variability in transdermal fentanyl absorption in cancer pain patients

Fentanyl Transdermal Absorption Linked to Pharmacokinetic Characteristics in Patients Undergoing Palliative Care

The role of psychosocial stress in the development of chronic musculoskeletal pain disorders: protocol for a systematic review and meta-analysis

Stress and Self-Efficacy as Long-Term Predictors for Chronic Low Back Pain: A Prospective Longitudinal Study

Causal mechanisms of a healthy lifestyle intervention for patients with musculoskeletal pain who are overweight or obese

Biomarkers of stress in behavioural medicine

Applying causal mediation methods to clinical trial data: What can we learn about why our interventions (don't) work?

When pain gets stuck: The evolution of pain chronification and treatment resistance

A motivation-decision model of pain: The role of opioids

Durchhaltestrategien -ein in Schmerzforschung und Therapie vernachlässigtes Phänomen

Fear-avoidance-and endurance-related responses to pain: Development and validation of the Avoidance-Endurance Questionnaire (AEQ)

Acquisition and extinction of operant pain-related avoidance behavior using a 3 degreesof-freedom robotic arm

Fear-avoidance and its consequences in chronic musculoskeletal pain: a state of the art

Fear-avoidance model of chronic musculoskeletal pain: 12 years on

References 1. Brunette DM (2007) Critical Thinking. Understanding and evaluating Dental Research

Competency in generalist practice: a guide to theory and evidence-based decision making

Medical decision making, 2. Aufl

Clinical decision making in fluency disorders. Delmar, Cengage Learning

Critical thinking in clinical practice: improving the quality of judgments and decisions, 3. Aufl

Chronic pain after surgery: pathophysiology, risk factors and prevention

The pharmacological therapy of chronic neuropathic pain

Leitlinie Epidurale Rückenmarkstimulation zur Therapie chronischer Schmerzen -Langfassung

Neurophysiological effects of dorsal root ganglion stimulation (DRGS) in pain processing at the cortical level

Rational diagnosis and treatment: evidence-based clinical decision-making, 4

Ultrasound-guided stellate ganglion blocks combined with pharmacological and occupational therapy in Complex Regional Pain Syndrome (CRPS): a pilot case series ad interim

Effectiveness, safety, and predictive potential in ultrasound-guided stellate ganglion blockades for the treatment of sympathetically maintained pain

Minimal volume of local anesthetic required for an ultrasound-guided SGB

Counselling and self-management therapies for temporomandibular disorders: a systematic review

Schindler HJ, Türp JC (Hrsg) Konzept Okklusionsschiene. Basistherapie bei schmerzhaften kraniomandibulären Dysfunktionen, 1. Aufl. Quintessenz

2020) 2931 -Are the DC/TMD suitable for diagnosis of TMDs in schoolchildren?

Entstehung der Schmerzchronifizierung

New concepts of pain

The efficacy of traditional, low-cost and nonsplint therapies for temporomandibular disorder: a randomized controlled trial

An evidence-based assessment of occlusal adjustment as a treatment for temporomandibular disorders

Mediators, moderators, and predictors of therapeutic change in cognitive-behavioral therapy for chronic pain

Schindler HJ, Türp JC (Hrsg) Konzept Okklusionsschiene. Basistherapie bei schmerzhaften kraniomandibulären Dysfunktionen, 1. Aufl. Quintessenz

Headache in school children: is the prevalence increasing?

