Effects on temporomandibular disorder in the treatment of tension-type headache with acupuncture and therapeutic exercises. A secondary analysis from a randomized controlled trial.

OBJECTIVES: To examine the effects of acupuncture and therapeutic exercise alone and in combination on temporomandibular joint symptoms in tension-type headache and to evaluate the potential interaction of existing temporomandibular dysfunction on the success of headache treatment. DESIGN: Pre-planned secondary analysis of a randomized controlled, non-blinded trial. SETTING: Outpatient clinic of a German university hospital. SUBJECTS: Ninety-six Participants with frequent episodic or chronic tension-type headache were randomized to one of four treatment groups. INTERVENTIONS: Six weeks of acupuncture or therapeutic exercise either as monotherapies or in combination, or usual care. Follow-up at 3 and 6 months. MAIN MEASURES: Subjective temporomandibular dysfunction symptoms were measured using the Functional Questionnaire Masticatory Organ, and the influence of this sum score and objective initial dental examination on the efficacy of headache treatment interventions was analyzed. RESULTS: Temporomandibular dysfunction score improved in all intervention groups at 3-month follow-up (usual care: 0.05 [SD 1.435]; acupuncture: -5 [SD 1.436]; therapeutic exercise: -4 [SD 1.798]; combination: -3 [SD 1.504]; P = 0.03). After 6 months, only acupuncture (-6 [SD 1.736]) showed a significant improvement compared to the usual care group (P < 0.01). Subjective temporomandibular dysfunction symptoms had no overall influence on headache treatment. CONCLUSIONS: Only acupuncture had long-lasting positive effects on the symptoms of temporomandibular dysfunction. Significant dental findings seem to inhibit the efficacy of acupuncture for tension-type headache.

Overview: Chronic Pain and Cannabis-Based Medicines.

Chronic pain is primarily conceptualized as a disease in its own right when it is associated with emotional distress and functional impairment. Pathophysiologically, dysfunction of the cortico-mesolimbic connectome is of major importance, with overlapping signals in the nociceptive and stress systems. The endocannabinoid system plays an important role in the central processing of nociceptive signals and regulates the central stress response. Clinically, there is moderate evidence that cannabis-based medicines (CBM) can contribute to a significant reduction in pain, especially the associated pain affect, and improvement in physical function and sleep quality in a proportion of patients with chronic pain. The analgesic effect appears to be largely independent of the cause of pain. In this context, CBM preferentially regulates stress-associated pain processing.

Clinical characterisation of women with persistent genital arousal disorder: the iPGAD-study.

Persistent Genital Arousal Disorder (PGAD) is a rare condition-mostly in women-where patients perceive prolonged genital arousal without any sexual desire or stimulation. Etiopathological considerations reach from peripheral to central issues over local disturbance of the pudendal nerve to neuropathy, psychosocial, and pharmacological theories. Since well controlled clinical studies about PGAD in conjunction with a mental and somatic health status are missing, this study is a detailed clinical investigation of PGAD patients compared to healthy controls. 26 women who fulfilled diagnostic criteria for PGAD were compared to 26 age matched healthy controls. Investigations included comparison of vegetative, gynaecological and sexual history, psychiatric features as well as a (neuro-)radiological, neurophysiological and gynaecological examination. Moreover, a detailed clinical characterisation of PGAD symptoms was performed. PGAD symptoms were mostly characterised as tingling or prickling and were permanently present. In over 80%, PGAD symptoms were located in the clitoris. Almost 70% reported radiations to other regions of the body. Most frequent trigger factors were tight clothes, mental stress, driving a car/bus/bicycle and sexual intercourse. Relieving factors were mainly distraction, relaxation, physical exercise, masturbation and swimming. In group comparisons, PGAD presented with significant higher rates of sexual dysfunctions, spontaneous orgasms, swelling of the genitals, extraordinary lubrication as well as higher rates in depression, agoraphobia, generalized anxiety disorder and lifetime panic disorder. Significantly more PGAD patients were diagnosed with restless legs symptoms. In contrast childhood traumatization, somatization disorder, suicidality, gynaecological as well as neurophysiological examination of the pudendal nerve were not different between the groups. MRI of the brain, pelvis and spinal cord was unsuspicious and incidental findings - including Tarlov cysts or pelvic venous congestion - were equally distributed among the groups. In summary, our study provides a careful characterization of women with PGAD highlighting a serious mental burden, most probably as a consequence of PGAD. With the current set of clinical investigations there was no evidence of a clear causal relationship to a specific clinical finding as it has been previously discussed. Future studies and additional techniques will have to further explore where and how in the peripheral or central nervous systems PGAD develops.

