Michael Bernateck

Auricular acupuncture for dental anxiety: a randomized controlled trial.

Auricular acupuncture can be an effective treatment for acute anxiety, but there is a lack of direct comparisons of acupuncture to proven standard drug treatments. In this study we compared the efficacy of auricular acupuncture with intranasal midazolam, placebo acupuncture, and no treatment for reducing dental anxiety. Patients having dental extractions (n = 67) were randomized to (i) auricular acupuncture, (ii) placebo acupuncture, and (iii) intranasal midazolam and compared with a no treatment group. Anxiety was assessed before the interventions, at 30 min, and after the dental extraction. Physiological variables were assessed continuously. With the no treatment group as control, the auricular acupuncture group, and the midazolam group were significantly less anxious at 30 min as compared with patients in the placebo acupuncture group (Spielberger Stait-Trait Anxiety Inventory X1, P = 0.012 and <0.001, respectively). In addition, patient compliance assessed by the dentist was significantly improved if auricular acupuncture or application of intranasal midazolam had been performed (P = 0.032 and 0.049, respectively). In conclusion, both, auricular acupuncture and intranasal midazolam were similarly effective for the treatment of dental anxiety.

Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis

IntroductionWe previously described the presence of nerve growth factor receptors in the inflamed synovial compartment. Here we investigated the presence of the corresponding nerve growth factors, with special focus on nerve growth factor (NGF).MethodsmRNA expression levels of four ligands (NGF, brain derived growth factor (BDNF), neurotrophin (NT)-3, NT-4) and their four corresponding receptors (tyrosine kinase (trk) A, trkB, trkC, NGFRp75) were determined in the synovial fluid (SF) cells of 9 patients with rheumatoid arthritis (RA) and 16 with spondyloarthritis (SpA) and compared with 7 osteoarthritis (OA) patients. NGF was also determined in synovial tissue (ST) biopsies of 10 RA and 10 SpA patients. The production of NGF by monocytes and lymphocytes was assessed by flow cytometry of SF cells, synovial tissue derived fibroblast-like synoviocytes (FLS) were assessed by ELISA on culture supernatant.ResultsSF cell analysis revealed a clear BDNF and NGF mRNA expression, with significantly higher NGF expression in RA and SpA patients than in the OA group. NGF expression was higher in ST samples of RA as compared to SpA. Using intracellular FACS analysis, we could demonstrate the presence of the NGF protein in the two inflammatory arthritis groups on both CD3+ T lymphocytes and CD14+ cells, i.e. monocytes/macrophages, whereas cultured FLS did not produce NGF in vitro.ConclusionsNeurotrophins and especially NGF are expressed in the synovial fluid and tissue of patients with peripheral synovitis. The presence of neurotrophins as well as their receptors, in particular the NGF/trkA-p75 axis in peripheral synovitis warrants further functional investigation of their active involvement in chronic inflammatory arthritis.

The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series

Cluster headache (CH) is a stereotyped primary headache characterized by strictly unilateral severe orbital or periorbital pain and categorized as either episodic or chronic (1,2). Its prevalence is 0.1% (3). Oxygen and sumatriptan are the treatments of choice for individual attacks, whereas verapamil, lithium, corticosteroids and other neuromodulators can suppress attacks during cluster periods (1). All standard medication treatments may be ineffective. Surgical treatment may be an option for medication non-responders, including deep brain (4) or occipital nerve stimulation (5). However, serious complications from brain surgery, including death, can occur (6). An Internet survey of 53 CH patients reported on claims that psilocybin is better at aborting acute attacks than either oxygen or sumatriptan and that LSD and psilocybin are both better at triggering and extending remission than standard drugs (7). However, due to hallucinogenicity and the absence of established medical indication, these drugs are criminalized and placed within the most restrictive Schedule I of the Controlled Substances Act, which sanctions only limited research use. Although the hallucinogenic properties of LSD and psilocybin are undesirable from both regulatory and patient safety perspectives, it was unclear to us at the outset whether a non-hallucinogenic analog could also provide meaningful relief to CH patients. To address the question of whether the CH relief associated with these two structurally diverse compounds is related to the mechanisms triggering intoxication, we decided to investigate the efficacy of a nonhallucinogenic analog of LSD. LSD’s hallucinogenic effects are completely lost when the double bond in the D ring is saturated and with substitution at R2 (e.g. by bromination in 2-bromo-LSD) (BOL-148) (8). BOL-148 has been studied in volunteers (up to 20mg per os) (9) and in patients suffering from vascular headaches but not, apparently, in patients with CH (9,10). These past studies concluded that BOL-148 is non-toxic and non-hallucinogenic. Only very mild side effects, if any, have been observed, when given in the dose range used in our project (30mg/kg/body weight) (9). No long-term behavioral or psychological effects from BOL-148 have been reported from past studies with more than 300 healthy, normal subjects (11), and 30mg BOL-148 administered daily over four to five weeks failed to alter active psychosis in chronically ill schizophrenic women (12).

