Processes In Central Nervous System Research Articles

When shared pain is not half the pain: enhanced central nervous system processing and verbal reports of pain in the presence of a solicitous spouse.

The experience of pain and pain behaviors is not only determined by physiological but also psychosocial factors. In this context, the learning history of the individual and specifically operant reinforcement related to spouse responses might play an important role. We investigated the effect of a solicitous and habitually pain-reinforcing spouse for the processing of pain in patients with chronic pain. Using multichannel electroencephalography, pain behaviors, and self-reports of pain, we examined 20 patients with chronic back pain (10 with solicitous and 10 with nonsolicitous spouses) and 10 matched healthy controls. The participants received a series of painful and nonpainful electrical stimuli applied to the site of pain (back) and a control area (finger) in the presence vs absence of the spouse. The global field power of the electroencephalogram with a focus in the frontal region was enhanced in patients with chronic back pain who had a solicitous spouse compared to those with a nonsolicitous spouse and the healthy controls. This was specific for the painful stimulation at the back and occurred only in the presence but not the absence of the spouse. Pain ratings of intensity and unpleasantness were also higher in the patients with solicitous spouses when the spouse was present during painful stimulation. These data suggest that significant other responses indicative of operant reinforcement may have a direct effect on the cerebral processing of pain and related pain perception.

The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination

BackgroundMyelination is a highly regulated process in the vertebrate central nervous system (CNS) whereby oligodendrocytes wrap axons with multiple layers of insulating myelin in order to allow rapid electrical conduction. Establishing the proper pattern of myelin in neural circuits requires communicative axo-glial interactions, however, the molecular interactions that occur between oligodendrocytes and axons during developmental myelination and myelin maintenance remain to be fully elucidated. Our previous work identified G protein-coupled receptor 62 (Gpr62), an uncharacterized orphan g-protein coupled receptor, as being selectively expressed by mature oligodendrocytes within the CNS, suggesting a potential role in myelination or axoglial interactions. However, no studies to date have assessed the functional requirement for Gpr62 in oligodendrocyte development or CNS myelination.MethodsTo address this, we generated a knockout mouse strain lacking the Gpr62 gene. We assessed CNS myelination during both postnatal development and adulthood using immunohistochemistry, electron microscopy and western blot. In addition, we utilized AAV-mediated expression of a tagged Gpr62 in oligodendrocytes to determine the subcellular localization of the protein in vivo.ResultsWe find that virally expressed Gpr62 protein is selectively expressed on the adaxonal myelin layer, suggestive of a potential role for Gpr62 in axo-myelinic signaling. Nevertheless, Gpr62 knockout mice display normal oligodendrocyte numbers and apparently normal myelination within the CNS during both postnatal development and adulthood.ConclusionsWe conclude that in spite of being well-placed to mediate neuronal-oligodendrocyte communications, Gpr62 is overall dispensable for CNS myelination.

Targeting the Gut Microbiota to Relieve the Symptoms of Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a common, chronic, functional disorder with a large impact on world population. Its pathophysiology is not completely revealed; however, it is certain that dysregulation of the bidirectional communications between the central nervous system (CNS) and the gut leads to motility disturbances, visceral hypersensitivity, and altered CNS processing characterized by differences in brain structure, connectivity and functional responsiveness. Emerging evidence suggests that gut microbiota exerts a marked influence on the host during health and disease. Gut microbiome disturbances can be also important for development of IBS symptoms and its modulation efficiently contributes to the therapy. In this work, we review the current knowledge about the IBS therapy, the role of gut microbiota in pathogenesis of IBS, and we discuss that its targeting may have significant impact on the effectiveness of IBS therapy.

