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Sample records for capsaicin induced trigeminal

  1. Hunting for origins of migraine pain: cluster analysis of spontaneous and capsaicin-induced firing in meningeal trigeminal nerve fibers

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    Andrei eZakharov

    2015-07-01

    Full Text Available Trigeminal nerves in meninges are implicated in generation of nociceptive firing underlying migraine pain. However, the neurochemical mechanisms of nociceptive firing in meningeal trigeminal nerves are little understood. In this study, using suction electrode recordings from peripheral branches of the trigeminal nerve in isolated rat meninges, we analyzed spontaneous and capsaicin-induced orthodromic spiking activity. In control, biphasic single spikes with variable amplitude and shapes were observed. Application of the TRPV1 agonist capsaicin to meninges dramatically increased firing whereas the amplitudes and shapes of spikes remained essentially unchanged. This effect was antagonized by the specific TRPV1 antagonist capsazepine. Using the clustering approach, several groups of uniform spikes (clusters were identified. The clustering approach combined with capsaicin application allowed us to detect and to distinguish ‘responder’ (65% from ‘non-responder’ clusters (35%. Notably, responders fired spikes at frequencies exceeding 10 Hz, high enough to provide postsynaptic temporal summation of excitation at spinal cord level. Almost all spikes were suppressed by TTX suggesting an involvement of the TTX-sensitive sodium channels in nociceptive signaling at the peripheral branches of trigeminal neurons. Our analysis also identified transient (desensitizing and long-lasting (slowly desensitizing, responses to the continuous application of capsaicin. Thus, the persistent activation of nociceptors in capsaicin-sensitive nerve fibers shown here may be involved in trigeminal pain signaling and plasticity along with the release of migraine-related neuropeptides from TRPV1 positive neurons. Furthermore, cluster analysis could be widely used to characterize the temporal and neurochemical profiles of other pain transducers likely implicated in migraine.

  2. Trigeminal ganglion neurons of mice show intracellular chloride accumulation and chloride-dependent amplification of capsaicin-induced responses.

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    Nicole Schöbel

    Full Text Available Intracellular Cl(- concentrations ([Cl(-](i of sensory neurons regulate signal transmission and signal amplification. In dorsal root ganglion (DRG and olfactory sensory neurons (OSNs, Cl(- is accumulated by the Na(+-K(+-2Cl(- cotransporter 1 (NKCC1, resulting in a [Cl(-](i above electrochemical equilibrium and a depolarizing Cl(- efflux upon Cl(- channel opening. Here, we investigate the [Cl(-](i and function of Cl(- in primary sensory neurons of trigeminal ganglia (TG of wild type (WT and NKCC1(-/- mice using pharmacological and imaging approaches, patch-clamping, as well as behavioral testing. The [Cl(-](i of WT TG neurons indicated active NKCC1-dependent Cl(- accumulation. Gamma-aminobutyric acid (GABA(A receptor activation induced a reduction of [Cl(-](i as well as Ca(2+ transients in a corresponding fraction of TG neurons. Ca(2+ transients were sensitive to inhibition of NKCC1 and voltage-gated Ca(2+ channels (VGCCs. Ca(2+ responses induced by capsaicin, a prototypical stimulus of transient receptor potential vanilloid subfamily member-1 (TRPV1 were diminished in NKCC1(-/- TG neurons, but elevated under conditions of a lowered [Cl(-](o suggesting a Cl(--dependent amplification of capsaicin-induced responses. Using next generation sequencing (NGS, we found expression of different Ca(2+-activated Cl(- channels (CaCCs in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca(2+ imaging and electrophysiological recordings. In a behavioral paradigm, NKCC1(-/- mice showed less avoidance of the aversive stimulus capsaicin. In summary, our results strongly argue for a Ca(2+-activated Cl(--dependent signal amplification mechanism in TG neurons that requires intracellular Cl(- accumulation by NKCC1 and the activation of CaCCs.

  3. Trigeminal postherpetic neuralgia responsive to treatment with capsaicin 8 % topical patch: a case report.

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    Sayanlar, Jennifer; Guleyupoglu, Nilufer; Portenoy, Russell; Ashina, Sait

    2012-10-01

    Postherpetic neuralgia has been variably defined but is generally understood to be pain that persists for longer than a few months after an attack of herpes zoster. Pain persists for years in approximately 10 % of those afflicted with acute herpes zoster. The likelihood of postherpetic neuralgia increases with older age, severity of the zoster, trigeminal location, and other factors. Postherpetic neuralgia is a neuropathic pain and treatment usually involves sequential trials of topical and systemic drugs; a variety of other therapies may be considered in refractory cases. A new topical capsaicin 8 % patch has been approved for this indication based on the positive studies in patients with non-trigeminal postherpetic neuralgia. Experience with the use of the capsaicin 8 % patch for trigeminal distribution neuralgia is lacking. We report a case of trigeminal postherpetic neuralgia which was safely and effectively treated with capsaicin 8 % patch.

  4. The effect of capsaicin on expression patterns of CGRP in trigeminal ganglion and trigeminal nucleus caudalis following experimental tooth movement in rats

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    ZHOU, Yang; LONG, Hu; YE, Niansong; LIAO, Lina; YANG, Xin; JIAN, Fan; WANG, Yan; LAI, Wenli

    2016-01-01

    ABSTRACT Objectives The aim of this study was to explore the effect of capsaicin on expression patterns of calcitonin gene-related peptide (CGRP) in the trigeminal ganglion (TG) and trigeminal subnucleus caudalis (Vc) following experimental tooth movement. Material and Methods Male Sprague-Dawley rats were used in this study and divided into small-dose capsaicin+force group, large-dose capsaicin+force group, saline+force group, and no force group. Closed coil springs were used to mimic orthodontic forces in all groups except for the no force group, in which springs were inactivated. Capsaicin and saline were injected into periodontal tissues. Rats were euthanized at 0 h, 12 h, 1 d, 3 d, 5 d, and 7 d following experimental tooth movement. Then, TG and Vc were obtained for immunohistochemical staining and western blotting against CGRP. Results Immunohistochemical results indicated that CGRP positive neurons were located in the TG, and CGRP immunoreactive fibers were distributed in the Vc. Immunohistochemical semiquantitative analysis and western blotting analysis demonstrated that CGRP expression levels both in TG and Vc were elevated at 12 h, 1 d, 3 d, 5 d, and 7 d in the saline + force group. However, both small-dose and large-dose capsaicin could decrease CGRP expression in TG and Vc at 1 d and 3 d following experimental tooth movement, as compared with the saline + force group. Conclusions These results suggest that capsaicin could regulate CGRP expression in TG and Vc following experimental tooth movement in rats. PMID:28076465

  5. Gastroprotection induced by capsaicin in healthy human subjects

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    Gyula Mózsik; János Szolcsányi; István Rácz

    2005-01-01

    AIM: To evaluate the gastro-protective effect of capsaicin against the ethanol- and indomethacin (IND)-induced gastric mucosal damage in healthy human subjects.METHODS: The effects of small doses (1-8 μg/mL,100 mL) of capsaicin on the gastric acid secretion basal acid output (BAO) and its electrolyte concentration,gastric transmucosal potential difference (GTPD),ethanol- (5 mL 300 mL/L i.g.) and IND- (3x25 mg/d)induced gastric mucosal damage were tested in a randomized, prospective study of 84 healthy human subjects. The possible role of desensitization of capsaicin-sensitive afferents was tested by repeated exposures and during a prolonged treatment.RESULTS: Intragastric application of capsaicin decreased the BAO and enhanced "non-parietal" component, GTPD in a dose-dependent manner. The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application,which was reproducible. Gastric microbleeding induced by IND was inhibited by co-administration with capsaicin,but was not influenced by two weeks pretreatment with a daily capsaicin dose of 3x400 μg i.g.CONCLUSION: Capsaicin in low concentration range protects against gastric injuries induced by ethanol or IND, which is attributed to stimulation of the sensory nerve endings.

  6. Characterization of capsaicin induced responses in mice vas deferens

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    Sheykhzade, Majid; Gupta, Saurabh; Sørensen, Tinne;

    2011-01-01

    Calcitonin gene-related peptide (CGRP) is extensively distributed in primary afferent sensory nerves, including those innervating the genitourinary tract. Capsaicin can stimulate the release of CGRP from intracellular stores of these nerves, but this phenomenon has not been investigated in......-depth in isolated preparations. The present study sets out to study and characterize the capsaicin as well as CGRP-induced responses in isolated mouse vas deferens. The effects of capsaicin and CGRP family of peptides were studied on electrically-induced twitch responses in the absence or presence of transient...... receptor potential cation channel vanilloid subfamily member 1 (TRPV1) antagonist and CGRP receptor antagonists. Twitch responses were attenuated by capsaicin (1nM-30nM) and CGRP family of peptides. The potency order was CGRP>intermedin-long (IMDL)~[Cys(Et)(2,7)]aCGRP~adrenomedullin (AM)>[Cys(ACM)(2,7)]a...

  7. Maresin 1 Inhibits TRPV1 in Temporomandibular Joint-Related Trigeminal Nociceptive Neurons and TMJ Inflammation-Induced Synaptic Plasticity in the Trigeminal Nucleus

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    Chul-Kyu Park

    2015-01-01

    Full Text Available In the trigeminal system, disruption of acute resolution processing may lead to uncontrolled inflammation and chronic pain associated with the temporomandibular joint (TMJ. Currently, there are no effective treatments for TMJ pain. Recently, it has been recognized that maresin 1, a newly identified macrophage-derived mediator of inflammation resolution, is a potent analgesic for somatic inflammatory pain without noticeable side effects in mice and a potent endogenous inhibitor of transient receptor potential vanilloid 1 (TRPV1 in the somatic system. However, the molecular mechanisms underlying the analgesic actions of maresin 1 on TMJ pain are unclear in the trigeminal system. Here, by performing TMJ injection of a retrograde labeling tracer DiI (a fluorescent dye, I showed that maresin 1 potently inhibits capsaicin-induced TRPV1 currents and neuronal activity via Gαi-coupled G-protein coupled receptors in DiI-labeled trigeminal nociceptive neurons. Further, maresin 1 blocked TRPV1 agonist-evoked increases in spontaneous excitatory postsynaptic current frequency and abolished TMJ inflammation-induced synaptic plasticity in the trigeminal nucleus. These results demonstrate the potent actions of maresin 1 in regulating TRPV1 in the trigeminal system. Thus, maresin 1 may serve as a novel endogenous inhibitor for treating TMJ-inflammatory pain in the orofacial region.

  8. Capsaicin attenuates LPS-induced inflammatory cytokine production by upregulation of LXRα.

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    Tang, Jing; Luo, Kang; Li, Yan; Chen, Quan; Tang, Dan; Wang, Deming; Xiao, Ji

    2015-09-01

    Here, we investigated the role of LXRα in capsaicin mediated anti-inflammatory effects. Results revealed that capsaicin inhibits LPS-induced IL-1β, IL-6 and TNF-α production in a time- and dose-dependent manner. Moreover, capsaicin increases LXRα expression through PPARγ pathway. Inhibition of LXRα activation by siRNA diminished the inhibitory action of capsaicin on LPS-induced IL-1β, IL-6 and TNF-α production. Additionally, LXRα siRNA abrogated the inhibitory action of capsaicin on p65 NF-κB protein expression. Thus, we propose that the anti-inflammatory effects of capsaicin are LXRα dependent, and LXRα may potentially link the capsaicin mediated PPARγ activation and NF-κB inhibition in LPS-induced inflammatory response.

  9. The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats.

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    Kooshki, Razieh; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed; Raoof, Maryam

    2016-04-01

    It is widely accepted that the spinal trigeminal nuclear complex, especially the subnucleus caudalis (Vc), receives input from orofacial structures. The neuropeptides orexin-A and -B are expressed in multiple neuronal systems. Orexin signaling has been implicated in pain-modulating system as well as learning and memory processes. Orexin 1 receptor (OX1R) has been reported in trigeminal nucleus caudalis. However, its roles in trigeminal pain modulation have not been elucidated so far. This study was designed to investigate the role of Vc OX1R in the modulation of orofacial pain as well as pain-induced learning and memory deficits. Orofacial pain was induced by subcutaneous injection of capsaicin in the right upper lip of the rats. OX1R agonist (orexin-A) and antagonist (SB-334867-A) were microinjected into Vc prior capsaicin administration. After recording nociceptive times, learning and memory was investigated using Morris water maze (MWM) test. The results indicated that, orexin-A (150 pM/rat) significantly reduced the nociceptive times, while SB334867-A (80 nM/rat) exaggerated nociceptive behavior in response to capsaicin injection. In MWM test, capsaicin-treated rats showed a significant learning and memory impairment. Moreover, SB-334867-A (80 nM/rat) significantly exaggerated learning and memory impairment in capsaicin-treated rats. However, administration of orexin-A (100 pM/rat) prevented learning and memory deficits. Taken together, these results indicate that Vc OX1R was at least in part involved in orofacial pain transmission and orexin-A has also a beneficial inhibitory effect on orofacial pain-induced deficits in abilities of spatial learning and memory.

  10. Biomimetic proopiomelanocortin suppresses capsaicin-induced sensory irritation in humans

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    Sayed Ali Fatemi

    2016-01-01

    Full Text Available Sensitive skin is a frequently mentioned cosmetic complaint. Addition of a biomimetic of neuromediator has recently appeared as a promising new way to cure skin care product problems. This study was aimed to assess the inhibitory effect of a biomimetic lipopeptide derived from proopiomelanocortin (bPOMC on capsaicin-induced sensory irritation in human volunteers and also to compare its protective effect with that of the well-known anti irritant strontium chloride. The effect of each test compound was studied on 28 selected healthy volunteers with sensitive skin in accordance with a double-blind vehicle-controlled protocol. From day 1 to day 13 each group was applied the test compound (bPOMC or strontium chloride to one wing of the nose and the corresponding placebo (vehicle to the other side twice daily. On days 0 and 14, acute skin irritation was induced by capsaicin solution and quantified using clinical stinging test assessments. Following the application of capsaicin solution, sensory irritation was evaluated using a 4-point numeric scale. The sensations perceived before and after treatment (on days 0 and 14 was calculated for the two zones (test materials and vehicle. Ultimately the percentage of variation between each sample and the placebo and also the inhibitory effect of bPOMC compared to that of strontium chloride were reported. Clinical results showed that after two weeks treatment, the levels of skin comfort reported in the group treated with bPOMC were significantly higher than those obtained in the placebo group and the inhibitory effect of bPOMC was about 47% higher than that of strontium chloride. The results of the present study support the hypothesis that biomimetic peptides may be effective on sensitive skin.

  11. Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy.

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    Hong, Zai-Fa; Zhao, Wen-Xiu; Yin, Zhen-Yu; Xie, Cheng-Rong; Xu, Ya-Ping; Chi, Xiao-Qin; Zhang, Sheng; Wang, Xiao-Min

    2015-01-01

    Cholangiocarcinoma (CCA), a devastating cancer with a poor prognosis, is resistant to the currently available chemotherapeutic agents. Capsaicin, the major pungent ingredient found in hot red chili peppers of the genus Capsicum, suppresses the growth of several malignant cell lines. Our aims were to investigate the role and mechanism of capsaicin with respect to the sensitivity of CCA cells to chemotherapeutic agents. The effect of capsaicin on CCA tumor sensitivity to 5-fluorouracil (5-FU) was assessed in vitro in CCA cells and in vivo in a xenograft model. The drug sensitivity of QBC939 to 5-FU was significantly enhanced by capsaicin compared with either agent alone. In addition, the combination of capsaicin with 5-FU was synergistic, with a combination index (CI) capsaicin. Moreover, the decrease in AKT and S6 phosphorylation induced by 5-FU was effectively reversed by capsaicin, indicating that capsaicin inhibits 5-FU-induced autophagy by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in CCA cells. Taken together, these results demonstrate that capsaicin may be a useful adjunct therapy to improve chemosensitivity in CCA. This effect likely occurs via PI3K/AKT/mTOR pathway activation, suggesting a promising strategy for the development of combination drugs for CCA.

  12. Capsaicin-induced cell death in a human gastric adenocarcinoma cell line

    Institute of Scientific and Technical Information of China (English)

    Yi-Ching Lo; Yuan-Chen Yang; I-Chieh Wu; Fu-Chen Kuo; Chi-Ming Liu; Hao-Wei Wang; Chao-Hung Kuo; Jeng-Yi Wu; Deng-Chyang Wu

    2005-01-01

    AIM: Capsaicin, a pungent ingredient found in red pepper,has long been used in spices, food additives, and drugs.Cell death induced by the binding of capsaicin was examined in a human gastric adenocarcinoma cell line (AGS cells).METHODS: By using XTT-based cytotoxicityassay, flow cytometry using the TUNEL method, and quantitation of DNA fragmentation, both cell death and DNA fragmentation were detected in AGS cells treated with capsaicin. By using Western blotting methods, capsaicin reduced the expression of Bcl-2, the antiapoptotic protein, in AGS cells in a concentration-dependent manner.RESULTS: After incubation of AGS cells with capsaicin for 24 h, cell viability decreased significantly in a dose-dependent manner. After incubation of AGS cells with capsaicin for 24 h, apoptotic bodies also significantly increased, and were again correlated with the dose of capsaicin. When the concentration of capsaicin was 1 mmol/L, the amount of DNA fragments also increased. Similar results werealso in the lower traces.CONCLUSION: These results suggest that capsaicininduced cell death might be via a Bcl-2 sensitive apoptotic pathway. Therefore, capsaicin might induce protection from gastric cancer.

  13. Capsaicin-induced corneal lesions in mice and the effects of chemical sympathectomy.

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    Shimizu, T; Izumi, K; Fujita, S; Koja, T; Sorimachi, M; Ohba, N; Fukuda, T

    1987-11-01

    Effects of chemical sympathectomy on corneal changes induced in mice by a s.c. injection of capsaicin were investigated. Pretreatment with a s.c. injection of 6-hydroxydopamine (6-OHDA) on the 1st and 2nd postnatal day or on the 14th and 15th postnatal day led to a marked suppression of the capsaicin-induced corneal lesions. This suppressive effect also was evident in case of administration after capsaicin treatment. Intraventricular injection of 6-OHDA had a slight, transient effect. DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], another potent substance used for sympathetic denervation, had a suppressive effect similar to that of 6-OHDA. The concentration of capsaicin in tissues of the head was unaltered with 6-OHDA. The content of substance P (SP) in the ocular anterior segments was decreased, dose-dependently, with capsaicin administration. Neonatal administration of 6-OHDA decreased the rate of capsaicin-induced reduction of SP. However, this effect of 6-OHDA was too slight to explain the suppression of the corneal lesions, as the intensity score of lesions with a large dose of capsaicin after 6-OHDA was lower than that with a small dose of capsaicin without 6-OHDA, whereas SP content in the former was still much lower than that in the latter. On the other hand, the content of norepinephrine in the ocular tissues was decreased in the presence of 6-OHDA but not capsaicin. These results suggest that the corneal changes induced by capsaicin are largely inhibited by a decreased activity in the peripheral sympathetic system.

  14. Effects of the CGRP receptor antagonist BIBN4096BS on capsaicin-induced carotid haemodynamic changes in anaesthetised pigs.

    NARCIS (Netherlands)

    K. Kapoor (Kapil); U. Arulmani (Udayasankar); J.P. Heiligers (Jan); I.M. Garrelds (Ingrid); E.W. Willems (Edwin); H. Doods (Henri); C.M. Villalón (Carlos); P.R. Saxena (Pramod Ranjan)

    2003-01-01

    textabstract1. Calcitonin gene-related peptide (CGRP), a potent vasodilator released from capsaicin-sensitive trigeminal sensory nerves, seems to be involved in the pathogenesis of migraine. Hence, CGRP receptor antagonists may serve as a novel treatment for migraine. This study wa

  15. Intrapericardial capsaicin and bradykinin induce different cardiac-somatic and cardiovascular reflexes in rats.

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    Liu, Xiaohua; Zhang, Qi; Han, Man; Du, Jianqing

    2016-07-01

    Patients with myocardial infarction experience various types of chest pain and autonomic disturbance symptoms. Studies in rats have shown that pericardial infusions of certain chemicals induce cardiac-related muscle pain and cardiovascular reflexes. In the present study, bradykinin or capsaicin was injected into the pericardial sac and the resulting cardiac-somatic reflexes and blood pressure (BP) alterations were record. We found that the cardiac-somatic reflex induced by bradykinin had a longer latency, shorter duration, and lower firing rate than that induced by capsaicin (preflex induced by bradykinin (p>0.05) but reduced the reflex induced by capsaicin (p0.05). These results suggest that bradykinin and capsaicin activate different pathways to induce cardiac-somatic and cardiovascular reflexes and that the vagus nerve is involved in TRPV1-related muscle pain modulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Peripheral lidocaine, but not ketamine inhibit capsaicin-induced hyperalgesia in humans

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    Gottrup, Hanne; Bach, Flemming Winther; Arendt-Nielsen, Lars

    2000-01-01

    micrograms capsaicin was injected intradermally in one volar forearm 10 min after the skin had been pretreated with lidocaine 20.0 mg in 2.0 ml or 0.9% saline 2.0 ml at the capsaicin injection site. In experiment 2, a similar capsaicin test was given 10 min after the skin had been pretreated with ketamine 5......We examined the effect of the subcutaneous infiltration of ketamine, lidocaine and saline before injury on capsaicin-induced pain and hyperalgesia. Twelve healthy volunteers participated in two separate, randomized, double-blind, placebo-controlled crossover experiments. In experiment 1, 100...... mg in 2.0 ml or 0.9% saline 2.0 ml. To control for possible systemic effects, the capsaicin injection site was pretreated by injection of saline into the skin and the contralateral arm was treated with active drug, and vice versa. Outcome measures were spontaneous pain, pain evoked by punctate...

  17. Capsaicin-induced neurogenic inflammation in pig skin

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    Di Giminiani, Pierpaolo; Petersen, Lars J; Herskin, Mette S

    2014-01-01

    Topical capsaicin is a well-established model of experimental hyperalgesia. Its application to the study of animals has been limited to few species. The effect of topical capsaicin on hyperalgesia in porcine skin was evaluated as part of a study of inflammatory pain in the pig. Two experiments we...

  18. Involvement of Endoplasmic Reticulum Stress in Capsaicin-Induced Apoptosis of Human Pancreatic Cancer Cells

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    Shengzhang Lin

    2013-01-01

    Full Text Available Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990 with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153, a marker of the endoplasmic-reticulum-stress- (ERS- mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78, phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK, and phosphoeukaryotic initiation factor-2α (phospho-eIF2α, activating transcription factor 4 (ATF4 and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.

