scholarly journals Connections between Immune-Derived Mediators and Sensory Nerves for Itch Sensation

2021 ◽  
Vol 22 (22) ◽  
pp. 12365
Author(s):  
Sumika Toyama ◽  
Mitsutoshi Tominaga ◽  
Kenji Takamori
Keyword(s):  
Immune Cell ◽  
Current Knowledge ◽  
Neuronal Response ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Chronic Itch ◽  
Itch Sensation ◽  
Receptor Blockers ◽  
New Treatments

Although histamine is a well-known itch mediator, histamine H1-receptor blockers often lack efficacy in chronic itch. Recent molecular and cellular based studies have shown that non-histaminergic mediators, such as proteases, neuropeptides and cytokines, along with their cognate receptors, are involved in evocation and modulation of itch sensation. Many of these molecules are produced and secreted by immune cells, which act on sensory nerve fibers distributed in the skin to cause itching and sensitization. This understanding of the connections between immune cell-derived mediators and sensory nerve fibers has led to the development of new treatments for itch. This review summarizes current knowledge of immune cell-derived itch mediators and neuronal response mechanisms, and discusses therapeutic agents that target these systems.

Capsaicin-sensitive afferent nerves activate submucosal secretomotor neurons in guinea pig ileum

1995 ◽  
Vol 269 (2) ◽  
pp. G203-G209 ◽  
Author(s):  
S. Vanner ◽  
W. K. MacNaughton
Keyword(s):  
Guinea Pig ◽  
Ion Transport ◽  
Short Circuit ◽  
Ussing Chamber ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Guinea Pig Ileum ◽  
Secretomotor Neurons

This study examined whether capsaicin-sensitive sensory nerves regulate intestinal ion transport using both Ussing chamber and intracellular recording techniques in in vitro submucosal preparations from the guinea pig ileum. In Ussing chamber studies, serosal application of capsaicin (20 nM-20 microM) evoked a biphasic dose-dependent increase in short-circuit current (Isc) (maximal effective concentration 200 nM and 2 microM, respectively). In chloride-free buffer, capsaicin responses were significantly reduced. Capsaicin evoked little or no response when extrinsic sensory nerve fibers had been surgically removed and tetrodotoxin and low-calcium and high-magnesium solutions blocked responses to capsaicin. In epithelial preparations devoid of submucosal neurons, capsaicin had virtually no effect, suggesting that responses evoked by capsaicin-sensitive nerves result from activation of submucosal secretomotor neurons. Intracellular recordings from single submucosal neurons demonstrated that superfusion with capsaicin (2 microM) depolarized neurons with an associated decreased conductance. Depolarizations were completely desensitized when capsaicin was reapplied, but synaptic inputs were unaffected. This study suggests that capsaicin-sensitive nerves can regulate ion transport in the gastrointestinal tract by release of neurotransmitter(s) that activate submucosal secretomotor neurons.

Relationships between permeable vessels, nerves, and mast cells in rat cutaneous neurogenic inflammation

1990 ◽  
Vol 68 (6) ◽  
pp. 2305-2311 ◽  
Author(s):  
J. N. Baraniuk ◽  
M. L. Kowalski ◽  
M. A. Kaliner
Keyword(s):  
Electrical Stimulation ◽  
Mast Cells ◽  
Neurogenic Inflammation ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Neurokinin A ◽  
Rat Skin ◽  
Protein Extravasation ◽  
Stimulation Of

Electrical stimulation of rat sensory nerves produces cutaneous vasodilation and plasma protein extravasation, a phenomenon termed “neurogenic inflammation”. Rat skin on the dorsum of the paw developed neurogenic inflammation after electrical stimulation of the saphenous nerve. In tissue sections, the extravasation of the supravital dye monastral blue B identified permeable vessels. Mast cells were identified by toluidine blue stain. Permeable vessels were significantly more dense in the superficial 120 microns of the dermis than in the deeper dermis, whereas mast cells were significantly more frequent in the deeper dermis. The relationships between nociceptive sensory nerve fibers, permeable vessels, and mast cells were examined by indirect immunohistochemistry for calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and substance P (SP). CGRP-, NKA-, and SP-containing nerves densely innervated the superficial dermis and appeared to innervate the vessels that became permeable during neurogenic inflammation. In contrast, mast cells were not associated with either permeable vessels or nerve fibers. These data suggest that electrical stimulation of rat sensory nerves produces vascular permeability by inducing the release of neuropeptides that may directly stimulate the superficial vascular bed. Mast cells may not be involved in this stage of cutaneous neurogenic inflammation in rat skin.

Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE2-dependent activation of α1- and α2-adrenoceptors on renal sensory nerve fibers

2007 ◽  
Vol 293 (4) ◽  
pp. R1561-R1572 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith ◽  
Jan Mulder ◽  
Tomas Hökfelt
Keyword(s):  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Pelvic Wall ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion ◽  
Renal Sympathetic

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA). To test whether the ERSNA-induced increases in ARNA involved norepinephrine activating α-adrenoceptors on the renal sensory nerves, we examined the effects of renal pelvic administration of the α1- and α2-adrenoceptor antagonists prazosin and rauwolscine on the ARNA responses to reflex increases in ERSNA (placing the rat's tail in 49°C water) and renal pelvic perfusion with norepinephrine in anesthetized rats. Hot tail increased ERSNA and ARNA, 6,930 ± 900 and 4,870 ± 670%·s (area under the curve ARNA vs. time). Renal pelvic perfusion with norepinephrine increased ARNA 1,870 ± 210%·s. Immunohistochemical studies showed that the sympathetic and sensory nerves were closely related in the pelvic wall. Renal pelvic perfusion with prazosin blocked and rauwolscine enhanced the ARNA responses to reflex increases in ERSNA and norepinephrine. Studies in a denervated renal pelvic wall preparation showed that norepinephrine increased substance P release, from 8 ± 1 to 16 ± 1 pg/min, and PGE2 release, from 77 ± 11 to 161 ± 23 pg/min, suggesting a role for PGE2 in the norepinephrine-induced activation of renal sensory nerves. Prazosin and indomethacin reduced and rauwolscine enhanced the norepinephrine-induced increases in substance P and PGE2. PGE2 enhanced the norepinephrine-induced activation of renal sensory nerves by stimulation of EP4 receptors. Interaction between ERSNA and ARNA is modulated by norepinephrine, which increases and decreases the activation of the renal sensory nerves by stimulating α1- and α2-adrenoceptors, respectively, on the renal pelvic sensory nerve fibers. Norepinephrine-induced activation of the sensory nerves is dependent on renal pelvic synthesis/release of PGE2.

scholarly journals Recruitment of immunocompetent cells after dentinal injuries in innervated and denervated young rat molars: an immunohistochemical study.

1995 ◽  
Vol 43 (9) ◽  
pp. 871-879 ◽  
Author(s):  
I Fristad ◽  
K J Heyeraas ◽  
I H Kvinnsland ◽  
R Jonsson
Keyword(s):  
Inferior Alveolar Nerve ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Immunocompetent Cells ◽  
Pulp Tissue ◽  
Protein Gene Product ◽  
Calcitonin Gene ◽  
Rat Molars ◽  
Rat Molar

The dental pulp represents a peripheral end-organ deprived of a collateral nerve supply. After inferior alveolar nerve (IAN) axotomy, rat molar pulp is denervated over a period of at least 6 days. Therefore, rat molar pulp was used as an experimental model to study the effect of sensory nerve fibers on influx of immunocompetent cells after dentinal injury. In the present study we performed a quantitative analysis of CD43+, CD4+, CD11b+, and I-A antigen-expressing cells subjacent to dentinal cavities in denervated and innervated first mandibular molars. For visualization of nerve fibers, antibodies to protein gene product (PGP) 9.5, the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and the sympathetic neuropeptide Y (NPY) were used. Immunohistochemistry was performed by the avidin-biotin-peroxidase method. In the innervated teeth, a correlation between increased sensory nerve density and influx of immunocompetent cells was found. Compared to the contralateral innervated molars, a significant reduction in recruitment of immunocompetent cells was found in the denervated pulp tissue subjacent to the dentinal cavities. The rat molar represents a unique model to illustrate the influence of sensory nerves and neuropeptides on inflammation and recruitment of immunocompetent cells.

