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Journal of Integrative Neuroscience May 2024In this study, we explored the effects of chiropractic spinal adjustments on resting-state electroencephalography (EEG) recordings and early somatosensory evoked... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
In this study, we explored the effects of chiropractic spinal adjustments on resting-state electroencephalography (EEG) recordings and early somatosensory evoked potentials (SEPs) in Alzheimer's and Parkinson's disease.
METHODS
In this randomized cross-over study, 14 adults with Alzheimer's disease (average age 67 ± 6 years, 2 females:12 males) and 14 adults with Parkinson's disease (average age 62 ± 11 years, 1 female:13 males) participated. The participants underwent chiropractic spinal adjustments and a control (sham) intervention in a randomized order, with a minimum of one week between each intervention. EEG was recorded before and after each intervention, both during rest and stimulation of the right median nerve. The power-spectra was calculated for resting-state EEG, and the amplitude of the N30 peak was assessed for the SEPs. The source localization was performed on the power-spectra of resting-state EEG and the N30 SEP peak.
RESULTS
Chiropractic spinal adjustment significantly reduced the N30 peak in individuals with Alzheimer's by 15% ( = 0.027). While other outcomes did not reach significance, resting-state EEG showed an increase in absolute power in all frequency bands after chiropractic spinal adjustments in individuals with Alzheimer's and Parkinson's disease. The findings revealed a notable enhancement in connectivity within the Default Mode Network (DMN) at the alpha, beta, and theta frequency bands among individuals undergoing chiropractic adjustments.
CONCLUSIONS
We found that it is feasible to record EEG/SEP in individuals with Alzheimer's and Parkinson's disease. Additionally, a single session of chiropractic spinal adjustment reduced the somatosensory evoked N30 potential and enhancement in connectivity within the DMN at the alpha, beta, and theta frequency bands in individuals with Alzheimer's disease. Future studies may require a larger sample size to estimate the effects of chiropractic spinal adjustment on brain activity. Given the preliminary nature of our findings, caution is warranted when considering the clinical implications.
CLINICAL TRIAL REGISTRATION
The study was registered by the Australian New Zealand Clinical Trials Registry (registration number ACTRN12618001217291 and 12618001218280).
Topics: Humans; Female; Male; Parkinson Disease; Aged; Cross-Over Studies; Alzheimer Disease; Electroencephalography; Middle Aged; Evoked Potentials, Somatosensory; Pilot Projects; Manipulation, Chiropractic
PubMed: 38812396
DOI: 10.31083/j.jin2305098 -
Scientific Reports May 2024Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition...
Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition referred to as "syndrome T". Peripheral neuropathy, described in untreated thyroid disease, could be a contributing mechanism. We analysed autonomic and somatosensory function in 29 patients with AIT and treated hypothyroidism and 27 healthy volunteers. They underwent heart rate variability (HRV) analysis and quantitative sensory testing (n = 28), comprising 13 parameters of small and large nerve fibre function and pain thresholds. Autonomic cardiovascular function was assessed in rest, deep respiration and orthostasis. Additionally, biomarkers for autoimmunity and thyroid function were measured. Anxiety, depression and QoL were assessed using validated questionnaires. 36% of the patients showed at least one sign of somatosensory small or large fibre dysfunction. 57% presented with mild hyperalgesia to at least one stimulus. Several markers of autonomic function and some detection thresholds were related to the antibody titres. Anxiety, depression scores and QoL correlated to antibody titres and HRV measures. Autonomic and somatosensory dysfunction indicate that in treated hypothyroidism and AIT a subgroup of patients suffers from neuropathic symptoms leading to impaired QoL. Additionally, mild hyperalgesia as a possible sensitisation phenomenon should be considered a target for symptomatic treatment.
Topics: Humans; Female; Male; Middle Aged; Adult; Autonomic Nervous System; Quality of Life; Thyroiditis, Autoimmune; Heart Rate; Hypothyroidism; Thyroxine; Aged; Somatosensory Disorders; Anxiety
PubMed: 38811750
DOI: 10.1038/s41598-024-63158-w -
Frontiers in Neuroscience 2024Differences in metabolic homeostasis, diabetes, and obesity between males and females are evident in rodents and humans. Vagal sensory neurons in the vagus nerve ganglia...