Non-pharmacological migraine treatment -A practice-oriented summary

Zentrum Schmerztherapie junger Menschen

Hintergrund: Die X-chromosomal vererbte lysosomale Speichererkrankung M. Fabry wird durch eine Mutation des (die alpha-Galaktosidase A kodierenden) GLA-Gens hervorgerufen und zählt zu den sog. seltenen schwerwiegenden progressiven Stoffwechselerkrankungen, die heute durch eine Enzymersatz-oder Chaperontherapie grundsätzlich behandelbar sind. Betroffene weisen eine große und nicht selten uncharakteristische Symptomvielfalt auf (wie z. B. akral betonte Parästhesien und neuropathische (Brenn-)Schmerzen, episodische Schmerzkrisen, Dyshidrose, Temperaturintoleranz, Angiokeratome, Herz-und Nierenerkrankungen sowie zerebrovaskuläre Symptome, etc.), die eine frühzeitige Diagnosestellung erschweren und damit die Effektivität ursächlicher Therapien einschränken. Zielsetzung: Entwicklung eines Online-Tools zur automatisierten phänotypischen Risikoprofilierung von Patienten mit chronischen Schmerzen bzgl. Vorliegen eines M. Fabry auf der Grundlage bereits bestehender Strukturen und Prozesse der Web-Applikation iDocLive®. Methodik: Evaluation, Gewichtung/Graduierung und Aggregation typischer klinischer Symptome und Symptomcluster des M. Fabry mit dem Ziel der Entwicklung eines Diagnosealgorithmus unter Berücksichtigung des Kerndatensatzes des Deutschen Schmerzfragebogens der Deutschen Gesellschaft für Schmerzmedizin (DGS) durch eine interdisziplinäre Gruppe klinischer Experten. Überprüfung des Algorithmus anhand des Bestandsdatensatzes des PraxisRegister Schmerz. Ergebnisse: Unter konservativer Anwendung des Diagnosealgorithmus konnten im Bestandsdatensatz des PraxisRegister Schmerz (Status quo 31.12.2019, n = 260.013) 149 Patienten (0,057 %; Prävalenz: 1 von 1745) mit einer eindeutigen sowie weitere 314 (0,121 %) mit einer auffälligen Konstellation klinischer/phänotypischer Symptome identifiziert werden. Ausblick: Nach Implementierung des in Phase 1 entwickelten Algorithmus in die dem PraxisRegister Schmerz konzeptionell zugrunde liegende Web-Applikation iDocLive® sind in Phase 2 (ab Herbst 2020) die entsprechende Real-World-Anwendung und die kontinuierliche Schärfung des Algorithmus zur phänotypischen Risikoprofilierung unter Verwendung genotypischer Informationen geplant. 

