Pathophysiology of nasal congestion

Nasal congestion is a common symptom in rhinitis (both allergic and nonallergic), rhinosinusitis and nasal polyposis. Congestion can also be caused by physical obstruction of nasal passages and/or modulation of sensory perception. Mucosal inflammation underlies many of the specific and interrelated factors that contribute to nasal congestion, as well as other symptoms of both allergic rhinitis and rhinosinusitis. A wide range of biologically active agents (eg, histamine, tumor necrosis factor-α, interleukins, cell adhesion molecules) and cell types contribute to inflammation, which can manifest as venous engorgement, increased nasal secretions and tissue swelling/edema, ultimately leading to impaired airflow and the sensation of nasal congestion. Inflammation-induced changes in the properties of sensory afferents (eg, expression of peptides and receptors) that innervate the nose can also contribute to altered sensory perception, which may result in a subjective feeling of congestion. Increased understanding of the mechanisms underlying inflammation can facilitate improved treatment selection and the development of new therapies for congestion

Connectivity differences between Gulf War Illness (GWI) phenotypes during a test of attention

One quarter of veterans returning from the 1990–1991 Persian Gulf War have developed Gulf War Illness (GWI) with chronic pain, fatigue, cognitive and gastrointestinal dysfunction. Exertion leads to characteristic, delayed onset exacerbations that are not relieved by sleep. We have modeled exertional exhaustion by comparing magnetic resonance images from before and after submaximal exercise. One third of the 27 GWI participants had brain stem atrophy and developed postural tachycardia after exercise (START: Stress Test Activated Reversible Tachycardia). The remainder activated basal ganglia and anterior insulae during a cognitive task (STOPP: Stress Test Originated Phantom Perception). Here, the role of attention in cognitive dysfunction was assessed by seed region correlations during a simple 0-back stimulus matching task (“see a letter, push a button”) performed before exercise. Analysis was analogous to resting state, but different from psychophysiological interactions (PPI). The patterns of correlations between nodes in task and default networks were significantly different for START (n = 9), STOPP (n = 18) and control (n = 8) subjects. Edges shared by the 3 groups may represent co-activation caused by the 0-back task. Controls had a task network of right dorsolateral and left ventrolateral prefrontal cortex, dorsal anterior cingulate cortex, posterior insulae and frontal eye fields (dorsal attention network). START had a large task module centered on the dorsal anterior cingulate cortex with direct links to basal ganglia, anterior insulae, and right dorsolateral prefrontal cortex nodes, and through dorsal attention network (intraparietal sulci and frontal eye fields) nodes to a default module. STOPP had 2 task submodules of basal ganglia–anterior insulae, and dorsolateral prefrontal executive control regions. Dorsal attention and posterior insulae nodes were embedded in the default module and were distant from the task networks. These three unique connectivity patterns during an attention task support the concept of Gulf War Disease with recognizable, objective patterns of cognitive dysfunction

Covariates of corticotropin-releasing hormone (CRH) concentrations in cerebrospinal fluid (CSF) from healthy humans

BACKGROUND: Define covariates of cerebrospinal corticotropin-releasing hormone (CRH) levels in normal humans. CRH(CSF )was measured in 9 normal subjects as part of an intensive study of physiological responses stressors in chronic pain and fatigue states. CRH(CSF )was first correlated with demographic, vital sign, HPA axis, validated questionnaire domains, baseline and maximal responses to pain, exercise and other stressors. Significant factors were used for linear regression modeling. RESULTS: Highly significant correlations were found despite the small number of subjects. Three models were defined: (a) CRH(CSF )with blood glucose and sodium (explained variance = 0.979, adjusted R(2 )= 0.958, p = 0.02 by 2-tailed testing); (b) CRH(CSF )with resting respiratory and heart rates (R(2 )= 0.963, adjusted R(2 )= 0.939, p = 0.007); and (c) CRH(CSF )with SF-36 Vitality and Multidimensional Fatigue Inventory Physical Fatigue domains (R(2 )= 0.859, adjusted R(2 )= 0.789, p = 0.02). CONCLUSIONS: Low CRH(CSF )was predicted by lower glucose, respiratory and heart rates, and higher sodium and psychometric constructs of well being. Responses at peak exercise and to other acute stressors were not correlated. CRH(CSF )may have reflected an overall, or chronic, set-point for physiological responses, but did not predict the reserves available to respond to immediate stressors

