Activation of oxytocin receptor in the trigeminal ganglion attenuates orofacial ectopic pain attributed to inferior alveolar nerve injury

2020 ◽  
Author(s):  
Chao-Lan Huang ◽  
Fei Liu ◽  
Yan-Yan Zhang ◽  
Jiu Lin ◽  
Min Fu ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Trigeminal Ganglion ◽  
Inferior Alveolar Nerve ◽  
Oxytocin Receptor ◽  
Mechanical Hypersensitivity ◽  
Tnf Α ◽  
Whisker Pad ◽  
Pre Treatment ◽  
Spinal Trigeminal Nucleus Caudalis ◽  
Factor Α

Oxytocin receptor (OXTR), a G protein-coupled receptor, has been demonstrated to play a significant role in analgesia after activation by its canonical agonist, oxytocin (OXT) in the dorsal root ganglion (DRG). However, the role of OXTR in the trigeminal nervous system on the orofacial neuropathic pain is still little known. In the present study, we aimed to investigate the regulation effect and mechanism of OXTR in the trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis (SpVc) on orofacial ectopic pain induced by trigeminal nerve injury. Inferior alveolar nerve (IAN) was transected to establish trigeminal ectopic pain model. Von Frey filaments behavioral test demonstrated IAN transection (IANX) evoked mechanical hypersensitivity in the whisker pad since from day 1 to at least day 14 after surgery. In addition, administration of OXT (50 μM and 100 μM) into the TG attenuated the mechanical hypersensitivity induced by IANX, which was reversed by pre-treatment with L-368,899 (a selective antagonist of OXTR) into the TG. In addition, immunofluorescence (IF) showed the expression of OXTR in neurons in the TG and SpVc. Furthermore, western blot (WB) analysis indicated that the upregulated expression of OXTR, calcitonin gene-related peptide (CGRP), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the TG and SpVc after IANX was inhibited by the administration of OXT into the TG. And the inhibition effect of OXT on the expression of CGRP, IL-1β, and TNF-α was abolished by pre-application of L-368,899 into the TG.

scholarly journals TNF-α-Mediated RIPK1 Pathway Participates in the Development of Trigeminal Neuropathic Pain in Rats

2022 ◽  
Vol 23 (1) ◽  
pp. 506
Author(s):  
Jo Young Son ◽  
Jin Sook Ju ◽  
Yu Mi Kim ◽  
Dong Kuk Ahn
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Mechanical Allodynia ◽  
Inflammatory Responses ◽  
Inferior Alveolar Nerve ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Factor Α ◽  
Inferior Alveolar Nerve Injury

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) participates in the regulation of cellular stress and inflammatory responses, but its function in neuropathic pain remains poorly understood. This study evaluated the role of RIPK1 in neuropathic pain following inferior alveolar nerve injury. We developed a model using malpositioned dental implants in male Sprague Dawley rats. This model resulted in significant mechanical allodynia and upregulated RIPK1 expression in the trigeminal subnucleus caudalis (TSC). The intracisternal administration of Necrosatin-1 (Nec-1), an RIPK1 inhibitor, blocked the mechanical allodynia produced by inferior alveolar nerve injury The intracisternal administration of recombinant rat tumor necrosis factor-α (rrTNF-α) protein in naive rats produced mechanical allodynia and upregulated RIPK1 expression in the TSC. Moreover, an intracisternal pretreatment with Nec-1 inhibited the mechanical allodynia produced by rrTNF-α protein. Nerve injury caused elevated TNF-α concentration in the TSC and a TNF-α block had anti-allodynic effects, thereby attenuating RIPK1 expression in the TSC. Finally, double immunofluorescence analyses revealed the colocalization of TNF receptor and RIPK1 with astrocytes. Hence, we have identified that astroglial RIPK1, activated by the TNF-α pathway, is a central driver of neuropathic pain and that the TNF-α-mediated RIPK1 pathway is a potential therapeutic target for reducing neuropathic pain following nerve injury.