  19. Lipopolysaccharide-induced hyperalgesia of intracranial capsaicin sensitive afferents in conscious rats

    NARCIS (Netherlands)

    Kemper, RHA; Spoelstra, MB; Meijler, WJ; Ter Horst, GJ

    1998-01-01

    Migraineous and non-migraineous headache is reported to be at highest intensity after an infection. This study investigated whether activation of the immune system can induce hyperalgesia in intracranial capsaicin sensitive afferents. The effects of intraperitoneal injected lipopolysaccharides (LPS)

  20. Capsaicin triggers immunogenic PEL cell death, stimulates DCs and reverts PEL-induced immune suppression.

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    Granato, Marisa; Gilardini Montani, Maria Saveria; Filardi, Mariarosari; Faggioni, Alberto; Cirone, Mara

    2015-10-06

    Capsaicin, the pungent alkaloid of red pepper has been extensively studied for its many properties, especially the anti-inflammatory and anti-oxidant ones. It binds to vanilloid receptor 1, although it has been reported to be able to mediate some effects independently of its receptor. Another important property of Capsaicin is the anticancer activity against highly malignant tumors, alone or in combination with other chemotherapeutic agents. In this study, we found that Capsaicin induced an apoptotic cell death in PEL cells correlated with the inhibition of STAT3. STAT3 pathway, constitutively activated in PEL cells, is essential for their survival. By STAT3 de-phosphorylation, Capsaicin reduced the Mcl-1 expression level and this could represent one of the underlying mechanisms leading to the Capsaicin-mediated cell death and autophagy induction. Next, by pharmacological or genetic inhibition, we found that autophagy played a pro-survival role, suggesting that its inhibition could be exploited to increase the Capsaicin cytotoxic effect against PEL cells. Finally, we show that Capsaicin induced DAMP exposure, as for an immunogenic cell death, directly promoted DC activation and, more importantly, that it counteracted the immune-suppression, in terms of DC differentiation, mediated by the PEL released factors.

  1. Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy.

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    Zai-Fa Hong

    Full Text Available Cholangiocarcinoma (CCA, a devastating cancer with a poor prognosis, is resistant to the currently available chemotherapeutic agents. Capsaicin, the major pungent ingredient found in hot red chili peppers of the genus Capsicum, suppresses the growth of several malignant cell lines. Our aims were to investigate the role and mechanism of capsaicin with respect to the sensitivity of CCA cells to chemotherapeutic agents. The effect of capsaicin on CCA tumor sensitivity to 5-fluorouracil (5-FU was assessed in vitro in CCA cells and in vivo in a xenograft model. The drug sensitivity of QBC939 to 5-FU was significantly enhanced by capsaicin compared with either agent alone. In addition, the combination of capsaicin with 5-FU was synergistic, with a combination index (CI < 1, and the combined treatment also suppressed tumor growth in the CCA xenograft to a greater extent than 5-FU alone. Further investigation revealed that the autophagy induced by 5-FU was inhibited by capsaicin. Moreover, the decrease in AKT and S6 phosphorylation induced by 5-FU was effectively reversed by capsaicin, indicating that capsaicin inhibits 5-FU-induced autophagy by activating the phosphoinositide 3-kinase (PI3K/protein kinase B (AKT/mammalian target of rapamycin (mTOR pathway in CCA cells. Taken together, these results demonstrate that capsaicin may be a useful adjunct therapy to improve chemosensitivity in CCA. This effect likely occurs via PI3K/AKT/mTOR pathway activation, suggesting a promising strategy for the development of combination drugs for CCA.

  2. Orally given gastroprotective capsaicin does not modify aspirin-induced platelet aggregation in healthy male volunteers (human phase I examination).

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    Sandor, B; Papp, J; Mozsik, Gy; Szolcsanyi, J; Keszthelyi, Zs; Juricskay, I; Toth, K; Habon, Tamas

    2014-12-01

    Capsaicin is a well-known component of red pepper. Recent studies have shown that capsaicin could prevent gastric ulcer provoked by various NSAID-s like acetylsalicylic acid (ASA). Primary objective of this human clinical phase I trial was to investigate whether two different doses of capsaicin co-administered with ASA could alter the inhibitory effect of ASA on platelet aggregation. 15 healthy male subjects were involved in the study and treated orally with 400 μg capsaicin, 800 μg capsaicin, 500 mg ASA, 400 μg capsaicin+500 mg ASA and 800 μg capsaicin+500 mg ASA. Blood was drawn before and 1, 2, 6 and 24 hours after the drug administration. After that epinephrine induced platelet aggregation was measured by optical aggregometry. Between treatments, volunteers had a 6-day wash-out period. Our results showed that capsaicin had no effect on platelet aggregation, while as expected, ASA monotherapy resulted in a significant and clinically effective platelet aggregation inhibition (p ≤ 0.001). The combined ASA-capsaicin therapies reached equivalent effectiveness in platelet aggregation inhibition as ASA monotherapy. Our investigation proved that capsaicin did not influence the inhibitory effect of ASA on platelet aggregation, thus the capsaicin-ASA treatment would combine the antiplatelet effect of ASA with the possible gastroprotection of capsaicin.

  3. Capsaicin-induced genotoxic stress does not promote apoptosis in A549 human lung and DU145 prostate cancer cells.

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    Lewinska, Anna; Jarosz, Paulina; Czech, Joanna; Rzeszutek, Iwona; Bielak-Zmijewska, Anna; Grabowska, Wioleta; Wnuk, Maciej

    2015-02-01

    Capsaicin is the major pungent component of the hot chili peppers of the genus Capsicum, which are consumed worldwide as a food additive. More recently, the selective action of capsaicin against cancer cells has been reported. Capsaicin was found to induce apoptosis and inhibit proliferation of a wide range of cancer cells in vitro, whereas being inactive against normal cells. As data on capsaicin-induced genotoxicity are limited and the effects of capsaicin against human lung A549 and DU145 prostate cancer cells were not explored in detail, we were interested in determining whether capsaicin-associated genotoxicity may also provoke A549 and DU145 cell death. Capsaicin-induced decrease in metabolic activity and cell proliferation, and changes in the cell cycle were limited to high concentrations used (≥ 100 μM), whereas, at lower concentrations, capsaicin stimulated both DNA double strand breaks and micronuclei production. Capsaicin was unable to provoke apoptotic cell death when used up to 250 μM concentrations. Capsaicin induced oxidative stress, but was ineffective in provoking the dissipation of the mitochondrial inner transmembrane potential. A different magnitude of p53 binding protein 1 (53BP1) recruitment contributed to diverse capsaicin-induced genotoxic effects in DU145 and A549 cells. Capsaicin was also found to be a DNA hypermethylating agent in A549 cells. In summary, we have shown that genotoxic effects of capsaicin may contribute to limited susceptibility of DU145 and A549 cancer cells to apoptosis in vitro, which may question the usefulness of capsaicin-based anticancer therapy, at least in a case of lung and prostate cancer.

  4. Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat.

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    Kang, J Y; Teng, C H; Wee, A; Chen, F C

    1995-05-01

    Capsaicin, the pungent ingredient of chilli, is gastroprotective against experimental gastric injury when given intragastrically. Epidemiological and clinical data suggest that chilli ingestion may have a beneficial effect on human peptic ulcer disease. This study showed a gastroprotective effect of intragastric capsaicin, in doses of 2 and 5 mg, on ethanol induced gastric mucosal injury using macroscopic, histological, scanning electron microscopic, and biochemical indices. Subcutaneous administration of 2 mg of capsaicin had the same gastroprotective effect as intragastric administration. Acute intragastric administration and chronic ingestion of chilli powder in doses comparable with that consumed in humans (up to 200 mg in single doses or 200 mg daily for four weeks) likewise protected the gastric mucosa. Both the mucosa and gastric juice had higher mucus contents when capsaicin or chilli rather than saline or solvent was used before ethanol challenge. In control animals capsaicin also increased gastric juice mucus content although the mucosal content was unaffected. Increased gastric mucus production may therefore be one mechanism by which capsaicin and chilli exert their gastroprotective effect although an alternative explanation is that the reduction in mucosal mucus depletion is secondary to the protective effect of capsaicin and chilli.

  5. Increased capsaicin-induced secondary hyperalgesia in patients with multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger

    2011-01-01

    in experimental pain models to provoke peripheral and central sensitization. In patients with symptoms elicited by odorous chemicals capsaicin-induced secondary hyperalgesia and temporal summation were assessed as markers for abnormal central nociceptive processing together with neurogenic inflammation (flare).......the underlying cause of pathophysiological mechanisms triggering multiple chemical sensitivity (MCS) remains disputed.Recently, alterations in the central nervous system, for example,central sensitization, similar to various chronic pain disorders, have been suggested. Capsaicin is used...

  6. Increased capsaicin-induced secondary hyperalgesia in patients with multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger;

    2011-01-01

    in experimental pain models to provoke peripheral and central sensitization. In patients with symptoms elicited by odorous chemicals capsaicin-induced secondary hyperalgesia and temporal summation were assessed as markers for abnormal central nociceptive processing together with neurogenic inflammation (flare).......the underlying cause of pathophysiological mechanisms triggering multiple chemical sensitivity (MCS) remains disputed.Recently, alterations in the central nervous system, for example,central sensitization, similar to various chronic pain disorders, have been suggested. Capsaicin is used...

  7. Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat.

    OpenAIRE

    1995-01-01

    Capsaicin, the pungent ingredient of chilli, is gastroprotective against experimental gastric injury when given intragastrically. Epidemiological and clinical data suggest that chilli ingestion may have a beneficial effect on human peptic ulcer disease. This study showed a gastroprotective effect of intragastric capsaicin, in doses of 2 and 5 mg, on ethanol induced gastric mucosal injury using macroscopic, histological, scanning electron microscopic, and biochemical indices. Subcutaneous admi...

  8. Capsaicin-induced neurogenic inflammation in pig skin: a behavioural study.

    Science.gov (United States)

    Di Giminiani, Pierpaolo; Petersen, Lars J; Herskin, Mette S

    2014-06-01

    Topical capsaicin is a well-established model of experimental hyperalgesia. Its application to the study of animals has been limited to few species. The effect of topical capsaicin on hyperalgesia in porcine skin was evaluated as part of a study of inflammatory pain in the pig. Two experiments were carried out on pigs of 27 ± 5 kg (n = 8) and 57 ± 3 kg (n = 16). Thermal and mechanical noxious stimuli were provided (CO2 laser and Pressure Application Measurement device) to assess avoidance behaviours. Capsaicin induced significant thermal hyperalgesia in the smaller pigs (P capsaicin application may be useful to investigate the mechanisms of primary hyperalgesia in this species, although some experimental conditions, such as the administration route and cutaneous morphology, need to be evaluated.

  9. Peripheral lidocaine, but not ketamine inhibit capsaicin-induced hyperalgesia in humans

    DEFF Research Database (Denmark)

    Gottrup, Hanne; Bach, Flemming Winther; Arendt-Nielsen, Lars

    2000-01-01

    We examined the effect of the subcutaneous infiltration of ketamine, lidocaine and saline before injury on capsaicin-induced pain and hyperalgesia. Twelve healthy volunteers participated in two separate, randomized, double-blind, placebo-controlled crossover experiments. In experiment 1, 100...... micrograms capsaicin was injected intradermally in one volar forearm 10 min after the skin had been pretreated with lidocaine 20.0 mg in 2.0 ml or 0.9% saline 2.0 ml at the capsaicin injection site. In experiment 2, a similar capsaicin test was given 10 min after the skin had been pretreated with ketamine 5...... and brush stimuli, and areas of brush-evoked and punctate-evoked hyperalgesia. Lidocaine reduced all measures compared with placebo (P ketamine failed to change any measures. Pain scores and areas of hyperalgesia were not affected when the contralateral site was infiltrated with ketamine...

  10. Peripheral Glutamate Receptors Are Required for Hyperalgesia Induced by Capsaicin

    Directory of Open Access Journals (Sweden)

    You-Hong Jin

    2012-01-01

    Full Text Available Transient receptor potential vanilloid1 (TRPV1 and glutamate receptors (GluRs are located in small diameter primary afferent neurons (nociceptors, and it was speculated that glutamate released in the peripheral tissue in response to activation of TRPV1 might activate nociceptors retrogradely. But, it was not clear which types of GluRs are functioning in the nociceptive sensory transmission. In the present study, we examined the c-Fos expression in spinal cord dorsal horn following injection of drugs associated with glutamate receptors with/without capsaicin into the hindpaw. The subcutaneous injection of capsaicin or glutamate remarkably evoked c-Fos expression in ipsilateral sides of spinal cord dorsal horn. This capsaicin evoked increase of c-Fos expression was significantly prevented by concomitant administration of MK801, CNQX, and CPCCOEt. On the other hand, there were not any significant changes in coinjection of capsaicin and MCCG or MSOP. These results reveal that the activation of iGluRs and group I mGluR in peripheral afferent nerves play an important role in mechanisms whereby capsaicin evokes/maintains nociceptive responses.

  11. Antioxidant activity of capsaicin on radiation-induced oxidation of murine hepatic mitochondrial membrane preparation

    Directory of Open Access Journals (Sweden)

    Gangabhagirathi R

    2015-06-01

    Full Text Available Ramachandran Gangabhagirathi,1 Ravi Joshi,2 1Bioorganic Division, 2Radiation and Photochemistry Division, Bhabha Atomic Research Center, Trombay, Mumbai, India Abstract: Capsaicin is the major capsaicinoid in chili peppers and is widely used as a spice. It is also used for topical applications in cases of peripheral neuropathy. The present study deals with its role in modulation of gamma radiation-induced damages of the biochemical constituents of rat liver mitochondrial membrane (RLM preparation. The extent of lipid hydroperoxide formation, depletion in protein thiols, and formation of protein carbonyls have been biochemically assessed in the presence of varying concentrations of capsaicin in RLM. Decrease in the activities of the important antioxidant enzyme superoxide dismutase, which is involved in the scavenging of free radicals, and the mitochondrial marker enzyme succinate dehydrogenase have been also looked into. Capsaicin has been found to efficiently inhibit radiation-induced biochemical alterations, namely lipid peroxidation and protein oxidation. It also significantly prevented radiation-induced loss in the activity of antioxidant enzyme and the important endogenous antioxidant glutathione. The study suggests that capsaicin can act as an antioxidant and radioprotector in physiological systems. Keywords: capsaicin, gamma radiation, radioprotection, lipid peroxidation, protein oxidation, enzyme activity

  12. Prophylactic proopiomelanocortin expression alleviates capsaicin-induced neurogenic inflammation in rat trachea.

    Science.gov (United States)

    Liu, Guei-Sheung; Huang, Hung-Tu; Lin, Che-Jen; Shi, Jhih-Yin; Liu, Li-Feng; Tseng, Rue-Tseng; Weng, Wen-Tsan; Lam, Hing-Chung; Wen, Zhi-Hong; Cheng, Tian-Lu; Hsu, Kuei-Sen; Tai, Ming-Hong

    2009-12-01

    Neurogenic inflammation frequently causes acute plasma leakage in airways and life-threatening pulmonary edema. However, limited strategies are available to alleviate neurogenic inflammation. Proopiomelanocortin (POMC) is the precursor of anti-inflammatory melanocortins, which have been proposed of therapeutic potential for various inflammatory diseases. The present study aimed to evaluate whether peripheral POMC expression ameliorated capsaicin-induced acute neurogenic inflammation in rat trachea. Prophylactic POMC expression was achieved by intravenous injection of adenovirus encoding POMC (Ad-POMC), which led to POMC expression in livers and elevated plasma adrenocorticotropin levels for approximately 60 days. After gene delivery for 7 days, neurogenic inflammation was induced in rats by capsaicin injection. The extent of capsaicin-evoked plasma leakage in trachea was alleviated in Ad-POMC-treated rats compared with animals of control groups (P neurogenic inflammation.

  13. Hypolipidemic and antioxidant effects of dietary curcumin and capsaicin in induced hypercholesterolemic rats.

    Science.gov (United States)

    Manjunatha, H; Srinivasan, K

    2007-12-01

    Health beneficial hypolipidemic and antioxidant influences of dietary spice principles--curcumin, capsaicin alone and in combination included in the diet for 8 weeks were evaluated in induced hypercholesterolemic rats, in order to verify if there is any additive or synergistic effect of these two bioactive compounds. Dietary curcumin (0.2%), capsaicin (0.015%) or their combination significantly countered the hypercholesterolemia brought about by high cholesterol feeding. Hepatic cholesterol was lowered by dietary spice principles only in normal rats. Liver triglyceride levels were lowered in both normal and hypercholesterolemic rats by capsaicin. Curcumin and capsaicin lowered hepatic and blood lipid peroxides in hypercholesterolemic rats, while the effect in blood was additive with their combination. Hepatic ascorbic acid was enhanced by dietary spice principles in normal rats; glutathione was enhanced by their combination only in hypercholesterolemic rats. Activities of serum glutathione reductase, glutathione transferase and catalase and hepatic glutathione reductase in normal rats and serum glutathione peroxidase in hypercholesterolemic rats were enhanced by dietary spice principles. While dietary curcumin and capsaicin normalized the changes in the levels of antioxidant molecules and activities of antioxidant enzymes to a significant extent, this effect was not generally additive when given in combination, and was higher than the individual effects only in a few instances.

  14. Autoradiographic localization of substance P receptors in the rat and bovine spinal cord and the rat and cat spinal trigeminal nucleus pars caudalis and the effects of neonatal capsaicin

    Energy Technology Data Exchange (ETDEWEB)

    Mantyh, P.W.; Hunt, S.P. (Medical Research Council Centre, Cambridge (UK). Medical School, MRC Neurochemical Pharmacology Unit)

    1985-04-22

    Substance P (SP) is a putative neurotransmitter in the central nervous system. In the present report the authors have used autoradiographic receptor binding techniques to investigate the distribution of SP receptor binding sites in the rat and bovine spinal cord and in the rat and cat spinal trigeminal nucleus pars caudalis. Although some quantitative differences were evident, all species appeared to have a similar distribution of SP receptor binding sites in both the spinal cord and in the spinal trigeminal nucleus pars caudalis. In the spinal cord the heaviest concentration of SP receptors is located in lamina X, while moderate to heavy concentrations were found in laminae I, II and V-IX. Very low concentrations of SP receptors were present in laminae III and IV. Examination of the cat and rat spinal trigeminal nucleus pars caudalis revealed a moderate density of SP receptor binding sites in laminae I and II, very low concentrations in laminae III and IV, and low to moderate concentrations in lamina V. Rats treated neonatally with capsaicin showed a small (11%) but significant (P < 0.02) increase in the levels of SP receptor binding sites in laminae I and II of the cervical and lumbar spinal cord while in all other laminae the levels remained unchanged.

  15. Capsaicin-induced changes in LTP in the lateral amygdala are mediated by TRPV1.

    Directory of Open Access Journals (Sweden)

    Carsten Zschenderlein

    Full Text Available The transient receptor potential vanilloid type 1 (TRPV1 channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA. Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1, AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.

  16. Effects of relaxation and stress on the capsaicin-induced local inflammatory response.

    Science.gov (United States)

    Lutgendorf, S; Logan, H; Kirchner, H L; Rothrock, N; Svengalis, S; Iverson, K; Lubaroff, D

    2000-01-01

    Although stress is known to modulate the inflammatory response, there has been little experimental examination of the effects of stress and stress reduction on inflammation in humans. In particular, the effects of stress and relaxation on neurogenic inflammation have been minimally studied. This study examines the effects of three experimental manipulations: mental stress, relaxation, and control on the local inflammatory response evoked by the intradermal injection of capsaicin, the active ingredient in chili peppers. Fifty subjects (28 men and 22 women) were pretrained in relaxation using an imagery-based relaxation tape and then randomized to experimental condition. Subjects participated in an evening reactivity session including 20 minutes of a stress (Stroop test), relaxation (tape), or control (video) manipulation, followed by a capsaicin injection in the forearm. Digitized flare measurements were taken for 1 hour postcapsaicin, and measurements of cardiovascular variables, cortisol, adrenocorticotrophic hormone, and norepinephrine were taken at regular intervals. The size of the maximum capsaicin-induced flare was significantly smaller in the relaxation condition than in the stress or control conditions, which did not differ from each other. Increases in norepinephrine, heart rate, and systolic blood pressure during the experimental task, but not after capsaicin, significantly predicted size of maximum flare and total area under the curve of flare measurements. These findings suggest that stress reduction may affect local inflammatory processes. Results are consistent with sympathetic modulation of the effects of relaxation on the flare response.

  17. Trigeminal nociception-induced, cerebral Fos expression in the conscious rat

    NARCIS (Netherlands)

    Ter Horst, GJ; Meijler, WJ; Korf, J; Kemper, RHA

    2001-01-01

    Little is known about trigeminal nociception-induced cerebral activity and involvement of cerebral structures in pathogenesis of trigeminovascular headaches such as migraine. Neuroimaging has demonstrated cortical, hypothalamic and brainstem activation during the attack and after abolition with suma

  18. Capsaicin protects endothelial cells and macrophage against oxidized low-density lipoprotein-induced injury by direct antioxidant action.

    Science.gov (United States)

    Chen, Kuo-Shuen; Chen, Pei-Ni; Hsieh, Yih-Shou; Lin, Chin-Yin; Lee, Yi-Hsun; Chu, Shu-Chen

    2015-02-25

    Atherosclerosis is a chronic inflammatory vascular disease. It is characterized by endothelial dysfunction, lipid accumulation, leukocyte activation, and the production of inflammatory mediators and reactive oxygen species (ROS). Capsaicin, a biologically active compound of the red pepper and chili pepper, has several anti-oxidant, anti-inflammatory, anti-cancer, and hypolipidemic biological effects. However, its protective effects on foam cell formation and endothelial injury induced by oxidized low-density lipoprotein (oxLDL) remain unclear. In this study, we evaluated the anti-oxidative activity of capsaicin, and determined the mechanism by which capsaicin rescues human umbilical vein endothelial cells (HUVECs) from oxLDL-mediated dysfunction. The anti-oxidative activity of capsaicin was defined by Apo B fragmentation and conjugated diene production of the copper-mediated oxidation of LDL. Capsaicin repressed ROS generation, as well as subsequent mitochondrial membrane potential collapse, cytochrome c expression, chromosome condensation, and caspase-3 activation induced by oxLDL in HUVECs. Capsaicin also protected foam cell formation in macrophage RAW 264.7 cells. Our results suggest that capsaicin may prevent oxLDL-induced cellular dysfunction and protect RAW 264.7 cells from LDL oxidation.

  19. Anti pruritic effects of topical crotamiton, capsaicin, and a corticosteroid on pruritogen-induced scratching behavior.

    Science.gov (United States)

    Sekine, Rika; Satoh, Takahiro; Takaoka, Ayumi; Saeki, Kazumi; Yokozeki, Hiroo

    2012-03-01

    Itch accompanies various skin diseases. As a number of mediators other than histamine can be involved in the itch sensation, H1 receptor antagonists are not necessarily effective in treating itch. External application of antipruritic drugs is occasionally used as an alternative therapy for pruritic skin conditions, such as pruritus on primary non-diseased, non-inflamed skin. Even so, the actual effects of these drugs on the itch sensation have yet to be studied in detail. To verify the antipruritic effects of crotamiton, capsaicin, and a corticosteroid on the itch sensation, we examined the inhibitory effects of these drugs on various pruritogen-induced scratching behaviors in mice. Topical application of 10% crotamiton moderately inhibited histamine-, serotonin-, and PAR-2 agonist-induced scratching behaviors. Topical capsaicin (0.025%) also exerted a moderate suppressive effect on histamine-, substance P-, and PAR-2 agonist-induced itch responses. Notably, topical corticosteroid (0.05% clobetasol propionate) remarkably inhibited the scratching behaviors induced by all of the pruritogenic agents tested. Therapeutic effects of capsaicin on substance P-induced pruritus did not seem to be mediated by desensitization of the TRPV1 (+) C fibers and/or by altered responsiveness of the mast cells. In addition, the antipruritic effects of crotamiton and corticosteroid appear to be, at least partly, associated with a TRPV1-independent pathway. This study examined the itch responses to pruritogens and demonstrated the mode of action of the externally applied antipruritic drugs. © 2011 John Wiley & Sons A/S.