Carolina Roldán-Majewski¹, Steffani Görl¹, Nikolaos Nikitas Giannakopoulos² ¹Goethe-Universität Frankfurt, Zahnärztliche Prothetik, Frankfurt, Germany; ²Universität Würzburg, Zahnärztliche Prothetik, Würzburg, Germany Introduction: Temporomandibular disorders (TMD) have been related to psychosocial factors, which appear as determinant or risk factors for the incidence or progression of this condition. How important are these factors in clinical decision-making during the TMD treatment? The present survey was intended to explore the opinion about the measurement method of psychosocial factors on TMD patients proposed by axis II of the diagnostic criteria for temporomandibular disorders (DC/TMD). Methods: The survey was constructed according to axis I and II items of the DC/TMD. They were revised by two psychologists and one dentist. The first group of survey participants consisted of RDC/TMD consortium network (current INfORM) members attending a closed workshop with the goal of improving the clinical applicability of axis II. A similar online survey was offered to a group attending an international conference on oral pain. This adapted version excluded all specific questions requiring previous knowledge of the DC/TMD and it was previously tested in a workgroup for TMD at Frankfurt University. Results: Group 1: Twenty-one participants (100 % of attendants) answered the survey. Of those, 71.4 % declared using axis II for all orofacial pain patients. Familiar pain and extent of whole-body pain (94.4 % and 93.8 % respectively) followed by pain interference, depression, and anxiety (77.8 %, 76.5 %, 72.2 % respectively) were considered the most relevant factors in clinical decision making. However, other psychological factors not included in axis II are believed to be important to be assessed in TMD patients: catastrophizing, coping ability, and stress (90 %, 89.5 %, 88.9 %). Group 2: From 125 conference attendants, 29.6 % (37) participated in this study. Clinical findings dominated clinical decision making. Familiar pain, pain intensity, and range of mandibular movement were reported as the most relevant factors in clinical decision making, followed by anxiety score. All psychological factors were attributed the same importance (3.2 out of 10). Reasons for not implementing axis II were mostly time demand. Comparison between groups: Nonparametrical tests showed statistically significant differences between groups for the importance of the elements of DC/TMD and for the importance to measure psychological factors in TMD patients. Group 1 weighted significantly higher the importance of the psychosocial factors in general. Significant differences were also observed by the evaluation of time-demand for DC/TMD between group 1 and those in group 2. Conclusion: The main challenges regarding the importance of using axis II in the clinical treatment of TMD were linked to the effective clinical applicability of psychosocial instruments. Axis II may still be in development, some instruments were not considered relevant for clinical decision making, and some not included psychosocial factors were designated important. Background: The purpose of this study was to examine the diagnostic accuracy of a three-items questionnaire (PEG) for grading chronification of nonodontogenic orofacial pain. Methods: Two hundred and eighty-six consecutive patients with nonodontogenic orofacial pain filled out the PEG questionnaire and the graded chronic pain status (GCPS, version 2). The PEG questionnaire consists of the following three items from the brief pain inventory (BPI): "average pain intensity" (P), "interference with enjoyment of life" (E), and "interference of general activity" (G) during the past week. The internal consistency of PEG was tested with Cronbach's α. The correlation between the scores of both instruments was examined with nonparametric tests (Spearman's ρ). The validity measures of the PEG included sensitivity, specificity, precision, and accuracy, which were calculated for three groups according to the PEG average score. Differences in the GCPS grade between the PEG groups were examined with the Mann-Whitney U test. The level of significance was set at p ≤ 0.05. Results: The mean age of the 213 patients (158 female) who were included in the analysis according to the eligibility criteria was 43.1 ± 16.7 years. Of the sample, 49.3 % had some orofacial pain-related disability (> 0 disability points at GCPS); the mean characteristic pain intensity (CPI) was 51.2 ± 23.2 and the average overall PEG score was 4.3 ± 2.7. There were no significant differences between sexes for any score. The correlation between pain-related disability and PEG score was strong, significant, and positive (ρ = 0.77; p < 0.001). The internal consistency of the PEG questionnaire was high (Cronbach's α = 0.86). The overall accuracy of the PEG was estimated at 69 %. Grading patients with the PEG yielded three chronification groups (mild, moderate, and severe pain-related disability), which differed from each other significantly regarding their GCPS grade (Kruskal-Wallis p < 0.001).

