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Frontiers in Cell and Developmental... 2021Asthma is a chronic inflammation of lower airway disease, characterized by bronchial hyperresponsiveness. Type I hypersensitivity underlies all atopic diseases including... (Review)
Review
Asthma is a chronic inflammation of lower airway disease, characterized by bronchial hyperresponsiveness. Type I hypersensitivity underlies all atopic diseases including allergic asthma. However, the role of neurotransmitters (NT) and neuropeptides (NP) in this disease has been less explored in comparison with inflammatory mechanisms. Indeed, the airway epithelium contains pulmonary neuroendocrine cells filled with neurotransmitters (serotonin and GABA) and neuropeptides (substance P[SP], neurokinin A [NKA], vasoactive intestinal peptide [VIP], Calcitonin-gene related peptide [CGRP], and orphanins-[N/OFQ]), which are released after allergen exposure. Likewise, the autonomic airway fibers produce acetylcholine (ACh) and the neuropeptide Y(NPY). These NT/NP differ in their effects; SP, NKA, and serotonin exert pro-inflammatory effects, whereas VIP, N/OFQ, and GABA show anti-inflammatory activity. However, CGPR and ACh have dual effects. For example, the ACh-M3 axis induces goblet cell metaplasia, extracellular matrix deposition, and bronchoconstriction; the CGRP-RAMP1 axis enhances Th2 and Th9 responses; and the SP-NK1R axis promotes the synthesis of chemokines in eosinophils, mast cells, and neutrophils. In contrast, the ACh-α7nAChR axis in ILC2 diminishes the synthesis of TNF-α, IL-1, and IL-6, attenuating lung inflammation whereas, VIP-VPAC1, N/OFQ-NOP axes cause bronchodilation and anti-inflammatory effects. Some NT/NP as 5-HT and NKA could be used as biomarkers to monitor asthma patients. In fact, the asthma treatment based on inhaled corticosteroids and anticholinergics blocks M3 and TRPV1 receptors. Moreover, the administration of experimental agents such as NK1R/NK2R antagonists and exogenous VIP decrease inflammatory mediators, suggesting that regulating the effects of NT/NP represents a potential novel approach for the treatment of asthma.
PubMed: 34055794
DOI: 10.3389/fcell.2021.663535 -
International Journal of Molecular... Oct 2022Disturbances in uterine contractile activity contribute to the development of inflammation, and recent evidence indicates that tachykinins, including substance P (SP)...
Disturbances in uterine contractile activity contribute to the development of inflammation, and recent evidence indicates that tachykinins, including substance P (SP) and neurokinin A (NKA), are involved in controlling uterine function. Here, we determined the effect of (-induced inflammation on expression of protein receptor subtypes for substance P (NK1R) and neurokinin A (NK2R) in the pig myometrium as well as their role in contractility of inflamed uterus. The severe acute endometritis developed in the group and the expression of NK1R and NK2R proteins increased in the myometrium. Compared to the pre-administration period, SP (10 M) reduced the amplitude and frequency in the myometrium of the group and the amplitude was higher and the frequency was lower versus other groups. NKA reduced the amplitude and increased the frequency in endometrium/myometrium of the group. In this group, the amplitude was lower and the frequency was higher than in the CON and SAL groups. Our research showed that NK2R (10 M) antagonist application abolished the NKA inhibitory effect on uterine amplitude. The application of the NK1R (10 M) antagonist together with SP revealed that the inhibitory effect of SP on uterine contractility is achieved independently of the NKR1. Additionally, taking into account the fact that NKA shows an inhibitory effect with the use of NK2R on uterine amplitude suggests the possibility of therapeutic use of the antagonist as a drug increasing uterine contractility in inflammation.
