Cardiovascular effects of auricular stimulation -a systematic review and meta-analysis of randomized controlled clinical trials.

Background: The number of randomized controlled trials using auricular stimulation (AS) such as transauricular vagus nerve stimulation, or other auricular electrostimulation or auricular acupuncture or acupressure, in experimental and clinical settings, has increased markedly over the last three decades. This systematic review focusses on cardiovascular effects of auricular stimulation. Methods and analysis: The following databases were searched: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, and Scopus Database. RCTs were reviewed that had been published in English and European languages. Data collection and analysis was conducted by two reviewers independently. Quality and risk assessment of included studies was performed and the meta-analysis of the effect of the most frequently assessed biomarkers. Results: Altogether, 78 trials were included. 38 studies assessed heart rate (HR), 19 studies analyzed heart rate variability (HRV), 31 studies analyzed blood pressure (BP) and 7 studies were identified that measured oxygen saturation (O2), 2 studies on baroreflex sensitivity and 2 studies on skin conductance were evaluated in this review. 26 studies contained continuous data and were eligible for meta-analysis, 50 trials reported non continuous data and were evaluated descriptively. The overall quality of the studies was moderate to low. AS leads to a significant reduction of HR, the changes though were not considered an adverse reaction. Furthermore, when looking at HRV, AS was able to reduce the LF/HF ratio significantly compared to control procedures. No other cardiovascular parameters (blood pressure, oxygen saturation, baroreflex sensitivity) were changed significantly. AS produced only minor side effects in all trials. Conclusion: AS can lead to clinically safe reduction of HR and changes in the LF/HF ratio of the HRV, which is presumably via an increase in vagal activity. More research is needed to clarify whether AS can be used to modulate tachycardia or indications with autonomic imbalance. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=231885 PROSPERO, ID CRD42021231885.

Evidence for a modulating effect of transcutaneous auricular vagus nerve stimulation (taVNS) on salivary alpha-amylase as indirect noradrenergic marker: A pooled mega-analysis.

BACKGROUND: Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has received tremendous attention as a potential neuromodulator of cognitive and affective functions, which likely exerts its effects via activation of the locus coeruleus-noradrenaline (LC-NA) system. Reliable effects of taVNS on markers of LC-NA system activity, however, have not been demonstrated yet. METHODS: The aim of the present study was to overcome previous limitations by pooling raw data from a large sample of ten taVNS studies (371 healthy participants) that collected salivary alpha-amylase (sAA) as a potential marker of central NA release. RESULTS: While a meta-analytic approach using summary statistics did not yield any significant effects, linear mixed model analyses showed that afferent stimulation of the vagus nerve via taVNS increased sAA levels compared to sham stimulation (b = 0.16, SE = 0.05, p = 0.001). When considering potential confounders of sAA, we further replicated previous findings on the diurnal trajectory of sAA activity. CONCLUSION(S): Vagal activation via taVNS increases sAA release compared to sham stimulation, which likely substantiates the assumption that taVNS triggers NA release. Moreover, our results highlight the benefits of data pooling and data sharing in order to allow stronger conclusions in research.

Stimulation of Lactation Using Acupuncture: A Case Study.

INTRODUCTION: Breastfeeding is a recognized preferred method of infant feeding; however, for many women, difficulties in breastfeeding result in termination before the recommended period of time. Acupuncture is suggested to be a promising option to treat lactation insufficiency and enhance the production of maternal milk. MAIN ISSUE: We have reported the case of a woman with lactation insufficiency due to Caesarean section and congenital unilateral invaginated nipple. Milk production started on the 3rd day following delivery. The newborn was not provided with any food or fluids other than mother's milk. At 5 days of life, the newborn required long feeding periods and lost 4% of his birth weight, with the participant reporting lactation insufficiency described by the perception of inadequate milk production. MANAGEMENT: Despite the implementation of conventional measures to improve lactation, the difficulties in breastfeeding persisted. Acupuncture was tried on Day 6 of life, and enhanced milk production was observed, which could be measured as the volume of residual milk extracted using the breast pump each time after the newborn achieved satiety. After acupuncture treatment there was an augmentation of maternal milk production from both breasts and successful lactation. CONCLUSION: This case study provides information that might be useful for prospective investigation of acupuncture's efficacy in women with lactation insufficiency.