The three-item PEG questionnaire is appropriate for grading nonodontogenic orofacial pain chronification. We propose its use for screening of orofacial pain. Fragestellung: Durch wiederholte Applikation von Lokalanästhetika in die Umgebung des Ganglion stellatum als Teil des sympathischen Grenzstrangs können neuropathische Schmerzen an den oberen Extremitäten und am Kopf gelindert werden. Die Vorzüge der ultraschallgezielten Ganglion-stellatum-Blockadetechnik (us-SGB) gegenüber der "blinden" Infiltration, nämlich die Reduktion von Nebenwirkungen [1] , [2] und Lokalanästhetikavolumina [3] , sind nachgewiesen und beschrieben. Ziel der vorliegenden Studie war nun die Validierung der ultraschallgezielten Punktionstechnik in den Musculus longus colli (MLC) durch die Erfassung der räumlichen Ausbreitung des Injektats mittels Magnetresonanztomografie (MRT). Die Wirkung der us-SGB wurde anhand von Hauttemperaturveränderungen und dem Auftreten der Horner-Trias objektiviert. Methoden: Bei 12 gesunden männlichen Probanden wurden doppelt verblindet, randomisiert insgesamt 37 ultraschallgezielte, transthyreoidale Stellatumblockaden (us-SGB) durchgeführt. Dabei wurden 3 ml Flüssigkeitsvolumen in den MLC injiziert, als Verum 3 ml Lokalanästhetikum Ropivacain 1 % und als Placebo 3 ml isotone Kochsalzlösung. Vor und nach der us-SGB erfolgte jeweils eine T2-gewichtete MRT-Untersuchung der Halsregion, um die räumlich-anatomische Verteilung des Injektats zu erfassen. Zur Wirkungskontrolle der Stellatumblockade wurden jeweils vor und nach der Intervention die Hauttemperatur an den oberen Extremitäten im Seitenvergleich bestimmt und Symptome der Horner-Trias sowie Nebenwirkungen dokumentiert. Ergebnisse: Die MRT bestätigte die korrekte Applikation aller Injektate in den Muskelbauch des MLC. Die Lokalisation bzw. Lage der maximalen axialen Injektatflächenverteilung reichte dabei vom mittleren Halswirbelkörper (HWK 5) bis zum oberen Brustwirbelkörper (BWK 1). Alle Probanden zeigten nach der us-SGB mit Verum (Ropivacain) signifikante Horner-Symptome und eine signifikante Temperaturdifferenz der oberen Extremitäten (M ± SD = 1,7 ± 1,8 °C, p < 0,01), während die Probanden nach der us-SGB mit Placebo keine Horner-Symptome und keine Temperaturdifferenz der oberen Extremitäten (M ± SD = 0,2 ± 0,5 °C, p = 0,29) aufwiesen. Diskussion und Schlussfolgerung: Die us-SGB per transthyreoidaler Punktion des MLC ermöglicht eine einfache Orientierung im Ultraschallbild. Die us-SGB ist sicher, nebenwirkungsarm und effektiv. Context: The Gastein Healing Gallery (GHG), as an important part of health resort medicine of the Gastein Valley in Austria, combines several treatment factors such as low-level radon exposure, high humidity, and mild hyperthermia in a moderate altitude above sea level. Patients regularly report marked clinical effects in a variety of domains, including symptoms, reduction of medication, physical functioning, and quality of life. Our objective was to assess the subjective effects of gallery sessions on medication intake and symptoms in a cohort of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or fibromyalgia syndrome (FMS) attending the GHG. Methods: We conducted 14 qualitative interviews with patients regularly attending the GHG in Austria. Interviews for the study were open ended and structured only to the extent of being guided by a set of predefined topics, including effects of the gallery visits on symptomatology and physical and mental health. Conversations were recorded and later transcribed verbatim. Content analysis was performed according to Mayring with the program MaxQDA. The creation of categories followed both deductive and inductive methods. Results: Fourteen patients took part in the interviews. The mean age was 58 years (SD 5.4); six patients were female. Four patients each suffered from RA or AS and six patients from FMS. On average, the patients had 11 stays with gallery sessions (min. 1, max. 35.). Of our participants, 14, 64, and 22 % rated the gallery sessions as extremely, very, and pretty successful, respectively. Five salient themes emerged from the analysis: 1) The ability to reduce or even to stop pain medications including opioids and cortisone as well as biologics, antiepileptics, or asthma medication; 2) The reduction of pain after every stay and prolongation of pain-free periods with regular stays; 3) Positive influence on mood and thoughts resulting in less depression and anxiety and more feelings of happiness; 4) Improvement of severity and frequency of fatigue, stiffness, and muscle cramps; and 5) Better sleep quality leading to more energy, better functioning during the day, and a more harmonic interaction with fellow human beings. Conclusions: In this qualitative study, patients across diagnostic groups report, in their own words, considerable improvements in medication use and symptoms of their chronic disease. Regular therapeutic visits to the GHG lead to an overall reduction of their medication intake or even stopping use of pain killers, biologics, or cortisone. Interestingly, patients indicate considerable improvements in a variety of different symptoms, including pain, stiffness, depression, and sleep, suggesting a complex effect of the mild radon hyperthermia in the Gallery on different physiological processes. To conclude, patients with RA, AS, or FMS benefit significantly from regular stays in the GHG with respect to their medication intake and multiple symptoms of their chronic diseases.