Topics: Animals; Female; Escherichia coli; Escherichia coli Infections; Inflammation; Neurokinin A; Substance P; Swine; Uterus
PubMed: 36361972
DOI: 10.3390/ijms232113184 -
Annals of Indian Academy of Neurology 2016Neurogenic inflammation, a well-defined pathophysiologial process is characterized by the release of potent vasoactive neuropeptides, predominantly calcitonin... (Review)
Review
Neurogenic inflammation, a well-defined pathophysiologial process is characterized by the release of potent vasoactive neuropeptides, predominantly calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A from activated peripheral nociceptive sensory nerve terminals (usually C and A delta-fibers). These peptides lead to a cascade of inflammatory tissue responses including arteriolar vasodilation, plasma protein extravasation, and degranulation of mast cells in their peripheral target tissue. Neurogenic inflammatory processes have long been implicated as a possible mechanism involved in the pathophysiology of various human diseases of the nervous system, respiratory system, gastrointestinal tract, urogenital tract, and skin. The recent development of several innovative experimental migraine models has provided evidence suggestive of the involvement of neuropeptides (SP, neurokinin A, and CGRP) in migraine headache. Antidromic stimulation of nociceptive fibers of the trigeminal nerve resulted in a neurogenic inflammatory response with marked increase in plasma protein extravasation from dural blood vessels by the release of various sensory neuropeptides. Several clinically effective abortive antimigraine medications, such as ergots and triptans, have been shown to attenuate the release of neuropeptide and neurogenic plasma protein extravasation. These findings provide support for the validity of using animal models to investigate mechanisms of neurogenic inflammation in migraine. These also further strengthen the notion of migraine being a neuroinflammatory disease. In the clinical context, there is a paucity of knowledge and awareness among physicians regarding the role of neurogenic inflammation in migraine. Improved understanding of the molecular biology, pharmacology, and pathophysiology of neurogenic inflammation may provide the practitioner the context-specific feedback to identify the novel and most effective therapeutic approach to treatment. With this objective, the present review summarizes the evidence supporting the involvement of neurogenic inflammation and neuropeptides in the pathophysiology and pharmacology of migraine headache as well as its potential significance in better tailoring therapeutic interventions in migraine or other neurological disorders. In addition, we have briefly highlighted the pathophysiological role of neurogenic inflammation in various other neurological disorders.
PubMed: 27293326
DOI: 10.4103/0972-2327.182302 -
Health Psychology Research 2022Migraine headache is a widespread and complex neurobiological disorder that is characterized by unilateral headaches that are often accompanied by photophobia and... (Review)
Review
Migraine headache is a widespread and complex neurobiological disorder that is characterized by unilateral headaches that are often accompanied by photophobia and phonophobia. Migraine is one of the leading chief complaints in the emergency department with negative impacts on quality of life and activities of daily living. The high number of emergency presentations also results in a significant economic burden. Its risk factors include family history, genetics, sex, race, socioeconomics, the existence of comorbid conditions, and level of education. Triggers include stress, light, noise, menstruation, weather, changes in sleep pattern, hunger, dehydration, dietary factors, odors, and alcohol. The International Headache Society has defined criteria for the diagnosis of migraine with and without aura. The pathophysiology of migraine headaches is multifactorial so there are a variety of treatment approaches. The current treatment approach includes abortive medications and prophylactic medications. Abortive medications include the first-line treatment of triptans, followed by ergot alkaloids, and calcitonin gene-related peptide (CGRP) receptor antagonists along with supplemental caffeine and antiemetics. Trigeminal afferents from the trigeminal ganglion innervate most cranial tissues and many areas of the head and face. These trigeminal afferents express certain biomarkers such as calcitonin gene-related peptide (CGRP), substance P, neurokinin A, and pituitary adenylate cyclase-activating polypeptide that are important to the pain and sensory aspect of migraines. In this comprehensive review, we discuss Zavegepant, a calcitonin gene-related peptide receptor antagonist, as a new abortive medication for migraine headaches.