Patients' perspectives on prescription cannabinoid therapies: a cross-sectional, exploratory, anonymous, one-time web-based survey among German patients.

Introduction: Since cannabinoids were partially legalized as prescription medicines in Germany in 2017, they are mostly used when conventional therapies do not suffice. Ambiguities remain regarding use, benefits and risks. This web-based survey explored the perspectives of patients whose experiences are not well enough known to date. Methods: In an anonymous, exploratory, cross-sectional, one-time web-based observational study, participants receiving cannabinoid therapy on prescription documented aspects of their medical history, diagnoses, attitudes toward cannabinoids, physical symptoms, and emotional states. Participants completed the questionnaires twice here: first regarding the time of the survey and then, retrospectively, for the time before their cannabinoid therapy. Participants were recruited in a stratified manner in three German federal states. Results: N = 216 participants (48.1% female, aged 51.8 ± 14.0) completed the survey, most of which (72%, n = 155) reported pain as their main reason for cannabinoid therapy. When comparing the current state with the retrospectively assessed state, participants reported greater satisfaction with their overall medical therapy (TSQM II: +47.9 ± 36.5, p < 0.001); improved well-being (WHO-5: +7.8 ± 5.9, p < 0.001) and fewer problems in PROMIS subscales (all p < 0.001). Patients suffering primarily from pain (72%, n = 155) reported a reduction of daily pain (NRS: -3.2 ± 2.0, p < 0.001), while participants suffering mainly from spasticity (8%, n = 17) stated decreased muscle spasticity (MSSS: -1.5 ± 0.6, p < 0.001) and better physical mobility (-0.8 ± 0.8, p < 0.001). Data suggests clinically relevant effects for most scores. Participants' attitudes toward cannabinoids (on a 5-point scale) improved (+1.1 ± 1.1, p < 0.001). Most patients (n = 146, 69%) did not report major difficulties with the cannabinoid prescription process, while (n = 27; 19%) had their cannabinoid therapy changed due to side effects. Discussion: Most participants experienced their therapy with cannabinoids as more effective than their previous therapy. There are extensive limitations to this cross-sectional study: the originally intended representativeness of the dataset was not reached, partly due to the SARS-CoV-2 pandemic; the sample has a larger proportion of privately insured and self-paying patients. Results does not suggest that cannabinoid patients belong to a particular clientele. Effect sizes observed for pain reduction, quality of life, social participation, and other outcomes suggest a therapeutic potential, particularly in the treatment of chronic pain.

EMG measured reaction time as a predictor of invalid symptom report in psychosomatic patients.

Background: Symptom validity tests (SVTs) and performance validity tests (PVTs) are important tools in sociomedical assessments, especially in the psychosomatic context where diagnoses mainly depend on clinical observation and self-report measures. This study examined the relationship between reaction times (RTs) and scores on the Structured Inventory of Malingered Symptomatology (SIMS). It was proposed that slower RTs and larger standard deviations of reaction times (RTSDs) would be observed in participants who scored above the SIMS cut-off (>16). Methods: Direct surface electromyography (EMG) was used to capture RTs during a computer-based RT test in 152 inpatients from a psychosomatic rehabilitation clinic in Germany. Correlation analyses and Mann-Whitney U were used to examine the relationship between RTs and SIMS scores and to assess the potential impact of covariates such as demographics, medical history, and vocational challenges on RTs. Therefore, dichotomized groups based on each potential covariate were compared. Results: Significantly longer RTs and larger RTSDs were found in participants who scored above the SIMS cut-off. Current treatment with psychopharmacological medication, diagnosis of depression, and age had no significant influence on the RT measures. However, work-related problems had a significant impact on RTSDs. Conclusion: There was a significant relationship between longer and more inconsistent RTs and indicators of exaggerated or feigned symptom report on the SIMS in psychosomatic rehabilitation inpatients. Findings from this study provide a basis for future research developing a new RT-based PVT.