Hintergrund: Das Fibromyalgiesyndrom (FMS) ist ein chronisches Schmerzsyndrom mit unterschiedlichen Symptomenkomplexen und Verlaufsformen. Eine objektive Diagnose und individualisierte Behandlung wird durch die unklare Pathophysiologie und breite phänotypische Varianz erschwert. Veränderungen in der Peripherie auf lokaler (Haut) und systemischer (Blut) Ebene sind in FMS beschrieben, deren potenziell pathophysiologische Beteiligung ist bislang jedoch nur fragmentär und uneinheitlich bekannt. microRNAs (miRNAs) sind posttranskriptionelle Schlüsselregulatoren, die maßgeblich auf die Genexpression einwirken. Abweichend exprimierte miRNAs erlauben dadurch Rückschlüsse auf FMS spezifische Änderungen im zellulären Kontext. Methodik: Wir rekrutierten FMS-Patientinnen (n = 39) und altersadaptierte gesunde Probandinnen (n = 23). Alle Teilnehmerinnen wurden neurologisch untersucht und mit Fragebögen bezüglich FMS-, Schmerz-und Depressionssymptomen charakterisiert. Als Biomaterial wurden Vollblut und aus diagnostischen Hautbiospien gewonnene primäre Keratinozyten-Zellkulturen untersucht. Aus den Proben extrahierte RNA wurde für small-RNA-Sequenzierungen genutzt, um Änderungen im jeweiligen miRNA-Transkriptom zu erfassen. Nachfolgend wurden von deregulierten miRNAs beeinflusste Zellprozesse bioinformatorisch determiniert und einzelne Schlüssel-miRNAs und deren Zielgene per qRT-PCR validiert. Ergebnisse: Im Vergleich zu gesunden Probandinnen zeigten 69 miR-NAs im Blut und 41 miRNAs in Keratinozyten von FMS-Patientinnen eine deregulierte Expression. Unter den abgeleiteten Genpfaden wurden die Fettsäuresynthese und Forkhead-Box-Protein O1 (FOXO1) (Blut), sowie der extrazelluläre Matrix-Rezeptor-Signalweg (Keratinozyten) als potenzielle Schlüsselpfade identifiziert. Die Hochregulation von miR-182-5p und miR-576-5p im Blut von FMS-Patientinnen in Relation zu Kontrollen konnte durch qRT-PCR bestätigt werden (p < 0,01 bzw. p < 0,001). Zusätzlich wurde die verminderte Expression der Zielgene Fatty Acid Synthase und FOXO1 im Blut der FMS-Patientinnen (p < 0,05 bzw. p < 0,0001) nachgewiesen. Schlussfolgerung: Wir weisen eine Deregulation der miRNA-Transkriptome in Blut und Hautzellen von FMS-Patientinnen nach. Diese peripheren miRNA-Signaturen könnten zukünftig zur objektiven Diagnose und Charakterisierung von FMS beitragen. Identifizierte regulierte Schlüsselpfade geben darüber hinaus wertvolle neue Einblicke in mögliche pathophysiologische Zusammenhänge. Since inflammatory bowel disease (IBD) is frequently associated with chronic abdominal pain and visceral hypersensitivity, affections to the sensory nerves within the enteric nervous system (ENS) appear to be pivotal. In both inflammatory bowel diseases, i. e. the transmural inflammation of Crohn's disease (CD) and the inflammation restricted to the colonic mucosa in ulcerative colitis (UC), infiltrations of the plexus by immune cells occur. However, the type of immune cells involved is so far unknown. Therefore, we characterized the immune cell infiltrations of myenteric plexus (MP) in CD and UC and compared them to control individuals. We identified 25 IBD patients (13 CD and 12 UC) and 13 controls that had received surgery (ileocecal resections or colectomy). The severity of both disease activity and abdominal pain was assessed by multiple questionnaires. Formalin-fixed, paraffin-embedded tissue was stained by classical immunohistochemistry: MP were identified by PGP9.5 expression, T-cells were characterized by their expression for CD3, CD4, CD8, Tregs for Foxp3, B-cells for CD20 and monocytic cells for CD68 and CD163. All cells were quantified within the plexus and within a defined area (100 µm around the plexus). The populations of CD4+ T-cells, macrophages and monocytes within ganglia of the MP were unchanged in CD and UC. However, infiltrations within and around the MP contained significantly more CD3+ T-cells in CD (135 ± 147 intraganglionic (intrag.) cells/mm²; 2619 ± 3273 periganglionic (perig.) cells/mm²) and UC (93 ± 87 intrag. cells/mm²; 961 ± 710 perig. cells/mm²) compared to the controls (24 ± 42 intrag. cells/mm²; 274 ± 333 perig. cells/mm²). These T-cells were mainly CD8+ T-cells in CD and UC (intrag. cells in CD: 303 ± 296 cells/mm² compared to 39 ± 56 cells/mm² in controls, perig. cells in CD: 4950 ± 4778 cells/mm² and UC: 576 ± 415 cells/mm² compared to 161 ± 212 cells/mm² in controls) as well as perig. Tregs in CD (Foxp3+ T-cells 38 ± 66 cells/mm² compared to 0 ± 0 cells/mm² in controls). CD20+ B-cells were also significantly increased in CD (1614± 000 perig. cells/mm² compared to 1 ± 3 perig. cells/mm² in controls and 64 ± 89 intrag. cells/mm² compared to 0 ± 0 intrag. cells/mm² in controls). CD68+ monocytes were increased in CD MP (11923 ± 8738 perig. cells/mm² compared to 3683 ± 2140 perig. cells/mm² in controls and 1051 ± 729 intrag. cells/mm² compared to 430 ± 349 intrag. cells/mm² in controls). The next step will be comparisons and associations of findings with clinical questionnaires. In IBD, intraganglionic infiltrations of MP are composed of CD3+CD8+ T-cells in CD. Moreover, CD20+ B-cells as well as CD68+ monocytes are found in MP infiltrations of CD. The periganglionar infiltrate includes CD3+CD8+ T-cells in CD and UC, Foxp3+ T-cells in CD and CD20-positive B-cells in CD. These findings indicate that altered peri-/intraganglionic inflammatory immune cell infiltration may play a role in IBD-associated abdominal pain.