  20. Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans

    DEFF Research Database (Denmark)

    Gottrup, Hanne; Hansen, Peter Orm; Arendt-Nielsen, Lars;

    2000-01-01

    We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments....... Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following...

  1. Reproducibility of the capsaicin-induced dermal blood flow response as assessed by laser Doppler perfusion imaging

    OpenAIRE

    Van der Schueren, B. J.; Hoon, J.N.; Vanmolkot, F H; Van Hecken, A; Depre, M; Kane, S A; De Lepeleire, I.; Sinclair, S R

    2007-01-01

    What is already known about this subjectCapsaicin rapidly produces local neurogenic inflammation (characterized by oedema and erythema) when locally administered to the human skin by binding to the TRPV1 receptor present on dermal sensory nerve endings.In nonhuman primates, a pharmacodynamic assay has been described and validated using capsaicin-induced dermal vasodilation measured by laser Doppler perfusion imaging to assess calcitonin gene-related peptide antagonist activity.Laser Doppler p...

  2. Capsaicin-induced transcriptional changes in hypothalamus and alterations in gut microbial count in high fat diet fed mice.

    Science.gov (United States)

    Baboota, Ritesh K; Murtaza, Nida; Jagtap, Sneha; Singh, Dhirendra P; Karmase, Aniket; Kaur, Jaspreet; Bhutani, Kamlesh K; Boparai, Ravneet K; Premkumar, Louis S; Kondepudi, Kanthi Kiran; Bishnoi, Mahendra

    2014-09-01

    Obesity is a global health problem and recently it has been seen as a growing concern for developing countries. Several bioactive dietary molecules have been associated with amelioration of obesity and associated complications and capsaicin is one among them. The present work is an attempt to understand and provide evidence for the novel mechanisms of anti-obesity activity of capsaicin in high fat diet (HFD)-fed mice. Swiss albino mice divided in three groups (n=8-10) i.e. control, HFD fed and capsaicin (2mg/kg, po)+HFD fed were administered respective treatment for 3months. After measuring phenotypic and serum related biochemical changes, effect of capsaicin on HFD-induced transcriptional changes in hypothalamus, white adipose tissue (WAT) (visceral and subcutaneous), brown adipose tissue (BAT) and gut microbial alterations was studied and quantified. Our results suggest that, in addition to its well-known effects, oral administration of capsaicin (a) modulates hypothalamic satiety associated genotype, (b) alters gut microbial composition, (c) induces "browning" genotype (BAT associated genes) in subcutaneous WAT and (d) increases expression of thermogenesis and mitochondrial biogenesis genes in BAT. The present study provides evidence for novel and interesting mechanisms to explain the anti-obesity effect of capsaicin.

  3. Hydrogen sulfide determines HNO-induced stimulation of trigeminal afferents.

    Science.gov (United States)

    Wild, Vanessa; Messlinger, Karl; Fischer, Michael J M

    2015-08-18

    Endogenous NO and hydrogen sulfide form HNO, which causes CGRP release via TRPA1 channel activation in sensory nerves. In the present study, stimulation of intact trigeminal afferent neuron preparations with NO donors, Na2S or both was analyzed by measuring CGRP release as an index of mass activation. Combined stimulation was able to activate all parts of the trigeminal system and acted synergistic compared to stimulation with both substances alone. To investigate the contribution of both substances, we varied their ratio and tracked intracellular calcium in isolated neurons. Our results demonstrate that hydrogen sulfide is the rate-limiting factor for HNO formation. CGRP has a key role in migraine pathophysiology and HNO formation at all sites of the trigeminal system should be considered for this novel means of activation.

  4. Trigeminal star-like platinum complexes induce cancer cell senescence through quadruplex-mediated telomere dysfunction.

    Science.gov (United States)

    Zheng, Xiao-Hui; Mu, Ge; Zhong, Yi-Fang; Zhang, Tian-Peng; Cao, Qian; Ji, Liang-Nian; Zhao, Yong; Mao, Zong-Wan

    2016-12-01

    Two trigeminal star-like platinum complexes were synthesized to induce the formation of human telomere G-quadruplex (hTel G4) with extremely high selectivity and affinity. The induced hTel G4 activates strong telomeric DNA damage response (TDDR), resulting in telomere dysfunction and cell senescence.

  5. Capsaicin sensitizes TRAIL-induced apoptosis through Sp1-mediated DR5 up-regulation: Involvement of Ca{sup 2+} influx

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Dong-Oh [Department of Biology Education, Daegu University, Gyungsan, Gyeongbuk 712–714 (Korea, Republic of); Kang, Chang-Hee; Kang, Sang-Hyuck [Department of Marine Life Sciences, Jeju National University, Jeju 690–756 (Korea, Republic of); Choi, Yung-Hyun [Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614–054 (Korea, Republic of); Hyun, Jin-Won; Chang, Weon-Young; Kang, Hee-Kyoung; Koh, Young-Sang; Maeng, Young-Hee; Kim, Young-Ree [School of Medicine, Jeju National University, Jeju-si 690–756 (Korea, Republic of); Kim, Gi-Young, E-mail: immunkim@jejunu.ac.kr [Department of Marine Life Sciences, Jeju National University, Jeju 690–756 (Korea, Republic of)

    2012-02-15

    Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various malignant cells, several cancers including human hepatocellular carcinoma (HCC) exhibit potent resistance to TRAIL-induced cell death. The aim of this study is to evaluate the anti-cancer potential of capsaicin in TRAIL-induced cancer cell death. As indicated by assays that measure phosphatidylserine exposure, mitochondrial activity and activation of caspases, capsaicin potentiated TRAIL-resistant cells to lead to cell death. In addition, we found that capsaicin induces the cell surface expression of TRAIL receptor DR5, but not DR4 through the activation Sp1 on its promoter region. Furthermore, we investigated that capsaicin-induced DR5 expression and apoptosis are inhibited by calcium chelator or inhibitors for calmodulin-dependent protein kinase. Taken together, our data suggest that capsaicin sensitizes TRAIL-mediated HCC cell apoptosis by DR5 up-regulation via calcium influx-dependent Sp1 activation. Highlights: ► Capsaicin sensitizes TRAIL-induced apoptosis through activation of caspases. ► Capsaicin induces expression of DR5 through Sp1 activation. ► Capsaicin activates calcium signaling pathway.

  6. Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC of the infraorbital nerve

    Directory of Open Access Journals (Sweden)

    Ma Fei

    2012-12-01

    Full Text Available Abstract Background Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity. Results The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70. Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks. Conclusions A simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2 is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.

  7. Pattern of neuropathic pain induced by topical capsaicin application in healthy subjects.

    Science.gov (United States)

    Lötsch, Jörn; Dimova, Violeta; Hermens, Hanneke; Zimmermann, Michael; Geisslinger, Gerd; Oertel, Bruno G; Ultsch, Alfred

    2015-03-01

    Human experimental pain models are widely used to study drug effects under controlled conditions, but they require further optimization to better reflect clinical pain conditions. To this end, we measured experimentally induced pain in 110 (46 men) healthy volunteers. The quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain) was applied on untreated ("control") and topical capsaicin-hypersensitized ("test") skin. Z-transformed QST-parameter values obtained at the test site were compared with corresponding values published from 1236 patients with neuropathic pain using Bayesian statistics. Subjects were clustered for the resemblance of their QST pattern to neuropathic pain. Although QST parameter values from the untreated site agreed with reference values, several QST parameters acquired at the test site treated with topical capsaicin deviated from normal. These deviations resembled in 0 to 7 parameters of the QST pattern observed in patients with neuropathic pain. Higher degrees (50%-60%) of resemblance to neuropathic QST pattern were obtained in 18% of the subjects. Inclusion in the respective clusters was predictable at a cross-validated accuracy of 86.9% by a classification and regression tree comprising 3 QST parameters (mechanical pain sensitivity, wind-up ratio, and z-transformed thermal sensory limen) from the control sites. Thus, we found that topical capsaicin partly induced the desired clinical pattern of neuropathic pain in a preselectable subgroup of healthy subjects to a degree that fuels expectations that experimental pain models can be optimized toward mimicking clinical pain. The subjects, therefore, qualify for enrollment in analgesic drug studies that use highly selected cohorts to enhance predictivity for clinical analgesia.

  8. Expression of inducible nitric oxide synthase in trigeminal ganglion cells during culture

    DEFF Research Database (Denmark)

    Jansen-Olesen, Inger; Zhou, MingFang; Zinck, Tina Jovanovic

    2005-01-01

    , reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. In trigeminal ganglia cells not subjected to culture, endothelial (e) and neuronal (n) but not inducible (i) NOS mRNA and protein were detected. Culture of rat neurones resulted in a rapid axonal outgrowth of NOS positive...... fibres. At 12, 24 and 48 hr of culture, NOS immunoreactivity was detected in medium-sized trigeminal ganglia cells. Western blotting and RT-PCR revealed an up-regulation of inducible iNOS expression during culture. However, after culture only low levels of eNOS protein was found while no eNOS and nNOS m......RNA and protein could be detected. The data suggest that iNOS expression may be a molecular mechanism mediating the adaptive response of trigeminal ganglia cells to the serum free stressful stimulus the culture environment provides. It may act as a cellular signalling molecule that is expressed after cell...

  9. Positive allosteric modulation of GABA-A receptors reduces capsaicin-induced primary and secondary hypersensitivity in rats

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Erichsen, Helle K; Brown, David T

    2012-01-01

    this concept being tested in humans. Prior to assessing the efficacy of GABA-A receptor PAMs in a human volunteer pain model we have compared compounds capable of variously modulating GABA-A receptor function in comparable rat models of capsaicin-induced acute nocifensive flinching behaviour and secondary...... mechanical hypersensitivity. The subtype-selective PAM NS11394 (0.3-10 mg/kg), and the non-selective PAM diazepam (1-5 mg/kg) variously reduced capsaicin-induced secondary mechanical hypersensitivity (180 min post-injection). However, the low efficacy subtype-selective PAM TPA023 (3-30 mg/kg) was completely......, albeit at doses previously shown to impair locomotor function. Our data indicate that GABA-A receptor PAMs with optimal selectivity and efficacy profiles reduce centrally-mediated mechanical hypersensitivity in capsaicin-injected rats, an observation that we expect can translate directly to human...

  10. Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice.

    Science.gov (United States)

    Liu, Zhaoguo; Zhu, Pingting; Tao, Yu; Shen, Cunsi; Wang, Siliang; Zhao, Lingang; Wu, Hongyan; Fan, Fangtian; Lin, Chao; Chen, Chen; Zhu, Zhijie; Wei, Zhonghong; Sun, Lihua; Liu, Yuping; Wang, Aiyun; Lu, Yin

    2015-07-01

    Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-κB), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels.

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    Iwaoka, Emiko; Wang, Shenglan; Matsuyoshi, Nobuyuki; Kogure, Yoko; Aoki, Shunji; Yamamoto, Satoshi; Noguchi, Koichi; Dai, Yi

    2016-01-01

    Evodiae fructus (EF), a fruit of Evodia rutaecarpa Bentham, has long been used as an analgesic drug in traditional Chinese and Japanese medicine. However, the underlying molecular mechanism of its pharmacological action is unclear. Here, using calcium imaging, whole-cell patch-clamp recording, and behavioral analysis, we investigated the pharmacological action of EF and its principal compound, evodiamine, on the transient receptor potential (TRP) V1 channels. Dorsal root ganglion (DRG) neurons and TRPV1- or TRPA1-transfected human embryonic kidney-derived (HEK) 293 cells were used for calcium imaging or whole-cell patch-clamp recording. Twenty male adult Sprague-Dawley rats were used for the capsaicin-induced thermal hyperalgesia behavioral analyses. We found that evodiamine induced significant increases in intracellular calcium and robust inward currents in a subpopulation of isolated rat DRG neurons, most of which were also sensitive to capsaicin. The effect of evodiamine was completely blocked by capsazepine, a competitive antagonist of TRPV1. Evodiamine induced significant inward currents in TRPV1-, but not TRPA1-transfected HEK293 cells. Pretreatment with evodiamine reduced capsaicin-induced currents significantly. Furthermore, the in vivo pre-treatment of evodiamine suppressed thermal hyperalgesia induced by intraplantar injection of capsaicin in rats. These results identify that the analgesic effect of EF and evodiamine may be due to the activation and subsequent desensitization of TRPV1 in sensory neurons.

  12. The reversible increase in tight junction permeability induced by capsaicin is mediated via cofilin-actin cytoskeletal dynamics and decreased level of occludin.

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    Tomoko Shiobara

    Full Text Available Previous results demonstrated that capsaicin induces the reversible tight junctions (TJ opening via cofilin activation. The present study investigated the mechanisms underlying the reversible TJ opening and compared the effect to the irreversible opening induced by actin inhibitors. Capsaicin treatment induced the F-actin alteration unique to capsaicin compared to actin-interacting agents such as latrunculin A, which opens TJ irreversibly. Along with TJ opening, capsaicin decreased the level of F-actin at bicellular junctions but increased it at tricellular junctions accompanied with its concentration on the apical side of the lateral membrane. No change in TJ protein localization was observed upon exposure to capsaicin, but the amount of occludin was decreased significantly. In addition, cosedimentation analyses suggested a decrease in the interactions forming TJ, thereby weakening TJ tightness. Introduction of cofilin, LIMK and occludin into the cell monolayers confirmed their contribution to the transepithelial electrical resistance decrease. Finally, exposure of monolayers to capsaicin augmented the paracellular passage of both charged and uncharged compounds, as well as of insulin, indicating that capsaicin can be employed to modulate epithelial permeability. Our results demonstrate that capsaicin induces TJ opening through a unique mechanism, and suggest that it is a new type of paracellular permeability enhancer.

  13. Evaluation through in vivo reflectance confocal microscopy of the cutaneous neurogenic inflammatory reaction induced by capsaicin in human subjects

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    Căruntu, Constantin; Boda, Daniel

    2012-08-01

    We perform an in vivo analysis of the effects of capsaicin on cutaneous microvascularization. A total of 29 healthy subjects are administered a solution of capsaicin (CAP group) or a vehicle solution (nonCAP group) on the dorsal side of the nondominant hand. The evaluation is performed using in vivo reflectance confocal microscopy (RCM). Ten minutes after administration, the area of the section, the perimeter, and the Feret's diameter of the capillaries in the dermal papillae become significantly larger in the CAP group as against the nonCAP group, and this difference is maintained until the conclusion of the experiment. In vivo RCM allows the investigation of cutaneous vascular reactions induced by capsaicin. As such, this method may constitute an useful technique both for research and clinical practice.

  14. Trigeminally induced cardiovascular reflex responses in spinalized rats.

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    Ideguchi, S; Hotta, H; Suzuki, A; Umino, M

    2000-03-15

    The effects on cardiovascular functions of noxious stimulation to the orofacial areas innervated by trigeminal afferent nerves were analyzed in urethane-anesthetized, spinal cord-intact rats and in rats acutely spinalized at the second cervical level. In the spinal cord-intact rats, pinching of the upper lip produced increases in both heart rate (HR) and mean arterial pressure (MAP). Both responses were considered to be due to activation of sympathetic efferent nerves to the cardiovascular organs. Both responses were attenuated but did not disappear after spinalization at the C2 level. In spinalized rats, sympathetic preganglionic neurons emerging from the thoracolumbar spinal cord could not receive any neural influences from the brain. The HR response in the spinal rats was abolished after either bilateral vagotomy or intravenous injection of a peripherally acting muscarinic cholinergic receptor antagonist, methylatropine. This suggests that the increase in HR was elicited via vagal cholinergic efferent fibers, probably by decreasing tonic activity of vagus nerves to the heart. In spinal rats, neither vagotomy nor cholinergic blockade affected the increase in MAP, but i.v. injection of the vasopressin V1 receptor antagonist, OPC-21268, abolished the response of MAP. This suggests that the response of MAP was due to peripheral vasoconstriction elicited by vasopressin secreted from the posterior pituitary lobe. The present study demonstrated that, in rats acutely spinalized at the C2 level, noxious stimulation of orofacial areas innervated by the trigeminal nerve could produce reflex increases both in HR, by decreasing cholinergic vagal nerve activity to the heart, and blood pressure, by secreting vasopressin from the pituitary gland, even though sympathetic efferent innervation to the cardiovascular organs could not be directly affected by trigeminal afferent nerve excitation.

  15. Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice : spinal cord c-Fos expression and behavior

    NARCIS (Netherlands)

    Eijkelkamp, Niels; Kavelaars, Annemieke; Elsenbruch, Sigrid; Schedlowski, Manfred; Holtmann, Gerald; Heijnen, Cobi J.

    2007-01-01

    Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice: spinal cord c-Fos expression and behavior. Am J Physiol Gastrointest Liver Physiol 293: G749-G757, 2007. First published July 26, 2007; doi:10.1152/ajpgi.00114.2007.During acute and chronic inflammation visceral pain perc

  16. Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice : spinal cord c-Fos expression and behavior

    NARCIS (Netherlands)

    Eijkelkamp, Niels; Kavelaars, Annemieke; Elsenbruch, Sigrid; Schedlowski, Manfred; Holtmann, Gerald; Heijnen, Cobi J.

    2007-01-01

    Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice: spinal cord c-Fos expression and behavior. Am J Physiol Gastrointest Liver Physiol 293: G749-G757, 2007. First published July 26, 2007; doi:10.1152/ajpgi.00114.2007.During acute and chronic inflammation visceral pain

  17. Effect of delayed intrathecal administration of capsaicin on neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats

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    Zhang K

    2014-09-01

    Full Text Available Kun Zhang,1 Somayaji Ramamurthy,1 Thomas J Prihoda,2 Maxim S Eckmann1 1Department of Anesthesiology, 2Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA Purpose: The current study was designed to examine the antinociceptive effect of intrathecally administered capsaicin, a transient receptor potential vanilloid 1 receptor agonist, in a rat model of neuropathic pain induced by unilateral sciatic nerve chronic constriction injury. Methods: Male adult Sprague Dawley rats were randomly assigned to six groups, and all rats underwent unilateral sciatic nerve chronic constriction injury. Two weeks after injury, five groups received intrathecal administration of either capsaicin in three different dosing regimens or equal volumes of vehicle. The other group received intrathecal capsaicin on the third day after nerve injury. The antinociceptive effect of capsaicin was assessed by measuring the capsaicin-induced change in thermal and mechanical response thresholds. Results: Capsaicin (150–300 µg/100–200 µL, when administered by fast infusion or chronic infusions at 8 µL/hour or 1 µL/hour, attenuated thermal hyperalgesia as indicated by significantly prolonging paw withdrawal latency to noxious thermal stimulation. The antinociceptive effect of capsaicin was more profound in the injured limb compared to that in the uninjured limb. When capsaicin was administered on the third day after nerve injury, it failed to attenuate thermal hyperalgesia. No significant effect on the mechanical response threshold was observed with intrathecally administered capsaicin. Conclusion: Our data suggest that intrathecal capsaicin could significantly attenuate thermal hyperalgesia, depending on the time when the drug is given after nerve injury, and that the antinociceptive efficacy of intrathecal capsaicin positively correlates with the previously reported dynamic profile of spinal transient receptor potential

  18. Intraplantar injection of bergamot essential oil into the mouse hindpaw: effects on capsaicin-induced nociceptive behaviors.

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    Sakurada, Tsukasa; Kuwahata, Hikari; Katsuyama, Soh; Komatsu, Takaaki; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Sakurada, Shinobu

    2009-01-01

    Despite the increasing use of aromatherapy oils, there have not been many studies exploring the biological activities of bergamot (Citrus bergamia, Risso) essential oil (BEO). Recently, we have investigated the effects of BEO injected into the plantar surface of the hindpaw in the capsaicin test in mice. The intraplantar injection of capsaicin produced an intense and short-lived licking/biting response toward the injected hindpaw. The capsaicin-induced nociceptive response was reduced significantly by intraplantar injection of BEO. The essential oils of Clary Sage (Salvia sclarea), Thyme ct. linalool (linalool chemotype of Thymus vulgaris), Lavender Reydovan (Lavandula hybrida reydovan), and True Lavender (Lavandula angustifolia), had similar antinociceptive effects on the capsaicin-induced nociceptive response, while Orange Sweet (Citrus sinensis) essential oil was without effect. In contrast to a small number of pharmacological studies of BEO, there is ample evidence regarding isolated components of BEO which are also found in other essential oils. The most abundant compounds found in the volatile fraction are the monoterpene hydrocarbons, such as limonene, gamma-terpinene, beta-pinene, and oxygenated derivatives, linalool and linalyl acetate. Of these monoterpenes, the pharmacological activities of linalool have been examined. Following intraperitoneal (i.p.) administration in mice, linalool produces antinociceptive and antihyperalgesic effects in different animal models in addition to anti-inflammatory properties. Linalool also possesses anticonvulsant activity in experimental models of epilepsy. We address the importance of linalool or linalyl acetate in BEO-or the other essential oil-induced antinociception.

  19. σ1 receptors are involved in the visceral pain induced by intracolonic administration of capsaicin in mice.

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    González-Cano, Rafael; Merlos, Manuel; Baeyens, José M; Cendán, Cruz M

    2013-03-01

    Visceral pain is an important and prevalent clinical condition whose treatment is challenging. Sigma-1 (σ1) receptors modulate somatic pain, but their involvement in pure visceral pain is unexplored. The authors evaluated the role of σ1 receptors in intracolonic capsaicin-induced visceral pain (pain-related behaviors and referred mechanical hyperalgesia to the abdominal wall) using wild-type (WT) (n = 12 per group) and σ1 receptor knockout (σ1-KO) (n = 10 per group) mice, selective σ1 receptor antagonists (BD-1063, S1RA, and NE-100), and control drugs (morphine and ketoprofen). The intracolonic administration of capsaicin (0.01-1%) induced concentration-dependent visceral pain-related behaviors and referred hyperalgesia in both WT and σ1-KO mice. However, the maximum number of pain-related behaviors induced by 1% capsaicin in σ1-KO mice (mean ± SEM, 22 ± 2.9) was 48% of that observed in WT animals (46 ± 4.2). Subcutaneous administration of the σ1 receptor antagonists BD-1063 (16-64 mg/kg), S1RA (32-128 mg/kg), and NE-100 (8-64 mg/kg) dose-dependently reduced the number of behavioral responses (by 53, 62, and 58%, respectively) and reversed the referred hyperalgesia to mechanical control threshold (0.53 ± 0.05 g) in WT mice. In contrast, these drugs produced no change in σ1-KO mice. Thus, the effects of these drugs are specifically mediated by σ1 receptors. Morphine produced an inhibition of capsaicin-induced visceral pain in WT and σ1-KO mice, whereas ketoprofen had no effect in either mouse type. These results suggest that σ1 receptors play a role in the mechanisms underlying capsaicin-induced visceral pain and raise novel perspectives for their potential therapeutic value.