PubMed: 35774914
DOI: 10.52965/001c.35506 -
The Neuroradiology Journal Jun 2014The trigemino-cardiac reflex during Onyx embolization for dural arteriovenous fistula may be caused by mechanical or chemical stimulus to the terminals of the... (Review)
Review
The trigemino-cardiac reflex during Onyx embolization for dural arteriovenous fistula may be caused by mechanical or chemical stimulus to the terminals of the unencapsulated Ruffini-like receptors stemming from A-axons in the dural connective tissue at sites of dural arteries and sinuses. Slow A (Aδ) and fast A (Aβ) neurons may play a role in the stimulus afferent pathway due to their higher mechanosensitivity and chemosensitivity. These afferent pathway nerves are cholinergic innervations of the dura mater, which also contains vasoactive neuropeptides such as calcitonin gene-related peptide, substance P, and neurokinin A. Stimulation of meningeal sensory fibres can evoke cerebral vasodilation through the peripheral release of neuropeptides, which play a role in headache pathogenesis. These myelinated A-fibers terminate in the deep part (laminae III-V) of the spinal dorsal horn. Its efferent pathway has been defined as the acetylcholinergic vagus nerve. The A11 nucleus, located in the posterior hypothalamus, providing the only known source of descending dopaminergic innervation for the spinal grey matter, can inhibit the neurons in the spinal dorsal horn.
Topics: Afferent Pathways; Animals; Brain; Dura Mater; Heart Rate; Humans; Mechanoreceptors; Models, Neurological; Nociceptors; Reflex; Trigeminal Nerve
PubMed: 24976196
DOI: 10.15274/NRJ-2014-10052 -
Cureus Jul 2022The role of neurogenic inflammation in various systemic diseases has been well established, but there is a dearth of studies and evidence regarding its role in... (Review)
Review
The role of neurogenic inflammation in various systemic diseases has been well established, but there is a dearth of studies and evidence regarding its role in periodontitis. This study aimed to systematically review the evidence in establishing the role of neurogenic inflammation in chronic periodontitis. Databases such as PubMed, Scopus, and Google Scholar were reviewed. We analyzed studies of any design that compared and evaluated the presence of neuropeptides such as substance P, calcitonin gene-related peptide, neurokinin A, neuropeptide Y, and vasoactive intestinal polypeptide in systemically healthy patients with and without periodontitis. We screened 2,495 articles and abstracts electronically and manually, which yielded 191 articles relevant to our study. Full-text examination of these 191 articles led to the final inclusion of 14 publications. Most studies here confirmed an association between various neuropeptides and periodontitis, but there is a high heterogeneity between the studies, making it necessary to clarify the mechanism between these two. Although most studies included in this review found a positive association between neurogenic inflammation and periodontitis, the evidence is of moderate to low quality.
PubMed: 35978739
DOI: 10.7759/cureus.26889 -
Biomolecular Concepts Jun 2013The neurokinin receptors are G-protein-linked receptors; three distinct molecules, called neurokinin-1, neurokinin-2, and neurokinin-3 receptors, have been identified.... (Review)
Review
The neurokinin receptors are G-protein-linked receptors; three distinct molecules, called neurokinin-1, neurokinin-2, and neurokinin-3 receptors, have been identified. Their physiological ligands are the tachykinins, which, in the mammalian gut, correspond to substance P, neurokinin A, and neurokinin B. In this apparatus, the main source of tachykinins is represented by intrinsic neurons located either in the myenteric plexus and projecting mainly to the muscle coat, or in the submucous plexus and projecting to the mucosa and submucosal blood vessels. The availability of specific antibodies has allowed identifying the sites of distribution of the neurokinin receptors in the gut, and important differences have been found among cell types and animal species. The complexity of the receptor distribution, either intraspecies or interspecies, is in agreement with the variegated picture coming out from physiological and pharmacological experiments. Interestingly, most of the knowledge on the tachykinin systems has been obtained from pathological conditions. Here, we tried to collect the main information available on the cellular distribution of the neurokinin receptors in the gut wall in the attempt to correlate their cell location with the several roles the tachykinins seem to play in the gastrointestinal apparatus.
Topics: Abdominal Muscles; Abdominal Wall; Animals; Gastrointestinal Tract; Humans; Neurons; Receptors, Tachykinin; Tachykinins
PubMed: 25436578
DOI: 10.1515/bmc-2013-0001