Therapeutic Use of Cannabinoids in Critically Ill Patients: A Survey of Intensive Care Physicians in Germany.

Background: In the course of the legalization of cannabis for therapeutic purposes in Germany, there has been growing interest in the medical use of cannabinoids. To date, the therapeutic potential of cannabinoids for the treatment of critically ill patients has not been explored. Objectives: This study aims to understand better whether and how frequently cannabinoids have been administered to critically ill patients in recent years. Study Design: Initially, a survey was conducted among physicians working in intensive care units (ICUs) at the Hannover Medical School. Subsequently, 653 physicians working in ICUs throughout Germany were surveyed. The frequency and regimen of cannabinoid therapy initiated by the participating physicians in the last 2 years at the time of the survey were characterized. Results: Eight out of 9 physicians at Hannover Medical School and 59 out of 653 physicians in ICUs in Germany participated. At Hannover Medical School, 6 out of 8 physicians and in ICUs in Germany, 16 out of 59 physicians had used cannabinoids in some patients (mainly 9-10) during the 2-year period studied, with dronabinol in doses between 1 and 20 mg being their cannabinoid of choice. Metabolic and psychological distress and medication savings, followed by pain and nausea/vomiting, were the most frequently cited indications for cannabinoid therapy. No relevant safety issues arrived. Lack of personal experience, limited evidence, and gaps in knowledge were the most commonly cited reservations about cannabinoid use. Conclusions: During a 2-year period, dronabinol is used in a few critically ill patients in ICUs. The main indications are to reduce metabolic and psychological distress and to save medication. The majority of participating physicians indicated that the use of cannabinoids in the context of critical care medicine needs further exploration.

Patient Experiences With Prescription Cannabinoids in Germany: Protocol for a Mixed Methods, Exploratory, and Anonymous Web-Based Survey.

BACKGROUND: Medical cannabinoids are controversial. Their use is comparatively rare, but it is rising. Since 2017, cannabinoids can be prescribed in Germany for a broader range of indications. Patient surveys on these drugs are hampered by the stigmatization of cannabinoids and their (still) low prevalence in medical contexts. Against this background, patients' willingness to provide information is limited. Moreover, it is logistically challenging to reach them with a survey. A thorough knowledge of currently ongoing therapies and their effects and side effects, however, is important for a more appropriate and effective use of cannabinoids in the future. OBJECTIVE: This study is an exploratory data collection using a representative sample. The main goal is to provide a detailed picture of the current use of medical cannabinoids in Germany. It is intended to identify subgroups that may benefit particularly well or poorly. METHODS: We are conducting a representative, anonymous, cross-sectional, one-time, web-based survey based on mixed methods in 3 German federal states. Health conditions under cannabinoid therapy and before are documented with validated, symptom-specific questionnaires. This allows an estimation of the effect sizes of these therapies. The selection of parameters and questionnaires was based on the results of independent qualitative interviews in advance. Representative samples of the hard-to-reach study population are obtained by cluster sampling via contracted physicians of the statutory health insurance companies. RESULTS: Recruitment was ongoing until the end of June 2022, with 256 enrolled participants. Validated questionnaires on pain, spasticity, anorexia or wasting, multiple sclerosis, nausea or vomiting, depression, and attention deficit hyperactivity disorder (ADHD) were selected. Symptom scores are being assessed for both current conditions under cannabinoid therapy and conditions prior to this therapy (in retrospect). Validated questionnaires are also used for treatment satisfaction and general quality of life. These are supplemented by existing diagnoses, a detailed medication history, any previous experiences with cannabis or illegal substances, experiences with the prescription process, and sociodemographic data. Based on the results of the previous qualitative interviews, questions were added regarding prior experience with relaxation methods and psychotherapy, personal opinions about cannabinoids, pre-existing or symptom-related psychological trauma, and different experiences with different cannabis-based therapies. CONCLUSIONS: The exploratory mixed methods approach of this project is expected to provide valid and relevant data as a basis for future clinical research. The study design may be representative for a large proportion of outpatients treated with cannabinoids in the German federal states studied. It may have less bias toward social desirability and may provide valuable information in addition to existing studies. Due to the observational and cross-sectional nature of this study, various limitations apply. Causal relations cannot be drawn. TRIAL REGISTRATION: German Clinical Trials Register DRKS00023344; https://drks.de/search/en/trial/DRKS00023344. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38814.