INTRODUCTION
Differences in metabolic homeostasis, diabetes, and obesity between males and females are evident in rodents and humans. Vagal sensory neurons in the vagus nerve ganglia innervate a variety of visceral organs and use specialized nerve endings to sense interoceptive signals. This visceral organ-brain axis plays a role in relaying interoceptive signals to higher brain centers, as well as in regulating the vago-vagal reflex. I hypothesized that molecularly distinct populations of vagal sensory neurons would play a role in causing differences in metabolic homeostasis between the sexes.
METHODS
SnRNA-Seq was conducted on dissociated cells from the vagus nerve ganglia using the 10X Genomics Chromium platform.
RESULTS
Single-nucleus RNA sequencing analysis of vagal sensory neurons from female and male mice revealed differences in the transcriptional profiles of cells in the vagus nerve ganglia. These differences are linked to the expression of sex-specific genes such as , , and . Among the 13 neuronal clusters, one-fourth of the neurons in male mice were located in the -enriched VN1 and VN8 clusters, which displayed higher enrichment of , , , and genes. In contrast, 70% of the neurons in females were found in -enriched clusters VN4, 6, 7, 10, 11, and 13, which showed enriched genes such as , , , , , , and . Two clusters of satellite cells were identified, one of which contained oligodendrocyte precursor cells in male mice. A small population of cells expressed and , indicating that they are epineural adipocytes.
DISCUSSION
Understanding the physiological implications of distinct transcriptomic profiles in vagal sensory neurons on energy balance and metabolic homeostasis would help develop sex-specific treatments for obesity and metabolic dysregulation.
PubMed: 38808032
DOI: 10.3389/fnins.2024.1393196 -
Medical Sciences (Basel, Switzerland) May 2024In clinical practice, the implementation of tailored treatment is crucial for assessing the patient's emotional processing profile. Here, we investigate all three levels... (Observational Study)
Observational Study
BACKGROUND
In clinical practice, the implementation of tailored treatment is crucial for assessing the patient's emotional processing profile. Here, we investigate all three levels of analysis characterizing emotion processing, i.e., recognition, representation, and regulation, in patients with peripheral neuropathic pain (PNP).
METHODS
Sixty-two patients and forty-eight healthy controls underwent quantitative sensory testing, i.e., psychophysical tests to assess somatosensory functions such as perception of cold (CDT), heat-induced pain (HPT), and vibration (VDT), as well as three standardized tasks to assess emotional processing: (1) the Ekman 60-Faces Test (EK-60F) to assess recognition of basic facial emotions, (2) the Reading the Mind in the Eyes Test (RME) to assess the ability to represent the feelings of another person by observing their eyes, and (3) the 20-item Toronto Alexithymia Scale (TAS-20) to assess emotional dysregulation, i.e., alexithymia.
RESULTS
General Linear Model analysis revealed a significant relationship between left index finger VDT z-scores in PNP patients with alexithymia. The RME correlated with VDT z-scores of the left little finger and overall score for the EK-60F.
CONCLUSIONS
In patients with PNP, emotion processing is impaired, which emphasizes the importance of assessing these abilities appropriately in these patients. In this way, clinicians can tailor treatment to the needs of individual patients.
Topics: Humans; Male; Female; Middle Aged; Neuralgia; Emotions; Aged; Adult; Affective Symptoms; Case-Control Studies
PubMed: 38804383
DOI: 10.3390/medsci12020027 -
Cureus Apr 2024Introduction The Hoffmann reflex (H reflex) is one of the most studied reflexes in human neurophysiological literature. Detection of the H reflex is useful in the...