Methoden: Verschiedene Datenbanken (Pubmed/MEDLINE, EMBASE, Cochrane Library, Livivo, OpenGrey, drks.de, Clinicaltrials.gov.) sowie zusätzliche relevante Literatur durch Handsuche bei relevanten Zeitschriften dienten der Literaturrecherche. Eingeschlossen wurden randomisierte kontrollierte klinische Studien bei Erwachsenen mit einer schmerzhaften CMD, wobei eine Okklusionsschiene als Therapiearm beinhaltet war. Ausschlusskriterien waren die Abwesenheit von Volltext oder fehlende relevante Information trotz wiederholter (Versuche zur) Kontaktaufnahme mit den Autoren, oder < 7 Teilnehmer pro Therapiearm. Die Messparameter von Interesse waren Intensität der Gesichtsschmerzen, Kieferöffnungskapazität, Kiefergelenksgeräusche, Palpationsschmerzen im Gesicht, Depression und Somatisierung. Die Abgrenzung zwischen funktionalen und dysfunktionalen chronischen Schmerzen wurde anhand festgelegter klinischer und anamnestischer Kriterien vorgenommen. Nachfolgend sind diese Kriterien als differenzierte Faktoren der Effektivität okklusaler Schienentherapie erforscht. Die Studienbewertung erfolgte mithilfe des Risk-of-Bias-Tool von Cochrane. Die Daten wurden von zwei unabhängigen Forschern extrahiert und anschließend mithilfe des Review Managers (RevMan 5.3) von Cochrane analysiert. Ergebnisse: Der systematische Review umfasste 102 Studien mit insgesamt häufig geringem oder unklarem Risk of Bias. Die häufigste Vergleichstherapie war keine Therapie, und bei der Mehrheit der Studien war die Schiene als alleinige aktive Therapie vorhanden. Die Beobachtungsdauer war bei 30 Studien unter 3 Monate, hingegen hatten 34 Studien über 6 Monate Beobachtungsdauer. 80 Studien konnten der Metaanalyse unterzogen werden. Probanden mit funktionalen Schmerzen erfuhren im Zeitraum von 0-6 Monaten nach Behandlung mit einer Okklusionsschiene eine statistisch signifikant effektivere Schmerzreduktion (p < 0,00001) und niedrigere Werte der Somatisierung (p = 0,01) und Depression (p = 0,002) als Probanden mit dysfunktionalen Schmerzen. Schlussfolgerung: Die routinemäßige Differenzierung der schmerzhaften CMD-Patienten mit funktionalem von solchen mit dysfunktionalem Schmerz scheint von klinischer Bedeutung für die Prognose und den Therapieeffekt der Okklusionsschienen zu sein. Registrierungsnummer der Review bei PROSPERO: CRD42019123169.

