Rhythmically Enhanced Music as Analgesic for Chronic Pain: A Pilot, Non-Controlled Observational Study

Chronic pain changes brain connectivity, brainwaves, and volume, often resulting in disability, anxiety, and depression. Opioid pain relievers impair function, with risk of addiction. Music analgesia research suggests that music for long-term analgesia includes slow tempo, pleasantness, and self-choice. Hypothesis: individuals listening to self-chosen music with embedded beats ½ h twice a day, could show brainwave entrainment (BWE) at healthy frequencies of healthy descending pain modulatory system. BWE may change brain activity, restoring organization in DPMS altered by chronic pain. Volunteers with chronic pain >1 year participated in a study of 4 weeks of listening to one half hour of music twice a day, and four weeks of non-listening, reporting pain and analgesic use bi-weekly using visual analog scale (VAS) and 0–10 numerical pain scores (NPS), medication types, and dosage. Volunteers selected from 27 half-hour pieces of music in several genres in a mobile app. Isochronic beats were embedded in the music with tempo, key, and isochronic theta frequencies proportional, to enhance the brain’s perception of rhythmic patterns and harmonics. Mean NPS showed a 26% reduction (p = 0.018). Significantly, mean medication dosage declined by over 60% (p = 0.008). Double-blind studies, larger populations are needed in future.

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MEG Can Map Short and Long-Term Changes in Brain Activity following Deep Brain Stimulation for Chronic Pain

PLoS ONE ◽

10.1371/journal.pone.0037993 ◽

2012 ◽

Vol 7 (6) ◽

pp. e37993 ◽

Cited By ~ 20

Author(s):

Hamid R. Mohseni ◽

Penny P. Smith ◽

Christine E. Parsons ◽

Katherine S. Young ◽

Jonathan A. Hyam ◽

...

Keyword(s):

Chronic Pain ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Brain Activity ◽

Long Term Changes ◽

Short And Long Term ◽

Deep Brain

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Effects of the antibiotic rifaximin on cortical functional connectivity are mediated through insular cortex

Scientific Reports ◽

10.1038/s41598-021-83994-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Davide Sometti ◽

Chiara Ballan ◽

Huiying Wang ◽

Christoph Braun ◽

Paul Enck

Keyword(s):

Functional Connectivity ◽

Animal Studies ◽

Brain Connectivity ◽

Brain Activity ◽

Insular Cortex ◽

Controlled Study ◽

Double Blind ◽

Memory Processing ◽

Before And After ◽

The Central Nervous System

AbstractIt is well-known that antibiotics affect commensal gut bacteria; however, only recently evidence accumulated that gut microbiota (GM) can influence the central nervous system functions. Preclinical animal studies have repeatedly highlighted the effects of antibiotics on brain activity; however, translational studies in humans are still missing. Here, we present a randomized, double-blind, placebo-controlled study investigating the effects of 7 days intake of Rifaximin (non-absorbable antibiotic) on functional brain connectivity (fc) using magnetoencephalography. Sixteen healthy volunteers were tested before and after the treatment, during resting state (rs), and during a social stressor paradigm (Cyberball game—CBG), designed to elicit feelings of exclusion. Results confirm the hypothesis of an involvement of the insular cortex as a common node of different functional networks, thus suggesting its potential role as a central mediator of cortical fc alterations, following modifications of GM. Also, the Rifaximin group displayed lower connectivity in slow and fast beta bands (15 and 25 Hz) during rest, and higher connectivity in theta (7 Hz) during the inclusion condition of the CBG, compared with controls. Altogether these results indicate a modulation of Rifaximin on frequency-specific functional connectivity that could involve cognitive flexibility and memory processing.

