Preliminary study of calcium homeostasis modulator 1 involved in trigeminal neuralgia

2020 ◽  
Author(s):  
Yi Liu ◽  
Keji Li ◽  
Dong Huang ◽  
Xuebin Yan
Keyword(s):  
Trigeminal Neuralgia ◽  
Calcium Homeostasis ◽  
Pain Threshold ◽  
Sham Group ◽  
Ruthenium Red ◽  
Infraorbital Nerve ◽  
Control Group ◽  
Skin Area ◽  
Spinal Nucleus ◽  
Mechanical Pain Threshold

Abstract Background: The aim of this study was to observe the changes in the expression of calcium homeostasis modulator 1 (CALHM1) in the trigeminal nucleus of the trigeminal neuralgia (TN) rats with the infraorbital nerve-chronic constrictive nerve injury (ION-CCI) and to explore the role of CALHM1 in TN.Methods: Thirty SD rats were randomly assigned to 5 groups, namely normal control group (Control group), sham operation group (Sham group), TN model group (ION-CCI group), ruthenium red treatment group (RuR group) and control group of ruthenium red (NS group), with 6 rats in each group. An animal model was established by loosely ligating the rat's infraorbital nerve with a chrome gut in the ION-CCI group, while mice in the sham group were only exposed to the nerve and did not receive ligature. The rats in the RuR group were intraperitoneally injected with 0.5 mg/kg of CALHM1 inhibitor ruthenium red on the 9th day after the infraorbital nerve ligation, while the rats in NS group were intraperitoneally injected with an equal volume of normal saline on the 9th day after surgery. All experimental rats were tested for pain behavior 1 day before surgery, 1, 3, 5, 7, 9, 11 and 14 days after surgery, including the mechanical pain threshold of VonFrey filament in the trigeminal innervated skin area and number of faces captured in video recording. The expression of CALHM1 in the trigeminal spinal nucleus was detected on the 15th day after operation in all experimental groups.Results: The expression of CALHM1 in the trigeminal spinal nucleus of the ION-CCI group was significantly higher than that of control group and sham group on the 3rd and 15th day after modeling. The intraperitoneal injection of CALHM1 inhibitor ruthenium red increased the mechanical pain threshold of ION-CCI rats and significantly reduced the number of scratches, but did not change the expression of CALHM1 in the trigeminal spinal nucleus.Conclusion: The expression of CALHM1 protein in the trigeminal spinal nucleus is involved in the central sensitization of TN pain, which can be induced by elevated expression. Moreover, the hyperalgesia can be improved by using CALHM1 inhibitor.

scholarly journals c-Abl-p38α signaling pathway mediates dopamine neuron loss in trigeminal neuralgia

2020 ◽  
Vol 16 ◽  
pp. 174480692093085 ◽  
Author(s):  
Jia Fu ◽  
Guo Mu ◽  
Ling Qiu ◽  
Jiaomei Zhao ◽  
Cehua Ou
Keyword(s):  
Trigeminal Neuralgia ◽  
Signaling Pathway ◽  
Dopaminergic Neurons ◽  
Pain Threshold ◽  
Kinase Inhibitor ◽  
Dopamine Neurons ◽  
Infraorbital Nerve ◽  
Neuron Death ◽  
Nonreceptor Tyrosine Kinase ◽  
Mechanical Pain Threshold

Trigeminal neuralgia is a common neuropathic pain in the head and face. The pathogenesis of trigeminal neuralgia is complex, and so far, the pathogenesis of trigeminal neuralgia involving peripheral and central nervous inflammation theory has not been explained clearly. The loss of dopamine neurons in striatum may play an important role in the development of trigeminal nerve, but the reason is not clear. C-Abl is a nonreceptor tyrosine kinase, which can be activated abnormally in the environment of neuroinflammation and cause neuron death. We found that in the rat model of infraorbital nerve ligation trigeminal neuralgia, the pain threshold decreased, the expression of c-Abl increased significantly, the downstream activation product p38 was also activated abnormally and the loss of dopamine neurons in striatum increased. When treated with imatinib mesylate (STI571), a specific c-Abl family kinase inhibitor, the p38 expression was decreased and the loss of dopaminergic neurons was reduced. The mechanical pain threshold of rats was also improved. In conclusion, c-abl-p38 signaling pathway may play an important role in the pathogenesis of trigeminal neuralgia, and it is one of the potential targets for the treatment of trigeminal neuralgia.

