scholarly journals N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

2020 ◽  
Author(s):  
Xinyu Yan ◽  
Han Han ◽  
Shizhen Zhang ◽  
Yanzhu Lu ◽  
Linghuan Ren ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tooth Movement ◽  
Orofacial Pain ◽  
Pain Modulation ◽  
Trigeminal Ganglia ◽  
Orphanin Fq ◽  
Pain Model ◽  
Calcitonin Gene ◽  
Agonist And Antagonist

Abstract Background: Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP.Methods: Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression.Results: Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG.Conclusions: N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

scholarly journals N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

2020 ◽  
Author(s):  
Xinyu Yan ◽  
Han Han ◽  
Shizhen Zhang ◽  
Yanzhu Lu ◽  
Linghuan Ren ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tooth Movement ◽  
Orofacial Pain ◽  
Pain Modulation ◽  
Trigeminal Ganglia ◽  
Orphanin Fq ◽  
Pain Model ◽  
Calcitonin Gene ◽  
Agonist And Antagonist

Abstract Background: Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP.Methods: Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression.Results: Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG.Conclusions: N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

scholarly journals N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

2020 ◽  
Author(s):  
Xinyu Yan ◽  
Han Han ◽  
Shizhen Zhang ◽  
Yanzhu Lu ◽  
Linghuan Ren ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tooth Movement ◽  
Orofacial Pain ◽  
Pain Modulation ◽  
Trigeminal Ganglia ◽  
Orphanin Fq ◽  
Pain Model ◽  
Calcitonin Gene ◽  
Agonist And Antagonist

Abstract Background: Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP. Methods: Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression.Results: Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG. Conclusions: N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

scholarly journals N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xinyu Yan ◽  
Han Han ◽  
Shizhen Zhang ◽  
Yanzhu Lu ◽  
Linghuan Ren ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tooth Movement ◽  
Orofacial Pain ◽  
Pain Modulation ◽  
Trigeminal Ganglia ◽  
Orphanin Fq ◽  
Pain Model ◽  
Calcitonin Gene ◽  
Agonist And Antagonist

Abstract Background Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP. Methods Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level was scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression. Results Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG. Conclusions N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

scholarly journals Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

2020 ◽  
Vol 21 (8) ◽  
pp. 2938
Author(s):  
Timea Aczél ◽  
Angéla Kecskés ◽  
József Kun ◽  
Kálmán Szenthe ◽  
Ferenc Bánáti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glial Cells ◽  
Orofacial Pain ◽  
Model Potential ◽  
Trigeminal System ◽  
Trigeminal Ganglia ◽  
Peripheral Sensitization ◽  
Satellite Glial Cells ◽  
Pain Model ◽  
Nociceptive Neurons

A large percentage of primary sensory neurons in the trigeminal ganglia (TG) contain neuropeptides such as tachykinins or calcitonin gene-related peptide. Neuropeptides released from the central terminals of primary afferents sensitize the secondary nociceptive neurons in the trigeminal nucleus caudalis (TNC), but also activate glial cells contributing to neuroinflammation and consequent sensitization in chronic orofacial pain and migraine. In the present study, we investigated the newest member of the tachykinin family, hemokinin-1 (HK-1) encoded by the Tac4 gene in the trigeminal system. HK-1 had been shown to participate in inflammation and hyperalgesia in various models, but its role has not been investigated in orofacial pain or headache. In the complete Freund’s adjuvant (CFA)-induced inflammatory orofacial pain model, we showed that Tac4 expression increased in the TG in response to inflammation. Duration-dependent Tac4 upregulation was associated with the extent of the facial allodynia. Tac4 was detected in both TG neurons and satellite glial cells (SGC) by the ultrasensitive RNAscope in situ hybridization. We also compared gene expression changes of selected neuronal and glial sensitization and neuroinflammation markers between wild-type and Tac4-deficient (Tac4-/-) mice. Expression of the SGC/astrocyte marker in the TG and TNC was significantly lower in intact and saline/CFA-treated Tac4-/- mice. The procedural stress-related increase of the SGC/astrocyte marker was also strongly attenuated in Tac4-/- mice. Analysis of TG samples with a mouse neuroinflammation panel of 770 genes revealed that regulation of microglia and cytotoxic cell-related genes were significantly different in saline-treated Tac4-/- mice compared to their wild-types. It is concluded that HK-1 may participate in neuron-glia interactions both under physiological and inflammatory conditions and mediate pain in the trigeminal system.