  20. Capsaicin ameliorates stress-induced Alzheimer's disease-like pathological and cognitive impairments in rats.

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    Jiang, Xia; Jia, Lin-Wei; Li, Xiao-Hong; Cheng, Xiang-Shu; Xie, Jia-Zhao; Ma, Zhi-Wei; Xu, Wei-Jie; Liu, Yue; Yao, Yun; Du, Lai-Ling; Zhou, Xin-Wen

    2013-01-01

    Hyperphosphorylated tau aggregated into neurofibrillary tangles is a hallmark lesion of Alzheimer's disease (AD) and is linked to synaptic and cognitive impairments. In animal models, cold water stress (CWS) can cause cognitive disorder and tau hyperphosphorylation. Capsaicin (CAP), a specific TRPV1 agonist, is neuroprotective against stress-induced impairment, but the detailed mechanisms are still elusive. Here, we investigated whether CAP mitigates CWS-induced cognitive and AD-like pathological alterations in rats. The animals were administered CAP (10 mg/kg in 0.2 ml, 0.1% ethanol) or a control (0.2 ml normal saline, 0.1% ethanol) by intragastric infusion 1 h before CWS treatment. Our results showed that CAP significantly attenuated CWS-induced spatial memory impairment and suppression of PP-DG long-term potentiation; CAP abolished CWS-induced dendritic regression and enhanced several memory-associated proteins decreased by CWS, such as synapsin I and PSD93; CAP also prevented CWS-induced tau hyperphosphorylation by abolishing inhibition of protein phosphatase 2A. Taken together, this study demonstrated that activation of TRPV1 can mitigate CWS-induced AD-like neuropathological alterations and cognitive impairment and may be a promising target for therapeutic intervention in AD.

  1. Pharmacological characterisation of capsaicin-induced relaxations in human and porcine isolated arteries

    NARCIS (Netherlands)

    S. Gupta (Sanjay); J. Lozano-Cuenca (Jair); C.M. Villalón (Carlos); R. de Vries (René); I.M. Garrelds (Ingrid); C.J.J. Avezaat (Cees); J.P. van Kats (Sjors); P.R. Saxena (Pramod Ranjan); A. Maassen VanDenBrink (Antoinette)

    2007-01-01

    textabstractCapsaicin, a pungent constituent from red chilli peppers, activates sensory nerve fibres via transient receptor potential vanilloid receptors type 1 (TRPV1) to release neuropeptides like calcitonin gene-related peptide (CGRP) and substance P. Capsaicin-sensitive nerves are widely distrib

  2. [ROLE OF CAPSAICIN-SENSITIVE NERVES IN THE REGULATION OF DEHYDROEPIANDROSTERONE SULFATE BLOOD CONTENT UNDER NORMAL AND FRUCTOSE-INDUCED METABOLIC SYNDROME].

    Science.gov (United States)

    Spiridonov, V K; Tolochko, Z S; Ovcjukova, M V; Kostina, N E; Obut, T A

    2015-08-01

    The effects of the stimulation of capsaicin-sensitive nerves (capsaicin, 1 mg/kg, s/c) and their eafferentation (capsaicin, 150 mg/kg, s/c) on the blood content of dehydroepiandrosterone sulfate (DHEAS) was investigated in normal rats and rats with fructose-induced metabolic syndrome (12.5% fructose solution, 10 weeks). An increase in blood of tryglyceride, lipid peroxidation, glucose (fasting and after loading glucose, 2 mg/kg, i/p) was considered as symptoms of metabolic syndrome. It was shown that in normal rats drinking tap water the stimulation of capsaicin-sensitive nerves resulted in the increase of DHEAS content while their deafferentation reduced the concentration of this hormone in the blood. The fructose diet caused the decrease in content of DHEAS, triglyceridemia, lipid peroxidation, impaired tolerance glucose. In rats with the metabolic syndrome the stimulation capsaicin-sensitive nerves prevented the fructose-induced decrease of DHEAS content as well as decreased the symptoms of metabolic syndrome. In fructose fed rats the stimulation-induced effects were prevented by the deafferentation of capsaicin-sensitive nerves. It is suggested that capsaicin-sensitive nerves contribute both to the regulation of blood content of DHEAS under normal and fructose-induced metabolic syndrome.

  3. Changes in synaptic effectiveness of myelinated joint afferents during capsaicin-induced inflammation of the footpad in the anesthetized cat.

    Science.gov (United States)

    Rudomin, P; Hernández, E

    2008-05-01

    The present series of experiments was designed to examine, in the anesthetized cat, the extent to which the synaptic efficacy of knee joint afferents is modified during the state of central sensitization produced by the injection of capsaicin into the hindlimb plantar cushion. We found that the intradermic injection of capsaicin increased the N2 and N3 components of the focal potentials produced by stimulation of intermediate and high threshold myelinated fibers in the posterior articular nerve (PAN), respectively. This facilitation lasted several hours, had about the same time course as the paw inflammation and was more evident for the N2 and N3 potentials recorded within the intermediate zone in the L6 than in the L7 spinal segments. The capsaicin-induced facilitation of the N2 focal potentials, which are assumed to be generated by activation of fibers signaling joint position, suggests that nociception may affect the processing of proprioceptive and somato-sensory information and, probably also, movement. In addition, the increased effectiveness of these afferents could activate, besides neurons in the intermediate region, neurons located in the more superficial layers of the dorsal horn. As a consequence, normal joint movements could produce pain representing a secondary hyperalgesia. The capsaicin-induced increased efficacy of the PAN afferents producing the N3 focal potentials, together with the reduced post-activation depression that follows high frequency autogenetic stimulation of these afferents, could further contribute to the pain sensation from non-inflamed joints during skin inflammation in humans. The persistence, after capsaicin, of the inhibitory effects produced by stimulation of cutaneous nerves innervating non-inflamed skin regions may account for the reported reduction of the articular pain sensations produced by trans-cutaneous stimulation.

  4. Anti-Inflammatory Effects of Capsaicin and Piperine on Helicobacter pylori-Induced Chronic Gastritis in Mongolian Gerbils.

    Science.gov (United States)

    Toyoda, Takeshi; Shi, Liang; Takasu, Shinji; Cho, Young-Man; Kiriyama, Yuka; Nishikawa, Akiyoshi; Ogawa, Kumiko; Tatematsu, Masae; Tsukamoto, Tetsuya

    2016-04-01

    Spices have been used for thousands of years, and recent studies suggest that certain spices confer beneficial effects on gastric disorders. The purpose of this study was to evaluate possible chemopreventive effects of spice-derived compounds on Helicobacter pylori (H. pylori)-induced gastritis. We examined the inhibitory effects of curcumin, capsaicin, and piperine on H. pylori in vitro by determining the colony-forming units and real-time RT-PCR in H. pylori stimulated AGS gastric cancer cells. For in vivo analysis, 6-week-old SPF male Mongolian gerbils were infected with H. pylori, fed diets containing 5000 ppm curcumin, 100 ppm capsaicin, or 100 ppm piperine, and sacrificed after 13 weeks. All three compounds inhibited in vitro proliferation of H. pylori, with curcumin being the most effective. Infiltration of neutrophils and mononuclear cells was suppressed by piperine both in the antrum and corpus of H. pylori-infected gerbils. Capsaicin also decreased neutrophils in the antrum and corpus and mononuclear cell infiltration and heterotopic proliferative glands in the corpus. mRNA expression of Tnf-α and formation of phospho-IκB-α in the antrum were reduced by both capsaicin and piperine. In addition, piperine suppressed expression of Il-1β, Ifn-γ, Il-6, and iNos, while H. pylori UreA and other virulence factors were not significantly attenuated by any compounds. These results suggest that capsaicin and piperine have anti-inflammatory effects on H. pylori-induced gastritis in gerbils independent of direct antibacterial effects and may thus have potential for use in the chemoprevention of H. pylori-associated gastric carcinogenesis. © 2015 John Wiley & Sons Ltd.

  5. Capsaicin induces cytotoxicity in pancreatic neuroendocrine tumor cells via mitochondrial action.

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    Skrzypski, M; Sassek, M; Abdelmessih, S; Mergler, S; Grötzinger, C; Metzke, D; Wojciechowicz, T; Nowak, K W; Strowski, M Z

    2014-01-01

    Capsaicin (CAP), the pungent ingredient of chili peppers, inhibits growth of various solid cancers via TRPV1 as well as TRPV1-independent mechanisms. Recently, we showed that TRPV1 regulates intracellular calcium level and chromogranin A secretion in pancreatic neuroendocrine tumor (NET) cells. In the present study, we characterize the role of the TRPV1 agonist - CAP - in controlling proliferation and apoptosis of pancreatic BON and QGP-1 NET cells. We demonstrate that CAP reduces viability and proliferation, and stimulates apoptotic death of NET cells. CAP causes mitochondrial membrane potential loss, inhibits ATP synthesis and reduces mitochondrial Bcl-2 protein production. In addition, CAP increases cytochrome c and cleaved caspase 3 levels in cytoplasm. CAP reduces reactive oxygen species (ROS) generation. The antioxidant N-acetyl-l-cysteine (NAC) acts synergistically with CAP to reduce ROS generation, without affecting CAP-induced toxicity. TRPV1 protein reduction by 75% reduction fails to attenuate CAP-induced cytotoxicity. In summary, these results suggest that CAP induces cytotoxicity by disturbing mitochondrial potential, and inhibits ATP synthesis in NET cells. Stimulation of ROS generation by CAP appears to be a secondary effect, not related to CAP-induced cytotoxicity. These results justify further evaluation of CAP in modulating pancreatic NETs in vivo.

  6. Evaluation of a novel mouse model of intracisternal strychnine-induced trigeminal allodynia.

    Science.gov (United States)

    Lee, Il-Ok; Whitehead, Ryan A; Ries, Craig R; Schwarz, Stephan K W; Puil, Ernest; MacLeod, Bernard A

    2013-08-01

    Intractable neuropathic dynamic allodynia remains one of the major symptoms of human trigeminal neuropathy and is commonly accepted to be the most excruciatingly painful condition known to humankind. At present, a validated animal model of this disorder is necessary for efficient and effective development of novel drug treatments. Intracisternal strychnine in rats has been shown to result in localized trigeminal dynamic allodynia, thus representing a possible model of trigeminal neuralgia. The purpose of this study was to validate a mouse model of trigeminal glycinergic inhibitory dysfunction using established positive (carbamazepine epoxide) and negative (morphine) controls. The actions of conventional first-line treatment (carbamazepine epoxide [CBZe]) and clinically ineffective morphine were tested for trigeminal dynamic mechanical allodynia produced by intracisternal strychnine. In mice under halothane anesthesia, we injected either strychnine (0.3 μg), strychnine with CBZe (4 ng), or artificial cerebrospinal fluid (aCSF) intracisternally (i.c.). In a separate set of experiments, subcutaneous morphine (3 mg·kg(-1) sc) was injected with intracisternal strychnine. Dynamic mechanical allodynia was induced by stroking the fur with polyethylene (PE-10) tubing. The response of each mouse was rated to determine its allodynia score, and scores of each group were compared. In addition, in a separate dichotomous disequilibrium study, pairs of mice were injected with strychnine/saline, strychnine/strychnine-CBZe, or strychnine/strychnine-morphine. A blinded observer recorded which mouse of each pair had the greater global pain behaviour. Strychnine (i.c.) produced higher quantitative allodynia scores in the trigeminal distribution (mean 81.5%; 95% confidence interval [CI] 76.4 to 86.6) vs the aCSF group (mean 11.3%; 95% CI 8.1 to 14.4) (P strychnine (mean 83.2%; 95% CI 78.1 to 88.4) vs strychnine alone (mean 3.2%; 95% CI -0.9 to 7.2) (P strychnine did not result in

  7. Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats

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    Esmaeal Tamaddonfard

    2015-08-01

    Full Text Available Objectives: Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist. Materials and Methods: A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c. injection of capsaicin (1.5 µg/20 µl into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test. Results: Intra-fourth ventricle injection of crocin (10 and 40 µg/rat and morphine (10 and 40 µg/rat and their co-administration (2.5 and 10 µg/rat of each suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat, was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity. Conclusion: The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.

  8. Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Tamaddonfard, Sina; Pourbaba, Salar

    2015-01-01

    Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist. A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c.) injection of capsaicin (1.5 µg/20 µl) into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test. Intra-fourth ventricle injection of crocin (10 and 40 µg/rat) and morphine (10 and 40 µg/rat) and their co-administration (2.5 and 10 µg/rat of each) suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat), was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity. The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.

  9. The potentiating effect of calcitonin gene-related peptide on transient receptor potential vanilloid-1 activity and the electrophysiological responses of rat trigeminal neurons to nociceptive stimuli.

    Science.gov (United States)

    Chatchaisak, Duangthip; Connor, Mark; Srikiatkhachorn, Anan; Chetsawang, Banthit

    2017-02-15

    Growing evidence suggests that calcitonin gene-related peptide (CGRP) participates in trigeminal nociceptive responses. However, the role of CGRP in sensitization or desensitization of nociceptive transduction remains poorly understood. In this study, we sought to further investigate the CGRP-induced up-regulation of transient receptor potential vanilloid-1 (TRPV1) and the responses of trigeminal neurons to nociceptive stimuli. Rat trigeminal ganglion (TG) organ cultures and isolated trigeminal neurons were incubated with CGRP. An increase in TRPV1 levels was observed in CGRP-incubated TG organ cultures. CGRP potentiated capsaicin-induced increase in phosphorylated CaMKII levels in the TG organ cultures. The incubation of the trigeminal neurons with CGRP significantly increased the inward currents in response to capsaicin challenge, and this effect was inhibited by co-incubation with the CGRP receptor antagonist, BIBN4068BS or the inhibitor of protein kinase A, H-89. These findings reveal that CGRP acting on trigeminal neurons may play a significant role in facilitating cellular events that contribute to the peripheral sensitization of the TG in nociceptive transmission.

  10. Thermal conditions influence changes in body temperature induced by intragastric administration of capsaicin in mice.

    Science.gov (United States)

    Mori, Noriyuki; Urata, Tomomi; Fukuwatari, Tsutomu

    2016-08-01

    Capsaicin has been reported to have unique thermoregulatory actions. However, changes in core temperature after the administration of capsaicin are a controversial point. Therefore, we investigated the effects of environmental thermal conditions on changes in body temperature caused by capsaicin in mice. We showed that intragastric administration of 10 and 15 mg/kg capsaicin increased tail temperature and decreased colonic temperatures in the core temperature (CT)-constant and CT-decreasing conditions. In the CT-increasing condition, 15 mg/kg capsaicin increased tail temperature and decreased colonic temperature. However, 10 mg/kg capsaicin increased colonic temperature. Furthermore, the amount of increase in tail temperature was greater in the CT-decreasing condition and lower in the CT-increasing condition, compared with that of the CT-constant condition. These findings suggest that the changes in core temperature were affected by the environmental thermal conditions and that preliminary thermoregulation state might be more important than the constancy of temperature to evaluate the effects of heat diffusion and thermogensis.

  11. Neural proliferation and restoration of neurochemical phenotypes and compromised functions following capsaicin-induced neuronal damage in the nodose ganglion of the adult rat.

    Directory of Open Access Journals (Sweden)

    Zachary Rex Gallaher

    2011-02-01

    Full Text Available We previously reported that neuronal numbers within adult nodose ganglia (NG were restored to normal levels 60 days following the capsaicin-induced destruction of nearly half of the neuronal population. However, the nature of this neuronal replacement is not known. Therefore, we aimed to characterize neural proliferation, neurochemical phenotypes, and functional recovery within adult rat NG neurons following capsaicin-induced damage. Sprague-Dawley rats received intraperitoneal injections of capsaicin or vehicle solution, followed by BrdU injections to reveal cellular proliferation. NG were collected at multiple times post-treatment (up to 300 days and processed for immunofluorescence, real-time RT-PCR, and dispersed cell cultures. Capsaicin-induced cellular proliferation, indicated by BrdU/Ki-67-labeled cells, suggests that lost neurons were replaced through cell division. NG cells expressed the stem cell marker, nestin, indicating that these ganglia have the capacity to generate new neurons. BrdU incorporation within beta-III tubulin-positive neuronal profiles following capsaicin suggests that proliferating cells matured to become neurons. NG neurons displayed decreased NMDAR expression up to 180 days post-capsaicin. However, both NMDAR expression within the NG and synaptophysin expression within the central target of NG neurons, the NTS, were restored to pre-injury levels by 300 days. NG cultures from capsaicin-treated rats contained bipolar neurons, normally found only during development. To test the functional recovery of NG neurons, we injected the satiety molecule, CCK. The effect of CCK on food intake was restored by 300 days post-capsaicin. This restoration may be due to the regeneration of damaged NG neurons or generation of functional neurons that replaced lost connections.

  12. KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion

    DEFF Research Database (Denmark)

    Lukács, M; Warfvinge, K; Kruse, L S

    2016-01-01

    modify the neurogenic inflammatory response in the trigeminal ganglion. METHODS: Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were...... investigated using immunohistochemistry and Western blot. FINDINGS: Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. CONCLUSIONS...

  13. Aging impairs afferent nerve function in rat intestine. Reduction of mesenteric hyperemia induced by intraduodenal capsaicin and acid.

    Science.gov (United States)

    Seno, K; Lam, K; Leung, J W; Leung, F W

    1996-02-01

    The high incidence of peptic ulcer disease despite decreased acid secretion in the elderly suggests an impairment of mucosal defense mechanism with aging. Stimulation of the intestinal mucosal afferent nerves by intraduodenal application of capsaicin or hydrochloric acid (HCl) increases superior mesenteric artery (SMA) blood flow and protects the duodenal mucosa against deep damage. We tested the hypothesis that the intestinal hyperemia induced by intraduodenal capsaicin or HCL is significantly reduced in older (12 months) rats compared with younger (2 months) rats. Mesenteric blood flow was measured by pulsed Doppler flowmetry in anesthetized rats with the flow probe around the SMA. Two milliliters per kilogram of 160 microM capsaicin or 0.1 N HCl administered intraduodenally increased SMA blood flow significantly in both age groups. The peak response in SMA blood flow, however, was significantly smaller in the older rats than in the younger rats. These observations support the hypothesis that impairment of afferent nerve function occurs with aging in the rat intestine.

  14. Protective effect of capsaicin against methyl methanesulphonate induced toxicity in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg(9).

    Science.gov (United States)

    Khanam, Saba; Fatima, Ambreen; Jyoti, Rahul Smita; Ali, Fahad; Naz, Falaq; Shakya, Barkha; Siddique, Yasir Hasan

    2017-04-01

    Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the main component in hot peppers, including red chili peppers, jalapenos, and habanero, belonging to the genus Capsicum. Capsaicin is a potent antioxidant that interferes with free radical activities. In the present study, the possible protective effect of capsaicin was studied against methyl methanesulphonate (MMS) induced toxicity in third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg(9). The third instar was allowed to feed on the diet having different doses of capsaicin and MMS separately and in combination. The results suggested that the exposure of third instar larvae to the diet having MMS alone showed significant hsp70 expression as well as tissue DNA and oxidative damage, whereas the larvae feed on the diet having MMS and capsaicin showed a decrease in the toxic effects for 48-h of exposure. In conclusion, capsaicin showed a dose-dependent decrease in the toxic effects induced by MMS in the third instar larvae of transgenic Drosophila melanogaster. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  15. Capsaicin causes inactivation and degradation of the androgen receptor by inducing the restoration of miR-449a in prostate cancer.

    Science.gov (United States)

    Zheng, Long; Chen, Jiaqi; Ma, Zhenkun; Liu, Wei; Yang, Fei; Yang, Zhao; Wang, Ke; Wang, Xinyang; He, Dalin; Li, Lei

    2015-08-01

    Capsaicin, a novel antitumor agent extracted from chili peppers, has been proven to induce growth inhibition in various types of cancer including prostate cancer. However, the detailed mechanisms remain largely undiscovered. In the present study, we explored the regulation of the androgen receptor (AR) by capsaicin and further researched the mechanisms of their interaction in AR-positive prostate cancer cells. In the present study, cell viability was assessed by MTT assay. Cell cycle distribution was determined using flow cytometry. Expression levels of cyclin D1, miR-449a, AR and prostate-specific antigen (PSA) were assessed by quantitative real-time polymerase chain reaction or western blot analysis. To further confirm the relationship among miR-449a, AR and prostate cancer proliferation, miR-449a was overexpressed by a lentivirus in prostate cancer cells. We discovered that capsaicin prevented tumor proliferation and cell cycle progression through inactivation and degradation of AR. We also found that restoration of miR-449a induced by capsaicin treatment resulted in the inhibition of AR signaling. Finally, we demonstrated that increased expression of miR-449a sensitized prostate cancer to capsaicin treatment. Finally, our experimental results indicated that capsaicin negatively modulates the activity of AR at the mRNA and protein levels by restoring miR-449a profiling in prostate cancer. In addition, increased expression of miR-449a may facilitate the sensitivity of prostate cancer to capsaicin treatment. Thus, capsaicin may be developed as a novel anti-AR drug for the therapy of prostate cancer.

  16. Identifying the Integrated Neural Networks Involved in Capsaicin-Induced Pain Using fMRI in Awake TRPV1 Knockout and Wild-Type Rats

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    Jason Richard Yee

    2015-02-01

    Full Text Available In the present study, we used functional MRI in awake rats to investigate the pain response that accompanies intradermal injection of capsaicin into the hindpaw. To this end, we used BOLD imaging together with a 3D segmented, annotated rat atlas and computational analysis to identify the integrated neural circuits involved in capsaicin-induced pain. The specificity of the pain response to capsaicin was tested in a transgenic model that contains a biallelic deletion of the gene encoding for the transient receptor potential cation channel subfamily V member 1 (TRPV1. Capsaicin is an exogenous ligand for the TRPV1 receptor, and in wild-type rats, activated the putative pain neural circuit. In addition, capsaicin-treated wild-type rats exhibited activation in brain regions comprising the Papez circuit and habenular system, systems that play important roles in the integration of emotional information, and learning and memory of aversive information, respectively. As expected, capsaicin administration to TRPV1-KO rats failed to elicit the robust BOLD activation pattern observed in wild-type controls. However, the intradermal injection of formalin elicited a significant activation of the putative pain pathway as represented by such areas as the anterior cingulate, somatosensory cortex, parabrachial nucleus, and periaqueductal gray. Notably, comparison of neural responses to capsaicin in wild-type versus knock-out rats uncovered evidence that capsaicin may function in an antinociceptive capacity independent of TRPV1 signaling. Our data suggest that neuroimaging of pain in awake, conscious animals has the potential to inform the neurobiological basis of full and integrated perceptions of pain.

  17. Transient cold pain has no effect on cutaneous vasodilatation induced by capsaicin: a randomized-control-crossover study in healthy subjects.