Effectiveness of Acupuncture for Pain Control After Cesarean Delivery: A Randomized Clinical Trial.

IMPORTANCE: A pharmacological approach to pain control after cesarean delivery is often insufficient on its own. Acupuncture is a promising method for mitigating postoperative pain and reducing postoperative opioid requirements. OBJECTIVE: To evaluate the efficacy and effectiveness of acupuncture as an adjunctive therapy for pain control after cesarean delivery, compared with a placebo intervention and standard care alone. DESIGN, SETTING, AND PARTICIPANTS: This single-center, placebo-controlled, patient- and assessor-blinded randomized clinical trial was conducted from January 13, 2015, to June 27, 2018, at a tertiary university hospital in Greifswald, Germany. Participants were women who were scheduled for elective cesarean delivery under spinal anesthesia and were randomized to either the acupuncture group (n = 60) or placebo group (n = 60). Another 60 consecutive patients who met the eligibility criteria and received the standard postoperative analgesia were selected to form a nonrandomized standard care group. The intention-to-treat analysis was performed from August 19, 2019, to September 13, 2019. INTERVENTIONS: In addition to standard pain treatment, each patient in the acupuncture group received auricular and body acupuncture with indwelling intradermal needles, whereas patients in the placebo group were treated with nonpenetrating placebo needles. MAIN OUTCOMES AND MEASURES: The primary outcome was pain intensity on movement, which was measured using an 11-item verbal rating scale. Secondary outcomes were analgesia-related adverse effects, analgesics consumption, time to mobilization and Foley catheter removal, quality of patient blinding to randomization, and patient satisfaction with treatment of pain. RESULTS: A total of 180 female patients (mean [SD] age, 31 [5] years) were included in the intention-to-treat analysis. The mean pain intensity on movement in the acupuncture group on the first postoperative day was lower than in the placebo group (4.7 [1.8] vs 6.0 [2.0] points; Cohen d, 0.73; 95% CI, 0.31-1.01; P = .001) and the standard care group (6.3 [1.3] points; Cohen d, 1.01; 95% CI, 0.63-1.40; P < .001). On the first postoperative day, 59 patients (98%) in the acupuncture group were fully mobilized vs 49 patients (83%) in the placebo group (relative risk [RR], 1.18; 95% CI, 1.06-1.33; P = .01) and 35 patients (58%) in the standard care group (RR, 1.69; 95% CI, 1.36-2.09; P < .001). The Foley catheter was removed in a total of 57 patients (93%) from the acupuncture group vs 43 patients (72%) from the placebo group (RR, 1.33; 95% CI, 1.12-1.57; P = .003) and 42 patients (70%) from the standard care group (RR, 1.37; 95% CI, 1.14-1.62; P = .002). Other parameters were comparable across the 3 study groups. CONCLUSIONS AND RELEVANCE: Results of this trial showed that acupuncture was safe and effective in reducing pain and accelerating mobilization of patients after cesarean delivery. With consideration for personnel and time expenditures, acupuncture can be recommended as routine, supplemental therapy for pain control in patients after elective cesarean delivery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02364167.

Pain perception during injection of local anesthesia in pedodontics.