Traumatic Events, Posttraumatic Stress Disorder, and Central Sensitization in Chronic Pain Patients of a German University Outpatient Pain Clinic.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and traumatic life events are often coupled to chronic pain, possibly linked by central sensitization. We wanted to assess the prevalence of traumatic events and PTSD in chronic pain patients of a German university hospital outpatient pain clinic. Moreover, we evaluated the extent of indicators and co-occurring traits of central sensitization in comorbid patients. METHODS: We retrospectively divided 914 chronic pain patients into four groups depending on their trauma severity: no trauma, accidental trauma, interpersonal trauma, and PTSD. We collected electronic pain drawings focusing on pain area and widespreadness, as well as information about pain intensity, sleep impairment, disability, stress, anxiety, depression, and somatization. Differences between groups were calculated using Kruskal-Wallis with post-hoc Mann-Whitney tests. RESULTS: Of 914 patients, 231 (25%) had no trauma, 210 (23%) had accidental traumas, 283 (31%) had interpersonal traumas, 99 (11%) had PTSD, and 91 (10%) could not be classified. We observed statistically significant differences between groups in pain area and widespreadness, as well as maximal pain, sleep impairment, disability, stress, anxiety, depression, and somatization. The severity of symptoms increased with trauma severity. CONCLUSIONS: Traumatic life events and PTSD are frequent in chronic pain patients. The increased pain area and widespreadness, as well as the increased negative impact on co-occurring traits of sensory sensitivity (anxiety, depression, somatization), are compatible with central sensitization in comorbid patients. Therefore, a heightened awareness of the comorbidity between traumatic experiences and chronic pain is recommended.

Effects of acupuncture and medical training therapy on depression, anxiety, and quality of life in patients with frequent tension-type headache: A randomized controlled study.

OBJECTIVES: To compare the effects of acupuncture and medical training therapy in combination or individually with usual care on quality of life, depression, and anxiety in patients with tension-type headache. METHODS: In this single-center, prospective, randomized, controlled, unblinded trial, 96 adults (38.7(+/-13.3) years of age; 75 females/20 males/one dropout) with frequent episodic or chronic tension-type headache were randomized to one of four treatment groups (n = 24). The treatment groups received six weeks of either acupuncture or medical training therapy as monotherapies or in combination (12 interventions each), or usual care. We assessed depressiveness (PHQ-9), anxiety (GAD-7), and health-related quality of life (SF-12) as secondary outcome parameters at baseline, six weeks, three months, and six months after initiation of treatment. Linear mixed models were calculated. RESULTS: Both, acupuncture (baseline to six-weeks change scores: mean: -2(standard deviation: 2.5 points), three months: -2.4(2.4), six-months -2.7(3.6)) and the combination of acupuncture and medical training therapy (-2.7(4.9), -2.2(4.0), -2.2(4.2)) (each within-group p < .05) significantly reduced depressiveness-scores (PHQ-9) to a greater extent than medical training therapy (-0.3(2.0), -0.5(1.6), -0.9(2.6)) or usual care alone (-0.8(2.9), 0.1(2.8), 0.2(3.6)). We found similar results with anxiety scores and the physical sum scores of the SF-12. No severe adverse events occurred. CONCLUSIONS: Acupuncture and the combination of acupuncture and medical training therapy elicit positive effects on depression, anxiety, quality of life, and symptom intensity in patients with episodic and chronic tension-type headache. Acupuncture appears to play a central role in mediating the therapeutic effects, underscoring the clinical relevance of this treatment. An additive benefit of the combination of both therapies does not appear to be relevant.Trial registration: Registered on 11 February 2019. German Clinical Trials Register, DRKS00016723.