scholarly journals Optimization of Ultrasonic-Microwave Assisted Extraction and Hepatoprotective Activities of Polysaccharides from Trametes orientalis

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 147 ◽  
Author(s):  
Yi Zheng ◽  
Jue Cui ◽  
An-Hui Chen ◽  
Zhi-Min Zong ◽  
Xian-Yong Wei
Keyword(s):  
Elevated Serum ◽  
Alcohol Exposure ◽  
Raw Material ◽  
Microwave Assisted Extraction ◽  
Microwave Assisted ◽  
Assisted Extraction ◽  
Injury Model ◽  
Tnf Α ◽  
Pre Treatment ◽  
Factor Α

Ultrasonic-microwave assisted extraction (UMAE) of Trametes orientalis polysaccharides was optimized by response surface methodology. Hepatoprotective effects of a purified T. orientalis polysaccharide (TOP-2) were evaluated by alcohol-induced liver injury model mice. The optimal UMAE parameters were indicated as below: ratio of water to raw material 28 mL/g, microwave power 114 W, extraction time 11 min. The polysaccharides yield was 7.52 ± 0.12%, which was well consistent with the predicted value of 7.54%. Pre-treatment with TOP-2 effectively increased the liver index and spleen index in alcohol-treated mice. The elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of mice after alcohol exposure were inhibited by TOP-2 administration. The liver tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels have decreased significantly as a result of alcohol exposure, while pre-treatment with TOP-2 could mitigate these consequences. Furthermore, pre-treatment with TOP-2 could efficiently boost the superoxidase dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, and observably constrain the malondialdehyde (MDA) level. The findings suggest that TOP-2 might be useful for alleviating the alcohol-induced hepatotoxicity via its antioxidant and anti-inflammatory potential.

Effects of tumor necrosis factor α on leptin-sensitive intestinal vagal mechanoreceptors in the cat

2013 ◽  
Vol 91 (11) ◽  
pp. 941-950 ◽  
Author(s):  
Nathalie Quinson ◽  
Véronique Vitton ◽  
Michel Bouvier ◽  
Jean-Charles Grimaud ◽  
Anne Abysique
Keyword(s):  
Tumour Necrosis ◽  
Discharge Frequency ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Pre Treatment ◽  
Factor Α ◽  
Necrosis Factor

The involvement of tumour necrosis factor α (TNF-α) in inflammatory bowel disease (IBD) has been established, and anti-TNF-α has been suggested as a therapeutic approach for the treatment of these pathologies. We studied the effects of TNF-α on leptin-sensitive intestinal vagal units to determine whether TNF-α exerts its effects through the intestinal vagal mechanoreceptors and to investigate its interactions with substances regulating food intake. The activity of intestinal vagal mechanoreceptors was recorded via microelectrodes implanted into the nodose ganglion in anesthetized cats. TNF-α (1 μg, i.a.) increased the discharge frequency of leptin-activated units (type 1 units; P < 0.05) and had no effect on the discharge frequency of leptin-inhibited units (type 2 units). When TNF-α was administered 20 min after sulfated cholecystokinin-8 (CCK), its excitatory effects on type 1 units were significantly enhanced (P < 0.0001) and type 2 units were significantly (P < 0.05) activated. Pre-treatment with Il-1ra (250 μg, i.a.) blocked the excitatory effects of TNF-α on type 1 units whereas the excitatory effects of TNF-α administration after CCK treatment on type 2 units were not modified. The activation of leptin-sensitive units by TNF-α may explain, at least in part, the weight loss observed in IBD.