OBJECTIVE: Few studies have examined pain levels for the injection of local anesthesia in children, though it is a routine technique in pediatric dentistry. The objective of the study was to evaluate the difference in the assessment of procedural pain by the child, parent, dental practitioner, and independent observers during injection of local anesthesia for dental treatment in pediatric dentistry. METHOD AND MATERIALS: In total, 27 male and 22 female children (5 to 17 years of age, mean ± SD 9.8 ± 4.0 years) received local anesthesia (LA) via infiltration or mandibular alveolar blocks according to a standard protocol. After the dental treatment, the children assessed the pain levels for the procedures on a visual analog scale (VAS), while their parents and the dental practitioner used a numeric rating scale (0 to 10). Independent observers also assessed pain via video tape for an evaluation after blinding. The heart rate was monitored continuously during the procedure. The Bland-Altman method was used to quantify the comparison between pain ratings. RESULTS: The assessed level of pain by dental practitioner, parent, and child during injection of LA differed clearly (child: 3.94 ± 2.71; parent: 3.31 ± 2.60; dental practitioner: 3.02 ± 1.98; video observer 1: 1.76 ± 2.56; video observer 2: 1.89 ± 2.55). In 42.9% of cases the dental practitioner's rating and the self--reported pain by the child during injection of LA differed by ≥ 2 on the numeric rating scale, which is clinically a highly different and relevant assessment. CONCLUSION: As pain perception in children during the injection of local anesthetic and its assessment varies considerably depending on the assessing person and the treated child, dental practitioners and researchers should be cautious in interpreting the patient's pain perception.

Auricular Acupuncture for Preoperative Anxiety-Protocol of Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Preoperative anxiety causes profound psychological and physiological reactions that may lead to a worse postoperative recovery, higher intensity of acute and persistent postsurgical pain and impaired quality of life in the postoperative period. Previous randomized controlled trials (RCTs) suggest that auricular acupuncture (AA) is safe and effective in the treatment of preoperative anxiety; however there is a lack of systematic evidence on this topic. Therefore, this protocol was developed following the PRISMA guidelines to adequately evaluate the existing literature regarding the value of AA for the reduction in anxiety in patients in a preoperative setting, compared to other forms of acupuncture, pharmacological, or no control interventions and measured with questionnaires regarding anxiety and fear. Methods: The following databases will be searched: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, and Scopus Database. RCTs will be included if an abstract is available in English. Data collection and analysis will be conducted by two reviewers independently. Quality and risk assessment of included studies will be done using the Cochrane 5.1.0 handbook criteria and meta-analysis of effectiveness and symptom scores will be conducted using the statistical software RevMan V.5.3. Conclusions: This systematic review will evaluate the efficacy and safety of AA for preoperative anxiety. Since all data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. The results may be published in a peer-reviewed journal or be presented in relevant conferences. Registration number: PROSPERO ID CRD42020.

Acupuncture for Relief of Gag Reflex in Patients Undergoing Transoesophageal Echocardiography-A Protocol for a Randomized Placebo-Controlled Trial.

Background: Gagging during transesophageal echocardiography examination (TEE) can be distressing and even dangerous for patients. The needling of acupuncture point CV24 was described to be effective in reducing the gag reflex during TEE in patients with ischemic stroke or transient ischemic attack. Methods: We describe a proposal for a prospective, randomized, patient, practitioner and assessor-blinded, single-center trial with two arms/groups; real acupuncture will be compared to placebo acupuncture. A total of 60 (30 per group) patients scheduled for elective TEE in order to exclude a cardiac embolic source, endocarditis or for valve failure evaluation will be recruited according to patients' selection criteria and receive either indwelling fixed intradermal needles at acupoints CV24 and bilateral PC6 or placebo needles at the same areas. Patients, the practitioners who will perform the TEE procedure, and the assessor of the outcome measures will be unaware of the group's (real or placebo) allocation. Results: The primary outcome is the intensity of gagging, measured using verbal rating scale (VRS-11) from 0 = no gagging to 10 = intolerable gagging. Secondary outcomes include the incidence of gagging, the use of rescue medication, patients' satisfaction with relief of unwanted side effects during TEE procedure, success of patients' blinding (patients' opinion to group allocation), heart rate and oxygen saturation measured by pulse oxymetry. Conclusions: To study the effects of acupuncture against gagging during TEE, we test the needling of acupoints CV24 and PC6 bilaterally. A placebo acupuncture is used for the control group. Trial registration number: NCT NCT0382142.

Treating Therapy-Resistant Headache After Aneurysmal Subarachnoid Hemorrhage with Acupuncture.