    Science.gov (United States)

    Pud, Dorit; Andersen, Ole Kaeseler; Arendt-Nielsen, Lars; Yarnitsky, David

    2006-05-01

    Cooling the skin induces sympathetically driven vasoconstriction, along with some vasoparalytic dilatation at lowermost temperatures. Neurogenic inflammation, on the other hand, entails vasodilatation. In the present study, we examined the dynamic vasomotor balance of capsaicin-induced vasodilatation within the area of the induced neurogenic inflammation, with and without superimposed cooling. In a randomized-control-crossover fashion, a sample of 14 healthy volunteers participated in three experiments: (1) exposure to each 0 degrees C cold pain stimulus and a neutral 30 degrees C stimulus (control) for 30 s to the volar forearms by contact thermal thermode (1.6x1.6 cm(2)), (2) injection of 50 microg intradermal capsaicin without cooling and (3) injection of capsaicin followed by application of 0 degrees C cold pain stimulation for 30 s within the area of the secondary hyperalgesia. Repetitive vascular measurements over skin area of 4.0x4.0 cm(2) of blood flux (BF) were acquired before and during the 5 min after stimulation. A marked increase in BF (i.e. vasodilatation) at the location of the cold stimulus in comparison to control (30 degrees C) (F=11.97, p=0.004) within the first 3 min was demonstrated. Two-way repeated-measures ANOVA indicated no interaction between the experimental conditions (capsaicin with or without cold) and time (F=0.934, p=0.454). The cold pain stimulation was found to be insignificant in its influence on BF evoked by capsaicin (F=0.018, p=0.894). The results of our study indicate that (1) transient cooling causes significant vasodilatation, (2) intradermal injection of capsaicin is dominant in inducing vasodilatation, and (3) the cold-pain-evoked vasodilatation has no modulative effect on the capsaicin-evoked cutaneous vasodilatation.

  18. Material basis for inhibition of dragon's blood on capsaicin-induced TRPV1 receptor currents in rat dorsal root ganglion neurons.

    Science.gov (United States)

    Wei, Li-Si; Chen, Su; Huang, Xian-Ju; Yao, Jing; Liu, Xiang-Ming

    2013-02-28

    The effects of dragon's blood and its components cochinchinenin A, cochinchinenin B, loureirin B as well as various combinations of the three components on capsaicin-induced TRPV1 receptor currents were studied in acutely dissociated DRG neurons using both voltage and current whole-cell patch clamp technique. The results indicated that dragon's blood and its three components concentration-dependently reduce the peak amplitudes of capsaicin-induced TRPV1 receptor currents. There was no significant difference between the effects of dragon's blood and the combination wherein the three components were present in respective mass fractions in dragon's blood. The respective concentrations of the three components used alone were all higher than the total concentration of three components used in combination when the percentage inhibition of the peak amplitude was 50%. The proportion of three components was adjusted and the total concentration reduced, the resulting combination still inhibit the currents with a lower IC50 value, and inhibit capsaicin-induced membrane depolarization on current clamp. The combination of three components not only increase the capsaicin IC50 value, but also reduce the capsaicin maximal response. These result suggested that analgesic effect of dragon's blood may be partly explained on the basis of silencing pain signaling pathways caused by the inhibition of dragon's blood on capsaicin-induced TRPV1 receptor currents in DRG neurons and could be due to the synergistic effect of the three components. Antagonism of the capsaicin response by the combination of three components is not competitive. The analgesic effect of dragon's blood was also confirmed using animal models. Copyright © 2013. Published by Elsevier B.V.

  19. Activation of TRPV1 by capsaicin induces functional Kinin B1 receptor in rat spinal cord microglia

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    Talbot Sébastien

    2012-01-01

    Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines and oxydative stress, which are enhanced by transient receptor potential vanilloid subtype 1 (TRPV1 activation. To examine the link between TRPV1 and B1R in inflammatory pain, this study aimed to determine the ability of TRPV1 to regulate microglial B1R expression in the spinal cord dorsal horn, and the underlying mechanism. Methods B1R expression (mRNA, protein and binding sites was measured in cervical, thoracic and lumbar spinal cord in response to TRPV1 activation by systemic capsaicin (1-50 mg/kg, s.c in rats pre-treated with TRPV1 antagonists (capsazepine or SB-366791, the antioxidant N-acetyl-L-cysteine (NAC, or vehicle. B1R function was assessed using a tail-flick test after intrathecal (i.t. injection of a selective B1R agonist (des-Arg9-BK, and its microglial localization was investigated by confocal microscopy with the selective fluorescent B1R agonist, [Nα-bodipy]-des-Arg9-BK. The effect of i.t. capsaicin (1 μg/site was also investigated. Results Capsaicin (10 to 50 mg/kg, s.c. enhanced time-dependently (0-24h B1R mRNA levels in the lumbar spinal cord; this effect was prevented by capsazepine (10 mg/kg, i.p.; 10 μg/site, i.t. and SB-366791 (1 mg/kg, i.p.; 30 μg/site, i.t.. Increases of B1R mRNA were correlated with IL-1β mRNA levels, and they were significantly less in cervical and thoracic spinal cord. Intrathecal capsaicin (1 μg/site also enhanced B1R mRNA in lumbar spinal cord. NAC (1 g/kg/d × 7 days prevented B1R up-regulation, superoxide anion production and NF-kB activation induced by capsaicin (15 mg/kg. Des-Arg9-BK (9.6 nmol/site, i.t. decreased by 25-30% the nociceptive threshold at 1 min post-injection in capsaicin-treated rats (10-50 mg/kg while it was without effect in control rats. Des-Arg9-BK-induced thermal hyperalgesia was blocked by capsazepine, SB-366791 and by antagonists/inhibitors of B1R (SSR240612, 10 mg/kg, p

  20. Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion

    DEFF Research Database (Denmark)

    Lukács, M; Haanes, K A; Majláth, Zs

    2015-01-01

    induces inflammatory activation in the trigeminal ganglion. METHODS: We performed topical administration of inflammatory soup (IS) or Complete Freund's Adjuvant (CFA) onto an exposed area of the rat dura mater in vivo for 20 min. The window was closed and the rats were sacrificed after 4 h and up to 7...... days. Myography was performed on middle meningeal arteries. The trigeminal ganglia were removed and processed for immunohistochemistry or Western blot. RESULTS: Both CFA and IS induced enhanced expression of pERK1/2, IL-1β and CGRP in the trigeminal ganglia. The pERK1/2 immunoreactivity was mainly seen...... vasoconstrictor response to IS, but not to CFA. CONCLUSIONS: These results suggest that the application of IS or CFA onto the dura mater causes long-term activation of the TG and demonstrate the importance of the neuro-glial interaction in the activation of the trigeminovascular system....

  1. Estrous Cycle Induces Peripheral Sensitization in Trigeminal Ganglion Neurons: An Animal Model of Menstrual Migraine.

    Science.gov (United States)

    Saleeon, Wachirapong; Jansri, Ukkrit; Srikiatkhachorn, Anan; Bongsebandhu-phubhakdi, Saknan

    2016-02-01

    Many women experience menstrual migraines that develop into recurrent migraine attacks during menstruation. In the human menstrual cycle, the estrogen level fluctuates according to changes in the follicular and luteal phases. The rat estrous cycle is used as an animal model to study the effects of estrogen fluctuation. To investigate whether the estrous cycle is involved in migraine development by comparing the neuronal excitability of trigeminal ganglion (TG) neurons in each stage of the estrous cycle. Female rats were divided into four experimental groups based on examinations of the cytologies of vaginal smears, and serum analyses of estrogen levels following each stage of the estrous cycle. The rats in each stage of the estrous cycle were anesthetized and their trigeminal ganglia were removed The collections of trigeminal ganglia were cultured for two to three hours, after which whole-cell patch clamp experiments were recorded to estimate the electrophysiological properties of the TG neurons. There were many vaginal epithelial cells and high estrogen levels in the proestrus and estrus stages of the estrous cycle. Electrophysiological studies revealed that the TG neurons in the proestrus and estrus stages exhibited significantly lower thresholds of stimulation, and significant increase in total spikes compared to the TG neurons that were collected in the diestrus stage. Our results revealed that high estrogen levels in the proestrus and estrus stages altered the thresholds, rheobases, and total spikes of the TG neurons. High estrogen levels in the estrous cycle induced an increase in neuronal excitability and the peripheral sensitization of TG neurons. These findings may provide an explanation for the correlation of estrogen fluctuations during the menstrual cycle with the pathogenesis of menstrual migraines.

  2. Combined treatment with capsaicin and resveratrol enhances neuroprotection against glutamate-induced toxicity in mouse cerebral cortical neurons

    NARCIS (Netherlands)

    Lee, J.G.; Yon, J.M.; Lin, C.; Jung, A.Y.; Jung, K.Y.; Nam, S.Y.

    2012-01-01

    Capsaicin and resveratrol as natural products have a variety of beneficial effects. However, capsaicin is also a neurotoxic agent, rendering its effect on the nervous system confusing. The aim of this study was to investigate whether capsaicin and/or resveratrol have a protective effect against

  3. Combined treatment with capsaicin and resveratrol enhances neuroprotection against glutamate-induced toxicity in mouse cerebral cortical neurons

    NARCIS (Netherlands)

    Lee, J.G.; Yon, J.M.; Lin, C.; Jung, A.Y.; Jung, K.Y.; Nam, S.Y.

    2012-01-01

    Capsaicin and resveratrol as natural products have a variety of beneficial effects. However, capsaicin is also a neurotoxic agent, rendering its effect on the nervous system confusing. The aim of this study was to investigate whether capsaicin and/or resveratrol have a protective effect against glut

  4. Combined treatment with capsaicin and resveratrol enhances neuroprotection against glutamate-induced toxicity in mouse cerebral cortical neurons

    NARCIS (Netherlands)

    Lee, J.G.; Yon, J.M.; Lin, C.; Jung, A.Y.; Jung, K.Y.; Nam, S.Y.

    2012-01-01

    Capsaicin and resveratrol as natural products have a variety of beneficial effects. However, capsaicin is also a neurotoxic agent, rendering its effect on the nervous system confusing. The aim of this study was to investigate whether capsaicin and/or resveratrol have a protective effect against glut

  5. Warm SPA-induced hyperthermia confers protection to rats against airway inflammation evoked by capsaicin and substance P.

    Science.gov (United States)

    Fu, Yaw-Syan; Wang, Peng-Han; Liu, Shang-Pin; Huang, Wen-Hung; Huang, Hung-Tu

    2010-06-24

    Solus par aqua (SPA) is a traditional health care therapy. Warm SPA may enhance immunity and cellular defense to protect body against diseases. The present study investigated whether the warm SPA could confer protection to neurogenic inflammation in rats. The rats were immersed in water where the body core temperatures were maintained at hyperthermia (41.5 degrees C) or normothermia (37 degrees C) for a period of 15min. After SPA for 1 or 6 days, neurogenic inflammation was induced by intravenous injection of capsaicin (90microg/kg) or substance P (SP; 3microg/kg). The plasma leakage and arterial pressures in rats after neurogenic inflammation were monitored. The extent of capsaicin- or SP-induced plasma leakage and hypotension was significantly attenuated in rats on day 1 after SPA hyperthermia. However, such resistance to neurogenic inflammation was not found on day 6 after hyperthermia. Western blotting analysis showed that the expression of heat shock protein 72 (HSP 72) in the trachea on days 1 and 2 after hyperthermia was 9.61-fold and 6.66-fold, respectively, of that in normothermia. Afterwards, the hyperthermia-induced HSP 72 upregulation gradually declined in a time-dependent manner. Thus, SPA hyperthermia may protect rats against neurogenic inflammation through modulation of HSP expression.

  6. Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-{kappa}B translocation and ROS production in synoviocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China); Li, Junying, E-mail: jyli04@nankai.edu.cn [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China)

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer Moderate extracellular acidification regulates intracellular Ca{sup 2+} mobilization. Black-Right-Pointing-Pointer Moderate acidification activates NF-{kappa}B nuclear translocation in synoviocytes. Black-Right-Pointing-Pointer Moderate acidification depresses the ROS production induced by capsaicin. Black-Right-Pointing-Pointer Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca{sup 2+} entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca{sup 2+} entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca{sup 2+} release from intracellular stores. The nuclear translocation of NF-{kappa}B was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-{kappa}B. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca{sup 2+} mobilization, activating NF-{kappa}B nuclear translocation and depressing ROS production.

  7. Drug-Induced Hypersensitivity Syndrome Caused by Carbamazepine Used for the Treatment of Trigeminal Neuralgia

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    Yuko Ono

    2016-01-01

    Full Text Available An 88-year-old man was diagnosed with trigeminal neuralgia, and treatment of carbamazepine 200 mg/day was initiated. About 6 weeks later, the patient developed a skin rash accompanied by fever. He was admitted to hospital and diagnosed with drug-induced hypersensitivity syndrome (DIHS caused by carbamazepine. Oral carbamazepine treatment was stopped, but blood tests showed acute liver and acute renal failure. Drug-induced lymphocyte stimulation test (DLST for carbamazepine, human herpes virus-6 (HHV-6 IgG, and CMV-HRP were negative. Oral prednisolone therapy was begun 18 days later. The titer of HHV-6 IgG antibodies was then detected (640 times. Following treatment, liver and renal function improved and the erythema disappeared.

  8. Antiobese effects of capsaicin-chitosan microsphere (CCMS) in obese rats induced by high fat diet.

    Science.gov (United States)

    Tan, Sirong; Gao, Bing; Tao, Yi; Guo, Jiao; Su, Zheng-quan

    2014-02-26

    Chitosan (CTS) and capsaicin (CAP) are two kinds of effective ingredients for antiobesity, which are extracted from crab shells and Capsicum annuum. However, the strong taste of CAP makes it difficult to consume, and the antiobesity ability of CTS is limited. In this study, we prepared capsaicin-chitosan microspheres (CCMSs) by ion-cross-linking and spray drying and examined the antiobesity ability of CCMSs in obese rats. The effects of CCMSs on body weight, Lee's index, body fat, and serum lipids were investigated. The mRNA expression of PPARα, PPARγ, leptin, UCP2, GPR120, FTO, and adiponectin in the liver was determined by quantitative real-time PCR, and the protein expression of adiponectin, leptin, PPARα, UCP2, and hepatic lipase in serum was evaluated by enzyme-linked immunosorbent assay. CCMSs were prepared with 85.17% entrapment efficiency and 8.87% mean drug loading. Compared with chitosan microspheres, CAP, and Orlistat, the CCMSs showed better ability to control body weight, body mass index, organ index, body fat, proportion of fat to body weight, and serum lipids. The CCMSs upregulated the expressions of PPARα, PPARγ, UCP2, and adiponectin and downregulated the expression of leptin. CCMSs may thus be considered novel, safe, effective, and natural weight loss substances, and there is an additive effect between CTMS and capsaicin.

  9. Eugenol and carvacrol excite first- and second-order trigeminal neurons and enhance their heat-evoked responses.

    Science.gov (United States)

    Klein, A H; Joe, C L; Davoodi, A; Takechi, K; Carstens, M I; Carstens, E

    2014-06-20

    Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive transient receptor potential ankyrin (TRPA)-1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42 °C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue.

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

    Directory of Open Access Journals (Sweden)

    Elcio J Piovesan

    2016-06-01

    Full Text Available 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.

  11. Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates.

    Directory of Open Access Journals (Sweden)

    Abu Bakar Ali Asad

    Full Text Available Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored.Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8. BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail.Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8, while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures.These findings provide insights into the specific brain regions involved with aversive, 'pain-like', responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate

  12. Pre-treatment with capsaicin in a rat osteoarthritis model reduces the symptoms of pain and bone damage induced by monosodium iodoacetate.

    NARCIS (Netherlands)

    Kalff, K.M.; ElMouedden, M.; Egmond, J. van; Veening, J.G.; Joosten, L.A.B.; Scheffer, G.J.; Meert, T.F.; Vissers, K.C.P.

    2010-01-01

    A rat model of osteoarthritis was used to investigate the effect of pre-treatment with capsaicin on the symptoms of osteoarthritis induced by the injection of monosodium iodoacetate. This model mimics both histopathology and symptoms associated of human osteoarthritis. Injection of monosodium iodoac

  13. Development of anti-migraine therapeutics using the capsaicin-induced dermal blood flow model.

    Science.gov (United States)

    Buntinx, Linde; Vermeersch, Steve; de Hoon, Jan

    2015-11-01

    The efficacy of calcitonin gene-related peptide (receptor) (CGRP-(R)) blocking therapeutics in the treatment of acute migraine headache provided proof-of-concept for the involvement of CGRP in the pathophysiology of this disorder. One of the major hurdles for the development of any class of drugs, including CGRP blocking therapeutics, is the early clinical development process during which toxic and inefficacious compounds need to be eliminated as early as possible in order to focus on the most promising molecules. At this stage, human models providing proof of target engagement, combined with safety and tolerability studies, are extremely valuable in focusing on those therapeutics that have the highest engagement from the lowest exposure. They guide the go/no-go decision making, establish confidence in the candidate molecule by de-risking toxicity and safety issues and thereby speed up the early clinical development. In this review the focus is on the so called 'capsaicin model' as a typical example of a target engagement biomarker used as a human model for the development of CGRP blocking therapeutics. By applying capsaicin onto the skin, TRPV1 channels are activated and a CGRP-mediated increase in dermal blood flow can be quantified with laser Doppler perfusion imaging. Effective CGRP blocking therapeutics in turn, display blockade of this response. The translation of this biomarker model from animals to humans is discussed as well as the limitations of the assay in predicting the efficacy of anti-migraine drugs.

  14. Molecular Study of Capsaicin in Aqueous and Hydrophobic Environments

    OpenAIRE

    Lambert, Joseph Walter

    2006-01-01

    Anyone who has eaten spicy foods has experienced the adverse effects of capsaicin, the pungent chemical found in hot chili that causes a burning sensation. The specific action of capsaicin occurs by the activation of receptors in sensory neurons. This thesis investigates the interaction of capsaicin with model cell membranes representing the structure of neurons. In particular, we are interested in the changes induced by capsaicin to the structure and dynamics of membranes. Molecular dyna...

  15. Role of capsaicin-sensitive C-fiber afferents in neuropathic pain-induced synaptic potentiation in the nociceptive amygdala

    Directory of Open Access Journals (Sweden)

    Nakao Ayano

    2012-07-01

    Full Text Available Abstract Background Neurons in the capsular part of the central nucleus of the amygdala (CeC, a region also called "nociceptive amygdala," receive nociceptive information from the dorsal horn via afferent pathways relayed from the lateral parabrachial nucleus (LPB. As the central amygdala is known to be involved in the acquisition and expression of emotion, this pathway is thought to play central roles in the generation of affective responses to nociceptive inputs. Excitatory synaptic transmission between afferents arising from the LPB and these CeC neurons is potentiated in arthritic, visceral, neuropathic, inflammatory and muscle pain models. In neuropathic pain models following spinal nerve ligation (SNL, in which we previously showed a robust LPB-CeC potentiation, the principal behavioral symptom is tactile allodynia triggered by non-C-fiber low-threshold mechanoreceptor afferents. Conversely, recent anatomical studies have revealed that most of the spinal neurons projecting to the LPB receive C-fiber afferent inputs. Here, we examined the hypothesis that these C-fiber-mediated inputs are necessary for the full establishment of robust synaptic potentiation of LPB-CeC transmission in the rats with neuropathic pain. Results Postnatal capsaicin treatment, which has been shown to denervate the C-fibers expressing transient receptor potential vanilloid type-1 (TRPV1 channels, completely abolished eye-wiping responses to capsaicin eye instillation in rats, but this treatment did not affect mechanical allodynia in the nerve-ligated animals. However, the postnatal capsaicin treatment prevented LPB-CeC synaptic potentiation after SNL, unlike in the vehicle-treated rats, primarily due to the decreased incidence of potentiated transmission by elimination of TRPV1-expressing C-fiber afferents. Conclusions C-fiber-mediated afferents in the nerve-ligated animals may be a required facilitator of the establishment of nerve injury-evoked synaptic

  16. Integrating TRPV1 Receptor Function with Capsaicin Psychophysics

    Directory of Open Access Journals (Sweden)

    Gregory Smutzer

    2016-01-01

    Full Text Available Capsaicin is a naturally occurring vanilloid that causes a hot, pungent sensation in the human oral cavity. This trigeminal stimulus activates TRPV1 receptors and stimulates an influx of cations into sensory cells. TRPV1 receptors function as homotetramers that also respond to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Kinase-mediated phosphorylation of TRPV1 leads to increased sensitivity to both chemical and thermal stimuli. In contrast, desensitization occurs via a calcium-dependent mechanism that results in receptor dephosphorylation. Human psychophysical studies have shown that capsaicin is detected at nanomole amounts and causes desensitization in the oral cavity. Psychophysical studies further indicate that desensitization can be temporarily reversed in the oral cavity if stimulation with capsaicin is resumed at short interstimulus intervals. Pretreatment of lingual epithelium with capsaicin modulates the perception of several primary taste qualities. Also, sweet taste stimuli may decrease the intensity of capsaicin perception in the oral cavity. In addition, capsaicin perception and hedonic responses may be modified by diet. Psychophysical studies with capsaicin are consistent with recent findings that have identified TRPV1 channel modulation by phosphorylation and interactions with membrane inositol phospholipids. Future studies will further clarify the importance of capsaicin and its receptor in human health and nutrition.

  17. Integrating TRPV1 Receptor Function with Capsaicin Psychophysics.

    Science.gov (United States)

    Smutzer, Gregory; Devassy, Roni K

    2016-01-01

    Capsaicin is a naturally occurring vanilloid that causes a hot, pungent sensation in the human oral cavity. This trigeminal stimulus activates TRPV1 receptors and stimulates an influx of cations into sensory cells. TRPV1 receptors function as homotetramers that also respond to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Kinase-mediated phosphorylation of TRPV1 leads to increased sensitivity to both chemical and thermal stimuli. In contrast, desensitization occurs via a calcium-dependent mechanism that results in receptor dephosphorylation. Human psychophysical studies have shown that capsaicin is detected at nanomole amounts and causes desensitization in the oral cavity. Psychophysical studies further indicate that desensitization can be temporarily reversed in the oral cavity if stimulation with capsaicin is resumed at short interstimulus intervals. Pretreatment of lingual epithelium with capsaicin modulates the perception of several primary taste qualities. Also, sweet taste stimuli may decrease the intensity of capsaicin perception in the oral cavity. In addition, capsaicin perception and hedonic responses may be modified by diet. Psychophysical studies with capsaicin are consistent with recent findings that have identified TRPV1 channel modulation by phosphorylation and interactions with membrane inositol phospholipids. Future studies will further clarify the importance of capsaicin and its receptor in human health and nutrition.