scholarly journals Inhibitory Effects of Palmatine on P2X7 Receptor Expression in Trigeminal Ganglion and Facial Pain in Trigeminal Neuralgia Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Cancan Yin ◽  
Wenhao Shen ◽  
Mingming Zhang ◽  
Lequan Wen ◽  
Ruoyu Huang ◽  
...  
Keyword(s):  
Trigeminal Neuralgia ◽  
Trigeminal Ganglion ◽  
P2x7 Receptor ◽  
Facial Pain ◽  
Pain Threshold ◽  
Receptor Expression ◽  
Infraorbital Nerve ◽  
Distribution Area ◽  
Tnf Α ◽  
Mechanical Pain Threshold

Trigeminal Neuralgia (TN) refers to recurrent severe paroxysmal pain in the distribution area of the trigeminal nerve, which seriously affects the quality of life of patients. This research applied the chronic constriction injury of the infraorbital nerve (CCI—ION) approach to induce an animal model of TN in rats. The mechanical pain threshold of each group of rats was determined postoperatively; the expression of P2X7 receptor in trigeminal ganglion (TG) was assessed by qRT-PCR, immunofluorescence and Western blot; and the changes of the proinflammatory cytokines IL-1β and TNF-α in serum of rats were detected by ELISA. The results showed that the administration of palmatine in the TN rats could reduce the mechanical pain threshold, significantly decrease the expression of P2X7 receptor in TG, and lower the serum concentrations of IL-1β and TNF-α, compared to the sham group. In addition, the phosphorylation level of p38 in TG of TN rats was significantly decreased after treatment with palmatine. Likewise, inhibition of P2X7 expression by shRNA treatment could effectively counteract the adversary changes of pain sensitivity, IL-1β and TNF-α production, and p38 phosphorylation in TN rats. Our data suggest that palmatine may alleviate mechanical facial pain in TN rats possibly by reducing the expression of P2X7 receptor in TG of TN rats, which may be attributable to inhibiting p38 phosphorylation and reducing the release of IL-1β and TNF-α.

scholarly journals The Effect and Possible Mechanism of Intradiscal Injection of Simvastatin in the Treatment of Discogenic Pain in Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiaodong Huang ◽  
Changkun Zheng ◽  
Weiheng Wang ◽  
Xiaojian Ye ◽  
Chia-Ying Lin ◽  
...  
Keyword(s):  
Pain Threshold ◽  
Intervertebral Disk ◽  
Control Group ◽  
Discogenic Pain ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration ◽  
Tnf Α ◽  
Intradiscal Injection ◽  
Mechanical Pain Threshold ◽  
Cold Sensing

To study the effect of intradiscal injection of simvastatin on discogenic pain in rats and its possible mechanism, 30 adult female rats were used in this experiment. Twenty rats were randomly divided into sham operation group (Control group), intervertebral disk degeneration group (DDD group), intervertebral disk degeneration + hydrogel group (DDD + GEL group), and intervertebral disk degeneration + simvastatin group (DDD + SIM group). The mechanical pain threshold and cold sensation in rats were measured. The contents of NF-kappa B1, RelA, GAP43, SP, CGRP, TRPM 8, IL-1β, and TNF-α in the intervertebral disk (IVD), the corresponding contents of dorsal root ganglion (DRG) and plantar skin GAP43 and TRPM 8 were quantitatively detected by PCR. The corresponding IVDs were stained to detect their degeneration. There was no significant difference in the mechanical pain threshold between the groups at each time point. From the first day to the 8th week after surgery, the cold-sensing response of the DDD group was significantly higher than that of the Control group (P < 0.05). At 7 and 8 weeks postoperatively, the cold-sensing response of the DDD + SIM group was significantly lower than that of the DDD + GEL group (P < 0.05). The levels of NF-κB1, RelA, GAP43, SP, CGRP, TRPM8, IL-1β, and TNF-α in the IVD of DDD + SIM group were significantly lower than those in DDD group (P < 0.05). The content of GAP43 and TRPM8 in rat plantar skin decreased significantly and TRPM8 in DRG decreased significantly (P < 0.05).

scholarly journals Botulinum neurotoxin type-A when utilized in animals with trigeminal sensitization induced a antinociceptive effect