Introduction The Hoffmann reflex (H reflex) is one of the most studied reflexes in human neurophysiological literature. Detection of the H reflex is useful in the diagnosis of early polyneuropathy, S1 radiculopathy, early GBS, tibial neuropathy and sciatica, and sacral plexopathy. The H reflex is also used as a tool to measure the excitability of the nervous components of the arc, regardless of the sensitivity of the sensory organs. The monosynaptic nature of reflex circuits makes H-reflex an attractive tool for clinical neurophysiology and research. Objective The objective is to create reference data of soleus H-reflex latency in an adult population from a tertiary care center in India. Materials and methods Seven hundred eighty-four healthy volunteers underwent a physical examination and brief electrophysiological examination before elicitation of the soleus H reflex of both lower extremities using standard techniques. Reference values are expressed as mean ± standard deviation as well as the third and 97th percentiles for latency as the dependent variable. Results The study population included 346 (44.1%) women and 438 (55.9%) men. The men were aged 40.46 ± 14.76 years, and the women were aged 41.63 ± 13.49 years. The average weight of the men was 73.32 ± 10.28 kilograms, and the women were 62.91 ± 7.46 kilograms. The average height of the men was 172.06 ± 4.22 cm, and the women were 159.12 ± 2.42 cm. The third and 97th percentiles for H-reflex latency on the right side were 22.86 ms to 34.22 ms and on the left side were 22.86 ms to 35.39 ms. The average right tibial H latency and left tibial H latency were 28.18 ± 2.59 ms and 28.14 ± 2.70 ms, respectively. Conclusion A sizable subject population was used to provide reference data for this study. Because of the huge sample size and nearly appropriate coverage of different age groups, reference ranges have been established for various age, height, and BMI groups.
PubMed: 38800221
DOI: 10.7759/cureus.59083 -
Plastic and Reconstructive Surgery.... May 2024A 51-year-old woman with diabetes and depression was referred to the anesthesia pain clinic with a 15-year history of complex regional pain syndrome type I of the right...
A 51-year-old woman with diabetes and depression was referred to the anesthesia pain clinic with a 15-year history of complex regional pain syndrome type I of the right forearm and hand in the radial sensory nerve distribution. There was no recognized antecedent trauma and she had failed both medical treatment and radial sensory nerve decompression surgery. An ultrasound-guided local anesthetic block of the radial nerve in the upper arm resulted in partial and temporary improvement in pain. She subsequently underwent trial of a peripheral nerve stimulator (PNS) followed by permanent PNS implant placement over the radial nerve proper proximal to the elbow. Within the first month of use, she endorsed substantially improved pain and strength in her right hand. These improvements were sustained for more than 1 year. Applications of PNS technology for treatment of extremity complex regional pain syndrome and neuropathic extremity pain in general are reviewed.
PubMed: 38798938
DOI: 10.1097/GOX.0000000000005764 -
Frontiers in Genetics 2024Congenital insensitivity to pain with anhidrosis (CIPA, OMIM #256800), also known as hereditary sensory and autonomic neuropathy type Ⅳ (HSAN-IV), is a rare autosomal...
BACKGROUND
Congenital insensitivity to pain with anhidrosis (CIPA, OMIM #256800), also known as hereditary sensory and autonomic neuropathy type Ⅳ (HSAN-IV), is a rare autosomal recessive disorder characterized by recurrent episodic fevers, anhidrosis, insensitivity to noxious stimuli, self-mutilating behavior and intellectual disability. CIPA can be caused by the variants in gene, which encodes a high-affinity tyrosine kinase receptor for nerve growth factor. To ascertain the hereditary cause of a patient with CIPA accompanied by the additional symptoms of mild growth retardation, prone to fracture, underdeveloped nails of fingers and toes, irregular tooth alignment, enamel hypoplasia, postoperative wound healing difficulty, hand and limb deformity, and dislocation of hip joint, whole exome sequencing was used and revealed a compound heterozygous variant in .
METHODS
DNA was extracted from peripheral blood samples of pediatric patients and their parents, and subjected to comprehensive analysis using whole-exome sequencing (WES), followed by verification of variant sites in the gene through Sanger sequencing. To elucidate the functional impact of the newly discovered variants, an experimental system was established. Splicing analysis was conducted using PCR and Sanger sequencing, while expression levels were assessed through qPCR and Western blot techniques.
RESULTS
One hotspot variant c.851-33T>A(ClinVar ID: 21308) and a novel variant c.850 + 5G>A(ClinVar ID:3069176) was inherited from her father and mother, respectively, identified in the affected individuals. The c.850 + 5G>A variant in resulted in two forms of aberrant mRNA splicing: 13bp deletion (c.838_850del13, p. Val280Ser fs180) and 25bp deletion (826_850del25, p. Val276Ser fs180) in exon 7, both leading to a translational termination at a premature stop codon and forming a C-terminal truncated protein. The expression of two abnormal splicing isoforms was decreased both in the level of mRNA and protein.