Percutaneous Bioelectric Current Stimulation in the Treatment of Chronic Achilles Tendinopathy: Protocol for a Double-Blind, Placebo-Controlled Randomized Multicenter Trial.

BACKGROUND: The consensus for the optimal treatment strategy for chronic Achilles tendinopathy (AT) is still debated and treatment options are limited. This results in a significant medical need for more effective treatment options. OBJECTIVE: The aim of this study is to investigate the therapeutic effects of percutaneous bioelectric current stimulation (PBCS) on AT. METHODS: A multicenter, randomized, double-blind, placebo-controlled clinical trial will be conducted. A total of 72 participants with chronic (ie, >3 months) midpoint AT will be randomized and receive four PBCS sessions-either verum or placebo-over 3 weeks. Both groups will complete daily Achilles tendon loading exercises in addition to the intervention. Evaluation sessions will be completed at baseline and during the intervention (weeks 0-3). Self-reported outcome measures will be completed at follow-up at weeks 4, 12, 26, and 52. The primary outcomes are the Victorian Institute of Sports Assessment-Achilles questionnaire scores and statistical evaluation of intraindividual differences between baseline and 12-week evaluations after initial treatment of verum therapy compared to control. Secondary outcomes will assess Pain Disability Index scores; average pain, using the 11-point Numeric Rating Scale; return to sports; and use of emergency medication. RESULTS: The study began in May 2021. As of October 2022, we randomized 66 out of 72 participants. We anticipate completing recruitment by the end of 2022 and completing primary data analysis by March 2023. CONCLUSIONS: The study will evaluate the effects of PBCS on pain, physical function, and clinical outcomes. TRIAL REGISTRATION: German Clinical Trials Register DRKS00017293; https://tinyurl.com/mvz7s98k. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40894.

Neuronal effects of glabellar botulinum toxin injections using a valenced inhibition task in borderline personality disorder.

Previous studies have indicated that glabellar botulinum toxin (BTX) injections may lead to a sustained alleviation of depression. This may be accomplished by the disruption of a facial feedback loop, which potentially mitigates the experience of negative emotions. Accordingly, glabellar BTX injection can attenuate amygdala activity in response to emotional stimuli. A prototypic condition with an excess of negative emotionality and impulsivity accompanied by elevated amygdala reactivity to emotional stimuli is borderline personality disorder (BPD). In order to improve the understanding of how glabellar BTX may affect the processing of emotional stimuli and impulsivity, we conducted a functional magnetic resonance imaging (fMRI) study. Our hypotheses were (1) glabellar BTX leads to increased activation in prefrontal areas during inhibition performance and (2) BTX decreases amygdala activity during the processing of emotional stimuli in general. Using an emotional go-/no-go paradigm during fMRI, the interference of emotion processing and impulsivity in a sample of n = 45 women with BPD was assessed. Subjects were randomly assigned to BTX treatment or serial acupuncture (ACU) of the head. After 4 weeks, both treatments led to a reduction in the symptoms of BPD. However, BTX treatment was specifically associated with improved inhibition performance and increased activity in the motor cortex. In addition, the processing of negative emotional faces was accompanied by a reduction in right amygdala activity. This study provides the first evidence that glabellar BTX injections may modify central neurobiological and behavioural aspects of BPD. Since the control treatment produced similar clinical effects, these neurobiological findings may be specific to BTX and not a general correlate of symptomatic improvement.

Neurohumoral Profiles and Childhood Adversity of Patients with Multisomatoform Disorder and Pain as the Leading Bodily Symptom.