  18. Late sensory function after intraoperative capsaicin wound instillation

    DEFF Research Database (Denmark)

    Aasvang, E K; Hansen, J B; Kehlet, H

    2010-01-01

    BACKGROUND: Intense capsaicin-induced C-fiber stimulation results in reversible lysis of the nerve soma, thereby making capsaicin wound instillation of potential interest for the treatment of post-operative pain. Clinical histological and short-term sensory studies suggest that the C-fiber function...... is partly re-established after skin injection of capsaicin. However, no study has evaluated the long-term effects of wound instillation of purified capsaicin on sensory functions. METHODS: Patients included in a double-blind placebo-controlled randomized study of the analgesic effect of capsaicin after...... treatment. RESULTS: Twenty (100%) capsaicin and 16 (76%) placebo-treated patients were seen at the 2 1/2 year follow-up. Hyperalgesia was seen in five capsaicin- vs. one placebo-treated patient (P=0.2). The mechanical detection threshold was significantly increased on the operated side in the capsaicin vs...

  19. Trigeminal nerve injury induced thrombospondin-4 upregulation contributes to orofacial neuropathic pain states in a rat model

    Science.gov (United States)

    Li, Kang-Wu; Kim, Doo-Sik; Zaucke, Frank; Luo, Z. David

    2013-01-01

    Background Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause upregulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION). Methods Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 upregulation and orofacial behavioral hypersensitivity. Results Our data indicated that trigeminal nerve injury induced TSP4 upregulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 upregulation in Vc/C2 and behavioral hypersensitivity. Conclusions Our data support that infraorbital nerve injury leads to TSP4 upregulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. PMID:24019258

  20. Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to orofacial neuropathic pain states in a rat model.

    Science.gov (United States)

    Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D

    2014-04-01

    Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®

  1. Chemokine ligand 2 in the trigeminal ganglion regulates pain induced by experimental tooth movement.

    Science.gov (United States)

    Yang, Zhi; Luo, Wei; Wang, Jing; Tan, Yu; Fu, Runqing; Fang, Bing

    2014-07-01

    To test the hypothesis that the chemokine ligand 2/chemokine receptor 2 (CCL2/CCR2) signaling pathway plays an important role in pain induced by experimental tooth movement. Expression of CCL2/CCR2 in the trigeminal ganglion (TG) was determined by Western blotting 0 hours, 4 hours, 1 day, 3 days, 5 days, and 7 days after tooth movement. CCL2 localization and cell size distribution were revealed by immunohistochemistry. The effects of increasing force on CCL2 expression and behavioral changes were investigated. Furthermore, the effects of CCL2/CCR2 antagonists on these changes in pain behaviors were all evaluated. Exogenous CCL2 was injected into periodontal tissues and cultured TG neurons with different concentrations, and then the pain responses or c-fos expression were assessed. Experimental tooth movement led to a statistically significant increase in CCL2/CCR2 expression from day 3 to day 7, especially in small to medium-sized TG neurons. It also triggered an increase in the time spent on directed face-grooming behaviors in a force magnitude-dependent and CCL2 dose-dependent manner. Pain induced by experimental tooth movement was effectively blocked by a CCR2 antagonist and by CCL2 neutralizing antibody. Also, exogenous CCL2 led to an increase in c-fos expression in cultured TG neurons, which was blocked by CCL2 neutralizing antibody. The peripheral CCL2/CCR2 axis is modulated by experimental tooth movement and involved in the development of tooth movement pain.

  2. Neonatal sensory nerve injury-induced synaptic plasticity in the trigeminal principal sensory nucleus.

    Science.gov (United States)

    Lo, Fu-Sun; Erzurumlu, Reha S

    2016-01-01

    Sensory deprivation studies in neonatal mammals, such as monocular eye closure, whisker trimming, and chemical blockade of the olfactory epithelium have revealed the importance of sensory inputs in brain wiring during distinct critical periods. But very few studies have paid attention to the effects of neonatal peripheral sensory nerve damage on synaptic wiring of the central nervous system (CNS) circuits. Peripheral somatosensory nerves differ from other special sensory afferents in that they are more prone to crush or severance because of their locations in the body. Unlike the visual and auditory afferents, these nerves show regenerative capabilities after damage. Uniquely, damage to a somatosensory peripheral nerve does not only block activity incoming from the sensory receptors but also mediates injury-induced neuro- and glial chemical signals to the brain through the uninjured central axons of the primary sensory neurons. These chemical signals can have both far more and longer lasting effects than sensory blockade alone. Here we review studies which focus on the consequences of neonatal peripheral sensory nerve damage in the principal sensory nucleus of the brainstem trigeminal complex.

  3. Assessment of pain response in capsaicin-induced dynamic mechanical allodynia using a novel and fully automated brushing device.

    Science.gov (United States)

    du Jardin, Kristian Gaarn; Gregersen, Lise Skøtt; Røsland, Turid; Uggerhøj, Kathrine Hebo; Petersen, Lars Jelstrup; Arendt-Nielsen, Lars; Gazerani, Parisa

    2013-01-01

    Dynamic mechanical allodynia is traditionally induced by manual brushing of the skin. Brushing force and speed have been shown to influence the intensity of brush-evoked pain. There are still limited data available with respect to the optimal stroke number, length, force, angle and speed. Therefore, an automated brushing device (ABD) was developed, for which brushing angle and speed could be controlled to enable quantitative assessment of dynamic mechanical allodynia. To compare the ABD with manual brushing using capsaicin-induced allodynia, and to investigate the role of stroke angle and speed on pain intensity. Experimental dynamic mechanical allodynia was induced by an intradermal injection of capsaicin (100 µg) into the volar forearm of 12 healthy, male volunteers. Dynamic mechanical allodynia was rated on a 10 cm visual analogue scale (VAS) after each set of strokes at angles of 30°, 60° and 90° with speeds of 17 mm⁄s, 21 mm⁄s and 25 mm⁄s for each angle. A two-way ANOVA with repeated measures was performed to assess the influence of brushing parameters. To evaluate test-retest reliability, Bland-Altman 95% limits of agreement, including a coefficient of repeatability and an intraclass correlation coefficient (ICC), were determined. The angle and speed exhibited a significant impact on pain intensity (P<0.001 and P<0.015, respectively). Post hoc analysis showed that the highest pain intensity was recorded with an angle of 30° regardless of brushing speed. The ABD demonstrated superior test-retest reliability (coefficient of repeatability = 1.9 VAS; ICC=0.91) compared with manual brushing (coefficient of repeatability = 2.8 VAS; ICC=0.80; P<0.05). The most reliable combination of parameters (coefficient of repeatability = 1.3 VAS; ICC=0.97) was an angle of 60° and a speed of 21 mm⁄s. A controlled, automatic brushing method can be used for quantitative investigations of allodynic reactions, and is more reliable for quantitative assessment of dynamic

  4. Trigeminal Neuralgia

    Science.gov (United States)

    ... affect your interaction with friends and family, your productivity at work, and the overall quality of your ... www.mayoclinic.org/diseases-conditions/trigeminal-neuralgia/basics/definition/CON-20043802 . Mayo Clinic Footer Legal Conditions and ...

  5. Trigeminal Inflammatory Compression (TIC) injury induces chronic facial pain and susceptibility to anxiety-related behaviors.

    Science.gov (United States)

    Lyons, D N; Kniffin, T C; Zhang, L P; Danaher, R J; Miller, C S; Bocanegra, J L; Carlson, C R; Westlund, K N

    2015-06-04

    Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model.

  6. KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion.

    Science.gov (United States)

    Lukács, M; Warfvinge, K; Kruse, L S; Tajti, J; Fülöp, F; Toldi, J; Vécsei, L; Edvinsson, L

    2016-12-01

    Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can modify the neurogenic inflammatory response in the trigeminal ganglion. Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were investigated using immunohistochemistry and Western blot. Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. This is the first study that demonstrates that one dose of KYNA analog before application of CFA can give anti-inflammatory response in a model of trigeminal activation, opening a new line for further investigations regarding possible effects of KYNA derivates.

  7. Capsaicin mimics mechanical load-induced intracellular signaling events: involvement of TRPV1-mediated calcium signaling in induction of skeletal muscle hypertrophy.

    Science.gov (United States)

    Ito, Naoki; Ruegg, Urs T; Kudo, Akira; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi

    2013-01-01

    Mechanical load-induced intracellular signaling events are important for subsequent skeletal muscle hypertrophy. We previously showed that load-induced activation of the cation channel TRPV1 caused an increase in intracellular calcium concentrations ([Ca ( 2+) ]i) and that this activated mammalian target of rapamycin (mTOR) and promoted muscle hypertrophy. However, the link between mechanical load-induced intracellular signaling events, and the TRPV1-mediated increases in [Ca ( 2+) ]i are not fully understood. Here we show that administration of the TRPV1 agonist, capsaicin, induces phosphorylation of mTOR, p70S6K, S6, Erk1/2 and p38 MAPK, but not Akt, AMPK or GSK3β. Furthermore, the TRPV1-induced phosphorylation patterns resembled those induced by mechanical load. Our results continue to highlight the importance of TRPV1-mediated calcium signaling in load-induced intracellular signaling pathways.

  8. Capsaicin synergizes with camptothecin to induce increased apoptosis in human small cell lung cancers via the calpain pathway.

    Science.gov (United States)

    Friedman, Jamie R; Perry, Haley E; Brown, Kathleen C; Gao, Ying; Lin, Ju; Stevenson, Cathyrn D; Hurley, John D; Nolan, Nicholas A; Akers, Austin T; Chen, Yi Charlie; Denning, Krista L; Brown, Linda G; Dasgupta, Piyali

    2017-04-01

    Small cell lung cancer (SCLC) is characterized by excellent initial response to chemotherapy and radiation therapy with a majority of the patients showing tumor shrinkage and even remission. However, the challenge with SCLC therapy is that patients inevitably relapse and subsequently do not respond to the first line treatment. Recent clinical studies have investigated the possibility of camptothecin-based combination therapy as first line treatment for SCLC patients. Conventionally, camptothecin is used for recurrent SCLC and has poor survival outcomes. Therefore, drugs which can improve the therapeutic index of camptothecin should be valuable for SCLC therapy. Extensive evidence shows that nutritional compounds like capsaicin (the spicy compound of chili peppers) can improve the anti-cancer activity of chemotherapeutic drugs in both cell lines and animal models. Statistical analysis shows that capsaicin synergizes with camptothecin to enhance apoptosis of human SCLC cells. The synergistic activity of camptothecin and capsaicin is observed in both classical and variant SCLC cell lines and, in vivo, in human SCLC tumors xenotransplanted on chicken chorioallantoic membrane (CAM) models. The synergistic activity of capsaicin and camptothecin are mediated by elevation of intracellular calcium and the calpain pathway. Our data foster hope for novel nutrition based combination therapies in SCLC. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Role of ventrolateral orbital cortex muscarinic and nicotinic receptors in modulation of capsaicin-induced orofacial pain-related behaviors in rats.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Erfanparast, Amir; Abbas Farshid, Amir; Delkhosh-Kasmaie, Fatmeh

    2017-09-29

    Acetylcholine, as a major neurotransmitter, mediates many brain functions such as pain. This study was aimed to investigate the effects of microinjection of muscarinic and nicotinic acetylcholine receptor antagonists and agonists into the ventrolateral orbital cortex (VLOC) on capsaicin-induced orofacial nociception and subsequent hyperalgesia. The right side of VLOC was surgically implanted with a guide cannula in anaesthetized rats. Orofacial pain-related behaviors were induced by subcutaneous injection of a capsaicin solution (1.5µg/20µl) into the left vibrissa pad. The time spent face rubbing with ipsilateral forepaw and general behavior were recorded for 10min, and then mechanical hyperalgesia was determined using von Frey filaments at 15, 30, 45 and 60min post-capsaicin injection. Alone intra-VLOC microinjection of atropine (a muscarinic acetylcholine receptor antagonist) and mecamylamine (a nicotinic acetylcholine receptor antagonist) at a similar dose of 200ng/site did not alter nocifensive behavior and hyperalgesia. Microinjection of oxotremorine (a muscarinic acetylcholine receptor agonist) at doses of 50 and 100ng/site and epibatidine (a nicotinic acetylcholine receptor agonist) at doses of 12.5, 25, 50 and 100ng/site into the VLOC suppressed pain-related behaviors. Prior microinjections of 200ng/site atropine and mecamylamine (200ng/site) prevented oxotremorine (100ng/site)-, and epibatidine (100ng/site)-induced antinociception, respectively. None of the above-mentioned chemicals changed general behavior. These results showed that the VLOC muscarinic and nicotinic acetylcholine receptors might be involved in modulation of orofacial nociception and hypersensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Perineural capsaicin induces the uptake and transganglionic transport of choleratoxin B subunit by nociceptive C-fiber primary afferent neurons.

    Science.gov (United States)

    Oszlács, O; Jancsó, G; Kis, G; Dux, M; Sántha, P

    2015-12-17

    The distribution of spinal primary afferent terminals labeled transganglionically with the choleratoxin B subunit (CTB) or its conjugates changes profoundly after perineural treatment with capsaicin. Injection of CTB conjugated with horseradish peroxidase (HRP) into an intact nerve labels somatotopically related areas in the ipsilateral dorsal horn with the exceptions of the marginal zone and the substantia gelatinosa, whereas injection of this tracer into a capsaicin-pretreated nerve also results in massive labeling of these most superficial layers of the dorsal horn. The present study was initiated to clarify the role of C-fiber primary afferent neurons in this phenomenon. In L5 dorsal root ganglia, analysis of the size frequency distribution of neurons labeled after injection of CTB-HRP into the ipsilateral sciatic nerve treated previously with capsaicin or resiniferatoxin revealed a significant increase in the proportion of small neurons. In the spinal dorsal horn, capsaicin or resiniferatoxin pretreatment resulted in intense CTB-HRP labeling of the marginal zone and the substantia gelatinosa. Electron microscopic histochemistry disclosed a dramatic, ∼10-fold increase in the proportion of CTB-HRP-labeled unmyelinated dorsal root axons following perineural capsaicin or resiniferatoxin. The present results indicate that CTB-HRP labeling of C-fiber dorsal root ganglion neurons and their central terminals after perineural treatment with vanilloid compounds may be explained by their phenotypic switch rather than a sprouting response of thick myelinated spinal afferents which, in an intact nerve, can be labeled selectively with CTB-HRP. The findings also suggest a role for GM1 ganglioside in the modulation of nociceptor function and pain.

  11. NMDA-induced burst discharge in guinea pig trigeminal motoneurons in vitro.

    Science.gov (United States)

    Kim, Y I; Chandler, S H

    1995-07-01

    1. The responses of guinea pig trigeminal motoneurons (TMNs) to N-methyl-D,L-aspartate (NMA) were studied using brain stem slice preparations and whole cell patch-clamp (n = 89) or conventional microelectrode (n = 22) recording techniques. The primary goals of this study were to determine whether N-methyl-D-aspartate (NMDA) receptor activation would produce spontaneous bursting activity in TMNs and, if so, the underlying mechanisms responsible for the generation of these bursts. 2. Bath-applied NMA (100-300 microM, n = 80) in standard perfusion medium elicited depolarization, increase in apparent input resistance (Rinp), and rhythmic burst discharges (1-90 s in duration) from TMNs. These effects were blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5, 30 microM, n = 6), but not by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM, n = 10). Furthermore, the burst-inducing effect of NMA was not mimicked by the non-NMDA receptor agonists kainate (KA, 5-10 microM, n = 6) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 5-10 microM, n = 5). 3. In tetrodotoxin (TTX) treatment conditions (n = 13), NMA elicited depolarization, an increase in apparent Rinp, and rhythmic membrane potential oscillations without action potential bursts (i.e., plateau potentials), suggesting that the effects of NMA observed in the TTX-free condition resulted from activation of postsynaptic NMDA receptors. 4. Graded depolarization of neurons (n = 20) by intracellular direct current injection generally led to a graded increase in frequency and duration of the NMA-induced bursts and plateau potentials until these rhythmic events eventually became transformed into continuous spike discharge and maintained depolarization, respectively. Removal of Mg2+ from the perfusion medium (n = 11) also turned the bursts and plateau potentials into continuous spike discharge and maintained depolarization, respectively

  12. Experimental colitis in rats induces de novo synthesis of cytokines at distant intestinal sites: role of capsaicin-sensitive primary afferent fibers.

    Science.gov (United States)

    Mourad, Fadi H; Hamdi, Tamim; Barada, Kassem A; Saadé, Nayef E

    2016-06-01

    Increased levels of pro- and anti-inflammatory cytokines were observed in various segments of histologically-intact small intestine in animal models of acute and chronic colitis. Whether these cytokines are produced locally or spread from the inflamed colon is not known. In addition, the role of gut innervation in this upregulation is not fully understood. To examine whether cytokines are produced de novo in the small intestine in two rat models of colitis; and to investigate the role of capsaicin-sensitive primary afferents in the synthesis of these inflammatory cytokines. Colitis was induced by rectal instillation of iodoacetamide (IA) or trinitrobenzene sulphonic acid (TNBS) in adult Sprague-Dawley rats. Using reverse transcriptase (RT) and real-time PCR, TNF-α, and IL-10 mRNA expression was measured in mucosal scrapings of the duodenum, jejunum, ileum and colon at different time intervals after induction of colitis. Capsaicin-sensitive primary afferents (CSPA) were ablated using subcutaneous injections of capsaicin at time 0, 8 and 32 h, and the experiment was repeated at specific time intervals to detect any effect on cytokines expression. TNF-α mRNA expression increased by 3-40 times in the different intestinal segments (pcolitis. CSPA ablation completely inhibited this upregulation in the small intestine, but not in the colon. Similar results were obtained in TNBS-induced colitis at 24 h. Intestinal IL-10 mRNA expression significantly decreased at 12 h and then increased by 6-43 times (pcolitis induction, respectively (both pcolitis induction. Inflammatory cytokines are produced de novo in distant intestinal segments in colitis. CSPA fibers play a key role in the upregulation of this synthesis.

  13. Trigeminal neuralgia

    Science.gov (United States)

    Cruccu, Giorgio; Finnerup, Nanna B.; Jensen, Troels S.; Scholz, Joachim; Sindou, Marc; Svensson, Peter; Zakrzewska, Joanna M.; Nurmikko, Turo

    2016-01-01

    Trigeminal neuralgia (TN) is an exemplary condition of neuropathic facial pain. However, formally classifying TN as neuropathic pain based on the grading system of the International Association for the Study of Pain is complicated by the requirement of objective signs confirming an underlying lesion or disease of the somatosensory system. The latest version of the International Classification of Headache Disorders created similar difficulties by abandoning the term symptomatic TN for manifestations caused by major neurologic disease, such as tumors or multiple sclerosis. These diagnostic challenges hinder the triage of TN patients for therapy and clinical trials, and hamper the design of treatment guidelines. In response to these shortcomings, we have developed a classification of TN that aligns with the nosology of other neurologic disorders and neuropathic pain. We propose 3 diagnostic categories. Classical TN requires demonstration of morphologic changes in the trigeminal nerve root from vascular compression. Secondary TN is due to an identifiable underlying neurologic disease. TN of unknown etiology is labeled idiopathic. Diagnostic certainty is graded possible when pain paroxysms occur in the distribution of the trigeminal nerve branches. Triggered paroxysms permit the designation of clinically established TN and probable neuropathic pain. Imaging and neurophysiologic tests that establish the etiology of classical or secondary TN determine definite neuropathic pain. PMID:27306631

  14. Experimental evidence for alleviating nociceptive hypersensitivity by single application of capsaicin.

    Science.gov (United States)

    Ma, Xiao-Li; Zhang, Fang-Xiong; Dong, Fei; Bao, Lan; Zhang, Xu

    2015-04-22

    The single application of high-concentration of capsaicin has been used as an analgesic therapy of persistent pain. However, its effectiveness and underlying mechanisms remain to be further evaluated with experimental approaches. The present study provided evidence showing that the single application of capsaicin dose-dependently alleviated nociceptive hypersensitivity, and reduced the action potential firing in small-diameter neurons of the dorsal root ganglia (DRG) in rats and mice. Pre-treatment with capsaicin reduced formalin-induced acute nocifensive behavior after a brief hyperalgesia in rats and mice. The inhibitory effects of capsaicin were calcium-dependent, and mediated by the capsaicin receptor (transient receptor potential vanilloid type-1). We further found that capsaicin exerted inhibitory effects on the persistent nociceptive hypersensitivity induced by peripheral inflammation and nerve injury. Thus, these results support the long-lasting and inhibitory effects of topical capsaicin on persistent pain, and the clinic use of capsaicin as a pain therapy.

  15. Mild closed head traumatic brain injury-induced changes in monoamine neurotransmitters in the trigeminal subnuclei of a rat model: mechanisms underlying orofacial allodynias and headache

    Directory of Open Access Journals (Sweden)

    Golam Mustafa

    2017-01-01

    Full Text Available Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias, a hypersensitive pain response induced by non-painful stimulation. These allodynias, tested using thermal hyperalgesia, correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway, especially in the trigeminal nucleus caudalis. This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis, pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury, which are related to tactile allodynia, touch-pressure sensitivity, and visceral pain. Our results exhibited significant alterations in the excitatory monoamine, serotonin, in spinal trigeminal nucleus oralis and pars interpolaris which usually modulate tactile and mechanical sensitivity in addition to the thermal sensitivity. Moreover, we also detected a robust alteration in the expression of serotonin, and inhibitory molecule norepinephrine in the nucleus tractus solitaries, which might indicate the possibility of an alteration in visceral pain, and existence of other morbidities related to solitary nucleus dysfunction in this rodent model of mild to moderate closed head traumatic brain injury. Collectively, widespread changes in monoamine neurotransmitter may be related to orofacial allodynhias and headache after traumatic brain injury.

  16. Radiofrequency trigeminal rhizolysis for the treatment of trigeminal neuralgia secondary to brainstem infarction. Report of two cases.

    Science.gov (United States)

    Foroohar, M; Herman, M; Heller, S; Levy, R M

    1997-01-15

    Although percutaneous radiofrequency trigeminal rhizolysis (RFL) has been used to treat idiopathic trigeminal neuralgia thought secondary to multiple sclerosis, the use of RFL for trigeminal neuralgia caused by brainstem infarction has not been advocated. The authors report two patients with trigeminal neuralgia following pontine infarction in whom aggressive medical management failed, but who were successfully treated with RFL. Pain relief has persisted for the 3- and 6-year duration of follow-up examinations. Descending trigeminal reticular fibers may be affected by brainstem infarction and result in trigeminal neuralgia; thus, treatment by rhizotomy may be effective in decreasing the peripheral afferent input into the spinal trigeminal nucleus thus decreasing the pain. These two cases demonstrate the utility of RFL in the relief of ischemia-induced trigeminal neuralgia and lead the authors to suggest that its use be broadened to include this indication.

  17. GABAB receptors in the NTS mediate the inhibitory effect of trigeminal nociceptive inputs on parasympathetic reflex vasodilation in the rat masseter muscle.

