scholarly journals Nociceptive Sensory Fibers Drive Interleukin-23 Production in a Murine Model of Psoriasis via Calcitonin Gene-Related Peptide

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuan Zhang ◽  
Jiali Cao ◽  
Siqi Zhao ◽  
Xutong Yang ◽  
Jie Dong ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Γδ T Cells ◽  
Receptor Potential ◽  
Calcitonin Gene Related Peptide ◽  
Sensory Innervation ◽  
Transient Receptor Potential Vanilloid ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Sensory Denervation ◽  
Interleukin 23

Neuroimmunity is involved in the pathogenesis of psoriasis, but the mechanism underlying the interaction between the nervous system and the interleukin (IL)-23/IL-17 immune axis is yet unclear. This study reveals the essential role of the sensory neuron-derived calcitonin gene-related peptide (CGRP) in imiquimod (IMQ)-induced expression of IL-23. First, we show that the increased nociceptive behavior was consistent with the development of psoriasiform dermatitis, which requires intact sensory innervation. Systemic ultrapotent Transient receptor potential vanilloid 1 (TRPV1) agonist (resiniferatoxin, RTX) treatment-induced sensory denervation resulted in a significant decrease in IL-23 expression in this model, while the recombinant IL-23 treatment induced IL-17A expression was intact after RTX treatment. In addition, IMQ exposure induced a transient increase in CGRP expression in the dorsal root ganglion. The neuron-derived CGRP expression was completely abolished by sensory denervation, thereby downregulating IL-23 expression, which could be reversed through the introduction of CGRP into the denervated dorsal skin. Our results suggest that nociceptive sensory neurons may drive the production of IL-23, resulting in IL-17A production from γδ T cells via the neuropeptide CGRP in the pathology of psoriasis.

Ghrelin attenuated hyperalgesia induced by chronic nitroglycerin: CGRP and TRPV1 as targets for migraine management

Cephalalgia ◽  
2017 ◽  
Vol 38 (11) ◽  
pp. 1716-1730 ◽  
Author(s):  
Fereshteh Farajdokht ◽  
Gisou Mohaddes ◽  
Dariush Shanehbandi ◽  
Pouran Karimi ◽  
Shirin Babri
Keyword(s):  
Mrna Expression ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Calcitonin Gene Related Peptide ◽  
Transient Receptor Potential Vanilloid ◽  
Conditioned Place Aversion ◽  
Trigeminovascular System ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Transient Receptor

Background According to the neurovascular theory of migraine, activation of the trigeminovascular system contributes to the development of migraine. This study examined the effects of chronic intraperitoneal ghrelin (150 µg/kg) treatment on the development of chronic migraine induced by intermittent injection of nitroglycerin 10 mg/kg. Methods Baseline and post-drug (2 h following nitroglycerin injection) mechanical and thermal sensitivity were assessed by von Frey hair and tail immersion tests, respectively on days 1, 3, 5, 7, 9 and 11. Moreover, we investigated the effect of ghrelin treatment on nitroglycerin-induced aversive behavior by using a two-chamber conditioned place aversion paradigm. At the end of behavioral testing, on day 11, animals were sacrificed and plasma concentration of calcitonin gene-related peptide was measured using a rat-specific enzyme-linked immunosorbent assay kit. Also, real time polymerase chain reaction was used to quantify mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid 1 in the trigeminal ganglion. Results Our results indicated that nitroglycerin activated the trigeminovascular system, which was reflected by mechanical and thermal hypersensitivity and elevation of mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid-1, as migraine markers, and plasma calcitonin gene-related peptide levels. Moreover, chronic nitroglycerin injection induced conditioned place aversion and body weight loss. Nevertheless, ghrelin modulated nitroglycerin-triggered changes in transient receptor potential vanilloid-1 and calcitonin gene-related peptide expression, and mitigated nitroglycerin-induced hyperalgesia. Conclusion These results provide the first convincing evidence that ghrelin has a modulating effect on central sensitization induced by chronic intermittent nitroglycerin, and its antinociceptive effect may be related to a reduction of these factors in the trigeminal ganglion.