INTRODUCTION: Subarachnoid haemorrhage (SAH) is usually associated with severe headache, whereas the options of pharmacological analgesia are restricted. Acupuncture is a promising method in treatment of headaches associated with meningeal sensitivity or irritation, such as migraine or post-dural puncture headache. CASE REPORT: We report on 3 patients, who suffered severe headache due to aneurysmal SAH, and received acupuncture when pharmacological measures were exhausted. After acupuncture treatment all patients reported at least 50% pain reduction and could stop or reduce analgesics without side effects. DISCUSSION: Acupuncture may be an effective pain treatment method in patients suffering from headache due to SAH. Randomized trials using acupuncture as an add-on to standard analgesic therapy would help evaluate the role of acupuncture for this purpose.

Pain in the hand caused by a previously undescribed mechanism with possible relevance for understanding regional pain.

Background and aims A previously undescribed mechanism of pain in the ulnar side of the hand was observed in a series of four patients. All were found to have a sensitive point in the first interspace of the hand and possible entrapment of a terminal branch of ulnar nerve piercing the fascia in the first interphalangeal webspace was suggested. Methods Pressure on the sensitive point reproduced the ulnar sided hand pain. Diagnostic and therapeutic injection of the mixture of local anesthetic and corticosteroid were performed. The degree and duration of relief of pain was noted. Results In individuals with recent onset hand pain of this type the injections abolished pain for 2 or more years. In individuals with long-standing pain (longer than 3-6 months) the pain was abolished for periods of time lasting several hours to several weeks. The correspondence of the point, where injections were done with acupuncture point LI4 was noted. Conclusions The location of possible nerve entrapment corresponds with an acupuncture point LI4 and may additionally represent a previously undescribed myofascial trigger point. Implications The suggested mechanism of ulnar sided hand pain represents a miniature chronic constriction injury similar to the animal model of neuropathic pain and may have relevance for regional pain elsewhere in the body.

Auricular acupuncture for treatment of preoperative anxiety in patients scheduled for ambulatory gynaecological surgery: a prospective controlled investigation with a non-randomised arm.

OBJECTIVE: Auricular acupuncture (AA) is a promising alternative treatment for situational anxiety. The aim of this pilot investigation was to test the acceptability and feasibility of AA as a treatment for preoperative anxiety (PA) in preparation for a subsequent randomised controlled trial. METHODS: AA was offered for treatment of PA to female patients who were scheduled for ambulatory gynaecological surgery. In patients who agreed, indwelling fixed needles were applied bilaterally at the points MA-IC1, MA-TF1, MA-SC, MA-AH7 and MA-T the day before surgery. Patients who declined AA but agreed to be examined constituted the control group (no intervention). State anxiety (primary outcome) was measured using the State-Trait-Anxiety Inventory (STAI) before AA (time I), the evening before surgery (time II) and immediately before surgery (time III). Anxiety was measured with a 100 mm visual analogue scale (VAS-100); heart rate, blood pressure and serum cortisol were also quantified. RESULTS: Data from 62 patients (32 with AA and 30 with no intervention) were analysed. Whereas preoperative anxiety was reduced after AA the evening before surgery (P<0.01), anxiety levels in the control group increased from the first to the last measurement (P<0.001). Secondary outcomes were comparable between the patients from both groups. CONCLUSIONS: AA was acceptable and feasible as a treatment for preoperative anxiety. The results were used for the sample size calculation of a subsequent randomised controlled clinical trial. TRIAL REGISTRATION NUMBER: NCT02656966; Results.

Effects of Electrical Transcutaneous Vagus Nerve Stimulation on the Perceived Intensity of Repetitive Painful Heat Stimuli: A Blinded Placebo- and Sham-Controlled Randomized Crossover Investigation.