English

Endurance exercise is a model of physiological integration. There is no other animal activity in which cardiovascular, respiratory, metabolic-endocrine and neuromuscular functions are activated at the same time. Even apparently, silent functions are essential during exercise (digestive, renal). During long-term exercise, the absorption of water and carbohydrates is a determining factor in performance. Kidney function plays a fundamental role in trying to preserve the hydro-electrolyte balance during exercise. In this work we present an integrative physiological perspective during dynamic exercise (mobilization of a large muscle mass with a low to moderate degree of strength development), both from the point of view of health and performance. The response of the heart rate in the first moments of exercise is a good example of the feedforward mechanism. Overall, the nervous system has two control mechanisms: feedforward and feedback. These depend on the central command, a more functional than anatomical entity. The feedforward system allows to immediately start the cardiovascular and respiratory systems. This mechanism is important because it activates the organism to overcome resting state. The feedback system is equally important because it allows the central command to receive the necessary information to “order” the appropriate response according to the intensity of the exercise. The information for retrocontrol comes from various receptors located in: the muscles, the respiratory system and the cardiovascular system. It is complex information that the central nervous system processes with exquisite precision, as can be seen in in endurance exercise.

Fast improvements in functional status after osteopathic manipulative treatment based on myofascial release in patients with moderate or severe fibromyalgia: a retrospective study.

Fibromyalgia (FM) is a chronic pain syndrome characterized by a large variety of symptoms. Evidence suggests that an alteration of central nervous system processing of pain could be involved. The purpose of this study is to analyze clinical records of patients affected by FM who underwent osteopathic manipulative treatment (OMT), predominantly based on a myofascial release approach (MFR). This retrospective study considered records of 21 FM patients with moderate or severe functional impact, who consented to OMT in addition to their usual care. The assessment considered the following measures: FIQ (functional status), SF36 (quality of life), VAS (pain), TSK (kinesiophobia) and PSQI (quality of sleeping). Patients were preliminarily assessed over a 1month run-in phase, then after 1, 2 and 4months; a 1month follow-up was also considered. After one month, 71% of patients reported a decrease in functional impact and scores remained stable until follow-up (from 69.8 to 52.37, p≤0.001). Overall, after four months, patients improved their quality of life, with a score ranging from 33.47 to 42.6 (p≤0.05). We also observed a reduction of pain (p≤0.05). A series of OMT sessions based on MFR could play a therapeutic role in improving functional status, pain and quality of life over a period of 4months.

69-Year Old Man With Dysphagia and Nasal Regurgitation

69-Year Old Man With Dysphagia and Nasal Regurgitation

Early Evidence Indicates Vitamin D Improves Symptoms of Irritable Bowel Syndrome: Nursing Implications and Future Research Opportunities.

Irritable bowel syndrome (IBS) affects approximately 11.2% of the population. Yet, full understanding of its etiology and optimal treatment remains elusive. Understanding of the underlying pathophysiology of IBS has been limited. However, research is beginning to identify the cause as multifactorial (e.g., low-grade local mucosal inflammation, systemic immune activation, altered intestinal permeability, intestinal hypersensitivity, altered central nervous system processing, changes in intestinal microbiota). Understanding of the role of vitamin D in intestinal inflammation, immunity, and gastrointestinal conditions is increasing but is not yet fully understood. Growing evidence has linked vitamin D deficiency with a variety of gastrointestinal disorders, including inflammatory bowel disease, diverticulitis, colorectal cancer, and IBS. Several studies have demonstrated that individuals with IBS are more likely to have vitamin D deficiency than healthy controls. Recent vitamin D supplementation studies have shown improvement in quality of life and reduction in IBS symptoms (including abdominal pain, distention, flatulence, constipation, and visceral sensitivity) but the mechanism remains unclear. Nurses are well positioned to educate patients about the importance of sufficient vitamin D for overall health in individuals with IBS as well as participate in well-designed therapeutic studies to explore whether enhanced vitamin D status will ultimately help treat IBS more effectively.

Watching Your Neck: The Influence of Real-Time Visual Feedback on Cervical Joint Position Sense in Chronic Neck Pain.

Patients with neck pain demonstrate a variety of sensorimotor impairments, such as decreased cervical joint position sense (CJPS) acuity, which might also be associated with an impaired internal body representation. The present study evaluated the effect of real-time visual feedback of the individual's own neck on CJPS compared to observing a book. Twenty-three patients with neck pain participated in the experiment and received the interventions in randomized order on separate days in a within-subject pretest-posttest design. Before and immediately after each intervention, CJPS was measured by a therapist blinded to the intervention. The results demonstrate a significantly different development of CJPS (p = .04), with increased CJPS acuity after observing one's own neck and decreased acuity after observing a book. Real-time visual feedback of the neck improved CJPS acuity in patients with neck pain without active movements of the neck, indicating the importance of central nervous system processing for CJPS acuity.