2016 ◽  
Vol 74 (6) ◽  
pp. 462-469 ◽  
Author(s):  
Elcio J Piovesan ◽  
Michael Oshinsky ◽  
Stephen Silberstein ◽  
Pedro Andre Kowacs ◽  
Edison Matos Novak ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Botulinum Neurotoxin ◽  
Sham Group ◽  
Saline Solution ◽  
Antinociceptive Effect ◽  
Isotonic Saline ◽  
Type A ◽  
Infraorbital Nerve ◽  
Control Group ◽  
Botulinum Neurotoxin Type A

ABSTRACT Purpose of the study was evaluate the possible antinociceptive effect of botulinum neurotoxin type-A (BoNT/A) in an experimental model of trigeminal neuralgia. Method Neuropathic pain was induced by surgical constriction of the infraorbital nerve in rats. A control group underwent a sham procedure consisting of surgical exposure of the nerve. Subgroups of each group received either BoNT/A or isotonic saline solution. The clinical response was assessed with the -20°C test. Animals that underwent nerve constriction developed sensitization; the sham group did not. Results The sensitization was reversed by BoNT/A treatment evident 24 hours following application. Pronociceptive effect was observed in the sham group following BoNT/A. Conclusion BoNT/A has an antinociceptive effect in sensitized animals and a pronociceptive effect in non-sensitized animals.

scholarly journals An Effective Phytoconstituent Aconitine: A Realistic Approach for the Treatment of Trigeminal Neuralgia

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Dilek Çankal ◽  
Esra Küpeli Akkol ◽  
Yeliz Kılınç ◽  
Mert İlhan ◽  
Raffaele Capasso
Keyword(s):  
Spinal Cord ◽  
Trigeminal Neuralgia ◽  
Motor Coordination ◽  
Infraorbital Nerve ◽  
Control Group ◽  
Albino Rats ◽  
Dependent Manner ◽  
Significant Difference ◽  
Wistar Albino Rats ◽  
Dose Dependent

Trigeminal neuralgia pain remains a challenge to treat. Natural compounds may be promising options for relieving pain. This study was aimed at investigating the effects of aconitine in a rat model of trigeminal neuralgia pain. Infraorbital nerve chronic constriction injury was performed in adult Wistar Albino rats. After the neuropathic pain developed, the rats were assigned to one of the treatment groups: carbamazepine 40 or 80 mg/kg; aconitine 0.25, 0.50, or 0.75 mg/kg; or saline injection (control group). Behavioral testing with von Frey filaments and the rotarod test were carried out before the surgical procedure and on the 24th to 29th postoperative days. Following the completion of tests, ipsilateral and contralateral spinal cords were harvested for Western blot analyses to assess NR-1 protein expression. ANOVA followed by Mann-Whitney U test was performed for the statistical analyses. P values of <0.05 were considered significant. Aconitine significantly reduced mechanical sensitivity in a dose-dependent manner. A significant reduction in motor coordination was noted for the higher doses of aconitine which was similar with the 40 and 80 mg/kg doses of carbamazepine. NR-1 expression was reduced in the ipsilateral spinal cord, whereas no significant difference was noted between the groups in the expression of NR-1 in the contralateral spinal cord. Aconitine had a significant pain relieving effect, which was similar to carbamazepine, in a dose-dependent manner. Aconitine may be an alternative pharmacological agent for the control of trigeminal neuralgia pain.

scholarly journals Clinically Meaningful Interpretation of Quantitative Sensory Testing As a Measure of Pain Sensitivity in Patients with Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 526-526
Author(s):  
Amanda M Brandow ◽  
Rebecca Farley ◽  
Julie A. Panepinto
Keyword(s):  
Pain Sensitivity ◽  
Pain Threshold ◽  
Control Group ◽  
Prior History ◽  
Heat Pain ◽  
Healthy Controls ◽  
Cold Pain ◽  
Heat Pain Threshold ◽  
Mechanical Pain Thresholds ◽  
Mechanical Pain Threshold