Xuan-Trang Nguyen¹, Thuy-Trang Nguyen-Lage² ¹Praxis, Facharzt für Gynäkologie, Geburtshilfe, Allgemeinmedizin, spezielle Schmerztherapie, Akupunktur, Göttingen, Deutschland; ²Eichsfeld Klinikum Heilbad Heiligenstadt, Pädiatrie, Göttingen, Deutschland Hintergrund: Bei 20.000 Schmerzpatienten seit 1975 habe ich zum Teil die ganze Familie über drei Generationen behandelt. Darunter waren 860 Kinder bis zum 18. Lebensjahr (4,3 %.). Deren Beschwerden umfassen die gesamten Krankheiten der Pädiatrie -Asthma bronchiale, Infektanfälligkeit, Nacken-Schulter-Arm-Syndrom, Migräne, Cephalgie, Nabelkolik, Konzentrationsschwäche, Aufmerksamkeits-Defizit-Hyperaktivitätsstörung ( ADHS), Gille-de-la-Tourette-Syndrom -und machen dabei den größten Teil der Beschwerden aus. Methoden: Schmerztherapeutische Intervention mit Laserakupunktur und bei älteren Kindern auch Nadelakupunktur, gezielte Neuraltherapie und ggf. Phytotherapie, Physiotherapie, TENS und mild analgetisch wirkenden Medikamenten ist ein Beispiel wirksamer, nebenwirkungsarmer Schmerztherapie im Kindesalter, die unter dem gesundheitlich-kurativen wie -präventiven Aspekt weiterverbreitet werden und unter medizinischen wie volkswirtschaftlichen Gesichtspunkten einen hohen Stellenwert in der pädiatrischen Behandlung haben sollte. Ergebnis: Eine effektive Schmerztherapie bereits im Kindesalter ist somit nicht nur ein Gebot der Humanität, um den Kindern und späteren Erwachsenen viel Leid zu ersparen, sondern auch von volkswirtschaftlicher Relevanz. Diskussion: Da es bis jetzt kaum Pädiater gibt, die sich mit der speziellen Schmerztherapie im Kindesalter befassen und an Schmerzkonferenzen oder anderen Schmerzfortbildungen teilnehmen, soll diese Arbeit einerseits aufzeigen, wie wichtig die pädiatrische Schmerztherapie ist, und den präventiven Aspekt pädiatrischer Schmerztherapie verdeutlichen. Denn wie auch bei der Schmerztherapie Erwachsener ist es hier sehr wichtig, vielleicht noch mehr, die Schmerzen der Kinder anhaltend zu beseitigen und einem Neuauftreten vorzubeugen, um den Kindern eine gute schulische und berufliche Ausbildung ohne Beeinträchtigung durch Schmerzen zu ermöglichen. Außerdem sollen eine Chronifizierung der Schmerzen und mögliche Folgeerkrankungen durch jahrzehntelangen Analgetikagebrauch abgewendet, andererseits Anstoß für eine bessere Schmerztherapieaus-und -weiterbildung im pädiatrischen Bereich gegeben werden. Durch die erhöhten Anforderungen in Schule und beruflicher Ausbildung sowie die vielfältigen medialen Ablenkungen sind die Kinder heute erhöhtem Stress ausgesetzt, der vorbestehende