Clinical and functional profile of children with autism spectrum disorders

Introduction. Currently, the gain in the number of children patients diagnosed with Autism Spectrum Disorders (ASD) has been recorded. The key feature of the given group is the polysystemic expression, with considerable disruption of the central nervous system, gastrointestinal tract and immune processes. The research of their counteraction and development is essential for determining tactics for ASD patients’ combination treatment. Aim of the study is to present a clinical and functional patient profile with Autism Spectrum Disorders based on the clinical, medical and social trial. Materials and methods. We conducted a pilot observational, comparative study within two groups of children (62 ASD patients and 48 healthy children dominated by boys). The examination included receiving complaints, objective assessment by the paediatrician and neurologist, filling in medical records, covering complaints and the results of patients’ objective examination and parents/caretakers surveys. Results. The study revealed the predominance of complaints about mental disruptions over somatic complaints. Notably, parents/ caretakers indicated the presence of sleep disturbances (up to 22.5%) and specific eating habits (up to 27.4%) in their children. Young patients in the group under consideration exposed signs of allergic diseases chronic intoxication syndromes and micronutrient deficiencies. Nearly one-third of children reported the presence of functional disorders/digestive diseases. Conclusion. Young patients with Autism Spectrum Disorder are diagnosed with burdened physical status in the form of functional disruptions and diseases. These findings necessitate the paediatrician’s active early detection of organs’ malformation and require somatic systematic monitoring by the psychiatrist and skilled attendance of other medical specialists.

Cerebrospinal fluid proteomics targeted for central nervous system processes in bipolar disorder.

The etiopathology of bipolar disorder is largely unknown. We collected cerebrospinal fluid (CSF) samples from two independent case-control cohorts (total n = 351) to identify proteins associated with bipolar disorder. A panel of 92 proteins targeted towards central nervous system processes identified two proteins that replicated across the cohorts: the CSF concentrations of testican-1 were lower, and the CSF concentrations of C-type lectin domain family 1 member B (CLEC1B) were higher, in cases than controls. In a restricted subgroup analysis, we compared only bipolar type 1 with controls and identified two additional proteins that replicated in both cohorts: draxin and tumor necrosis factor receptor superfamily member 21 (TNFRSF21), both lower in cases than controls. This analysis additionally revealed several proteins significantly associated with bipolar type 1 in one cohort, falling just short of replicated statistical significance in the other (tenascin-R, disintegrin and metalloproteinase domain-containing protein 23, cell adhesion molecule 3, RGM domain family member B, plexin-B1, and brorin). Next, we conducted genome-wide association analyses of the case-control-associated proteins. In these analyses, we found associations with the voltage-gated calcium channel subunit CACNG4, and the lipid-droplet-associated gene PLIN5 with CSF concentrations of TNFRSF21 and CLEC1B, respectively. The reported proteins are involved in neuronal cell-cell and cell-matrix interactions, particularly in the developing brain, and in pathways of importance for lithium's mechanism of action. In summary, we report four novel CSF protein associations with bipolar disorder that replicated in two independent case-control cohorts, shedding new light on the central nervous system processes implicated in bipolar disorder.

How to Approach a Patient with Difficult-to-Treat IBS

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder characterized by recurrent or chronic abdominal pain associated with diarrhea and/or constipation.1 IBS has been redefined as a disorder of gut–brain interaction, which is classified by GI symptoms related to any combination of the following: motility disturbance, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered central nervous system processing.2 The severity of IBS is determined by the individual’s symptom experience and behaviors rather than by objective tests or histopathological markers in the bowel.