scholarly journals DIC imaging for identification of motor and sensory nerves

2016 ◽  
Vol 09 (05) ◽  
pp. 1643001
Author(s):  
Dayu Chen ◽  
Yuxiang Wu ◽  
Tao Sui ◽  
Shaoqun Zeng ◽  
Xiaojian Cao ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Nerve Repair ◽  
Sensory Nerve ◽  
Distribution Patterns ◽  
Rapid Identification ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Label Free ◽  
Staining Methods ◽  
Dorsal Nerve

Identification of motor and sensory nerves is important in applications such as nerve injury repair. Conventional practice relies on time consuming staining methods for this purpose. Here, we use laser scanning infrared differential interference contrast (IR-DIC) microscopy for label-free observation of the two types of nerve. Ventral and dorsal nerve roots of adult beagle dogs were collected and sections of different thicknesses were imaged with an IR-DIC microscope. Different texture patterns of the IR-DIC images of the motor and sensory nerve can be distinguished when the section thickness increases to 40[Formula: see text][Formula: see text]m. This suggests that nerve fibers in motor and sensory nerves have different distribution patterns. The result hints a potential new way for more rapid identification of nerve type in peripheral nerve repair surgery.

scholarly journals Dysmetabolic neuropathy in children with diabetes type I

2019 ◽  
pp. 52-55
Author(s):  
David Chkhartishvili ◽  
George Natriashvili
Keyword(s):  
Nerve Conduction ◽  
Sensory Nerve ◽  
Diabetic Polyneuropathy ◽  
Nerve Fibers ◽  
Diabetes Type ◽  
Sensory Nerves ◽  
Type I ◽  
Sensorimotor Polyneuropathy ◽  
High Hba1c ◽  
Diabetes Type I

Neuropathy is the most frequent symptomatic complication of diabetes. Diabetic polyneuropathy (DPN) is the most common variety of neuropathy, which represents chronic symmetrical sensorimotor polyneuropathy. (DPN) typically begins as a generalized asymptomatic dysfunction of peripheral nerve fibers, which may be revealed by electromyography. However, nerve conduction study (NCS) is a sensitive method for early detecting of peripheral neuropathy. We have performed NCS in 69 children with poorly compensated diabetes type I aged 7-18 y. Study protocol included testing of peripheral motor and sensory nerve conduction velocities (NCVs) and compound motor and sensory nerve action potential amplitudes. We revealed subclinical abnormalities, which were symmetric, suggestive of DPN and reflecting disorders of predominantly motor, rather than sensory nerves. In addition, nerve conduction abnormalities were correlated with high HbA1c level, patient age and disease (diabetes) duration. Poor metabolic control was the most important contributor to abnormal electrophysiological parameters.

scholarly journals Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system

2014 ◽  
Vol 306 (8) ◽  
pp. G686-G698 ◽  
Author(s):  
Daniel P. Poole ◽  
Mike Lee ◽  
Patrick Tso ◽  
Nigel W. Bunnett ◽  
Sek Jin Yo ◽  
...  
Keyword(s):  
Lysophosphatidic Acid ◽  
Interstitial Fluid ◽  
Protein Hydrolysate ◽  
Sensory Nerve ◽  
Endocrine System ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Dependent Manner ◽  
Direct Stimulation ◽  
Lymphatic Fluid

Lymphatic fluid is a plasma filtrate that can be viewed as having biological activity through the passive accumulation of molecules from the interstitial fluid. The possibility that lymphatic fluid is part of an active self-contained signaling process that parallels the endocrine system, through the activation of G-protein coupled receptors (GPCR), has remained unexplored. We show that the GPCR lysophosphatidic acid 5 (LPA5) is found in sensory nerve fibers expressing calcitonin gene-related peptide (CGRP) that innervate the lumen of lymphatic lacteals and enteric nerves. Using LPA5 as a model for nutrient-responsive GPCRs present on sensory nerves, we demonstrate that dietary protein hydrolysate (peptone) can induce c-Fos expression in enterocytes and nerves that express LPA5. Mesenteric lymphatic fluid (MLF) mobilizes intracellular calcium in cell models expressing LPA5 upon feeding in a time- and dose-dependent manner. Primary cultured neurons of the dorsal root ganglia expressing CGRP are activated by MLF, which is enhanced upon LPA5 overexpression. Activation is independent of the known LPA5 agonists, lysophosphatidic acid and farnesyl pyrophosphate. These data bring forth a pathway for the direct stimulation of sensory nerves by luminal contents and interstitial fluid. Thus, by activating LPA5 on sensory nerves, MLF provides a means for known and yet to be identified constituents of the interstitial fluid to act as signals to comprise a “neurolymphocrine” system.