    Science.gov (United States)

    Ishii, Hisayoshi; Izumi, Hiroshi

    2012-03-15

    The present study was designed to examine whether trigeminal nociceptive inputs are involved in the modulation of parasympathetic reflex vasodilation in the jaw muscles. This was accomplished by investigating the effects of noxious stimulation to the orofacial area with capsaicin, and by microinjecting GABA(A) and GABA(B) receptor agonists or antagonists into the nucleus of the solitary tract (NTS), on masseter hemodynamics in urethane-anesthetized rats. Electrical stimulation of the central cut end of the cervical vagus nerve (cVN) in sympathectomized animals bilaterally increased blood flow in the masseter muscle (MBF). Increases in MBF evoked by cVN stimulation were markedly reduced following injection of capsaicin into the anterior tongue in the distribution of the lingual nerve or lower lip, but not when injected into the skin of the dorsum of the foot. Intravenous administration of either phentolamine or propranolol had no effect on the inhibitory effects of capsaicin injection on the increases of MBF evoked by cVN stimulation, which were largely abolished by microinjecting the GABA(B) receptor agonist baclofen into the NTS. Microinjection of the GABA(B) receptor antagonist CGP-35348 into the NTS markedly attenuated the capsaicin-induced inhibition of MBF increase evoked by cVN stimulation, while microinjection of the GABA(A) receptor antagonist bicuculline did not. Our results indicate that trigeminal nociceptive inputs inhibit vagal-parasympathetic reflex vasodilation in the masseter muscle and suggest that the activation of GABA(B) rather than GABA(A) receptors underlies the observed inhibition in the NTS.

  18. The pungent substances piperine, capsaicin, 6-gingerol and polygodial inhibit the human two-pore domain potassium channels TASK-1, TASK-3 and TRESK.

    Science.gov (United States)

    Beltrán, Leopoldo R; Dawid, Corinna; Beltrán, Madeline; Gisselmann, Guenter; Degenhardt, Katharina; Mathie, Klaus; Hofmann, Thomas; Hatt, Hanns

    2013-01-01

    For a long time, the focus of trigeminal chemoperception has rested almost exclusively on TRP channels. However, two-pore domain (K2P) potassium channels have recently been identified as targets for substances associated with typical trigeminal sensations, such as numbing and tingling. In addition, they have been shown to be modulated by several TRP agonists. We investigated whether the pungent substances piperine, capsaicin, 6-gingerol and polygodial have an effect on human K2P channels. For this purpose, we evaluated the effects of these pungent substances on both wild-type and mutant K2P channels by means of two-electrode voltage-clamp experiments using Xenopus laevis oocytes. All four pungent substances were found to inhibit the basal activity of TASK-1 (K2P 3.1), TASK-3 (K2P 9.1), and TRESK (K2P 18.1) channels. This inhibitory effect was dose-dependent and, with the exception of polygodial on TASK-1, fully reversible. However, only piperine exhibited an IC50 similar to its reported EC50 on TRP channels. Finally, we observed for TASK-3 that mutating H98 to E markedly decreased the inhibition induced by piperine, capsaicin, and 6-gingerol, but not by polygodial. Our data contribute to the relatively sparse knowledge concerning the pharmacology of K2P channels and also raise the question of whether K2P channels could be involved in the pungency perception of piperine.

  19. The pungent substances piperine, capsaicin, 6-gingerol and polygodial inhibit the human two-pore domain potassium channels TASK-1, TASK-3 and TRESK

    Directory of Open Access Journals (Sweden)

    Leopoldo Raul Beltran

    2013-11-01

    Full Text Available For a long time, the focus of trigeminal chemoperception has rested almost exclusively on TRP channels. However, two-pore domain (K2P potassium channels have recently been identified as targets for substances associated with typical trigeminal sensations, such as numbing and tingling. In addition, they have been shown to be modulated by several TRP agonists. We investigated whether the pungent substances piperine, capsaicin, 6-gingerol and polygodial have an effect on human K2P channels. For this purpose, we evaluated the effects of these pungent substances on both wild-type and mutant K2P channels by means of two-electrode voltage-clamp experiments using Xenopus laevis oocytes. All four pungent substances were found to inhibit the basal activity of TASK-1 (K2P 3.1, TASK-3 (K2P 9.1, and TRESK (K2P 18.1 channels. This inhibitory effect was dose-dependent and, with the exception of polygodial on TASK-1, fully reversible. However, only piperine exhibited an IC50 similar to its reported EC50 on TRP channels. Finally, we observed for TASK-3 that mutating H98 to E markedly decreases the inhibition induced by piperine, capsaicin, and 6-gingerol, but not by polygodial. Our data contribute to the relatively sparse knowledge concerning the pharmacology of K2P channels and also raise the question of whether K2P channels could be involved in the pungency perception of piperine.

  20. Repetitive Transcranial Magnetic Stimulation (rTMS)-Induced Trigeminal Autonomic Cephalalgia

    Science.gov (United States)

    DURMAZ, Onur; ATEŞ, Mehmet Alpay; ŞENOL, Mehmet Güney

    2015-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is an effective and novel treatment method that has been approved for the treatment of refractory depression by the U.S. Food and Drug Administration. The most common side effects of rTMS are a transient headache that usually responds to simple analgesics, local discomfort in the stimulation area, dizziness, ipsilateral lacrimation and, very rarely, generalized seizure. TMS is also regarded as a beneficial tool for investigating mechanisms underlying headache. Although rTMS has considerable benefits in terms of headache, there is the potential for rare side effects. In this report, we present the case of a patient with no history of autonomic headache who underwent a course of rTMS for refractory unipolar depression caused by an inadequate response to pharmacotherapy. After his fourth rTMS session, the patient developed sudden headaches with characteristics of trigeminal autonomic cephalalgia on the stimulated side, representing a noteworthy example of the potential side effects of rTMS. PMID:28360729

  1. Light-Emitting Diode Phototherapy Reduces Nocifensive Behavior Induced by Thermal and Chemical Noxious Stimuli in Mice: Evidence for the Involvement of Capsaicin-Sensitive Central Afferent Fibers.

    Science.gov (United States)

    Pigatto, Glauce Regina; Coelho, Igor Santos; Aquino, Rosane Schenkel; Bauermann, Liliane Freitas; Santos, Adair Roberto Soares

    2017-07-01

    Low-intensity phototherapy using light fonts, like light-emitting diode (LED), in the red to infrared spectrum is a promising alternative for the treatment of pain. However, the underlying mechanisms by which LED phototherapy reduces acute pain are not yet well understood. This study investigated the analgesic effect of multisource LED phototherapy on the acute nocifensive behavior of mice induced by thermal and chemical noxious stimuli. The involvement of central afferent C fibers sensitive to capsaicin in this effect was also investigated. Mice exposed to multisource LED (output power 234, 390, or 780 mW and power density 10.4, 17.3, and 34.6 mW/cm(2), respectively, from 10 to 30 min of stimulation with a wavelength of 890 nm) showed rapid and significant reductions in formalin- and acetic acid-induced nocifensive behavior. This effect gradually reduced but remained significant for up to 7 h after LED treatment in the last model used. Moreover, LED (390 mW, 17.3 mW/cm(2)/20 min) irradiation also reduced nocifensive behavior in mice due to chemical [endogenous (i.e., glutamate, prostaglandins, and bradykinin) or exogenous (i.e., formalin, acetic acid, TRPs and ASIC agonist, and protein kinase A and C activators)] and thermal (hot plate test) stimuli. Finally, ablating central afferent C fibers abolished LED analgesia. These experimental results indicate that LED phototherapy reduces the acute painful behavior of animals caused by chemical and thermal stimuli and that LED analgesia depends on the integrity of central afferent C fibers sensitive to capsaicin. These findings provide new information regarding the underlying mechanism by which LED phototherapy reduces acute pain. Thus, LED phototherapy may be an important tool for the management of acute pain.

  2. Capsaicin, Nociception and Pain.

    Science.gov (United States)

    Frias, Bárbara; Merighi, Adalberto

    2016-06-18

    Capsaicin, the pungent ingredient of the hot chili pepper, is known to act on the transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1). TRPV1 is involved in somatic and visceral peripheral inflammation, in the modulation of nociceptive inputs to spinal cord and brain stem centers, as well as the integration of diverse painful stimuli. In this review, we first describe the chemical and pharmacological properties of capsaicin and its derivatives in relation to their analgesic properties. We then consider the biochemical and functional characteristics of TRPV1, focusing on its distribution and biological effects within the somatosensory and viscerosensory nociceptive systems. Finally, we discuss the use of capsaicin as an agonist of TRPV1 to model acute inflammation in slices and other ex vivo preparations.

  3. Direct action of capsaicin in brown adipogenesis and activation of brown adipocytes.

    Science.gov (United States)

    Kida, Ryosuke; Yoshida, Hirofumi; Murakami, Masaru; Shirai, Mitsuyuki; Hashimoto, Osamu; Kawada, Teruo; Matsui, Tohru; Funaba, Masayuki

    2016-01-01

    The ingestion of capsaicin, the principle pungent component of red and chili peppers, induces thermogenesis, in part, through the activation of brown adipocytes expressing genes related to mitochondrial biogenesis and uncoupling such as peroxisome proliferator-activated receptor (Ppar) γ coactivator-1α (Pgc-1α) and uncoupling protein 1 (Ucp1). Capsaicin has been suggested to induce the activation of brown adipocytes, which is mediated by the stimulation of sympathetic nerves. However, capsaicin may directly affect the differentiation of brown preadipocytes, brown adipocyte function, or both, through its significant absorption. We herein demonstrated that Trpv1, a capsaicin receptor, is expressed in brown adipose tissue, and that its expression level is increased during the differentiation of HB2 brown preadipocytes. Furthermore, capsaicin induced calcium influx in brown preadipocytes. A treatment with capsaicin in the early stage of brown adipogenesis did not affect lipid accumulation or the expression levels of Fabp4 (a gene expressed in mature adipocytes), Pparγ2 (a master regulator of adipogenesis) or brown adipocyte-selective genes. In contrast, a treatment with capsaicin in the late stage of brown adipogenesis slightly increased the expression levels of Fabp4, Pparγ2 and Pgc-1α. Although capsaicin did not affect the basal expression level of Ucp1, Ucp1 induction by forskolin was partially inhibited by capsaicin, irrespective of the dose of capsaicin. The results of the present study suggest the direct effects of capsaicin on brown adipocytes or in the late stage of brown adipogenesis.

  4. The blink reflex and the corneal reflex are followed by cortical activity resembling the nociceptive potentials induced by trigeminal laser stimulation in man.

    Science.gov (United States)

    de Tommaso, M; Libro, G; Guido, M; Sciruicchio, V; Puca, F

    2001-09-07

    Laser stimulation of the supraorbital regions evokes brain potentials (LEPs) related to trigeminal nociception. The aim of this study was to record the R2 component of the blink reflex and the corneal reflex in 20 normal subjects, comparing the scalp activity following these reflexes with the nociceptive potentials evoked by CO2 laser stimulation of supraorbital regions. Cortical and muscular reflexes evoked by stimulation of the first trigeminal branch were recorded simultaneously. The R2 component of the blink reflex and the corneal reflex were followed by two cortical peaks, which resembled morphologically N-P waves of LEPs. The two peaks demonstrated a difference in latency of approximately 40 ms, which is consistent with activation time of nociception. This finding suggests that these reflexes are induced by activation of small pain-related fibers.

  5. Increases in PKC gamma expression in trigeminal spinal nucleus is associated with orofacial thermal hyperalgesia in streptozotocin-induced diabetic mice.

    Science.gov (United States)

    Xie, Hong-Ying; Xu, Fei; Li, Yue; Zeng, Zhao-Bin; Zhang, Ran; Xu, Hui-Jun; Qian, Nian-Song; Zhang, Yi-Guan

    2015-01-01

    Painful diabetic polyneuropathy (PDN) at the early phrase of diabetes frequently exhibits increased responsiveness to nociception. In diabetic patients and animal models, alterations in the transmission of orofacial sensory information have been demonstrated in trigeminal system. Herein, we examined the changes of protein kinase Cγ subunit (PKCγ) in trigeminal spinal nucleus (Sp5C) and observed the development of orofacial thermal sensitivity in streptozotocin (STZ)-induced type 1 diabetic mice. With hyperglycemia and body weight loss, STZ mice exhibited orofacial thermal hyperalgesia, along with increased PKCγ expression in Sp5C. Insulin treatment at the early stage of diabetes could alleviate the orofacial thermal hyperalgesia and impaired increased PKCγ in Sp5C in diabetic mice. In summary, our results demonstrate that PKCγ might be involved in orofacial thermal hyperalgesia of diabetes, and early insulin treatment might be effective way to treat orofacial PDN.

  6. Painful Traumatic Trigeminal Neuropathy.

    Science.gov (United States)

    Rafael, Benoliel; Sorin, Teich; Eli, Eliav

    2016-08-01

    This article discusses neuropathic pain of traumatic origin affecting the trigeminal nerve. This syndrome has been termed painful traumatic trigeminal neuropathy by the International Headache Society and replaces atypical odontalgia, deafferentation pain, traumatic neuropathy, and phantom toothache. The discussion emphasizes the diagnosis and the early and late management of injuries to the trigeminal nerve and subsequent painful conditions.

  7. [Trigeminal autonomic cephalgias].

    Science.gov (United States)

    Maximova, M Yu; Piradov, M A; Suanova, E T; Sineva, N A

    2015-01-01

    Review of literature on the trigeminal autonomic cephalgias are presented. Trigeminal autonomic cephalgias are primary headaches with phenotype consisting of trigeminal pain with autonomic sign including lacrimation, rhinorrhea and miosis. Discussed are issues of classification, pathogenesis, clinical picture, diagnosis, differential diagnosis and treatment of this headache. Special attention is paid to cluster headache, paroxysmal hemicrania, SUNCT syndrome, hemicrania continua.

  8. Different Effects of Capsaicin on IA and IK in Pain-conduct Neurons of Rats

    Institute of Scientific and Technical Information of China (English)

    FU Hui; LIU Hui; CAO Xuehong; HU Yan; XIANG Jizhou; LIU Lieju

    2006-01-01

    The different effects of capsaicin on IA and IK currents in pain-conduct neurons of trigeminal ganglia (TG) were investigated. In cultured TG neurons of rats, whole-cell patch clamp techniques were used to record the IA and IK before and after capsaicin perfused. Results revealed that 1 μmol/L capsaicin could inhibit the amplitude of IA by 48.2% (n=10, P<0.05), but had no inhibitory effect on IK (n=7, P>0.05). Ten μmol/L capsaicin could significantly inhibit the amplitude of IA by 93.2% (n=8, P<0.01), but only slightly inhibit the amplitude of IK by 13.2% (n=7,P<0.05). Neither 1 μmol/L nor 10 μmol/L capsaicin had effects on the active curve of IA and IK.It was concluded that capsaicin could selectively inhibit the IA current, and this effect might involve in the analgesic mechanisms of capsaicin.

  9. Increased COX2 in the trigeminal nucleus caudalis is involved in orofacial pain induced by experimental tooth movement.

    Science.gov (United States)

    Gao, Yuan; Duan, Yin-Zhong

    2010-03-01

    Pain is among the major problems during orthodontic treatment. Recent studies have shown that central Cyclooxygenase2 (COX2) pathway was involved in several pain models. The present study investigated whether inducible COX2 within the trigeminal nucleus caudalis (Vc) contributed to experimental tooth movement pain in freely moving rats. Elastic rubber bands were inserted between the first and second maxillary molars bilaterally to establish tooth movement model. The directed mouth wiping behavior was used to evaluate the pain during tooth movement. COX2 distribution in Vc was studied by immunohistochemistry and the changes of COX2 expression were detected by Western blot at different time point after rubber band insertion. Our results showed that tooth movement significantly increased COX2 expression in Vc and the time spent on mouth wiping, reaching a maximum at 1 day and then decreasing gradually. Furthermore, the rhythm change of COX2 expression in Vc and the mouth wiping behavior were much correlative with each other. All of the COX2-immunoreactive structures in Vc exhibited NeuN-immunopositive staining and most of these COX2-immunoreactive neurons were Fos-immunopositive. Importantly, the mouth wiping behavior could be attenuated by intracisternal injection of NS-398 (a selective COX2 inhibitor) but not by periodontal administration of NS-398. All these results suggested that increased COX2 in Vc was involved in tooth movement pain and thus may be a central target for orthodontic pain treatment.

  10. Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors.

    Science.gov (United States)

    Huang, Ming; Cheng, Gen; Tan, Han; Qin, Rui; Zou, Yimin; Wang, Yun; Zhang, Ying

    2017-09-01

    Capsaicin, the ingredient responsible for the pungent taste of hot chili peppers, is widely used in the study and management of pain. Recently, its neuroprotective effect has been described in multiple studies. Herein, we investigated the underlying mechanisms for the neuroprotective effect of capsaicin. Direct injection of capsaicin (1 or 3nmol) into the peri-infarct area reduced the infarct volume and improved neurological behavioral scoring and motor coordination function in the middle cerebral artery occlusion (MCAO)/reperfusion model in rats. The time window of the protective effect of capsaicin was within 1h after reperfusion, when excitotoxicity is the main reason of cell death. In cultured cortical neurons, administration of capsaicin attenuated glutamate-induced excitotoxic injury. With respect to the mechanisms of the neuroprotective effect of capsaicin, reduced calcium influx after glutamate stimulation was observed following capsaicin pretreatment in cortical neurons. Trpv1 knock-out abolished the inhibitory effect of capsaicin on glutamate-induced calcium influx and subsequent neuronal death. Reduced expression of GluN1 and GluN2B, subunits of NMDA receptor, was examined after capsaicin treatment in cortical neurons. In summary, our studies reveal that the neuroprotective effect of capsaicin in cortical neurons is TRPV1-dependent and down-regulation of the expression and function of NMDA receptors contributes to the protection afforded by capsaicin. Copyright © 2017. Published by Elsevier Inc.

  11. Capsaicin mediates induces apoptosis in human renal carcinoma 786-O cells%辣椒素诱导人肾癌细胞凋亡及其机制的研究

    Institute of Scientific and Technical Information of China (English)

    刘涛; 陶皇恒; 王刚; 方志海; 杨中华; 王行环; 周家杰

    2015-01-01

    Objective To explore the chemopreventive potential of capsaicin in renal cell carci-noma (RCC)786-O cells,as well as the possible mechanism involved. Methods The inhibitive effect of capsaicin on 786-O cells proliferation was determined with MTT assays.ROS generation was detected by ROS kit.Apoptosis rate was detected with flow cytometry and hochest staining. Capsazepine,a specific inhibitor of TRPV1,was used to investigate whether TRPV1 mediated pro-liferation inhibition,ROS and apoptosis increase induced by capsaicin.Western blot assays were con-ducted to determine the changes of apoptotic related proteins. Results Treatment of capsaicin re-duced growth of 786-O cells (P <0.05)and induced obvious ROS generation (P <0.01).Besides, capsaicin induced obvious cell apoptosis (P <0.05).However,the proliferation inhibition,ROS and apoptosis increase induced by capsaicin all could be attenuated by TRPV1 antagonist capsazepine. Capsaicin induced up-regulated expression of pro-apoptotic genes including c-myc,FADD,Bax and cleaved-caspase-3,-8,and-9,while down-regulation of anti-apoptotic gene Bcl2. Conclusions We demonstrate capsaicin is able to inhibit the proliferation of 786-O cells,and to induce cell apoptosis through changing the expression of apoptosis-related proteins,which indicates that capsaicin is an ef-ficient and potential drug for therapy and management of human RCC.%目的:探讨辣椒素对人肾癌786-O 细胞凋亡的诱导作用及其相关机制.方法MTT 检测辣椒素对细胞增殖能力的影响;活性氧试剂盒检测细胞活性氧水平;流式细胞术及 Ho-chest 染色法检测辣椒素对细胞凋亡的影响;使用 TRPV1拮抗剂辣椒平探讨 TRPV1在辣椒素抑制786-O 细胞增殖能力、增加细胞活性氧水平及促进细胞凋亡等效应中的介导作用;Western blot 检测凋亡相关分子表达水平.结果辣椒素显著降低786-O 细胞增殖能力(P <0.05);导致细胞活性氧水平上升(P <0.01)

  12. Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses

    Directory of Open Access Journals (Sweden)

    Victor Fattori

    2016-06-01

    Full Text Available In this review, we discuss the importance of capsaicin to the current understanding of neuronal modulation of pain and explore the mechanisms of capsaicin-induced pain. We will focus on the analgesic effects of capsaicin and its clinical applicability in treating pain. Furthermore, we will draw attention to the rationale for other clinical therapeutic uses and implications of capsaicin in diseases such as obesity, diabetes, cardiovascular conditions, cancer, airway diseases, itch, gastric, and urological disorders.

  13. RPF101, a new capsaicin-like analogue, disrupts the microtubule network accompanied by arrest in the G2/M phase, inducing apoptosis and mitotic catastrophe in the MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Sá-Júnior, Paulo Luiz de [Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil); Pasqualoto, Kerly Fernanda Mesquita [Biochemistry and Biophysical Laboratory, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil); Ferreira, Adilson Kleber [Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil); Tavares, Maurício Temotheo; Damião, Mariana Celestina Frojuello Costa Bernstorff [Department of Pharmacy, School of Pharmaceutical Sciences, University of Sao Paulo, Prof. Lineu Prestes Avenue, 580, Postal Code: 05508-000, Sao Paulo (Brazil); Azevedo, Ricardo Alexandre de [Biochemistry and Biophysical Laboratory, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil); Câmara, Diana Aparecida Dias; Pereira, Alexandre; Madeiro de Souza, Dener [Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil); Parise Filho, Roberto, E-mail: roberto.parise@usp.br [Department of Pharmacy, School of Pharmaceutical Sciences, University of Sao Paulo, Prof. Lineu Prestes Avenue, 580, Postal Code: 05508-000, Sao Paulo (Brazil)

    2013-02-01

    Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Capsaicin, which is the primary pungent compound in red peppers, was reported to selectively inhibit the growth of a variety tumor cell lines. Here, we report for the first time a novel synthetic capsaicin-like analogue, RPF101, which presents a high antitumor activity on MCF-7 cell line, inducing arrest of the cell cycle at the G2/M phase through a disruption of the microtubule network. Furthermore, it causes cellular morphologic changes characteristic of apoptosis and a decrease of Δψm. Molecular modeling studies corroborated the biological findings and suggested that RPF101, besides being a more reactive molecule towards its target, may also present a better pharmacokinetic profile than capsaicin. All these findings support the fact that RPF101 is a promising anticancer agent. -- Highlights: ► We report for the first time that RPF101 possesses anticancer properties. ► RPF101 induces apoptosis of human breast cancer cells. ► RPF 101 decreases mitochondrial potential and induces DNA fragmentation.