NEURAL ACTIVITY AND LANDING BIOMECHANICS: EXPLORING THE RELATIONSHIPS BETWEEN THE BRAIN, BODY, AND ACL INJURY-RISK

Background:Anterior cruciate ligament (ACL) injuries predominantly occur via non-contact mechanisms, secondary to motor coordination errors resulting in aberrant frontal plane knee loads that exceed the thresholds of ligament integrity. However, central nervous system processing underlying high injury-risk motor coordination errors remain unknown, limiting the optimization of current injury reduction strategies.Purpose:To evaluate the relationships between brain activity during motor tasks with injury-risk loading during a drop vertical jump.Methods:Thirty female high school soccer players (16.10 ± 0.87 years, 165.10 ± 4.64 cm, 63.43 ± 8.80 kg) were evaluated with 3D biomechanics during a standardized drop vertical jump from a 30 cm box and peak knee abduction moment was extracted as the injury-risk variable of interest. A neuroimaging session to capture neural activity (via blood-oxygen-level-dependent signal) was then completed which consisted of 4 blocks of 30 seconds of repeated bilateral leg press action paced to a metronome beat of 1.2 Hz with 30 seconds rest between blocks. Knee abduction moment was evaluated relative to neural activity to identify potential neural contributors to injury-risk.Results:There was a direct relationship between increased landing knee abduction moment and increased neural activation within regions corresponding to the lingual gyrus, intracalcarine cortex, posterior cingulate cortex, and precuneus (r2= 0.68, p corrected < .05, z max > 3.1; Table 1 & Figure 1).Conclusion:Elevated activity in regions that integrate sensory, spatial, and attentional information may contribute to elevated frontal plane knee loads during landing. Interestingly, a similar activation pattern related to high-risk landing mechanics has been found in those following injury, indicating that predisposing factors to injury may be accentuated by injury or that modern rehabilitation does not recover prospective neural control deficits. These data uncover a potentially novel brain marker that could guide the discovery of neural-therapeutic targets that reduce injury risk beyond current prevention methods.Figure 1:The drop vertical jump landing assessment (left) and neural activity associated with abduction loading (right).

The central nervous system can directly regulate breast cancer progression and blockage by quercetin.

BackgroundNeuroinflammation involving the central nervous system (CNS), such as depression, is associated with a significantly increased risk of cancer and cancer-specific mortality due to breast cancer. It is of great significance to learn about the regulatory process of CNS in breast cancer progression.MethodsWe established a depressive MMTV-PyVT mouse model. The expression levels of neurotransmitters in the serum of depression animal models were assessed by enzyme-linked immunosorbent assay (ELISA). Changes of the microglia cells in the mice’s brains were evaluated by immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). Breast cancer progression was assessed by immunohistochemistry (IHC) analysis. To further investigate the mechanism by which ant-depressant drugs disrupt breast cancer progression, protein sequencing and network pharmacology were applied to identify related targets. Furthermore, we used conditioned medium from BV-2 microglia to culture breast cancer cells and treated the cells with quercetin at different concentrations; cell viability was assessed by the MTT assay.ResultsOur results show a possible regulatory target between neuroinflammation in the CNS and development of breast cancer, along with the reversal effect of quercetin on breast cancer progression.ConclusionsChronic stress may be an indicator of breast cancer and that quercetin could be an effective treatment for breast cancer patients with chronic stress.

Functional Brain Imaging During Rest and Pain: Differences According to Race and Knee Osteoarthritis

Considerable evidence suggests that knee osteoarthritis (OA)-related clinical pain and disability significantly differs according to racial background. However, brain mechanisms underlying these differences are not well understood. We investigated altered central pain processing in a sample comprised of Non-Hispanic Black (NHB) and Non-Hispanic White (NHW) adults with and without knee OA. NHB and NHW participants with knee OA (n = 123) and without knee OA (N = 41) were recruited to complete a brain imaging protocol using Arterial Spin Labeling (ASL) on a 3T fMRI scanner. Participant's regional cerebral blood flow (rCBF), a measure of brain activation, was examined at rest and during pressure pain stimulation. Aim 1 was to examine altered central processing in people with knee OA compared to people without knee OA. Aim 2 assessed racial group differences in central processing among NHB and NHW adults with knee OA. People with knee OA showed significant differences in rCBF at rest and during pain in the anterior cingulate cortex, sensory-motor cortex, para-hippocampal gyrus, and amygdala in comparison to people without knee OA. For people with knee OA, ethnic differences between NHWs (n = 52) and NHBs (n = 71) were present in the cingulate gyrus, amygdala, thalamus, sensory-motor cortex, and cerebellum. Comparing people with knee OA to people without knee OA at rest while controlling for race, we found a significant effect in the thalamus (p = .036) and amygdala (p = .046). For people with knee OA, NHBs vs NHWs showed a significant effect for the difference score (pain - rest) in the cerebellum (p = .012) when controlling for age and education. These results indicate that knee OA and racial background may be important contributors to altered central nervous system processing of pain. Supported in part by NIH/NIA grant AG033906 and the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 T64) and the University of Alabama at Birmingham (ULITR000165).