BACKGROUND: Transcutaneous vagus nerve stimulation (TVNS) is a promising treatment for acute and chronic pain. However, experimental studies yielded controversial results. We examined if TVNS reduces the perceived intensity of repetitive painful heat stimulation and temporal summation of pain (TSP) in healthy volunteers in comparison with placebo and sham stimulation, as well as no intervention. METHODS: In 4 sessions, 90 heat pulse stimuli at individual pain tolerance temperature were applied to the ventral forearm of 49 healthy volunteers (25 women) using a Contact Heat Evoked Potential Stimulator thermode (Medoc, Ramat Yishai, Israel). Pain intensity was assessed with verbal ratings on a numeric pain scale (0-100) at every tenth heat pulse. After the first session in which pain intensities without intervention were evaluated, participants completed 3 sessions in a single-blinded randomized crossover manner: (1) sham stimulation applied at the earlobes, (2) placebo stimulation (inactive device), or (3) TVNS applied at the cymbas conchae. Primary data were analyzed using analysis of variance for repeated measures and t test for paired samples. RESULTS: Pain intensity decreased during all interventions as compared to no intervention (ηp = 0.22, P < .001; mean difference TVNS versus no intervention 9.5; 95% confidence interval [CI], 3.6-15.4; P < .001). Hypoalgesic effect of TVNS was better than that of placebo and sham in men before the onset of TSP (mean differences for TVNS versus placebo 6.2; 95% CI, 0.2-12.1; TVNS versus sham 6.2; 95% CI, 0.2-12.1; P < .05). In women, TSP response under TVNS was decreased if compared to no intervention (median difference, 7.5; 95% CI, 3.5-15.0; P = .003). CONCLUSIONS: TVNS, placebo, and sham stimulation exerted comparable effects under experimental heat pain stimulation. Only in male participants, TVNS was superior to sham and placebo conditions in the reduction of heat pain before the onset of TSP.

Auricular Acupoints with Reduced Skin Resistance: Detection in Patients Scheduled for Hip Arthroplasty.

Objective: The detection of auricular acupuncture (AA) points by measuring electrical skin resistance (ESR) is often used in diagnostics and therapy; however, systematic investigations of ESR in AA points are rare. The aim of this study was to examine the frequency of detection of AA points with reduced ESR in patients scheduled for unilateral hip arthroplasty. Materials and Methods: Data were obtained from 2 prospective clinical trials, which studied the perioperative analgesic effects of AA in patients with unilateral degenerative hip osteoarthritis. Three AA points (MA-TF1, MA-AH4, and MA-IC1) were examined in these patients before arthroplasty surgery using a SVESA (Neuralstift SVESA 1070, SVESA, Muenchen, Germany) neural pen. The frequency of AA points detection on the ipsi- and contralateral sides of the affected hip joint was registered and analyzed with a χ2 test. Results: The data of 114 patients (60 females) were available for analysis. AA points with lower ESR were detected more frequently on the side ipsilateral to the affected joint rather than on the contralateral side: 81% versus 37% of patients (P < 0.0001). None of the AA points could be identified at all in 13% of patients with diabetes mellitus versus 3% of patients without diabetes mellitus (P = 0.07). Conclusions: AA points with low ESR were detected more frequently on the side ipsilateral to the underlying pathology. This finding is in agreement with neurophysiologic data. The therapeutic value of this finding should be clarified in future studies.

Transcutaneous auricular vagal nerve stimulation (taVNS) might be a mechanism behind the analgesic effects of auricular acupuncture.

BACKGROUND: Randomized clinical trials (RCT) demonstrated that auricular acupuncture (AA) is effective in treatment of acute and chronic pain, although the mechanisms behind AA are not elucidated. METHODS: The data concerning the localization of AA points, which are commonly used to treat pain, were extracted from the meta-analysis of 17 RCTs and evaluated using the anatomical map of auricular afferent nerve supply. RESULTS: Fifteen out of 20 specific AA points, used in the treatment of pain, are situated in areas innervated mostly by the auricular branch of the vagal nerve (ABVN), whereas sham stimulation was applied at the helix of the auricle, innervated by cervical nerves. CONCLUSION: Considering the clinical data relating to the anatomy of neural pathways and experimental findings of the mechanisms of transcutaneous auricular vagal nerve stimulation, the analgesic effects of AA may be explained by stimulation of ABVN.

Preliminary findings of cerebral responses on transcutaneous vagal nerve stimulation on experimental heat pain.

