GABA increases electrical excitability in a subset of human unmyelinated peripheral axons

A proportion of small diameter primary sensory neurones innervating human skin are chemosensitive. They respond in a receptor dependent manner to chemical mediators of inflammation as well as naturally occurring algogens, thermogens and pruritogens. The neurotransmitter GABA is interesting in this respect because in animal models of neuropathic pain GABA pre-synaptically regulates nociceptive input to the spinal cord. However, the effect of GABA on human peripheral unmyelinated axons has not been established

Is Sham Laser a Valid Control for Acupuncture Trials?

Methodological problems of acupuncture trials focus on adequate placebo controls. In this trial we evaluated the use of sham laser acupuncture as a control procedure. Thirty-four healthy volunteers received verum laser (invisible infrared laser emission and red light, 45 s and 1 J per point) and sham laser (red light) treatment at three acupuncture points (LI4, LU7 and LR3) in a randomized, double-blinded, cross-over design. The main outcome measure was the ratio of correct to incorrect ratings of treatment immediately after each session. The secondary outcome measure was the occurrence of deqi-like sensations at the acupuncture points and their intensity on a 10-fold visual analog scale (VAS; 10 being the strongest sensible sensation). We pooled the results of three former trials to evaluate the credibility of sham laser acupuncture when compared to needle acupuncture. Fifteen out of 34 (44%) healthy volunteers (age: 28 ± 10.7 years) identified the used laser device after the first session and 14 (41%) after the second session. Hence, both treatments were undistinguishable (P = .26). Deqi-like sensations occurred in 46% of active laser (2.34 VAS) and in 49.0% of sham laser beams (2.49 VAS). The credibility of sham laser was not different from needle acupuncture. Sham laser acupuncture can serve as a valid placebo control in laser acupuncture studies. Due to similar credibility and the lack of sensory input on the peripheral nervous system, sham laser acupuncture can also serve as a sham control for acupuncture trials, in order to evaluate needling effects per se

Berührt sein – Ein Fallbericht zur Rolle von WATSU (WasserShiatsu) in der Rehabilitation nach Polytrauma