Morphine Induces Upregulation of Neuronally Expressed CB2 Receptors in the Spinal Dorsal Horn of Rats.

Background: Cannabinoid receptors play a key role in regulating numerous physiological processes, including immune function and reward signaling. Originally, endocannabinoid contributions to central nervous system processes were attributed to CB1 receptors, but technological advances have confirmed the expression of CB2 receptors in both neurons and glia throughout the brain. Mapping of these receptors is less extensive than for CB1 receptors, and it is still not clear how CB2 receptors contribute to processes that involve endocannabinoid signaling. Objectives: The goal of our study was to assess the effects of peripheral nerve injury and chronic morphine administration, two manipulations that alter endocannabinoid system function, on CB2 receptor expression in the spinal dorsal horn of rats. Methods: Twenty-four male Sprague Dawley rats were assigned to chronic constriction injury (CCI), sham surgery, or pain naïve groups, with half of each group receiving once daily injections of morphine (5 mg/kg) for 10 days. On day 11, spinal cords were isolated and prepared for fluorescent immunohistochemistry. Separate sections from the deep and superficial dorsal horn were stained for neuronal nuclei (NeuN), CD11b, or 4',6-diamidino-2-phenylindole (DAPI) to mark neurons, microglia, and cell nuclei, respectively. Double labeling was used to assess colocalization of CB2 receptors with NeuN or microglial markers. Quantification of mean pixel intensity for each antibody was assessed using a fluorescent microscope, and CB2 receptor expressing cells were also counted manually. Results: Surgery increased DAPI cell counts in the deep and superficial dorsal horn, with CCI rats displaying increased CD11b labeling ipsilateral to the nerve injury. Surgery also decreased NeuN labeling in both regions, an effect that was blocked by morphine administration. CB2 receptors were expressed, predominantly, on NeuN-labeled cells with significant increases in CB2 receptor labeling across all surgery groups in both deep and superficial areas following morphine administration. Conclusions: Our findings provide supporting evidence for the expression of CB2 receptors on neurons and reveal upregulation of receptor expression in the dorsal spinal cord following surgery and chronic morphine administration, with the latter producing a larger effect. Synergistic effects of morphine-cannabinoid treatments, therefore, may involve CB2-mu opioid receptor interactions, pointing to novel therapeutic treatments for a variety of medical conditions.

Positive Long-Term Effects of Third Molar Extraction on Taste Function.

Taste and other neurosensory defects have been reported postoperatively in a number of patients who have undergone mandibular third molar extraction (TME). Although the taste deficits are generally believed to resolve within a year, the long-term effects of TME remain unknown. We retrospectively examined the whole-mouth taste function of 891 individuals who had received TMEs, on average, more than 2 decades earlier, and 364 individuals who had not undergone TME. All had been extensively tested for chemosensory function at the University of Pennsylvania Smell and Taste Center over the course of the last 20 years. The whole-mouth identification test incorporated 2 presentations each of 5 different concentrations of sucrose, sodium chloride, citric acid, and caffeine. Analyses of covariance (age = covariate) found those with histories of TME to exhibit better overall test scores for all 4 taste qualities than nonoperated controls. Such scores were not associated with the time since the TME. In both groups, women outperformed men and function declined with age. The basis of this phenomenon, which requires confirmation from prospective studies, is unknown, but could reflect sensitization of CN VII nerve afferents or the partial release of the tonic inhibition that CN VII exerts on CN IX via central nervous system processes.