Schmerzen verstärkt oder neue Schmerzsyndrome auslöst. Hinzu kommen Schmerzen im Bereich des Halteapparats durch Zunahme der Körpergröße, schnelleres Längenwachstum und mangelnde körperliche Bewegung. Kinder mit Schmerzen können sich aber nicht ausreichend in Schule oder Berufsausbildung konzentrieren, was schließlich zu schlechteren Qualifikationen einerseits und häufigem Krankenstand und Arbeitsausfall andererseits führt. (13, 5 vs. 14,9 Jahre) und benötigte innerhalb der zwei Jahre doppelt so häufig einen zweiten Aufenthalt (18,9 vs. 9,3 %) . Die auffälligsten Unterschiede ergaben sich jedoch bei der Analyse der Nebendiagnosen. Lediglich 2 CRPS-Patienten (1,9 %) hatten eine JIA, während dies bei 11,9 % der übrigen Patienten der Fall war (p < 0,01). Es fand sich kein CRPS-Patient mit einer Oligo-JIA in der Vorgeschichte. Bezüglich der JIA-Kategorien fanden sich vor allem polyartikuläre Verläufe (4,7 %) und Psoriasis-Arthritiden (3,3 %) in der Gruppe der übrigen Schmerzpatienten. In beiden Gruppen fand sich kein Fall einer systemischen JIA. Die Analyse der psychiatrisch-psychologischen Nebendiagnosen zeigte einen Unterschied bezüglich der F32./F33.-Gruppe (depressive Episode; rezidivierende depressive Störung) und der Anpassungsstörungen (F43.2) mit überwiegend depressiver Symptomatik, welche sich bei den CRPS-Patienten seltener fanden (24,5 vs. 38,6 %; p < 0,01). Diskussion: Dies ist unseres Wissens nach die bislang größte untersuchte Kohorte kindlicher und jugendlicher CRPS-Fälle. Es fand sich kein Hinweis für eine prädisponierende Rolle der JIA bei der Entwicklung eines CRPS. Die JIA scheint jedoch ein Risikofaktor für die Entwicklung einer Schmerzstörung insbesondere bei polyartikulären Verläufen und einer Psoriasisarthritis zu sein. Auch scheint die depressive Vulnerabilität in der Gruppe der CRPS-Fälle seltener als bei anderen chronischen Schmerzpatienten. Interventions-und Kontrollgruppe zeigten signifikant weniger Kopfschmerztage am Ende der Studienzeit. Patienten der Kontrollgruppe wurden über den Studienzeitraum empfindlicher für elektrische Schmerzreize (A: 12,34 mA; E: 11,5 mA; z = -2,283; p = 0,022). Schlussfolgerungen: Neben einer speziellen ambulanten Kopfschmerztherapie zeigt das tägliche Durchführen der "DHÜ" einen zusätzlichen, reduzierenden Effekt auf die Kopfschmerzintensität, die kopfschmerzbedingte Beeinträchtigung sowie einen positiven Effekt auf das Allgemeinbefinden junger Kopfschmerzpatienten. Der zusätzliche Nutzen der Übung kommt durch die signifikante Reduktion des Analgetikagebrauchs deutlich zum Vorschein.