OBJECTIVE: Patients suffering from chronic pain often present with multifactorial underlying conditions, sometimes without concrete pathological physical findings. Functional somatic syndromes (FSS) and somatoform disorders show a high prevalence of 8-20% and are often associated with adverse childhood experiences (ACE) and chronic stress. As many different FSS have overlapping symptoms, the concept of multisomatoform disorder (MSD) has been introduced as an encompassing concept. We hypothesize that a common neurohumoral profile is present in patients with MSD that is distinct from gender- and age-matched controls and thus provides insight into possible common underlying mechanisms. DESIGN: In 151 patients with MSD (138 females) and 149 matched controls (131 females), we determined ACE by the Childhood Trauma Questionnaire (CTQ) and chronic stress by the Trier Inventory for Chronic Stress (TICS). Furthermore, the serum levels of leptin, FSH, LH, cortisol, DHEA-S, and IGF-1 have been assessed. RESULTS: There were significant differences in the levels of leptin, FSH, IGF-1, and cortisol between patients and controls, mainly driven by female participants. Levels of leptin were significantly correlated with BMI in patients, in controls, and in the female subgroup. This correlation was exaggerated in female patients when compared to female controls. Both CTQ and TICS predicted MSD directly and indirectly through the levels of leptin. CONCLUSION: There is evidence of a distinct neurohumoral profile in female patients with MSD when compared to matched healthy controls, similar to what has been demonstrated in other chronic pain states. The observed profile can be taken as possible evidence for a dysregulated response to chronic stress and metabolic balance as well as a state of hypocortisolism and HPA-axis dysfunction. ACE and chronic stress play a major role in the development of MSD and altered neurohumoral profile.

Clinical effects of glabellar botulinum toxin injections on borderline personality disorder: A randomized controlled trial.

BACKGROUND: Inhibition of frowning via injections of botulinum toxin A (BTX) into the glabellar region has shown beneficial effects in the treatment of major depression. Preliminary research suggests that improvements in the affective domain are not depression-specific, but may also translate to other psychiatric disorders. AIM: This 16-week, single-blind, two-center randomized controlled trial investigated the influence of BTX on clinical symptoms of borderline personality disorder (BPD). METHODS: Fifty-four patients with BPD were randomly assigned to treatment with BTX (n = 27) or a minimal acupuncture (ACU) control condition (n = 27). Clinical outcomes were followed at 2, 4, 6, 8, 12, and 16 weeks. Primary endpoint was the relative score change on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) 8 weeks after baseline relative to the control group and adjusted for treatment center. Secondary and additional outcome variables were self-rated borderline symptoms, comorbid symptoms of depression, psychological distress, and clinical global impression. RESULTS: Participants showed significant improvements at the primary efficacy endpoint in both treatment groups (BTX: M = -0.39, SD = 0.39; ACU: M = -0.35, SD = 0.42), but no superior effect of the BTX condition in comparison with the control intervention was found-F(1,5323) = 0.017, p = 0.68). None of the secondary or additional outcomes yielded significant group differences. Side effects were mild and included headache, transient skin or muscle irritations, and dizziness. CONCLUSION: Evidence regarding the efficacy of BTX for BDP remains limited, and the design of adequate control conditions presents an opportunity for further research.ClinicalTrials.gov registry: Botulinum Toxin A for Emotional Stabilization in Borderline Personality Disorder (BPD), NCT02728778, https://clinicaltrials.gov/ct2/show/NCT02728778.

Leptin promoter methylation in female patients with painful multisomatoform disorder and chronic widespread pain.

BACKGROUND: Different functional somatic syndromes (FSS), fibromyalgia (FMS) and other unexplained painful conditions share many common clinical traits and are characterized by troubling and functionally disabling somatic symptoms. Chronic pain is most frequently reported and at the center of patients' level of disease burden. The construct of multisomatoform disorder (MSD) allows to subsume severely impaired patients suffering from FSS, FMS and other unexplained painful conditions to be examined for common underlying processes. Altered leptin levels and a pathological response of the HPA-axis as a result of chronic stress and childhood trauma have been suggested as one of the driving factors of disease development and severity. Previous studies have demonstrated that methylation of the leptin promoter can play a regulatory role in addiction. In this study, we hypothesized that methylation of the leptin promoter is influenced by the degree of childhood traumatization and differs between patients with MSD and controls. A cohort of 151 patients with MSD and 149 matched healthy volunteers were evaluated using clinical and psychometric assessment while methylation level analysis of the leptin promoter was performed using DNA isolated from whole blood. RESULTS: In female controls, we found CpG C-167 to be negatively correlated with leptin levels, whereas in female patients CpG C-289, C-255, C-193, C-167 and methylation cluster (C-291 to C-167) at putative bindings sites for transcription factors Sp1 and c/EBPalpha were negatively correlated with leptin levels. Methylation levels were significantly lower in female patients CpG C-289 compared with controls. When looking at female patients with chronic widespread pain methylation levels were significantly lower at CpG C-289, C-255 and methylation cluster (C-291 to C-167). CONCLUSION: Our findings support the hypothesis that epigenetic regulation of leptin plays a role in the regulation of leptin levels in patients with MSD. This effect is more pronounced in patients with chronic widespread pain.