scholarly journals Behavioral Responses and Expression of Nociceptin/Orphanin FQ and Its Receptor (N/OFQ-NOP System) during Experimental Tooth Movement in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zhengyu Liao ◽  
Hu Long ◽  
Zhiping Song ◽  
Yuwei He ◽  
Wenli Lai
Keyword(s):  
Periodontal Ligament ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Behavioral Responses ◽  
Regulatory Function ◽  
Orphanin Fq ◽  
Protein Levels ◽  
Large Fluctuations ◽  
Experimental Tooth Movement

Objective. To determine behavioral testing after experimental tooth movement in rats and to explore the role of nociceptin/orphanin FQ and its receptor (the N/OFQ-NOP system) in pain induced by experimental tooth movement. Design. The mouth-wiping behavior of rats was assessed by studying behavioral responses after experimental tooth movement. The distribution of N/OFQ in the periodontal ligament, the trigeminal ganglion (TG), and the caudal one-third of the trigeminal subnucleus caudalis (Vc) was assessed by immunohistochemistry. The variations in N/OFQ expression in the TG and Vc were measured by Western blotting. The ongoing changes in the gene expression of the prepronociceptin gene and opioid receptor-like 1 receptor were assessed in the TG and Vc by real-time polymerase chain reaction (RT-PCR). Results. Overall, the mouth-wiping behavior increased significantly. The behavior first increased and then gradually decreased to a low level, showing cyclical variation. N/OFQ immunoreactivity increased in the periodontal ligament after tooth movement. ppN/OFQ mRNA and protein levels showed a time-dependent increase in the TG and were positively correlated with pain stimulus. NOP gene levels showed large fluctuations. In the Vc, the expression and changes in the N/OFQ-NOP system showed the opposite trend as those noted in TG and the periodontal membrane. Conclusion. The N/OFQ system may have a complex regulatory function in the pain induced by tooth movement and may be related to inflammation caused by orthodontic tooth movement and periodontal damage. The specific mechanism remains to be further studied.

scholarly journals The role of periodontal ASIC3 in orofacial pain induced by experimental tooth movement in rats

2015 ◽  
Vol 38 (6) ◽  
pp. 577-583 ◽  
Author(s):  
Meiya Gao ◽  
Hu Long ◽  
Wenqiang Ma ◽  
Lina Liao ◽  
Xin Yang ◽  
...  
Keyword(s):  
Tooth Movement ◽  
Orofacial Pain ◽  
Experimental Tooth Movement

PD-L1 and PD-1 expressed in trigeminal ganglia may inhibit pain in an acute migraine model

Cephalalgia ◽  
2019 ◽  
Vol 40 (3) ◽  
pp. 288-298
Author(s):  
Suming Shi ◽  
Yuhang Han ◽  
Dan Wang ◽  
Ping Guo ◽  
Jiali Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Calcitonin Gene Related Peptide ◽  
Trigeminal Ganglia ◽  
Acute Migraine ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Tnf Α ◽  
Immunofluorescence Labeling