Hintergrund: Die herausragende Bedeutung von Körperkontakt für den Menschen ist bekannt und nachgewiesen. Während aber intensiver Körperkontakt in der medizinischen Versorgung von Frühgeborenen etabliert ist, wird Berührung in schulmedizinische Therapiekonzepte für Erwachsene bisher nur marginal integriert. Massnahmen aus der Komplementärmedizin berücksichtigen den individuellen Bedarf an körperlicher Nähe und leisten einen klinischen Mehrwert für den Gesundungsprozess. In besonderer Weise nimmt sich WATSU (WasserShiatsu) achtsamer Berührung an: Während der Behandlung ruht die PatientIn eine Stunde lang auf Händen, Armen oder Schultern ihrer TherapeutIn und wird in grossräumigen, langsamen Kreisbewegungen in 35° C warmem Wasser bewegt, gedehnt und massiert. Die Arbeitsweise vermittelt Geborgenheit und Nähe, habituelle Haltemuster können gelöst und neue Bewegungsoptionen aufgezeigt werden. In der wissenschaftlichen Literatur werden WATSU u.a. die Reduktion von muskulären Verspannungen, Schmerzen und Stress zugeordnet. Methoden: An einem Fallbeispiel wird WATSU als Therapiebaustein in der Rehabilitation nach einem Polytrauma dargestellt. Eine 52-jährige Frau erlitt bei einem Motorradunfall schwerste Verletzungen (Rippenserienfrakturen, Einblutung in den Lungenflügel, Beckenringfraktur, Trümmerfraktur des Oberschenkelknochens). Die Patientin litt unter Schmerzen und Bewegungseinschränkungen, aber auch verminderter psychischer Belastbarkeit (Schreckhaftigkeit, Albträume). Auf eigenen Wunsch ergänzte sie ihre ambulante Rehabilitation um sechs WATSU-Sitzungen (1x pro Woche). Sie führte während dieser Zeit ein Tagebuch über ihre Therapieerfahrung, welches sie später zur wissenschaftlichen Auswertung zur Verfügung stellte. Diese erfolgte nach dem Triangulationsmodell nach Mayring. Resultate: Die Tagebucheinträge der Patientin umfassen emotionale, mentale und körperliche Inhalte. Bemerkungen ohne Bezug zu WATSU reflektieren in erster Linie Erfahrungen im Zusammenhang mit therapeutischen und medizinischen Interventionen, zu einem geringen Anteil aber auch körperliche Aktivitäten in der Freizeit. Im Zusammenhang mit WATSU schildert sie u.a. wie dieses zu erhöhter Selbstakzeptanz und zur Korrektur ihres Körperschemas beitrug. Sie beschreibt Veränderungen der Wahrnehmung, häufig verbunden mit starken Emotionen: «Ich spürte Bewegungen, die in den letzten drei Monaten überhaupt nicht mehr möglich waren. Es waren «fremde Bewegungen», […] über deren Intensität ich erstaunt war.», «[Während WATSU] habe ich schmerzlich festgestellt, dass ich nur in meinem Unfallbein existiere, alles dreht sich nur um das. […] Aber ich habe auch noch einen rechten Arm, einen Kopf, mein linkes Superbein leistet extrem viel! … Irgendwann liefen die Tränen, erst lautlos, dann hemmungslos.» Rumpfmobilisation im WATSU stand für sie in direkter Verbindung zu vertiefter Atmung, beschriebene Reaktionen wie langanhaltendes Zittern des ganzen Körpers (beginnend beim betroffenen Bein) können als Stressabbau des autonomen Nervensystems gedeutet werden. Inhaltlich, aber auch in der Art der Beschreibung unterscheiden sich die WATSU-bezogenen Textteile deutlich von jenen, in denen es um andere therapeutische und medizinische Interventionen geht: etwa bleibt der Themenkreis «Mentale und emotionale Achtsamkeit» ausschliesslich den WATSU-bezogenen Schilderungen vorbehalten, während «Schmerz» in Zusammenhang mit dieser Therapie nie thematisiert wird. Schlussfolgerung: WATSU wurde von dieser Patientin als in ihrer komplexen rehabilitativen Situation sehr hilfreich dargestellt. Es habe ihre Aufmerksamkeit weg von Problemen und Missempfindungen hin zu positiven Gefühlen und erfreulichen Körpererfahrungen gelenkt. Dieser Falldarstellung ist nur ein Einzelbericht, weist aber darauf hin, dass WATSU eine Bereicherung des klinischen Settings darstellen könnte. Wünschenswert wäre die weitere wissenschaftliche Überprüfung von WATSU hinsichtlich differenzierter Indikationen und klinischer Effekte

Applications, indications, and effects of passive hydrotherapy WATSU (WaterShiatsu)—A systematic review and meta-analysis

BACKGROUND: WATSU (portmanteau word: water and shiatsu) is a form of passive hydrotherapy in chest-deep thermoneutral water (35°C = 95°F = 308.15 K). It combines elements of myofascial stretching, joint mobilization, massage, and shiatsu and is reported to be used to address physical and mental issues. The objective of this systematic review (PROSPERO Registration No. CRD42016029347) and the meta-analyses was to assess the applications, indications, and the effects of WATSU to form a basis for further studies. METHODS: A search for "WATSU OR watershiatsu OR (water AND shiatsu)" was conducted without any restrictions in 32 databases. Peer reviewed original articles addressing WATSU as a stand-alone hydrotherapy were assessed for risk of bias. Quantitative data of effects on pain, physical function, and mental issues were processed in random model meta-analyses with subgroup analyses by study design. Effect sizes were expressed as Hedges's g (± 95% confidence intervals). RESULTS: Of 1,906 unique citations, 27 articles regardless of study design were assessed for risk of bias. WATSU has been applied to individuals of all ages. Indications covered acute (e.g. pregnancy related low back pain) and chronic conditions (e.g. cerebral palsy) with beneficial effects of WATSU regarding e.g. relaxation or sleep quality. Meta-analyses suggest beneficial effect sizes of WATSU on pain (overall Hedges's g = -0.71, 95% CI = -0.91 to -0.51), physical function (overall Hedges's g = -0.76, 95% CI = -1.08 to -0.44), and mental issues (overall Hedges's g = -0.68, 95% CI = -1.02 to -0.35). CONCLUSION: Various applications, indications and beneficial effects of WATSU were identified. The grade of this evidence is estimated to be low to moderate at the best. To strengthen the findings of this study, high-quality RCTs are needed. PMID: 32168328 PMCID: PMC7069616 DOI: 10.1371/journal.pone.022970

