Tachykinin Antagonists in Asthma and Inflammation
Sami I. Said in Proinflammatory and Antiinflammatory Peptides, 2020
The evidence reviewed in this chapter indicates that at several locations of the body a TKergic innervation exists from which peptides of the TK family are released, especially during inflammation and in response to potentially harmful/tissue-threatening stimuli. The released TKs produce a number of powerful biological effects which are proinflammatory or frankly inflammatory; in various viscera, including the airways, a powerful contraction of smooth muscles also occurs. These events, which are receptor-mediated and collectively termed “neurogenic inflammation,” provide a mechanism through which the sensory nervous system contributes to initiation and maintenance of the inflammatory process. The preclinical evidence collected thus far, and reviewed in this chapter, indicates that blockade of neurogenic inflammation can be effectively achieved, in a number of animal models of disease, by occluding postjunctional TK receptors with TK receptor antagonists. From the above, a possible therapeutic usefulness of TK receptor antagonists can be envisaged in diseases as diverse as asthma/bronchial hyperreactivity, psoriasis, rheumatoid arthritis, inflammatory bowel diseases, cystitis, and migraine. This hypothesis is currently under evaluation.
Neuronal Mechanisms of Cutaneous Blood Flow
Geoffrey Burnstock, Susan G. Griffith in Nonadrenergic Innervation of Blood Vessels, 2019
The purpose of cutaneous vasodilatation in response to a noxious stimulus probably lies in the faster removal by the increased blood flow of toxic exogenous substances that penetrate the skin, or of endogenous substances that mediate inflammation and pain. In addition, increased plasma extravasation enables the removal of larger molecules via the lymphatic system. Vasodilatation and plasma extravasation are predominant in the inital phases of inflammation. Inflammation is a process which proceeds in several phases with the main purpose to repair the damaged tissue. Neurogenic influences during the early stages of inflammation have been suspected for a long time. Many recent observations have shown that antidromic vasodilatation represents at least one of the neuronal mechanisms involved. In consequence, the concept “neurogenic inflammation” was introduced (see Reference 54).
Altered Somatosensory Pathways
Golara Honari, Rosa M. Andersen, Howard Maibach in Sensitive Skin Syndrome, 2017
In contrast to the traditional view that the peripheral nervous system and the immune system serve separate functions, it is now evident that the peripheral nervous system directly communicates with the immune system (11). Pioneering experiments by Bayliss in 1901 revealed cutaneous vasodilation after the stimulation of cut dorsal nerve roots (13), which led to the concept of neurogenic inflammation. Neurogenic inflammation is the inflammation caused by the activation of primary sensory nerve terminals, which is characterized by four hallmarks of inflammation, that is, redness (rubor) and warmth (calor) (secondary to vasodilation), swelling (tumor, secondary to plasma extravasation), and pain/hypersensitivity (dolor, secondary to altered excitability of sensory neurons) in addition to granulocyte infiltration in postcapillary venules.
An Amplifying Cascade of Contact Lens-Related End-of-Day Hyperaemia and Dryness Symptoms
Published in Current Eye Research, 2018
The epithelium is a contributor to inflammation in response to its desiccation and hyper-osmolarity, for example, besides being a target for inflammatory mediators produced in response to DED.32 Activated corneal nerves release neuropeptides (neurogenic inflammation), which contribute to other forms of inflammatory response.47 Thus, ongoing nociceptor activity can itself cause inflammation, which presumably can contribute to corneal hyperalgesia.48 For example, corneal nerves can become sensitized by local inflammatory mediators such as prostaglandins and bradykinin and thus exhibit spontaneous activity.47 Neuroplastic hypersensitivity explains how a given stimulus can provoke a response, which escalates in intensity over time and lasts longer.48 This manifestation of neural plasticity is known as peripheral sensitization.48 SCL inflammation stimulated by evaporation-related hyper-osmolarity may increase symptoms by these mechanisms for peripheral sensitization. Thus, neurogenic inflammation is the process by which inflammatory mediators, including neuropeptides, are released from afferent nerve terminals in a target tissue and trigger inflammation with associated vasodilatation, plasma extravasation and hypersensitivity.49 This neurogenic process explains a link between symptoms and redness. Similar mechanisms may contribute to the amplifying evaporative cascade for SCL dryness symptoms discussed below.
János Szolcsányi and capsaicin research – from the early years to his legacy
Published in Temperature, 2023
● Plasma extravasation in response to antidromic electrical stimulation of sensory nerves (e.g. the saphenous nerve) has been quantified on the basis of tissue deposition of Evans’ blue, a substance known to strongly bind to plasma albumin. The response was apparently not decreased by antagonists acting at muscarinic or nicotinic acetylcholine receptors, some serotonin receptors (methysergide), β- and α-adrenergic, histamine (now: H1) receptors or a cholinesterase inhibitor. Irritant substances like capsaicin, mustard oil (allyl isothiocyanate) and others also elicited plasma extravasation. All these stimuli became largely ineffective after chronic/subacute, but not acute sensory denervation, as well as after systemic desensitization to capsaicin. Thus, neurogenic inflammation is produced by sensory nerves that release a mediator or mediators (whose identity, however, remained unknown).
The Relationship Between Corneal Dendritic Cells, Corneal Nerve Morphology and Tear Inflammatory Mediators and Neuropeptides in Healthy Individuals
Published in Current Eye Research, 2019
Luisa H. Colorado, Maria Markoulli, Katie Edwards
Neurogenic inflammation involves a change in the sensory nerve endings by the release of neuropeptides, because of the activity of inflammatory mediators, modifying the function of sensory neurons.39 Neurogenic inflammation research has been undertaken in disease processes such as arthritis, colitis, bladder inflammation, and asthma.40 In the trigeminovascular system, neuropeptide release further activates trigeminal afferents, inducing sensitization.41 Neuropeptides such as substance P are contained within sensory fibers and these, as well as cytokines, may be released to further modulate inflammatory events.42 The positive associations found in this study between nerve parameters in the avascular central corneal and DC density in healthy subjects supports that the ocular nervous and immune systems are interlinked, specifically in those individuals undergoing presumed immune activity response evidenced by increased number of DCs migration in the central cornea. It is also hypothesized that these correlations change in direction and are stronger and more significant during inflammation. Reduced nerve density and increased DCs has been demonstrated in a dry eye with and without Sjögren syndrome43 and during infectious keratitis,8 with strong negative correlations between these parameters not only in the affected but also the fellow eye,44 indicating a systemic effect.
Related Knowledge Centers
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