Transcutaneous vagal nerve stimulation (TVNS) is a promising complementary method of pain relief. However, the neural networks associated with its analgesic effects are still to be elucidated. Therefore, we conducted two functional magnetic resonance imaging (fMRI) sessions, in a randomized order, with twenty healthy subjects who were exposed to experimental heat pain stimulation applied to the right forearm using a Contact Heat-Evoked Potential Stimulator. While in one session TVNS was administered bilaterally to the concha auriculae with maximal, non-painful intensity, the stimulation device was switched off in the other session (placebo condition). Pain thresholds were measured before and after each session. Heat stimulation elicited fMRI activation in cerebral pain processing regions. Activation magnitude in the secondary somatosensory cortex, posterior insula, anterior cingulate and caudate nucleus was associated with heat stimulation without TVNS. During TVNS, this association was only seen for the right anterior insula. TVNS decreased fMRI signals in the anterior cingulate cortex in comparison with the placebo condition; however, there was no relevant pain reducing effect over the group as a whole. In contrast, TVNS compared to the placebo condition showed an increased activation in the primary motor cortex, contralateral to the site of heat stimulation, and in the right amygdala. In conclusion, in the protocol used here, TVNS specifically modulated the cerebral response to heat pain, without having a direct effect on pain thresholds.

Remote Effects of Electromagnetic Millimeter Waves on Experimentally Induced Cold Pain: A Double-Blinded Crossover Investigation in Healthy Volunteers.

BACKGROUND: The hypoalgesic effect of electromagnetic millimeter waves (MW) is well studied in animal model; however, the results of human research are controversial. The aim of this study was to evaluate the effects of various frequency ranges of MW on hypoalgesia using the cold pressor test (CPT). METHODS: Experimental pain was induced using standardized CPT protocols in 20 healthy male volunteers. The skin of the lower part of sternum was exposed to MW with a frequency of 42.25 GHz (active generator); MW within 50-75 GHz frequency range (noise generator); or an inactive MW device (placebo generator) in a random crossover double-blinded manner. Pain threshold, measured using the CPT, was the primary outcome. Other CPT parameters, heart rate, blood pressure, incidence of subjective sensations (paresthesia) during exposure, as well as quality of volunteers' blinding were also recorded. The end points of the condition with exposure to 42.25 GHz, were compared with baseline; exposure to noise 50-75 GHz; and placebo generators. RESULTS: Pain threshold increased during exposure to the 42.25 GHz generator when compared with baseline: median difference (MD), 1.97 seconds (95% confidence interval [CI], 0.35-3.73) and noise generator: MD, 1.27 seconds (95% CI, 0.05-2.33) but not compared with the placebo generator. Time to onset of cold and increasing pain sensations as well as diastolic blood pressure increased under the exposure to the 42.25 GHz generator when compared with baseline and noise generator. Other outcome measures were comparable among the study conditions. CONCLUSIONS: We were able to partially confirm the previously suggested hypoalgesic effects of low-intensity electromagnetic MW. However, the effect was indistinguishable from the placebo condition in our investigation.

Auricular Acupuncture for Exam Anxiety in Medical Students-A Randomized Crossover Investigation.

Auricular acupuncture (AA) is effective in the treatment of preoperative anxiety. The aim was to investigate whether AA can reduce exam anxiety as compared to placebo and no intervention. Forty-four medical students were randomized to receive AA, placebo, or no intervention in a crossover manner and subsequently completed three comparable oral anatomy exams with an interval of 1 month between the exams/interventions. AA was applied using indwelling fixed needles bilaterally at points MA-IC1, MA-TF1, MA-SC, MA-AT1 and MA-TG one day prior to each exam. Placebo needles were used as control. Levels of anxiety were measured using a visual analogue scale before and after each intervention as well as before each exam. Additional measures included the State-Trait-Anxiety Inventory, duration of sleep at night, blood pressure, heart rate and the extent of participant blinding. All included participants finished the study. Anxiety levels were reduced after AA and placebo intervention compared to baseline and the no intervention condition (p < 0.003). AA was better at reducing anxiety than placebo in the evening before the exam (p = 0.018). Participants were able to distinguish between AA and placebo intervention. Both AA and placebo interventions reduced exam anxiety in medical students. The superiority of AA over placebo may be due to insufficient blinding of participants.