S100B is increased in Parkinson’s disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-α pathway

Peer reviewedPublisher PD

Concentric and eccentric endurance exercise reverse hallmarks of T-Cell senescence in pre-diabetic subjects

The peripheral T-cell pool undergoes a striking age associated remodeling which is accelerated by progressive insulin resistance. Exercise training is known to delay several aspects of T-cell senescence. The purpose of the current study was to investigate the effect of 3 weeks regular concentric or eccentric endurance exercise training on the composition of the T-cell compartment in pre-diabetic subjects. Sixteen male older adults with impaired glucose tolerance were recruited and performed either concentric exercise (CE) or eccentric exercise (EE) walking 3 times a week for 3 weeks. Fasting venous blood sampling was performed before training and after the training intervention. Various T-cell subpopulations were analyzed by flow cytometry. We did not find significant time × group effects (interaction) but found several significant time effects for cell type ratios and cell subsets proportions. There was an increase of the CD4+/CD8+ (0.55 ± 0.85%; p = 0.033) and CD4+/CD3+ ratio (5.63 ± 8.44%; p = 0.018) and a decrease of the CD8+/CD3+ ratio (-0.95 ± 1.64%; p = 0.049) after training. We found proportional increases of CD4+/CCR7+/CD45RO+ central memory cells (5.02 ± 7.68%; p = 0.030), naïve CD8+/CCR7+/CD45RO- (3.00 ± 6.68%; p = 0.047) and CD8+/CCR7+/CD45RO+ central memory cells (3.01 ± 3.70%; p = 0.009), while proportions of CD4+/CCR7-/CD45RO- TEMRA cells (-2.17 ± 4.66%; p = 0.012), CD8+/CCR7-/CD45RO- TEMRA cells (-5.11 ± 7.02%; p = 0.018) and CD16+ cells (-4.67 ± 6.45%; p = 0.016) decreased after training. 3 weeks of either CE or EE were effective in reversing hallmarks of T-cell senescence in pre-diabetic subjects. It is suggested that exercise stimulates production and mobilization of naïve T-cells, while differentiated TEMRA cells might disappear by apoptosis

Acupuncture in acute herpes zoster pain therapy (ACUZoster) - design and protocol of a randomised controlled trial

Background: Acute herpes zoster is a prevalent condition. One of its major symptoms is pain, which can highly influence patient's quality of life. Pain therapy is limited. Acupuncture is supposed to soften neuropathic pain conditions and might therefore act as a therapeutic alternative. Objective of the present study is to investigate whether a 4 week semi-standardised acupuncture is non-inferior to sham laser acupuncture and the anticonvulsive drug gabapentine in the treatment of pain associated with herpes zoster. Methods/Design: Three-armed, randomised, placebo-controlled trial with a total follow-up time of 6 months. Up to estimated 336 patients (interim analyses) with acute herpes zoster pain (VAS > 30 mm) will be randomised to one of three groups (a) semi-standardised acupuncture (168 patients); (b) gabapentine with individualised dosage between 900-3600 mg/d (84 patients); (c) sham laser acupuncture. Intervention takes place over 4 weeks, all patients will receive analgesic therapy (non-opioid analgesics: metamizol or paracetamol and opioids: tramadol or morphine). Therapy phase includes 4 weeks in which group (a) and (c) consist of 12 sessions per patient, (b) visits depend on patients needs. Main outcome measure is to assess the alteration of pain intensity before and 1 week after treatment sessions (visual analogue scale VAS 0-100 mm). Secondary outcome measure are: alteration of pain intensity and frequency of pain attacks; alteration of different aspects of pain evaluated by standardised pain questionnaires (NPI, PDI, SES); effects on quality of life (SF 36); analgesic demand; alteration of sensoric perception by systematic quantitative sensory testing (QST); incidence of postherpetic neuralgia; side effects and cost effectiveness. Credibility of treatments will be assessed. Discussion: This study is the first large-scale randomised placebo controlled trial to evaluate the efficacy of acupuncture compared to gabapentine and sham treatment and will provide valuable new information about the clinical and physiological effects of acupuncture and gabapentine in the treatment of acute herpes zoster pain. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if acupuncture can be shown to be an effective treatment strategy in acute herpes zoster pain

Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo - therapeutic potential for peripheral neuropathies: results of a randomised controlled trial

Background: Flupirtine is an analgesic with muscle-relaxing properties that activates Kv7 potassium channels. Kv7 channels are expressed along myelinated and unmyelinated peripheral axons where their activation is expected to reduce axonal excitability and potentially contribute to flupirtine’s clinical profile. Trial design: To investigate the electrical excitability of peripheral myelinated axons following orally administered flupirtine, in-vitro experiments on isolated peripheral nerve segments were combined with a randomised, double-blind, placebo-controlled, phase I clinical trial (RCT). Methods: Threshold tracking was used to assess the electrical excitability of myelinated axons in isolated segments of human sural nerve in vitro and motoneurones to abductor pollicis brevis (APB) in situ in healthy subjects. In addition, the effect of flupirtine on ectopic action potential generation in myelinated axons was examined using ischemia of the lower arm. Results: Flupirtine (3-30 μM) shortened the relative refractory period and increased post-conditioned superexcitability in human myelinated axons in vitro. Similarly, in healthy subjects the relative refractory period of motoneurones to APB was reduced 2 hours after oral flupirtine but not following placebo. Whether this effect was due to a direct action of flupirtine on peripheral axons or temperature could not be resolved. Flupirtine (200 mg p.o.) also reduced ectopic axonal activity induced by 10 minutes of lower arm ischemia. In particular, high frequency (ca. 200 Hz) components of EMG were reduced in the post-ischemic period. Finally, visual analogue scale ratings of sensations perceived during the post-ischemic period were reduced following flupirtine (200 mg p.o.). Conclusions: Clinical doses of flupirtine reduce the excitability of peripheral myelinated axons. Trial registration: ClinicalTrials registration is NCT01450865

Improvements in Chilean patients with obesity following a 5-month multidisciplinary exercise program: A feasibility study

Background: The aim of this study was to determine the effects of a multidisciplinary exercise program on physical fitness, metabolic profile and nutritional status of obese patients. Methods: Seventeen women and four men (N.=21, age 18 to 60 years), with severe obesity (BMI=35-40 kg/m2, N.=7), morbid obesity (BMI=40-50 kg/m2, N.=9), and super obesity (BMI>50 kg/m2, N.=5), took part in a physical exercise program with nutritional and psychological support. The intermittent physical exercise program was applied three times per week (1 hour/session), with 4-8 exercises with weights. Three series were carried out for 60 s each, with increasing intensity leading to exhaustion at the end of the period and with 1-2 min recovery between series. Outcomes include the BMI, waist contour, blood pressure, cardiorespiratory fitness, exercise capacity, maximum dynamic strength, hand grip strength, basal glucose and lipid profiles. Results: The patients decreased in weight and BMI (P<0.05). Morbid (N.=9) and super obese (N.=5) improved their cardiorespiratory fitness (P=0.005 and 0.040) and lowered their triglycerides (-25.70% and -15.38%; P=0.008). Hand grip strength improved in the super obese (P<0.001). Descriptively, patients with super obesity had the largest improvements. Conclusions: Multi-modal lifestyle and exercise interventions improve the condition especially in super obese patients. The improved health status may improve the outcome of secondary steps in weight loss, such as bariatric surgery. The program was feasible to be executed and patients compliant to the intervention