Adjuvant auricular electroacupuncture and autogenic training in rheumatoid arthritis: a randomized controlled trial. Auricular acupuncture and autogenic training in rheumatoid arthritis.

Background: In contrast to psychological interventions the usefulness of acupuncture as an adjuvant therapy in rheumatoid arthritis (RA) has not yet been demonstrated. Objective: The efficacy of auricular electroacupuncture (EA) was directly compared with autogenic training (AT). Methods: Patients with RA (n = 44) were randomized into EA or AT groups. EA and lessons in AT were performed once weekly for 6 weeks. Primary outcome measures were the mean weekly pain intensity and the disease activity score 28 (DAS 28); secondary outcome measures were the use of pain medication, the pain disability index (PDI), the clinical global impression (CGI) and pro-inflammatory cytokine levels, which were assessed during the study period and 3 months after the end of treatment. Results: At the end of the treatment and at 3-month follow-up a clinically meaningful and statistically significant improvement (p < 0.05) could be observed in all outcome parameters and both groups. In contrast to the AT group, the onset of these effects in the EA group could already be observed after the 2nd treatment week. In the 4th treatment week the EA group reported significantly less pain than the AT group (p = 0.040). After the end of treatment (7th week) the EA group assessed their outcome as significantly more improved than the AT group (p = 0.035). The erythrocyte sedimentation rate in the EA group was significantly reduced (p = 0.010), and the serum concentration of tumor necrosis factor-alpha was significantly increased compared to the AT group (p = 0.020). Conclusions: The adjuvant use of both EA and AT in the treatment of RA resulted in significant short- and long-term treatment effects. The treatment effects of auricular EA were more pronounced.

The First Scintigraphic Detection of Tumor Necrosis Factor-alpha in Patients with Complex Regional Pain Syndrome Type 1

Tumor necrosis factor (TNF)-alpha has been identified as a pathogenic factor in many immunologically based diseases and complex regional pain syndrome (CRPS). In this case series, we used radiolabeled technetium anti-TNF-alpha antibody to scintigraphically image TNF-alpha in 3 patients with type 1 CRPS. The results show that TNF-alpha was localized only in affected hands of patients with early-stage CRPS. No uptake was seen in clinically unaffected hands and late-stage CRPS. Our findings support the growing evidence for neuroimmune disturbance in patients with CRPS and may have important further implications for specific anticytokine treatment in patients with CRPS.

Do Occlusal Splints Have an Effect on Complex Regional Pain Syndrome? A Randomized, Controlled Proof-of-concept Trial

ObjectivesStudies have suggested overlaps between various chronic pain conditions and painful temporomandibular disorders (TMDs). The objective of this pilot study was to assess the effectiveness of occlusal splint (OS) therapy on self-reported measures of pain in patients with chronic complex regional pain syndrome (CRPS) as compared with a nontreatment group. MethodsThe design was a prospective randomized controlled clinical trial. Twenty patients with CRPS were randomly assigned to either the OS or control group. The patients in the OS group were asked to use the OS at nighttime and for 3 hours during daytime for a total of 7 weeks; the control group had no stomatognathic intervention. The primary outcome was self-reported assessment of CRPS-related pain on numerical rating scales. Secondary outcome measures were the Temporomandibular Index (TMI), and the Short Form 36 Health Survey (SF-36). ResultsAll patients had TMD signs and symptoms, but OS had no effect on CRPS-related pain on the numerical rating scale (P>0.100). The changes in the TMI scores over time were 16.6%±24.6% (improvement) in the OS group and −21.3%±25.9% (impairment) in the control group that was significant (P=0.004). There were no differences in the changes of SF-36 scores between groups (P=0.636). DiscussionThe use of OS for 7 weeks has no impact on CRPS-related pain but improved signs and symptoms of TMD pain. Future studies should include an active control group and evaluate if long-term changes in measures of oral health impact general health in CRPS-related pain.

Sustained effects of comprehensive inpatient rehabilitative treatment and sleeping neck support in patients with chronic cervicobrachialgia: a prospective and randomized clinical trial.