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Intrauterine levobupivacaine for pain control during intrauterine device insertion

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20170596 ◽

2017 ◽

Vol 6 (3) ◽

pp. 1117

Author(s):

Nilufer Akgun ◽

Esra Keskin ◽

Muberra Namlı Kalem ◽

Batuhan Bakirarar

Keyword(s):

Pain Control ◽

Controlled Trial ◽

Intrauterine Device ◽

Saline Control ◽

Control Group ◽

Double Blind ◽

Pain Scores ◽

Significant Difference ◽

Vas Scores

Background: Safe, effective, long term and a reversible contraception method is offered by intrauterine devices (IUDs). The objective was to determine the potency of intrauterine administration of 5 cc levobupivacain for pain relief with IUD insertion, when compared with saline placebo.Methods: This was a prospective randomized, double blind placebo-controlled trial undergoing İUD insertion. The trial medication was intrauterine anesthesia, either 5 mL 0.9% saline (control group), or 5 mL 0.5% levobupivacaine. Our primary outcome was self-reported pain scores on a 10 cm visual analogue scale (VAS) immediately following IUD insertion.Results: 95 women were enrolled, and data for 88 women were analyzed. In IUD insertion procedure, no difference was observed between groups during teneculum placement and solution administration, in the course of VAS scores (p=0.349, p=0.396). There was a significant difference in the VAS scores measuring pain suffering during and after IUD procedure (p=0.001).Conclusions: Intrauterine instillation of 5 cc of levobupivacaine along with saline solution reduces pain with IUD insertion when compared to intrauterine saline placebo. Broad deviation in pain scores and persistent pain after IUD insertion recommends that patient would benefit from more functioning method of pain control than before at IUD insertion and during the post interval.

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Sub-Perception and Supra-Perception Spinal Cord Stimulation in Chronic Pain Syndrome: A Randomized, Semi-Double-Blind, Crossover, Placebo-Controlled Trial

Journal of Clinical Medicine ◽

10.3390/jcm9092810 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2810

Author(s):

Paweł Sokal ◽

Agnieszka Malukiewicz ◽

Sara Kierońska ◽

Joanna Murawska ◽

Cezary Guzowski ◽

...

Keyword(s):

Spinal Cord ◽

Chronic Pain ◽

Treatment Group ◽

Spinal Cord Stimulation ◽

Low Frequency ◽

Pain Syndrome ◽

Preoperative Period ◽

Double Blind ◽

Pain Scores ◽

Failed Back Surgery

Background: The introduction of modern sub-perception modalities has improved the efficacy of spinal cord stimulation (SCS) in refractory pain syndromes of the trunk and lower limbs. The objective of this study was to evaluate the effectiveness of low and high frequency SCS among patients with chronic pain. Material and methods: A randomised, semi-double-blind, placebo controlled, four period (4 × 2 weeks) crossover trial was conducted from August 2018 to January 2020. Eighteen patients with SCS due to failed back surgery syndrome and/or complex regional pain syndrome were randomised to four treatment arms without washout periods: (1) low frequency (40-60 Hz), (2) 1 kHz, (3) clustered tonic, and (4) sham SCS (i.e., placebo). The primary outcome was pain scores measured by visual analogue scale (VAS) preoperatively and during subsequent treatment arms. Results: Pain scores (VAS) reported during the preoperative period was M (SD) = 8.13 (0.99). There was a 50% reduction in pain reported in the low frequency tonic treatment group (M (SD) = 4.18 (1.76)), a 37% reduction in the 1 kHz treatment group (M (SD) = 5.17 (1.4)), a 34% reduction in the clustered tonic settings group (M (SD) = 5.27 (1.33)), and a 34% reduction in the sham stimulation group (M (SD) = 5.42 (1.22)). The reduction in pain from the preoperative period to the treatment period was significant in each treatment group (p < 0.001). Overall, these reductions were of comparable magnitude between treatments. However, the modality most preferred by patients was low frequency (55% or 10 patients). Conclusions: The pain-relieving effects of SCS reached significance and were comparable across all modes of stimulation including sham. Sub-perception stimulation was not superior to supra-perception. SCS was characterised by a high degree of placebo effect. No evidence of carryover effect was observed between subsequent treatments. Contemporary neuromodulation procedures should be tailored to the individual preferences of patients.