scholarly journals Effects of Divalent Ions and Drugs on Synaptic Transmission in Phasic Electroreceptors in a Mormyrid Fish

1971 ◽  
Vol 58 (5) ◽  
pp. 580-598 ◽  
Author(s):  
A. B. Steinbach ◽  
M. V. L. Bennett
Keyword(s):  
Synaptic Transmission ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Block Transmission ◽  
Afferent Nerve Fibers ◽  
Similar Chemical ◽  
Mormyrid Fish ◽  
Nerve Synapse ◽  
Skin Receptors

We recorded impulses in afferent nerve fibers innervating two kinds of phasic electroreceptors in a mormyrid fish. We used an isolated preparation of skin, receptors, and sensory nerves to estimate synaptic delays, and to change solution in contact with the receptor-nerve synapse. The minimum delays between stimuli and sensory nerve responses, which must be slightly larger than synaptic delays, are about 0.7 msec in medium receptors and about 0.25 msec in large receptors. This result supports previous suggestions that transmission is chemically mediated in medium receptors and electrically mediated in large receptors. Furthermore, Mg+2 depresses synaptic transmission in medium receptors, and has little effect on transmission in large receptors. A complex dependence of response on both Mg+2 and Ca+2 masks divalent ion dependence of transmission, but a large excess of Mg+2 cannot completely block transmission in medium electroreceptors. L-glutamate, and not cholinergic drugs, produces a sequence of excitation and depression of medium receptor response which indicates that a similar chemical is the transmitter in the afferent synapse.

scholarly journals Itch and Cough – Similar Role of Sensory Nerves in Their Pathogenesis

2020 ◽  
pp. S43-S54
Author(s):  
T. Pecova ◽  
I. Kocan ◽  
R. Vysehradsky ◽  
R. Pecova
Keyword(s):  
Sensory Nerve ◽  
Small Diameter ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Upper Respiratory Tract ◽  
C Fibers ◽  
Afferent Nerves ◽  
Sensory Fibers ◽  
Peripheral Sensory

Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subserve pruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Aδ nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields.

Nitric oxide modulates renal sensory nerve fibers by mechanisms related to substance P receptor activation

2001 ◽  
Vol 281 (1) ◽  
pp. R279-R290 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith ◽  
Tomas Hökfelt
Keyword(s):  
Nitric Oxide ◽  
Substance P ◽  
Sensory Nerve ◽  
Receptor Activation ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Renal Nerve ◽  
Inhibitory Neurotransmitter ◽  
Pelvic Perfusion ◽  
Pelvic Pressure

Nerve terminals containing neuronal nitric oxide synthase (nNOS) are localized in the renal pelvic wall where the sensory nerves containing substance P and calcitonin gene-related peptide (CGRP) are found. We examined whether nNOS is colocalized with substance P and CGRP. All renal pelvic nerve fibers that contained nNOS-like immunoreactivity (-LI) also contained substance P-LI and CGRP-LI. In anesthetized rats, renal pelvic perfusion with the nNOS inhibitor S-methyl-l-thiocitrulline (l-SMTC, 20 μM) prolonged the afferent renal nerve activity (ARNA) response to a 3-min period of increased renal pelvic pressure from 5 ± 0.4 to 21 ± 2 min ( P < 0.01, n = 14). The magnitude of the ARNA response was unaffected byl-SMTC. Similar effects were produced by N ω-nitro-l-arginine methyl ester (l-NAME) but not d-NAME. Increasing renal pelvic pressure produced similar increases in renal pelvic release of substance P before and during l-SMTC, from 5.9 ± 1.4 to 13.6 ± 4.2 pg/min before and from 4.9 ± to 12.6 ± 2.7 pg/min during l-SMTC. l-SMTC also prolonged the ARNA response to renal pelvic perfusion with substance P (3 μM) from 1.2 ± 0.2 to 5.6 ± 1.1 min ( P < 0.01, n = 9) without affecting the magnitude of the ARNA response. In conclusion: activation of NO may function as an inhibitory neurotransmitter regulating the activation of renal mechanosensory nerve fibers by mechanisms related to activation of substance P receptors.

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