Nova saznanja o neuralnoj regulaciji nosne sluznice kod ljudi

Nasal mucosa is innervated by multiple subsets of nociceptive, parasympathetic and sympathetic nerves. These play carefully coordinated roles in regulating glandular, vascular and other processes. These functions are vital for cleaning and humidifying ambient air before it is inhaled into the lungs. The recent recognition of distinct classes of nociceptive nerves with unique patterns of sensory receptors that include seven transmembrane G-protein coupled receptors, new families of transient receptor potential and voltage and calcium gated ion channels, and combinations of neurotransmitters that can be modulated during inflammation by neurotrophic factors has revolutionized our understanding of the complexity and subtlety of nasal innervation. These findings may provide a rational basis for responses to air temperature changes, culinary and botanical odorants ("aromatherapy"), and inhaled irritants in conditions as diverse as idiopathic nonallergic rhinitis, occupational rhinitis, hyposmia, and multiple chemical sensitivity.Nosnu sluznicu prožimaju višestruke podskupine nociceptivnih, parasimpatičkih i simpatičkih živaca koji imaju podrobno usklađene uloge u reguliranju žljezdanih, žilnih i drugih procesa. Ove funkcije su presudne za čišćenje i ovlaživanje zraka iz okoline prije negoli se udahne u pluća. Naše shvaćanje složene i fine naravi inervacije nosne sluznice radikalno se mijenja nedavnim prepoznavanjem različitih vrsta nociceptivnih živaca s jedinstvenim obrascima senzornih receptora koji obuhvaćaju sedam transmembranskih receptora vezanih s G-proteinom, nove porodice prolaznog receptorskog potencijala i napona te kalcijem ograničene (gated) ionske kanale i kombinacije neurotransmitora koje tijekom upale mogu mijenjati neurotropni čimbenici. Ovi nalazi mogli bi pružiti razumnu osnovu za odgovore na promjene u temperaturi zraka, kulinarske i botaničke mirise ("aromaterapija") i udisajne iritante u uvjetima tako ranovrsnim kao što su idiopatski nealergijski rinitis, profesionalni rinitis, hiposmija i višestruka kemijska osjetljivost

Human neuroglobin protein in cerebrospinal fluid

BACKGROUND: Neuroglobin is a hexacoordinated member of the globin family of proteins. It is predominantly localized to various brain regions and retina where it may play a role in protection against ischemia and nitric oxide-induced neural injury. Cerebrospinal fluid was collected from 12 chronic regional or systemic pain and 5 control subjects. Proteins were precipitated by addition of 50% 0.2 N acetic acid, 50% ethanol, 0.02% sodium bisulfite. The pellet was extensively digested with trypsin. Peptides were separated by capillary liquid chromatography using a gradient from 95% water to 95% acetonitrile in 0.2% formic acid, and eluted through a nanoelectrospray ionization interface into a quadrapole – time-of-flight dual mass spectrometer (QToF2, Waters, Milford, MA). Peptides were sequenced (PepSeq, MassLynx v3.5) and proteins identified using MASCOT (®). RESULTS: Six different neuroglobin peptides were identified in various combinations in 3 of 9 female pain subjects, but none in male pain, or female or male control subjects. CONCLUSION: This is the first description of neuroglobin in cerebrospinal fluid. The mechanism(s) leading to its release in chronic pain states remain to be defined