Flotation Restricted Environmental Stimulation Therapy for Chronic Pain: A Randomized Clinical Trial.

Importance: Flotation restricted environmental stimulation therapy (REST) is an emerging therapeutic intervention that, to our knowledge, has never been directly compared with an indistinguishable placebo in patients with chronic pain. Objective: To determine whether 5 flotation-REST sessions alleviate chronic pain. Design, Setting, and Participants: This single-blind, randomized clinical trial compared flotation-REST as an intervention for the treatment of chronic pain with indistinguishable placebo and wait-list control conditions at Hannover Medical School, Hannover, Germany. Men and women aged 18 to 75 years who had been diagnosed with chronic pain disorder with psychological and somatic factors (International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification, code F45.41) by physicians at the study center were randomly assigned to 1 of the 3 groups. Data were collected from June 26, 2018, to June 18, 2020. Interventions: Patients in the intervention and placebo groups underwent 5 treatment sessions lasting 60 to 90 minutes, each session separated by 4 days. The placebo treatment was delivered in the same floating tank but controlled for effortless floating and environmental stimulus restriction. Patients in the wait-list control group did not receive any additional treatment but were asked to continue any ongoing treatments at the time of enrollment. Main Outcomes and Measures: The primary outcome was a change in pain intensity 1 week after the last treatment session. The assessment was repeated at 12 and 24 weeks. Secondary outcomes included pain-related disability, pain area, pain widespreadness (number of body regions affected by pain), anxiety, depression, and quality of life, as well as several other short-term outcomes. Results: A total of 99 patients (mean [SD] age, 51.7 [12.3] years; 80 women [81%]) were included in the study. No differences were found among the groups in the primary outcomes (mean [SD] change in maximum pain: -7.6 [19.7] for the intervention group, -5.8 [12.7] for the placebo group, and 0.4 [14.0] for the wait-list control group; mean [SD] change in mean pain: -2.1 [19.4] for the intervention group,-4.2 [16.2] for the placebo group, and 2.0 [12.6] for the wait-list control group). Long-term secondary outcomes did not show significant differences. In the short term, patients in the intervention group showed significant improvements in pain intensity (-17.0 [17.1]; P < .001), relaxation (23.9 [22.6]; P < .001), anxiety (-10.1 [8.4]; P < .001), pain area (-3.6% [7.4%]; P < .001), and widespreadness (-2.0 [3.0]; P < .001), and similar changes where observed in the placebo group. Conclusions and Relevance: Patients with chronic pain experienced no long-term benefits from the 5 flotation-REST interventions. Clinically relevant short-term changes in pain in the placebo group suggest that improvements may not be caused by environmental stimulus restriction or effortless floating as previously thought. Trial Registration: ClinicalTrials.gov Identifier: NCT03584750.

Combination of acupuncture and medical training therapy on tension type headache: Results of a randomised controlled pilot study.