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Double-blind, placebo-controlled, dose-response trial of oral clodronate in patients with bone metastases.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.4.929 ◽

1995 ◽

Vol 13 (4) ◽

pp. 929-934 ◽

Cited By ~ 44

Author(s):

N O'Rourke ◽

E McCloskey ◽

F Houghton ◽

H Huss ◽

J A Kanis

Keyword(s):

Term Treatment ◽

Calcium Excretion ◽

Double Blind ◽

Double Blind Placebo ◽

Treatment Groups ◽

Pain Scores ◽

Long Term Treatment ◽

Significant Difference ◽

Oral Clodronate

PURPOSE Despite evidence that clodronate inhibits tumor-induced osteolysis, no studies have directly assessed the optimal dose for long-term treatment. The aim of this double-blind, placebo-controlled study was to determine the safety and efficacy of different doses of clodronate in affected patients. PATIENTS AND METHODS Eighty-four patients with tumor-induced osteolysis were randomized to receive treatment with placebo, or 400 mg, 1,600 mg, or 3,200 mg of clodronate, daily for 4 weeks. Patients were reviewed weekly during treatment. Fasting urinary calcium excretion was the primary variable used to assess response. Visual analog pain scores and adverse events were documented. RESULTS In the clodronate-treated groups, there was a dose-dependent reduction in fasting calcium excretion with a highly significant difference between placebo and 1,600 mg clodronate (P = .0002) and placebo and 3,200 mg clodronate (P = .0001), but no significant difference between 1,600 mg and 3,200 mg clodronate. There was no discernible change in pain scores or analgesic requirements. Bone-derived isoenzyme alkaline phosphatase values increased in all groups, with a significant difference between baseline and final values in the 1,600-mg and 3,200-mg groups (P < .01 and P = .03, respectively). Adverse events were distributed evenly across the four treatment groups. Compliance was greater than 99% in all treatment groups. CONCLUSION Oral clodronate at a dose of 1,600 mg or 3,200 mg will inhibit bone resorption. Since there was no significant difference between these two doses in terms of efficacy at 4 weeks, 1,600 mg/d can be recommended for long-term treatment. This dose is well tolerated and may promote bone repair, as judged by increases in bone alkaline phosphatase levels.

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Transcranial Magnetic Stimulation Alleviates Levodopa-Induced Dyskinesia in Parkinson's Disease and the Related Mechanisms: A Mini-Review

Frontiers in Neurology ◽

10.3389/fneur.2021.758345 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yi Wu ◽

Xue-bing Cao ◽

Wei-qi Zeng ◽

Heng Zhai ◽

Xiao-qian Zhang ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Brain Connectivity ◽

Specific Treatment ◽

Double Blind ◽

Flow Modulation ◽

Beneficial Effects ◽

Non Invasive ◽

Treatment Mechanisms

After long-term use of levodopa, Parkinson's patients almost inevitably develop dyskinesia, a kind of drug side effect manifesting as uncontrollable choreic movements and dystonia, which could be crippling yet have limited therapeutic options. Transcranial magnetic stimulation is the most widely studied non-invasive neuromodulation technology to treat levodopa-induced dyskinesia. Many studies have shown that transcranial magnetic stimulation has beneficial effects on levodopa-induced dyskinesia and is patient-tolerable, barely with reported adverse effects. Changes in brain connectivity, neuroplasticity, neurotransmitter, neurorestoration, and blood flow modulation could play crucial roles in the efficacy of transcranial magnetic stimulation for levodopa-induced dyskinesia. The appearance of new modes and application for emerging targets are possible solutions for transcranial magnetic stimulation to achieve sustained efficacy. Since the sample size in all available studies is small, more randomized double-blind controlled studies are needed to elucidate the specific treatment mechanisms and optimize treatment parameters.

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Testing the Food Experience in Healthy Human Volunteers: a Proof-of-Concept Study

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld-806 ◽

2020 ◽

Vol 29 (1) ◽

pp. 65-68

Author(s):

Teodora Pribic ◽

Quiro Lopez ◽

Eduardo Lucas ◽

Dan M. Livovsky ◽

Alex Rovira ◽

...

Keyword(s):