Die Beteiligung peripherer Rezeptoren und Neurotransmitter an den antihyperalgetischen Effekten der Akupunktur: ein aktuelles Review

2021 ◽  
Vol 02 (03) ◽  
pp. 191-192
Keyword(s):  
Transient Receptor Potential ◽  
Web Of Science ◽  
Receptor Potential ◽  
Calcitonin Gene Related Peptide ◽  
Corticotropin Releasing Factor ◽  
Transient Receptor Potential Vanilloid ◽  
Substanz P ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Transient Receptor

Der vorliegende Artikel analysiert die aktuellen präklinischen Studien zur Beteiligung peripherer Rezeptoren und Neuromediatoren an den antihyperalgetischen Effekten der Akupunktur. Die Datenbanken von PubMed, Scopus und Web of Science wurden mittels einer erweiterten Reviewmethode durchsucht. Anhand einer vordefinierten Suchstrategie wurden die präklinischen Artikel ausgewählt, welche die Rolle peripherer Rezeptoren und Neuromediatoren auf die schmerzkontrollierenden Effekte der Akupunktur bei Ratten und Mäusen untersuchten. Die Suche ergab 456 Artikel, von denen 29 die Einschlusskriterien der Studie erfüllten. Die ausgewählten Artikel behandelten folgende periphere Rezeptoren: Opioid- (n=9), Adenosin- (n=5), Cannabinoid- (n=5), Transient-Receptor-Potential-Vanilloid- (TRPV; n=3), Histamin- (n=2), adrenerge (n=1), muskarinerge (n=1), Corticotropin-releasing Factor (CRF)-(n=2), IL-1- (n=1) und Endothelinrezeptoren (n=1). Folgende Neuromediatoren korrelierten mit peripheren Effekten der Schmerzkontrolle: Opioidpeptide (n=4), Adenosin (n=3), Histamin (n=1), Substanz P (n=1), Calcitonin Gene-related Peptide (CGRP) (n=1), Anandamid (n=1), NO (n=1) sowie Noradrenalin (n=1).

Uterine Cervical Afferents in Thoracolumbar Dorsal Root Ganglia Express Transient Receptor Potential Vanilloid Type 1 Channel and Calcitonin Gene–related Peptide, but Not P2X3 Receptor and Somatostatin

2006 ◽  
Vol 104 (4) ◽  
pp. 651-657 ◽  
Author(s):  
Chuanyao Tong ◽  
Dawn Conklin ◽  
Brittany B. Clyne ◽  
Jennifer D. Stanislaus ◽  
James C. Eisenach
Keyword(s):  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Calcitonin Gene Related Peptide ◽  
Transient Receptor Potential Vanilloid ◽  
P2x3 Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Transient Receptor

Background Little is known regarding the phenotype of afferents that innervate the uterine cervix. Chronic estrogen sensitizes uterine cervical afferents to mechanical distension, but whether this reflects changes in afferent neurotransmitter or excitatory ion channel expression is unknown. The authors used immunocytochemistry to characterize uterine cervical afferents and the effects of estrogen on them. Methods Fluorogold was injected into the uterine cervix of intact rats (n = 7) and those with ovariectomy alone (n = 9) or with estrogen supplementation (n = 8). Bilateral dorsal root ganglia at T12-L2 were removed and immunostained for transient receptor potential vanilloid type 1 (TRPV1), P2X3 receptor, calcitonin gene-related peptide, and somatostatin. The proportion of fluorogold-traced dorsal root ganglion neurons expressing each of these markers was compared with untraced neurons. Results Most fluorogold-traced cells were found at L1 (> 55%) and were of small diameter (24 microm). TRPV1 expression was similar between traced and untraced cells, except the estrogen treatment increased TRPV1 expression in traced cells. Calcitonin gene-related peptide expression was greater in traced than in untraced cells, with no effect of experimental treatment. No traced cells expressed the P2X3 receptor or somatostatin, although each of these was present in untraced cells. Conclusion Uterine cervical afferents in the hypogastric nerve express TRPV1, an important nociceptive channel, which may play a role in estrogen-induced sensitization of cervical afferents. High expression of calcitonin gene-related peptide suggests a sensory and efferent role for this peptide. In contrast to other viscera, these afferents do not express somatostatin or P2X3 receptor, indicating a unique phenotype of these C fibers.

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