Acute Immunomodulatory Effects of Fentanyl and its Three New Analogues in Swiss Albino Mice

2017 ◽  
Vol 3 (1) ◽  
pp. 24 ◽  
Author(s):  
Shiv Kumar Yadav ◽  
Rahul Bhattacharya
Keyword(s):  
Pain Management ◽  
Opioid Receptor ◽  
Inflammatory Cytokines ◽  
Opioid Analgesic ◽  
Interleukin 10 ◽  
Acute Effect ◽  
Post Exposure ◽  
Tnf Α ◽  
Pre Treatment ◽  
Factor Α

Fentanyl is a potent synthetic opioid analgesic. However, due to its several limitations, new analogues are being synthesised for better pain management. We have earlier reported the synthesis and bio-efficacy of fentanyl and its eight new analogues (1-8) in mice. Among eight analogues tested, N-(1-(2-phenoxyethyl)-4-piperidinyl)propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) were found to be more effective and less toxic compared to fentanyl. Therapeutic efficacy of fentanyl and its analogues are known to be compromised due to many adverse effects, including alterations in the immune system. Therefore, the present study was undertaken to assess the acute effect of fentanyl and its three analogues (2, 5, and 6) on plasma levels of different pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and anti-inflammatory cytokines such as interleukin-10 (IL-10) at different time points. Mice were intraperitoneally treated with 0.50 LD50 of the compounds and cytokines were measured 1 h, 2 h, 4 h, and 24 h post-exposure. Compared to control, none of the treatments produced any change in TNF-α and IL-1β levels. However, IL-6 levels were significantly elevated between 1 h to 2 h post-exposure in fentanyl and analogue 2 treated groups. Further, IL-10 levels were found to be significantly increased in fentanyl, analogue 2, and 6 treated groups at 1 h and 2 h post-exposure. Pre-treatment of naltrexone (opioid receptor antagonist) blocked the effects of fentanyl, confirming that its effects were opioid receptor- dependent. However, effect of naltrexone on analogue 2 and 6 was not conclusively evidenced, indicating that immunomodulatory changes caused by the analogues could have some additional implications as well. The present study reveals undesirable effects of fentanyl and its new analogues on cytokines homeostasis, thereby limiting their use in pain management.

Expression of Sodium Channel SNS/PN3 and AnkyrinG mRNAs in the Trigeminal Ganglion after Inferior Alveolar Nerve Injury in the Rat

2000 ◽  
Vol 164 (2) ◽  
pp. 384-395 ◽  
Author(s):  
U. Bongenhielm ◽  
C.A. Nosrat ◽  
I. Nosrat ◽  
J. Eriksson ◽  
J. Fjell ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Nerve Injury ◽  
Trigeminal Ganglion ◽  
Inferior Alveolar Nerve ◽  
Inferior Alveolar Nerve Injury

Role of NF-κB in TNF-α-induced COX-2 Expression in Synovial Fibroblasts from Human TMJ

2007 ◽  
Vol 86 (4) ◽  
pp. 363-367 ◽  
Author(s):  
J. Ke ◽  
X. Long ◽  
Y. Liu ◽  
Y.F. Zhang ◽  
J. Li ◽  
...  
Keyword(s):  
Synovial Fibroblasts ◽  
Nuclear Factor Κb ◽  
Mobility Shift ◽  
Tnf Α ◽  
Cox 2 ◽  
Mobility Shift Assay ◽  
Pre Treatment ◽  
Factor Α ◽  
Necrosis Factor

In the temporomandibular joint (TMJ) synovium, cyclo-oxygenase-2 (COX-2) expression has been believed to be directly related to joint pain and synovitis. Here we investigated the role of Nuclear Factor κB (NF-κB) in the regulation of COX-2 expression in synovial fibroblasts from human TMJ induced by tumor necrosis factor-α (TNF-α). By reverse-transcriptase/polymerase chain-reaction (RT-PCR) and Western blotting analysis, TNF-α induced a dose- and time-dependent increase in COX-2 expression. Electrophoretic mobility shift assay (EMSA) revealed that transient NF-κB activation in the COX-2 promoter was triggered by TNF-α. In parallel with transient NF-κB activation, the rapid translocation of NF-κB, particularly the p65 subunit, from the cytoplasm into the nucleus was demonstrated. Pre-treatment with pyrolidine dithiocarbamate (PDTC), one of the NF-κB inhibitors, prevented binding to the COX-2 promoter and expression of COX-2 protein in response to TNF-α. These findings indicate that activation of NF-κB is responsible for TNF-α-induced COX-2 expression in synovial fibroblasts from the TMJ.