OBJECTIVES: The aim of this study was to compare the effects of acupuncture and medical training therapy alone and in combination with those of usual care on the pain sensation of patients with frequent episodic and chronic tension-type headache. DESIGN: This was a prospective single-centre randomised controlled trial with four balanced treatment arms. The allocation was carried out by pre-generated randomisation lists in the ratio 1:1:1:1 with different permutation block sizes. SETTING: The study was undertaken in the outpatient clinic of Rehabilitation Medicine of the Hannover Medical School.Participants and interventions: Ninety-six adult patients with tension-type headache were included and randomised into usual care (n = 24), acupuncture (n = 24), medical training (n = 24), and combination of acupuncture and medical training (n = 24). One patient was excluded from analysis because of withdrawing her/his consent, leaving 95 patients for intention to treat analysis. Each therapy arm consisted of 6 weeks of treatment with 12 interventions. Follow-up was at 3 and 6 months. MAIN OUTCOME MEASURES: Pain intensity (average, maximum and minimum), frequency of headache, responder rate (50% frequency reduction), duration of headache and use of headache medication.Clinical results: The combination of acupuncture and medical training therapy significantly reduced mean pain intensity compared to usual care (mean = -38%, standard deviation = 25%, p = 0.012). Comparable reductions were observed for maximal pain intensity (-25%, standard deviation = 20%, 0.014) and for minimal pain intensity (-35%, standard deviation = 31%, 0.03). In contrast, neither acupuncture nor medical training therapy differed significantly from usual care. No between-group differences were found in headache frequency, mean duration of headache episodes, and pain medication intake. At 3 months, the majority of all patients showed a reduction of at least 50% in headache frequency. At 6 months, significantly higher responder rates were found in all intervention groups compared to usual care. CONCLUSIONS: In contrast to monotherapy, only the combination of acupuncture and medical training therapy was significantly superior in reduction of pain intensity compared to usual care.Trial registration: Registered on 11 February 2019. German Clinical Trials Register, DRKS00016723.

Comparative effects of (S)-ketamine and racemic (R/S)-ketamine on psychopathology, state of consciousness and neurocognitive performance in healthy volunteers.

Ketamine and its (S)-enantiomer show distinct psychological effects that are investigated in psychiatric research. Its antidepressant activity may depend on the extent and quality of these psychological effects which may greatly differ between the enantiomers. Previous data indicate that the (S)-ketamine isomer is a more potent anesthetic than (R)-ketamine. In contrast, in subanesthetic doses (R)-ketamine seems to elicit fewer dissociative and psychotomimetic effects compared to (S)-ketamine. In this randomized double-blind placebo-controlled trial the effects of (R/S)-ketamine and (S)-ketamine on standardized neuropsychological and psychopathological measures were compared. After an initial bolus equipotent subanesthetic doses of (R/S)- and (S)-ketamine or placebo were given by continuous intravenous infusion to three groups of 10 healthy male volunteers each (n = 30). (R/S)-Ketamine and (S)-ketamine produced significant psychopathology and neurocognitive impairment compared to placebo. No significant differences were found between (R/S)-ketamine and (S)-ketamine. (S)-Ketamine administration did not result in reduced psychopathological symptomatology compared to (R/S)-ketamine as suggested by previous studies. However, this study revealed a somewhat more "negatively experienced" psychopathology with (S)-ketamine, which opens questions about potential "protective effects" associated with the (R)-enantiomer against some psychotomimetic effects induced by the (S)-enantiomer. As the antidepressant effect of ketamine might depend on a pleasant experience of altered consciousness and perceptions and avoidance of anxiety, the ideal ketamine composition to treat depression should include (R)-ketamine. Moreover, since preclinical data indicate that (R)-ketamine is a more potent and longer acting antidepressant compared to (S)-ketamine and (R/S)-ketamine, randomized controlled trials on (R)-ketamine and comparative studies with (S)-ketamine and (R/S)-ketamine are eagerly awaited.

Life-threatening course in coronavirus disease 2019 (COVID-19): Is there a link to methylenetetrahydrofolic acid reductase (MTHFR) polymorphism and hyperhomocysteinemia?

As the current COVID-19 pandemic develops and epidemiological data reveals differences in geographical spread as well as risk factors for developing a severe course of illness, hypotheses regarding possible underlying mechanisms need to be developed and tested. In our hypothesis, we explore the rational for a role of MTHFR polymorphism C677T as a possible explanation for differences in geographical and gender distribution in disease severity. We also discuss the role of the resulting hyper-homocysteinemia, its interaction with the C677T polymorphism and its influence on immune state as well as risk factors for severe disease. Finally, we consider possible dietary ways to influence the underlying pathomechanisms prophylactically and supportively.