Vasoactive intestinal peptide in human nasal mucosa

Vasoactive intestinal peptide (VIP), which is present with acetylcholine in parasympathetic nerve fibers, may have important regulatory functions in mucous membranes. The potential roles for VIP in human nasal mucosa were studied using an integrated approach. The VIP content of human nasal mucosa was determined to be 2.84 +/- 0.47 pmol/g wet weight (n = 8) by RIA. VIP-immunoreactive nerve fibers were found to be most concentrated in submucosal glands adjacent to serous and mucous cells. 125I-VIP binding sites were located on submucosal glands, epithelial cells, and arterioles. In short-term explant culture, VIP stimulated lactoferrin release from serous cells but did not stimulate [3H]glucosamine-labeled respiratory glycoconjugate secretion. Methacholine was more potent than VIP, and methacholine stimulated both lactoferrin and respiratory glycoconjugate release. The addition of VIP plus methacholine to explants resulted in additive increases in lactoferrin release. Based upon the autoradiographic distribution of 125I-VIP binding sites and the effects on explants, VIP derived from parasympathetic nerve fibers may function in the regulation of serous cell secretion in human nasal mucosa. VIP may also participate in the regulation of vasomotor tone

Increased brain white matter axial diffusivity associated with fatigue, pain and hyperalgesia in Gulf War illness

Background Gulf War exposures in 1990 and 1991 have caused 25% to 30% of deployed personnel to develop a syndrome of chronic fatigue, pain, hyperalgesia, cognitive and affective dysfunction. Methods Gulf War veterans (n = 31) and sedentary veteran and civilian controls (n = 20) completed fMRI scans for diffusion tensor imaging. A combination of dolorimetry, subjective reports of pain and fatigue were correlated to white matter diffusivity properties to identify tracts associated with symptom constructs. Results Gulf War Illness subjects had significantly correlated fatigue, pain, hyperalgesia, and increased axial diffusivity in the right inferior fronto-occipital fasciculus. ROC generated thresholds and subsequent binary regression analysis predicted CMI classification based upon axial diffusivity in the right inferior fronto-occipital fasciculus. These correlates were absent for controls in dichotomous regression analysis. Conclusion The right inferior fronto-occipital fasciculus may be a potential biomarker for Gulf War Illness. This tract links cortical regions involved in fatigue, pain, emotional and reward processing, and the right ventral attention network in cognition. The axonal neuropathological mechanism(s) explaining increased axial diffusivity may account for the most prominent symptoms of Gulf War Illness

Increased brain white matter axial diffusivity associated with fatigue, pain and hyperalgesia in Gulf War illness. PLoS One

Abstract Background: Gulf War exposures in 1990 and 1991 have caused 25% to 30% of deployed personnel to develop a syndrome of chronic fatigue, pain, hyperalgesia, cognitive and affective dysfunction

Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain

BACKGROUND: The mechanism(s) of nociceptive dysfunction and potential roles of opioid neurotransmitters are unresolved in the chronic pain syndromes of fibromyalgia and chronic low back pain. METHODS: History and physical examinations, tender point examinations, and questionnaires were used to identify 14 fibromyalgia, 10 chronic low back pain and 6 normal control subjects. Lumbar punctures were performed. Met-enkephalin-Arg(6)-Phe(7 )(MEAP) and nociceptin immunoreactive materials were measured in the cerebrospinal fluid by radioimmunoassays. RESULTS: Fibromyalgia (117.6 pg/ml; 85.9 to 149.4; mean, 95% C.I.; p = 0.009) and low back pain (92.3 pg/ml; 56.9 to 127.7; p = 0.049) groups had significantly higher MEAP than the normal control group (35.7 pg/ml; 15.0 to 56.5). MEAP was inversely correlated to systemic pain thresholds. Nociceptin was not different between groups. Systemic Complaints questionnaire responses were significantly ranked as fibromyalgia > back pain > normal. SF-36 domains demonstrated severe disability for the low back pain group, intermediate results in fibromyalgia, and high function in the normal group. CONCLUSIONS: Fibromyalgia was distinguished by higher cerebrospinal fluid MEAP, systemic complaints, and manual tender points; intermediate SF-36 scores; and lower pain thresholds compared to the low back pain and normal groups. MEAP and systemic pain thresholds were inversely correlated in low back pain subjects. Central nervous system opioid dysfunction may contribute to pain in fibromyalgia