CONCLUSION
In conclusion, this study elucidated the genetic cause of a patient with CIPA and identified a novel variant c.850 + 5G>A in , which broadened the and enriched the mutation spectrum.
PubMed: 38798698
DOI: 10.3389/fgene.2024.1345081 -
Research Square May 2024Hormonal regulation during food ingestion and its association with pain prompted the investigation of the impact of glucagon-like peptide-1 (GLP-1) on the transient...
Hormonal regulation during food ingestion and its association with pain prompted the investigation of the impact of glucagon-like peptide-1 (GLP-1) on the transient receptor potential vanilloid 1 (TRPV1). Both endogenous and synthetic GLP-1 and an antagonist of GLP-1, exendin 9-39, reduced heat sensitivity in naïve mice. GLP-1-derived peptides (liraglutide, exendin-4, and exendin 9-39) effectively inhibited capsaicin (CAP)-induced currents and calcium responses in cultured sensory neurons and TRPV1-expressing cell lines. Notably, the exendin 9-39 alleviated CAP-induced acute pain, as well as chronic pain induced by complete Freund's adjuvant (CFA) and spared nerve injury (SNI) in mice, without causing hyperthermia associated with other TRPV1 inhibitors. Electrophysiological analyses revealed that exendin 9-39 binds to the extracellular side of TRPV1, functioning as a noncompetitive inhibitor of CAP. Exendin 9-39 did not affect proton-induced TRPV1 activation, suggesting its selective antagonism. Among exendin 9-39 fragments, exendin 20-29 specifically binds to TRPV1, alleviating pain in both acute and chronic pain models without interfering with GLP-1R function. Our study revealed a novel role for GLP-1 and its derivatives in pain relief, proposing exendin 20-29 as a promising therapeutic candidate.
PubMed: 38798444
DOI: 10.21203/rs.3.rs-4233732/v1 -
Cancers May 2024Bone cancer and its related chronic pain are huge clinical problems since the available drugs are often ineffective or cannot be used long term due to a broad range of...
Osteosarcoma-Induced Pain Is Mediated by Glial Cell Activation in the Spinal Dorsal Horn, but Not Capsaicin-Sensitive Nociceptive Neurons: A Complex Functional and Morphological Characterization in Mice.
Bone cancer and its related chronic pain are huge clinical problems since the available drugs are often ineffective or cannot be used long term due to a broad range of side effects. The mechanisms, mediators and targets need to be identified to determine potential novel therapies. Here, we characterize a mouse bone cancer model induced by intratibial injection of K7M2 osteosarcoma cells using an integrative approach and investigate the role of capsaicin-sensitive peptidergic sensory nerves. The mechanical pain threshold was assessed by dynamic plantar aesthesiometry, limb loading by dynamic weight bearing, spontaneous pain-related behaviors via observation, knee diameter with a digital caliper, and structural changes by micro-CT and glia cell activation by immunohistochemistry in BALB/c mice of both sexes. Capsaicin-sensitive peptidergic sensory neurons were defunctionalized by systemic pretreatment with a high dose of the transient receptor potential vanilloid 1 (TRPV1) agonist resiniferatoxin (RTX). During the 14- and 28-day experiments, weight bearing on the affected limb and the paw mechanonociceptive thresholds significantly decreased, demonstrating secondary mechanical hyperalgesia. Signs of spontaneous pain and osteoplastic bone remodeling were detected both in male and female mice without any sex differences. Microglia activation was shown by the increased ionized calcium-binding adapter molecule 1 (Iba1) immunopositivity on day 14 and astrocyte activation by the enhanced glial fibrillary acidic protein (GFAP)-positive cell density on day 28 in the ipsilateral spinal dorsal horn. Interestingly, defunctionalization of the capsaicin-sensitive afferents representing approximately 2/3 of the nociceptive fibers did not alter any functional parameters. Here, we provide the first complex functional and morphological characterization of the K7M2 mouse osteosarcoma model. Bone-cancer-related chronic pain and hyperalgesia are likely to be mediated by central sensitization involving neuroinflammation via glial cell activation in the spinal dorsal horn, but not the capsaicin-sensitive sensory neuronal system.
PubMed: 38791867
DOI: 10.3390/cancers16101788