Abstract Patients with sickle cell disease (SCD) display hypersensitivity to thermal and/or mechanical stimuli compared to healthy controls when assessed with quantitative sensory testing (QST) suggesting impaired pain sensitivity. Impaired pain sensitivity is present when a defined stimulus (cold, heat, mechanical) produces exaggerated pain in a patient compared to healthy controls and suggests pain processing abnormalities in the peripheral and/or central nervous system. Existing studies report significant differences in mean/median thermal and/or mechanical pain thresholds between SCD patients and healthy controls. However, for clinical purposes it is important to understand if an individual patient meets criteria for impaired pain sensitivity. To date, thresholds above or below which a patient is defined as having impaired pain sensitivity have not been established in pediatric SCD patients. We sought to: 1) define thresholds for impaired cold, heat, and mechanical pain sensitivity in SCD patients ages ≥7 years and 2) determine the proportion of SCD patients meeting criteria for impaired pain sensitivity with each testing modality. Our secondary objective was to compare age, gender and prior history of pain between patients with and without impaired pain sensitivity. We conducted a cross-sectional study of SCD patients and healthy African American controls ages ≥ 7 years. Using QST we assessed cold, heat, and mechanical pain thresholds via the method of limits on the thenar eminence of the non-dominant hand and lateral dorsum of foot (randomized). Our primary outcome was threshold for impaired pain sensitivity defined as: 1) cold pain threshold that was one standard deviation (SD) above median cold pain threshold in the control group; 2) heat pain threshold that was one SD below median heat pain threshold in the control group; 3) mechanical pain threshold that was one SD below median mechanical pain threshold in the control group. Data were skewed so bootstrap resampling was used to obtain the 95% CI for the median that is congruent with the SD of the median. Mann-Whitney Test and Pearson Chi-square were used to compare age, gender, and prior history of pain (total number of lifetime emergency department visits and/or hospitalizations) between those with and without impaired pain sensitivity. A total of 55 SCD patients and 57 African American controls completed QST. There were no differences in mean±SD age (15.4±6.3 vs. 16.3±10.2 yrs, p=0.59) or gender (60% vs. 56% female, p=0.68) between groups. SCD genotypes were: 67% SS, 18% SC, 11% Sβ+ thal, 4% other. Table 1 displays thresholds for impaired pain sensitivity and proportions of SCD patients meeting criteria for impaired pain sensitivity. We found 21.8% (n=12) of SCD patients had impaired pain sensitivity with all 3 testing modalities and the majority (81.8%, n=45) had impaired pain sensitivity with one or more testing modalities. Only 18.2% (n=20) had no evidence of impaired pain sensitivity. There was no difference in median age, gender, or median number of pain encounters between those with and without impaired pain sensitivity (15 (IQR 10.5-19) vs. 13.5 yrs (IQR 11-21.5), p=0.939; 60% female in both groups; number of pain encounters: 9 (IQR 4-23.5) vs. 3 (IQR 0.25-19.8), p=0.132). Determining a threshold for impaired pain sensitivity is clinically meaningful. Using QST data, we established thresholds for impaired cold, heat and mechanical pain sensitivity. Based on these thresholds, almost a quarter of SCD patients were impaired in all 3 modalities tested and the majority were impaired in at least one modality. Impaired cold pain sensitivity was the most common finding supporting epidemiological data that increased numbers of pain events are associated with colder temperatures. If used clinically, QST could serve as a screening tool to phenotype SCD pain, guide further evaluation of the etiology of pain, guide treatment decisions, or serve as an outcome for an intervention aimed at altering pain sensitivity. Table 1. Thresholds for Impaired Pain Sensitivity and Proportion of SCD Patients with Impaired Pain Sensitivity (n=55) Threshold* Proportion Impaired Hand Cold Pain Threshold >17.01ºC 63.6% (n=35) Heat Pain Threshold <43.91ºC 60% (n=33) Mechanical Pain Threshold <4.42 g 41.8% (n=23) Foot Cold Pain Threshold >21.75ºC 58.2% (n=32) Heat Pain Threshold <42.39ºC 40% (n=22) Mechanical Pain Threshold <7.29 g 54.5% (n=30) *1 SD from Control Median Disclosures Brandow: NIH, ASH: Research Funding. Panepinto:HRSA, NIH: Research Funding; NKT Therapeutics, Inc: Consultancy.

scholarly journals Nav1.7 via Promotion of ERK in the Trigeminal Ganglion Plays an Important Role in the Induction of Pulpitis Inflammatory Pain

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Shukai Sun ◽  
Jiangxing Sun ◽  
Wenkai Jiang ◽  
Wei Wang ◽  
Longxing Ni
Keyword(s):  
Trigeminal Ganglion ◽  
Inflammatory Pain ◽  
Pain Threshold ◽  
Expression Levels ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Pulp Exposure ◽  
Mechanical Pain Threshold ◽  
Hematoxylin Eosin ◽  
Inhibitor Dose