The objective of this study was to investigate the long-term efficacy of inpatient rehabilitation using sleeping neck support in patients suffering from chronic cervicobrachialgia. A prospective, randomized clinical trial with a 12-month follow-up was done. A total of 149 patients suffering from chronic cervicobrachialgia received a 4-week inpatient rehabilitation programme. The patients were randomly divided into two groups. The patients in one group were given a special neck pillow to use during and after the rehabilitative treatment (n=76); the patients in the other group were not given the pillow (n=73). Two weeks before, during, and after (3, 6, 9, and 12 months) the 4-week treatment period, the patients completed a questionnaire dealing with the intensity of their cervicobrachial complaints (pain intensity, muscular tension, paraesthesia, and sleep disorders caused by pain or paraesthesia). During the inpatient treatment period, no significant differences were detected between the groups; however, 1–12 months after discharge, the group with sleeping neck support showed a significantly (P<0.05) smaller increase in the intensity of cervical spine pain. Sleep disturbances caused by pain were also reduced significantly (P<0.001 after 3 months, respectively, P<0.05 after 12 months). Inpatient rehabilitative treatment has sustained effects in patients suffering from chronic cervicobrachialgia, particularly when a sleeping neck support is added.

Ca++/CaMKII switches nociceptor‐sensitizing stimuli into desensitizing stimuli

Many extracellular factors sensitize nociceptors. Often they act simultaneously and/or sequentially on nociceptive neurons. We investigated if stimulation of the protein kinase C epsilon (PKCε) signaling pathway influences the signaling of a subsequent sensitizing stimulus. Central in activation of PKCs is their transient translocation to cellular membranes. We found in cultured nociceptive neurons that only a first stimulation of the PKCε signaling pathway resulted in PKCε translocation. We identified a novel inhibitory cascade to branch off upstream of PKCε, but downstream of Epac via IP3‐induced calcium release. This signaling branch actively inhibited subsequent translocation and even attenuated ongoing translocation. A second ‘sensitizing’ stimulus was rerouted from the sensitizing to the inhibitory branch of the signaling cascade. Central for the rerouting was cytoplasmic calcium increase and CaMKII activation. Accordingly, in behavioral experiments, activation of calcium stores switched sensitizing substances into desensitizing substances in a CaMKII‐dependent manner. This mechanism was also observed by in vivo C‐fiber electrophysiology corroborating the peripheral location of the switch. Thus, we conclude that the net effect of signaling in nociceptors is defined by the context of the individual cells signaling history.

Does local immersion in thermo-neutral bath influence surface EMG measurements? Results of an experimental trial

This study investigated the effect of water immersion on surface electromyography (EMG) signals recorded from the brachioradial muscle of 11 healthy subjects, both in a dry environment and a thermo-neutral forearm bath (36 degrees C). EMG measurements were registered in a sitting position, using waterproof electrodes under 3 conditions: relaxed muscle, maximum voluntary isometric contraction (MVC, 1s, grip test) and 70% of the MVC (5 s). In relaxed muscle, mean EMG values were significantly higher under immersion compared to the dry conditions (dry: 5.4+/-3.6 microV; water: 19.5+/-14.9 microV; p=0.014). In maximum voluntary isometric contraction, there was a significant difference, though not in the same direction (dry: 145.9+/-58.9 microV; water: 73.2+/-35.0 microV; p=0.003). Under 70% MVC, there was no difference between wet and dry conditions (dry: 102.4+/-75.0 microV; water: 100.4+/-65.3 microV; p=0.951). Results suggest that dry and underwater conditions influence EMG readings; however, the results are inconsistent. These findings indicate additional influences on resting muscle activity, as well as MVC. Further measurements with other muscle groups and different types of immersion are needed to clarify conflicting observations.

Influence of the temporomandibular joint on range of motion of the hip joint in patients with complex regional pain syndrome.

OBJECTIVE This study evaluated if patients with complex regional pain syndrome (CRPS) would have an increase in range of motion (ROM) after myofascial release and a similar ROM decrease after jaw clenching, whereas in healthy subjects these effects would be minimal or nonexistent. METHODS Documentation of patients with CRPS (n = 20) was established using the research diagnostic criteria for CRPS, questionnaires, average pain intensity for the past 4 weeks, and the temporomandibular index (TMI). Healthy subjects (n = 20, controls) also underwent the same testing. Hip ROM (alpha angle) was measured at 3 time points as follows: baseline (t1), after myofascial release of the temporomandibular joint (t2), and after jaw clenching for 90 seconds (t3). Comparison of the CRPS and control groups was made using t tests. RESULTS Mean TMI total score and mean pain reported for the last 4 weeks were significantly different between the 2 groups (P < .0005). Hip ROM at t1 was always slightly higher compared to t3, but t2 was always lower in value compared to t1 or t3 for both groups. The differences of all hip ROM values between the groups were significant (P < .0005). Moreover, the difference between t1 or t3 and t2 was significantly different within the CRPS group (t1 = 48.7 degrees ; t2 = 35.8 degrees ; P < .0005). CONCLUSIONS The results suggest that temporomandibular joint dysfunction plays an important role in the restriction of hip motion experienced by patients with CRPS, which indicated a connectedness between these 2 regions of the body.