Management of functional gastrointestinal disorders

Functional gastrointestinal (GI) disorders (eg irritable bowel syndrome and functional dyspepsia) are very common conditions which are associated with very poor quality of life and high healthcare utilisation. They are caused by disorders of GI functioning, namely altered gut sensitivity, motility, microbiota, immune functioning and central nervous system processing. They cause chronic symptoms throughout the gut (eg pain, dyspepsia and altered bowel habit), all of which are made worse by maladaptive patient behaviours, stress and psychological comorbidity. Management involves a biopsychosocial approach involving changes in lifestyle and diet, addressing coexisting psychological comorbidity and using medication to treat underlying pathophysiology. Pharmacological treatment with antispasmodics, neuromodulators, motility agents and antidepressants is effective. Psychotherapy in motivated individuals is equally effective. Success of treatment is increased by a good doctor-patient relationship and so this needs to be taken into account during the consultation.

MODERN APPROACH TO DYSPEPSIA.

SUMMARYDyspepsia is a disorder characterized by dyspeptic symptoms which are located in the epigastrium and related to digestion of food in the initial part of the digestive system. In functional dyspepsia, unlike organic dyspepsia, there is no underlying organic disease that would cause dyspeptic symptoms. Immune and mucosal function changes, gastric dysmotility, different composition of the gastrointestinal microbiota, and altered central nervous system processing are considered responsible for the onset of the disorder. The diagnosis is based on history, clinical presentation, and exclusion of other organic diseases of the gastrointestinal tract manifested by dyspeptic symptoms. Therapy includes eradication of Helicobacter pylori infection, proton pump inhibitors, prokinetics, neuromodulators, and herbal preparations. Unfortunately, in some patients, this therapy leads to little or no improvement. The prevalence of functional dyspepsia is increasing. It has become one of the more common gastroenterological diagnoses. In order to reduce the costs associated with the diagnosis and treatment of the disorder itself, its mechanisms need to be fully elucidated and thus enable finding appropriate therapy for all patient subgroups.

Central Nervous System Processing of Floral Odor and Mother's Milk Odor in Infants.

Newborns have a functioning sense of smell at birth, which appears to be highly significant for feeding and bonding. Still, little is known about the cerebral odor processing in this age group. Studies of olfactory function relied mostly on behavioral, autonomic, and facial responses of infants. The aim of the present study was to investigate central odor processing in infants focusing on electroencephalography (EEG)-derived responses to biologically significant odors, namely a food and a non-food odor. A total of 21 term-born, healthy infants participated (11 boys and 10 girls; age range 2-9 months, mean 5.3 ± 2.2 months). Odor stimuli were presented using a computer-controlled olfactometer. Breast milk was used as food odor. Farnesol was presented as a non-food odor. In addition, odorless air was used as a control stimulus. Each stimulus was presented 30 times for 1 s with an interstimulus interval of 20 s. EEG was recorded from 9 electrodes and analyzed in the frequency domain. EEG amplitudes in the delta frequency band differed significantly after presentation of food (breast milk) odor in comparison to the control condition and the non-food odor (farnesol). These changes were observed at the frontal recording positions. The present study indicates that central odor processing differs between a food and a non-food odor in infants. Results are interpreted in terms of focused attention towards a physiologically relevant odor (breast milk), suggesting that olfactory stimuli are of specific significance in this age group.

Biophotonic Strategies of Measurement and Stimulation of the Cranial and the Extracranial Lymphatic Drainage Function

In this review, we discuss the crucial role of cranial and the extracranial lymphatics in keeping the central nervous system (CNS) health. We talk about the important lymphatic mechanism of removal of metabolites and toxins from the brain, which orchestrates the regenerative processes in CNS. We debate a novel knowledge about the lymphatic mechanism responsible for maintaining the balance between the exit and the entrance of molecules and cells from and into CNS. Finally, we highlight the pioneering technologies of biophotonic stimulation of lymphatic drainage function that can open a new era for the development of novel bedside, readily applicable and commercially viable technologies for the treatment of brain diseases.