The trigeminal ganglion (TG) refers to sensory neurons bodies that innervate the spinal cord and peripheral axons that innervate teeth. The tetrodotoxin-sensitive sodium (NA) channels (Nav1.7) play important roles in the pathophysiology of pain. In this study, we investigated the TG expression of Nav1.7 and extracellular signal-regulated kinase (ERK) in a rat model of pulpitis to explore the correlation between these channels and inflammatory pain. Pulpitis was confirmed by hematoxylin-eosin staining. In this study, we demonstrated that the reflex of rats to mechanical stimulation increases after pulp exposure and that the exposed rat molar pulp can upregulate the expression of Nav1.7 and ERK in the rat TG. Three days after rat pulp exposure, the expression levels of the two ion channels in the TG increased. TG target injection of PF04856264, a Nav1.7 inhibitor, dose-dependently increased the mechanical pain threshold and was able to inhibit ERK expression. TG target injection of PD98059, an ERK inhibitor, dose-dependently increased the mechanical pain threshold. These factors simultaneously resulted in the highest production. In this study, with the established link to inflammatory pain, we found that Nav1.7 and ERK both play important roles in the induction of inflammatory pain caused by pulpitis. We also found a correlation between the expression levels of Nav1.7 and ERK and the degree of inflammatory pain. Furthermore, ERK signaling pathways were promoted by the Nav1.7 in TG after pulpitis.

Evaluation of endorphin content in the CSF of patients with trigeminal neuralgia before and after Gasserian ganglion thermocoagulation

1981 ◽  
Vol 55 (6) ◽  
pp. 935-937 ◽  
Author(s):  
Giuseppe Salar ◽  
Salvatore Mingrino ◽  
Marco Trabucchi ◽  
Angelo Bosio ◽  
Carlo Semenza
Keyword(s):  
Cerebrospinal Fluid ◽  
Trigeminal Neuralgia ◽  
Control Group ◽  
Gasserian Ganglion ◽  
Content Type ◽  
Group Of Seven ◽  
Idiopathic Trigeminal Neuralgia ◽  
Significant Difference ◽  
Before And After ◽  
Fine Print

✓ The β-endorphin content in cerebrospinal fluid (CSF) was evaluated in 10 patients with idiopathic trigeminal neuralgia during medical treatment (with or without carbamazepine) and after selective thermocoagulation of the Gasserian ganglion. These values were compared with those obtained in a control group of seven patients without pain problems. No statistically significant difference was found between patients suffering from trigeminal neuralgia and those without pain. Furthermore, neither pharmacological treatment nor surgery changed CSF endorphin values. It is concluded that there is no pathogenetic relationship between trigeminal neuralgia and endorphins.

scholarly journals Effects of Electroacupuncture on Pain Threshold of Laboring Rats and the Expression of Norepinephrine Transporter andα2 Adrenergic Receptor in the Central Nervous System

2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Qianli Tang ◽  
Qiuyan Jiang ◽  
Suren R. Sooranna ◽  
Shike Lin ◽  
Yuanyuan Feng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adrenergic Receptor ◽  
Pain Threshold ◽  
Norepinephrine Transporter ◽  
Control Group ◽  
Tail Flick ◽  
Pregnant Rats ◽  
Tail Flick Test ◽  
The Central Nervous System

To observe the effects of electroacupuncture on pain threshold of laboring rats and the expression of norepinephrine transporter andα2 adrenergic receptor in the central nervous system to determine the mechanism of the analgesic effect of labor. 120 pregnant rats were divided into 6 groups: a control group, 4 electroacupuncture groups, and a meperidine group. After interventions, the warm water tail-flick test was used to observe pain threshold. NE levels in serum, NET, andα2AR mRNA and protein expression levels in the central nervous system were measured. No difference in pain threshold was observed between the 6 groups before intervention. After intervention, increased pain thresholds were observed in all groups except the control group with a higher threshold seen in the electroacupuncture groups. Serum NE levels decreased in the electroacupuncture and MP groups. Increases in NET andα2AR expression in the cerebral cortex and decreases in enlarged segments of the spinal cord were seen. Acupuncture increases uptake of NE via cerebral NET and decreases its uptake by spinal NET. The levels ofα2AR are also increased and decreased, respectively, in both tissues. This results in a decrease in systemic NE levels and may be the mechanism for its analgesic effects.

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