scholarly journals Characterization of Garden Cress Mucilage and its Prophylactic Effect Against Indomethacin-Induced Enter-Colitis in Rats

2021 ◽  
Vol 11 (6) ◽  
pp. 13911-13923
Keyword(s):  
Antioxidant Activity ◽  
Oral Administration ◽  
Oil Industry ◽  
Garden Cress ◽  
Industry Waste ◽  
Tnf Α ◽  
Pre Treatment ◽  
Factor Α ◽  
Necrosis Factor

The utilization of industrial waste such as oil industry waste in the production of natural nutraceuticals is a very beneficial issue. So, the current study was established to assess the characteristics of the mucilage extracted from garden cress seeds meal and evaluate its efficacy in the protection against enter-colitis. A defatted powder meal of garden cress seeds was dissolved in distilled water to extract the mucilage either by heating at 80°C or by ultrasonication. Functional and chemical characteristics of the two types of mucilage were assessed. Rats received oral administration of the mucilage extracted by ultrasonication, which afforded the most promising antioxidant activity, for two weeks before and during the 7 days of oral administration by indomethacin (6 mg/kg/day). Compared with the rats injected with indomethacin without the pre-treatment with the mucilage, rats administrated with the mucilage showed a decrease in the erythrocyte sedimentation rate (ESR), intestinal tumor necrosis factor-α (TNF-α), and plasma lactate dehydrogenase (LDH) activity. Also, rats administered with the mucilage recorded lower intestinal malodealdehyde (MDA) and higher intestinal reduced glutathione (GSH) compared to those of rats injected with indomethacin without the pre-treatment with the mucilage. It can be concluded that the mucilage extracted from garden cress seeds meal can be considered as a natural nutraceutical with potent antioxidant activity exhibiting protective effect against enter-colitis.

scholarly journals Oxytocin-Dependent Regulation of TRPs Expression in Trigeminal Ganglion Neurons Attenuates Orofacial Neuropathic Pain following Infraorbital Nerve Injury in Rats

2020 ◽  
Vol 21 (23) ◽  
pp. 9173
Author(s):  
Masatoshi Ando ◽  
Yoshinori Hayashi ◽  
Suzuro Hitomi ◽  
Ikuko Shibuta ◽  
Akihiko Furukawa ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Trigeminal Ganglion ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Infraorbital Nerve ◽  
Transient Receptor Potential Vanilloid ◽  
Withdrawal Threshold ◽  
Whisker Pad ◽  
Ganglion Neurons

We evaluated the mechanisms underlying the oxytocin (OXT)-induced analgesic effect on orofacial neuropathic pain following infraorbital nerve injury (IONI). IONI was established through tight ligation of one-third of the infraorbital nerve thickness. Subsequently, the head withdrawal threshold for mechanical stimulation (MHWT) of the whisker pad skin was measured using a von Frey filament. Trigeminal ganglion (TG) neurons innervating the whisker pad skin were identified using a retrograde labeling technique. OXT receptor-immunoreactive (IR), transient receptor potential vanilloid 1 (TRPV1)-IR, and TRPV4-IR TG neurons innervating the whisker pad skin were examined on post-IONI day 5. The MHWT remarkably decreased from post-IONI day 1 onward. OXT application to the nerve-injured site attenuated the decrease in MHWT from day 5 onward. TRPV1 or TRPV4 antagonism significantly suppressed the decrement of MHWT following IONI. OXT receptors were expressed in the uninjured and Fluoro-Gold (FG)-labeled TG neurons. Furthermore, there was an increase in the number of FG-labeled TRPV1-IR and TRPV4-IR TG neurons, which was inhibited by administering OXT. This inhibition was suppressed by co-administration with an OXT receptor antagonist. These findings suggest that OXT application inhibits the increase in TRPV1-IR and TRPV4-IR TG neurons innervating the whisker pad skin, which attenuates post-IONI orofacial mechanical allodynia.

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