Background Neurogenic inflammation, mediated by the activation of primary neurons, is thought to be an important factor in migraine pathophysiology. Programmed cell death ligand-1 (PD-L1) can suppress the immune response through the Programmed cell death-1 receptor. However, the role of PD-L1/PD-1 in migraine remains unclear. In this study we evaluated the expression and role of PD-L1/PD-1 in the trigeminal ganglia in an animal model of acute migraine. Methods Acute nitroglycerin induces acute mechanical hyperalgesia that can be used as a readout of migraine-like pain. We investigated the expression of PD-L1 and PD-1 in the trigeminal ganglia in a mouse model by means of immunofluorescence labeling, quantitative reverse transcription-polymerase chain reaction and western blotting. We explored the effects of PD-1 in a migraine model by the von Frey test and by analyzing the expression of calcitonin gene-related peptide, interleukin-1β (IL-1β), interleukin-18 (IL-18), Tumor Necrosis Factor-α (TNF-α), interleukin-6 (IL-6) and transient receptor potential vanilloid (TRPV4) after the intravenous injection of a PD-1 inhibitor. Results PD-L1 and PD-1 immunoreactivity were present in healthy trigeminal ganglia neurons. The mRNA levels of PD-L1 and PD-1 were significantly elevated 2 h, 4 h and 6 h after acute nitroglycerin treatment ( p < 0.05). The protein levels of PD-L1 were significantly increased 2 h, 4 h and 6 h after treatment, and PD-1 was significantly increased at 2 h and 6 h. The blockade of PD-1 increased acute nitroglycerin-induced hyperalgesia, and this effect was accompanied by a more significant increase in calcitonin gene-related peptide, IL-1β, TNF-α, IL-6 and IL-18 in the trigeminal ganglia. Conclusion These findings suggest that PD-L1 and PD-1 might inhibit migraine-like pain by downregulating CGRP and inflammatory factors in the trigeminal ganglia. The use of PD-L1 and PD-1 as analgesics should be further studied.

Aquaporin 4 expression on trigeminal satellite glial cells under normal and inflammatory conditions

2017 ◽  
Vol 16 (1) ◽  
pp. 183-184
Author(s):  
D. Riccio ◽  
G. Magni ◽  
S. Ceruti ◽  
L. Arendt-Nielsen ◽  
P. Gazerani
Keyword(s):  
Glial Cells ◽  
Trigeminal Ganglia ◽  
Sensory Ganglia ◽  
Satellite Glial Cells ◽  
Pain Model ◽  
Aqp4 Expression ◽  
Inflammatory Conditions ◽  
Trigeminal Neurons ◽  
Deficient Mice

AbstractAimsLimited information is currently available for the expression and role of Aquaporin 4 (AQP4) (AQ4) in the peripheral nervous system (PNS). It has been demonstrated that AQP4 is expressed in sensory ganglia. Immunohistochemistry has revealed that satellite glial cells (SGCs) surrounding the cell bodies of the primary afferent sensory neurons in these sensory ganglia exclusively express AQP4 at a considerably lower level than what is seen in astrocytes. The pathophysiological relevance of AQP4 in peripheral nociception; however, remains unclear. Hence, this study aimed at investigating AQP4 expression in trigeminal neurons and SGCs under normal and inflammatory conditions relevant to craniofacial pain conditions.MethodsRat trigeminal ganglia (TG) were isolated from adult male Sprague-Dawley rats subjected to a model of trigeminal inflammation evoked by unilateral complete Freund’s adjuvant (CFA) injection in temporomandibular joint. Immunohistochemistry was performed on TG sections of CFA-treated animals. NeuN and GS markers were used for identification of neurons and SGCs, respectively. AQP4 expression was investigated in both ipsilateral and contralateral TG sections. The study protocol was approved by the local ethics committee.ResultsCo-localization of NeuN-AQP4 and GS-AQP4 were identified in both ipsi and contralateral trigeminal ganglia of the CFA-treated rats. However, we did not detect any difference between the ipsi- and contralateral side in terms of alteration in AQP4 receptor expression.ConclusionsAQP4 was expressed both on trigeminal neurons and SGCs and CFA did not cause a remarkable change in AQP4 expression, when ipsilateral and contralateral TG of the test animals was compared. Previously, it has been shown that in a neuropathic pain model no difference is detectable between wild type and AQP4-deficient mice, for mechanical and thermal perception; however, in formalin pain model AQP4-deficient mice have higher thermal pain thresholds. Further investigation is required to clarify role of AQP4 in pain.

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