Brain Connectivity ◽

Brain Activity ◽

Well Being ◽

Substantial Improvement ◽

Healthy Human ◽

Double Blind ◽

Human Volunteers ◽

Before And After ◽

Food Experience ◽

Increased Activity

Background and Aims: For a healthy food to be introduced to the consumer’s diet, it has to be attractive, yet testing for food acceptance and the sensory postprandial responses is still not standardized. The main objective of this study was to demonstrate that healthier foods can be obtained without impact on the responses to ingestion. Methods: A randomized, cross-over, double-blind, pilot study in non-obese, healthy men (n=8) comparing the responses to a standard sausage rich in animal fat (mortadella) versus a modified product based on a plant-derived fat analogue and an aroma. Palatability and postprandial sensations were measured on 10 cm scales and brain activity was evaluated by functional magnetic resonance imaging before and after each meal on separate days. Results: Both meals were rated equally palatable and induced the same degree of homeostatic sensations (satiety, fullness) with a similar hedonic dimension (improved mood and digestive well-being). Both meals induced similar changes in brain connectivity: decreased activity in the frontal-parietal, basal ganglia and thalamus, visual occipital, sensory-motor, temporal superior and in the “default-mode” networks, while increased activity was detected in the network associated with white matter. Conclusion: A substantial improvement in the nutritional profile of food can be achieved without affecting the responses to ingestion.

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Neurophysiological Biomarkers of Persistent Post-concussive Symptoms: A Scoping Review

Frontiers in Neurology ◽

10.3389/fneur.2021.687197 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sepehr Mortaheb ◽

Maria Maddalena Filippini ◽

Jean-François Kaux ◽

Jitka Annen ◽

Nicolas Lejeune ◽

...

Keyword(s):

Brain Connectivity ◽

Brain Activity ◽

Positive Finding ◽

Conventional Mri ◽

Pubmed Database ◽

Functional Patterns ◽

Task Positive Network ◽

The Relationship

Background and Objectives: Persistent post-concussive symptoms (PCS) consist of neurologic and psychological complaints persisting after a mild traumatic brain injury (mTBI). It affects up to 50% of mTBI patients, may cause long-term disability, and reduce patients' quality of life. The aim of this review was to examine the possible use of different neuroimaging modalities in PCS.Methods: Articles from Pubmed database were screened to extract studies that investigated the relationship between any neuroimaging features and symptoms of PCS. Descriptive statistics were applied to report the results.Results: A total of 80 out of 939 papers were included in the final review. Ten examined conventional MRI (30% positive finding), 24 examined diffusion weighted imaging (54.17% positive finding), 23 examined functional MRI (82.61% positive finding), nine examined electro(magneto)encephalography (77.78% positive finding), and 14 examined other techniques (71% positive finding).Conclusion: MRI was the most widely used technique, while functional techniques seem to be the most sensitive tools to evaluate PCS. The common functional patterns associated with symptoms of PCS were a decreased anti-correlation between the default mode network and the task positive network and reduced brain activity in specific areas (most often in the prefrontal cortex).Significance: Our findings highlight the importance to use functional approaches which demonstrated a functional alteration in brain connectivity and activity in most studies assessing PCS.

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Neurophysiological biomarkers of post-concussion syndrome: a scoping review

10.1101/2021.03.25.21254285 ◽

2021 ◽

Author(s):

Sepehr Mortaheb ◽

Maria Maddalena Filippini ◽

Jean-Francois Kaux ◽

Jitka Annen ◽

Nicolas Lejeune ◽

...

Keyword(s):

Scoping Review ◽

Brain Connectivity ◽

Brain Activity ◽

Descriptive Statistics ◽

Post Concussion Syndrome ◽

Conventional Mri ◽

Pubmed Database ◽

The Relationship

Background and objectives: Post-concussion syndrome (PCS) consists of neurologic and psy-chological complaints persisting after a mild traumatic brain injury (mTBI). It affects up to 50% of mTBI patients, causes long-term disability and reduces quality of life. The aim of this scoping review was to examine possible uses of different neuroimaging modalities in PCS. Methods: Articles from Pubmed database were screened to extract studies that investigated the relationship between any neuroimaging features and symptoms of PCS. Descriptive statistics were applied to report results. Results: 88 out of 939 papers were included in the final review. 12 examined conventional MRI (42% specificity), 27 diffusion weighted imaging (56% specificity), 25 functional MRI (84% specificity), 10 electro(magneto)encephalography (80% specificity), and 14 examined other tech-niques (71% specificity). Conclusion: MRI was the most widely used technique, while functional techniques seem to be the most sensitive tools to evaluate PCS. Common patterns associated with symptoms of PCS were a decreased anticorrelation between the default mode network and the task positive net-work and reduced brain activity in specific areas (most often prefrontal cortex). Significance: Our findings highlight the importance to use functional approaches which demonstrated a functional alternation in brain connectivity and activity in most studies assessing PCS.

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