  14. Cognitive effects of electro-acupuncture and pregabalin in a trigeminal neuralgia rat model induced by cobra venom

    Directory of Open Access Journals (Sweden)

    Chen RW

    2017-08-01

    Full Text Available Ruo-Wen Chen,1,2 Hui Liu,2 Jian-Xiong An,1,2 Xiao-Yan Qian,2 Yi-De Jiang,2 Doris K Cope,3 John P Williams,3 Rui Zhang,1 Li-Na Sun1 1Department of Anesthesiology, Weifang Medical University, Weifang City, Shandong, 2Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, China; 3Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Objective: The objective of this study was to investigate the effects of electro-acupuncture (EA and pregabalin on cognition impairment induced by chronic trigeminal neuralgia (TN in rats. Design: Controlled animal study. Setting: Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University. Subjects: Forty adult male Sprague Dawley rats. Methods: Rats were randomly divided into four groups. The TN model was induced by administration of cobra venom to the left infraorbital nerve. On postoperative day 14, either EA or pregabalin was administered, free behavioral activities were observed. Spatial learning and memory abilities were determined in the Morris water maze. The ultrastructural alterations of the Gasserian ganglion, medulla oblongata and hippocampus were examined by electron microscopy. The changes on long-term potentiation were investigated. Results: After treatment, the exploratory behavior increased and the grooming behavior decreased (P<0.05 for the EA group and pregabalin group compared with the cobra venom group; moreover, demyelination of neurons in Gasserian ganglion and medulla oblongata was reversed. The number of platform site crossings, the average percentages of time in the target quadrant and the field excitatory postsynaptic potential slopes increased (P<0.05 in the EA group compared to the cobra venom group. However, the pregabalin group

  15. Triptan-induced enhancement of neuronal nitric oxide synthase in trigeminal ganglion dural afferents underlies increased responsiveness to potential migraine triggers.

    Science.gov (United States)

    De Felice, Milena; Ossipov, Michael H; Wang, Ruizhong; Dussor, Gregory; Lai, Josephine; Meng, Ian D; Chichorro, Juliana; Andrews, John S; Rakhit, Suman; Maddaford, Shawn; Dodick, David; Porreca, Frank

    2010-08-01

    Migraine is a common neurological disorder often treated with triptans. Triptan overuse can lead to increased frequency of headache in some patients, a phenomenon termed medication overuse headache. Previous preclinical studies have demonstrated that repeated or sustained triptan administration for several days can elicit persistent neural adaptations in trigeminal ganglion cells innervating the dura, prominently characterized by increased labelling of neuronal profiles for calcitonin gene related peptide. Additionally, triptan administration elicited a behavioural syndrome of enhanced sensitivity to surrogate triggers of migraine that was maintained for weeks following discontinuation of drug, a phenomenon termed 'triptan-induced latent sensitization'. Here, we demonstrate that triptan administration elicits a long-lasting increase in identified rat trigeminal dural afferents labelled for neuronal nitric oxide synthase in the trigeminal ganglion. Cutaneous allodynia observed during the period of triptan administration was reversed by NXN-323, a selective inhibitor of neuronal nitric oxide synthase. Additionally, neuronal nitric oxide synthase inhibition prevented environmental stress-induced hypersensitivity in the post-triptan administration period. Co-administration of NXN-323 with sumatriptan over several days prevented the expression of allodynia and enhanced sensitivity to stress observed following latent sensitization, but not the triptan-induced increased labelling of neuronal nitric oxide synthase in dural afferents. Triptan administration thus promotes increased expression of neuronal nitric oxide synthase in dural afferents, which is critical for enhanced sensitivity to environmental stress. These data provide a biological basis for increased frequency of headache following triptans and highlight the potential clinical utility of neuronal nitric oxide synthase inhibition in preventing or treating medication overuse headache.

  16. Characterization of three different sensory fibers by use of neonatal capsaicin treatment, spinal antagonism and a novel electrical stimulation-induced paw flexion test

    Directory of Open Access Journals (Sweden)

    Yamaguchi Asuka

    2006-05-01

    Full Text Available Abstract In the present study, we first report an in vivo characterization of flexor responses induced by three distinct sine-wave stimuli in the electrical stimulation-induced paw flexion (EPF test in mice. The fixed sine-wave electric stimulations of 5 Hz (C-fiber, 250 Hz (Aδ-fiber and 2000 Hz (Aβ-fiber to the hind paw of mice induced a paw-flexion response and vocalization. The average threshold for paw flexor responses by sine-wave stimulations was much lower than that for vocalization. Neonatally (P3 pretreatment with capsaicin to degenerate polymodal substance P-ergic C-fiber neurons increased the threshold to 5 Hz (C-fiber stimuli, but not to 250 Hz (Aδ-fiber and 2000 Hz (Aβ-fiber. The flexor responses to 5 Hz stimuli were significantly blocked by intrathecal (i.t. pretreatment with both CP-99994 and MK-801, an NK1 and NMDA receptor antagonist, respectively, but not by CNQX, an AMPA/kainate receptor antagonist. On the other hand, the flexor responses induced by 250 Hz stimuli were blocked by MK-801 (i.t. but not by CP-99994 or CNQX. In contrast, flexor responses induced by 2000 Hz stimuli were only blocked by CNQX treatment. These data suggest that we have identified three pharmacologically different categories of responses mediated through different primary afferent fibers. Furthermore, we also carried out characterization of the in vivo functional sensitivity of each of the sensory fiber types in nerve-injured mice using the EPF test, and found that the threshold to both 250 Hz and 2000 Hz stimulations were markedly decreased, whereas the threshold to 5 Hz stimulations was significantly increased. Thus we found opposing effects on specific sensory fiber-mediated responses as a result of nerve injury in mice. These results also suggest that the EPF analysis is useful for the evaluation of plasticity in sensory functions in animal disease models.

  17. Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Chao Kang

    2017-05-01

    Full Text Available Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI responsible for the development of obesity. Capsaicin (CAP is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA measurements, and phylogenetic reconstruction of unobserved states (PICRUSt analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae, while it caused lower levels of members of the lipopolysaccharide (LPS-producing family S24_7. Predicted function analysis (PICRUSt showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB1 by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation.

  18. Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis

    DEFF Research Database (Denmark)

    Lukács, M; Warfvinge, K; Tajti, J

    2017-01-01

    BACKGROUND: Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund's Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a s...

  19. Perception of trigeminal mixtures.

    Science.gov (United States)

    Filiou, Renée-Pier; Lepore, Franco; Bryant, Bruce; Lundström, Johan N; Frasnelli, Johannes

    2015-01-01

    The trigeminal system is a chemical sense allowing for the perception of chemosensory information in our environment. However, contrary to smell and taste, we lack a thorough understanding of the trigeminal processing of mixtures. We, therefore, investigated trigeminal perception using mixtures of 3 relatively receptor-specific agonists together with one control odor in different proportions to determine basic perceptual dimensions of trigeminal perception. We found that 4 main dimensions were linked to trigeminal perception: sensations of intensity, warmth, coldness, and pain. We subsequently investigated perception of binary mixtures of trigeminal stimuli by means of these 4 perceptual dimensions using different concentrations of a cooling stimulus (eucalyptol) mixed with a stimulus that evokes warmth perception (cinnamaldehyde). To determine if sensory interactions are mainly of central or peripheral origin, we presented stimuli in a physical "mixture" or as a "combination" presented separately to individual nostrils. Results showed that mixtures generally yielded higher ratings than combinations on the trigeminal dimensions "intensity," "warm," and "painful," whereas combinations yielded higher ratings than mixtures on the trigeminal dimension "cold." These results suggest dimension-specific interactions in the perception of trigeminal mixtures, which may be explained by particular interactions that may take place on peripheral or central levels.

  20. Imaging the trigeminal nerve

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Radiology Department, Instituto Portugues de Oncologia Francisco Gentil, Centro de Lisboa, Rua Prof. Lima Basto, 1093, Lisboa (Portugal)], E-mail: borgalexandra@gmail.com; Casselman, Jan [Department of Radiology, A. Z. St Jan Brugge and A. Z. St Augustinus Antwerpen Hospitals (Belgium)

    2010-05-15

    Of all cranial nerves, the trigeminal nerve is the largest and the most widely distributed in the supra-hyoid neck. It provides sensory input from the face and motor innervation to the muscles of mastication. In order to adequately image the full course of the trigeminal nerve and its main branches a detailed knowledge of neuroanatomy and imaging technique is required. Although the main trunk of the trigeminal nerve is consistently seen on conventional brain studies, high-resolution tailored imaging is mandatory to depict smaller nerve branches and subtle pathologic processes. Increasing developments in imaging technique made possible isotropic sub-milimetric images and curved reconstructions of cranial nerves and their branches and led to an increasing recognition of symptomatic trigeminal neuropathies. Whereas MRI has a higher diagnostic yield in patients with trigeminal neuropathy, CT is still required to demonstrate the bony anatomy of the skull base and is the modality of choice in the context of traumatic injury to the nerve. Imaging of the trigeminal nerve is particularly cumbersome as its long course from the brainstem nuclei to the peripheral branches and its rich anastomotic network impede, in most cases, a topographic approach. Therefore, except in cases of classic trigeminal neuralgia, in which imaging studies can be tailored to the root entry zone, the full course of the trigeminal nerve has to be imaged. This article provides an update in the most recent advances on MR imaging technique and a segmental imaging approach to the most common pathologic processes affecting the trigeminal nerve.

  1. Cold and L-menthol-induced sensitization in healthy volunteers--a cold hypersensitivity analogue to the heat/capsaicin model.

    Science.gov (United States)

    Andersen, Hjalte H; Poulsen, Jeppe N; Uchida, Yugo; Nikbakht, Anahita; Arendt-Nielsen, Lars; Gazerani, Parisa

    2015-05-01

    Topical high-concentration L-menthol is the only established human experimental pain model to study mechanisms underlying cold hyperalgesia. We aimed at investigating the combinatorial effect of cold stimuli and topical L-menthol on cold pain and secondary mechanical hyperalgesia. Analogue to the heat-capsaicin model on skin sensitization, we proposed that cold/menthol enhances or prolong L-menthol-evoked sensitization. Topical 40% L-menthol or vehicle was applied (20 minutes) on the volar forearms of 20 healthy females and males (age, 28.7 ± 0.6 years). Cold stimulation of 5°C for 5 minutes was then applied to the treated area 3 times with 40-minute intervals. Cold detection threshold and pain, mechanical hyperalgesia (pinprick), static and dynamic mechanical allodynia (von Frey and brush), skin blood flow (laser speckle), and temperature (thermocamera) were assessed. Cold detection threshold and cold pain threshold (CPT) increased after L-menthol and remained high after the cold rekindling cycles (P menthol evoked secondary hyperalgesia to pinprick (P menthol (P menthol facilitated and prolonged L-menthol-induced cold pain and hyperalgesia. This model may prove beneficial for testing analgesic compounds when a sufficient duration of time is needed to see drug effects on CPT or mechanical hypersensitivity.

  2. Fos protein-like immunoreactive neurons induced by electrical stimulation in the trigeminal sensory nuclear complex of rats with chronically injured peripheral nerve.

    Science.gov (United States)

    Fujisawa, Naoko; Terayama, Ryuji; Yamaguchi, Daisuke; Omura, Shinji; Yamashiro, Takashi; Sugimoto, Tomosada

    2012-06-01

    The rat trigeminal sensory nuclear complex (TSNC) was examined for Fos protein-like immunoreactive (Fos-LI) neurons induced by electrical stimulation (ES) of the lingual nerve (LN) at 2 weeks after injury to the LN or the inferior alveolar nerve (IAN). Intensity-dependent increase in the number of Fos-LI neurons was observed in the subnucleus oralis (Vo) and caudalis (Vc) of the spinal trigeminal tract nucleus irrespective of nerve injury. The number of Fos-LI neurons induced by ES of the chronically injured LN at A-fiber intensity (0.1 mA) was significantly increased in the Vo but not the Vc. On the other hand, in rats with chronically injured IAN, the number of Fos-LI neurons induced by ES of the LN at C-fiber intensity (10 mA) was significantly increased in the Vc but not the Vo. These results indicated that injury of a nerve innervating intraoral structures increased the c-Fos response of Vo neurons to A-fiber intensity ES of the injured nerve. A similar nerve injury enhanced the c-Fos response of Vc neurons to C-fiber intensity ES of a spared uninjured nerve innervating an intraoral territory neighboring that of the injured nerve. The present result show that nerve injury causes differential effects on c-Fos expression in the Vo and Vc, which may explain complexity of neuropathic pain symptoms in clinical cases.

  3. Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet.

    Science.gov (United States)

    Kang, Chao; Wang, Bin; Kaliannan, Kanakaraju; Wang, Xiaolan; Lang, Hedong; Hui, Suocheng; Huang, Li; Zhang, Yong; Zhou, Ming; Chen, Mengting; Mi, Mantian

    2017-05-23

    Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI) responsible for the development of obesity. Capsaicin (CAP) is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD) supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA) measurements, and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae, while it caused lower levels of members of the lipopolysaccharide (LPS)-producing family S24_7. Predicted function analysis (PICRUSt) showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB1) by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation.IMPORTANCE Metabolic endotoxemia due to gut microbial dysbiosis is a major contributor to the pathogenesis of

  4. Effect of the gamma knife treatment on the trigeminal nerve root in Chinese patients with primary trigeminal neuralgia.

    Science.gov (United States)

    Song, Zhi-Xiu; Qian, Wei; Wu, Yu-Quan; Sun, Fang-Jie; Fei, Jun; Huang, Run-Sheng; Fang, Jing-Yu; Wu, Cai-Zhen; An, You-Ming; Wang, Daxin; Yang, Jun

    2014-01-01

    To understand the mechanism of the gamma knife treating the trigeminal neuralgia. Using the MASEP-SRRS type gamma knife treatment system, 140 Chinese patients with trigeminal neuralgia (NT) were treated in our hospital from 2002 to 2010, in which the pain relief rate reached 95% and recurrence rate was 3% only. We investigated the effect of the gamma knife treatment on the trigeminal nerve root in 20 Chinese patients with primary trigeminal neuralgia by the magnetic resonance imager (MRI) observation. 1) The cross-sectional area of trigeminal nerve root became smaller and MRI signals were lower in the treatment side than those in the non-treatment side after the gamma knife treatment of primary trigeminal neuralgia; 2) in the treatment side, the cross-sectional area of the trigeminal nerve root decreased significantly after the gamma knife treatment; 3) there was good correlation between the clinical improvement and the MRI findings; and 4) the straight distance between the trigeminal nerve root and the brainstem did not change after the gamma knife treatment. The pain relief induced the gamma knife radiosurgery might be related with the atrophy of the trigeminal nerve root in Chinese patients with primary trigeminal neuralgia.

  5. Hypolipidemic and antioxidant effects of curcumin and capsaicin in high-fat-fed rats.

    Science.gov (United States)

    Manjunatha, H; Srinivasan, K

    2007-06-01

    The beneficial hypolipidemic and antioxidant influences of the dietary spice compounds curcumin and capsaicin were evaluated. Curcumin, capsaicin, or their combination were included in the diet of high-(30%)-fat-fed rats for 8 weeks. Dietary high-fat-induced hypertriglyceridemia was countered by dietary curcumin, capsaicin, or their combination by 12%-20%. Curcumin, capsaicin, and their combination also produced a slight decrease in serum total cholesterol in these animals. Serum alpha-tocopherol content was increased by dietary curcumin, capsaicin, and their combination in high-fat-fed rats. Serum total thiol content in high-fat-fed animals and serum ascorbic acid in normal animals was elevated by the combination of curcumin and capsaicin. Hepatic glutathione was increased by curcumin, capsaicin, or their combination in normal animals. Hepatic glutathione and alpha-tocopherol were increased, whereas lipid peroxide level was reduced by dietary curcumin and combination of curcumin and capsaicin in high-fat-fed animals. Serum glutathione peroxidase and glutathione transferase in high-fat-fed rats were generally higher as a result of dietary curcumin, capsaicin, and the combination of curcumin and capsaicin. Hepatic glutathione reductase and glutathione peroxidase were significantly elevated by dietary spice principles in high-fat-fed animals. The additive effect of the 2 bioactive compounds was generally not evident with respect to hypolipidemic or antioxidant potential. However, the effectiveness of the combination was higher in a few instances.

  6. [Treatment of trigeminal neuralgia].

    Science.gov (United States)

    Bakker, Nicolaas A; van Dijk, J M C Marc; Wagemakers, Michiel; van der Weide, Hiske L; Beese, Uli; Metzemaekers, Jan D M

    2014-01-01

    Classic idiopathic trigeminal neuralgia is characterized by sharp unilateral shooting pain in the distribution of one or more branches of the trigeminal nerve. It involves a diagnosis of exclusion. Initially, therapy consists of medical therapy, preferably with carbamazepine or oxcarbazepine. For patients refractory to medical therapy, microvascular decompression of the trigeminal nerve provides the best long-term outcomes, at a relatively low complication risk. In case of surgical contraindications, there are other options: radiosurgery or a neurodestructive procedure of the trigeminal ganglion. Short-term outcomes after neurodestructive therapy are good, however effects diminish over time. Every patient with idiopathic trigeminal neuralgia in whom medical therapy has failed, should be counselled at an experienced centre in which neurosurgical treatment is available.

  7. Study on Vip protein expression in psoriatic epidermis with the topical treatment of capsaicin ointment

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To investigate the mechanism of capsaicin in treating active psoriasis vulgaris. Methods: VIP protein in active psoriatic lesions before and 30 days after the treatment of capsaicin ointment was detected by immunohistochemistry. Results:There was positive expression of VIP in all layers of psoriatic lesions epidermis (95.5 % ), but after the treatment of capsaicin ointment,there was nearly no expression of VIP protein in epidermis(22.2% ). Conclusion: Capsaicin inhibits proliferation and induces the differentiation of keratinocytes through down-regulating the expression of VIP in psoriatic epidermis.

  8. Pharmaceutical management of trigeminal neuralgia in the elderly

    NARCIS (Netherlands)

    Oomens, M.A.E.M.; Forouzanfar, T.

    2015-01-01

    Classical trigeminal neuralgia (CTN) is a severe neuropathic pain in the distribution of one or more branches of the trigeminal nerve, which occurs in recurrent episodes, causing deterioration in quality of life, affecting everyday habits and inducing severe disability. The aim of this review is to

  9. H2S-induced HCO3- secretion in the rat stomach--involvement of nitric oxide, prostaglandins, and capsaicin-sensitive sensory neurons.

    Science.gov (United States)

    Takeuchi, Koji; Ise, Fumitaka; Takahashi, Kento; Aihara, Eitaro; Hayashi, Shusaku

    2015-04-30

    Hydrogen sulfide (H2S) is known to be an important gaseous mediator that affects various functions under physiological and pathological conditions. We examined the effects of NaHS, a H2S donor, on HCO3(-) secretion in rat stomachs and investigated the mechanism involved in this response. Under urethane anesthesia, rat stomachs were mounted on an ex vivo chamber and perfused with saline. Acid secretion had been inhibited by omeprazole. The secretion of HCO3(-) was measured at pH 7.0 using a pH-stat method and by the addition of 10 mM HCl. NaHS (0.5-10 mM) was perfused in the stomach for 5 min. Indomethacin or L-NAME was administered s.c. before NaHS treatment, while glibenclamide (a KATP channel blocker), ONO-8711 (an EP1 antagonist), or propargylglycine (a cystathionine γ-lyase inhibitor) was given i.p. before. The mucosal perfusion of NaHS dose-dependently increased the secretion of HCO3(-), and this effect was significantly attenuated by indomethacin, L-NAME, and sensory deafferentation, but not by glibenclamide or ONO-8711. The luminal output of nitric oxide, but not the mucosal production of prostaglandin E2, was increased by the perfusion of NaHS. Mucosal acidification stimulated HCO3(-) secretion, and this response was inhibited by sensory deafferentation, indomethacin, L-NAME, and ONO-8711, but not by propargylglycine. These results suggested that H2S increased HCO3(-) secretion in the stomach, and this effect was mediated by capsaicin-sensitive afferent neurons and dependent on nitric oxide and prostaglandins, but not ATP-sensitive K(+) channels. Further study is needed to define the role of endogenous H2S in the mechanism underlying acid-induced gastric HCO3(-) secretion. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Electrical stimulation to the trigeminal proprioceptive fibres that innervate the mechanoreceptors in Müller's muscle induces involuntary reflex contraction of the frontalis muscles.

    Science.gov (United States)

    Matsuo, Kiyoshi; Osada, Yoshiro; Ban, Ryokuya

    2013-02-01

    The levator and frontalis muscles lack interior muscle spindles, despite consisting of slow-twitch fibres that involuntarily sustain eyelid-opening and eyebrow-raising against gravity. To compensate for this anatomical defect, this study hypothetically proposes that initial voluntary contraction of the levator fast-twitch muscle fibres stretches the mechanoreceptors in Müller's muscle and evokes proprioception, which continuously induces reflex contraction of slow-twitch fibres of the levator and frontalis muscles. This study sought to determine whether unilateral transcutaneous electrical stimulation to the trigeminal proprioceptive fibres that innervate the mechanoreceptors in Müller's muscle could induce electromyographic responses in the frontalis muscles, with monitoring responses in the orbicularis oculi muscles. The study population included 27 normal subjects and 23 subjects with aponeurotic blepharoptosis, who displayed persistently raised eyebrows on primary gaze and light eyelid closure. The stimulation induced a short-latency response in the ipsilateral frontalis muscle of all subjects and long-latency responses in the bilateral frontalis muscles of normal subjects. However, it did not induce long-latency responses in the bilateral frontalis muscles of subjects with aponeurotic blepharoptosis. The orbicularis oculi muscles showed R1 and/or R2 responses. The stimulation might reach not only the proprioceptive fibres, but also other sensory fibres related to the blink or corneal reflex. The experimental system can provoke a monosynaptic short-latency response in the ipsilateral frontalis muscle, probably through the mesencephalic trigeminal proprioceptive neuron and the frontalis motor neuron, and polysynaptic long-latency responses in the bilateral frontalis muscles through an unknown pathway. The latter neural circuit appeared to be engaged by the circumstances of aponeurotic blepharoptosis.

  11. Modulation of trigeminal laser evoked potentials and laser silent periods by homotopical experimental pain.

    Science.gov (United States)

    Romaniello, Antonietta; Arendt-Nielsen, Lars; Cruccu, Giorgio; Svensson, Peter

    2002-07-01

    Cutaneous laser stimulation activates predominantly the A-delta and C mechano-heat nociceptors. Applied to the perioral region, low intensity CO(2)-laser pulses evoke reproducible trigeminal cortical evoked potentials (LEPs). High intensity CO(2)-laser stimuli induce a reflex response in the contracted jaw-closing muscle, the so-called laser silent period (LSP). Both LEPs and LSP provide a useful tool to study the physiology of the trigeminal nociceptive system. In ten healthy subjects we recorded the subjective ratings of the perioral laser stimulation and the trigeminal LEPs and LSP before, during and after homotopic experimental tonic muscle (infusion of hypertonic saline into the masseter muscle) and tonic skin pain (topical application of capsaicin to the cheek). LEPs were recorded from the vertex at two stimulus intensities: low (1.1 x pain threshold, PTh) and high (1.5 x PTh). LSP from masseter and temporalis muscles were recorded bilaterally through surface electromyographic (EMG) electrodes. CO(2)-laser pulses were applied to the perioral region (V2/V3) on the painful and non-painful side. The amplitude of LEPs increased with higher stimulus intensities (P 0.20). The LSP in the masseter and temporalis muscles had similar onset-latency (80+/-5 ms), offset-latency (111+/-5 ms) and duration (31+/-4 ms). Experimental pain had no effect on the onset- and offset-latency (P>0.05). Experimental pain, whether from muscle or from skin, reduced the degree of suppression (PEMG curve (P< 0.005) of the LSP. The LSP was still suppressed during the post-pain recordings when the skin pain had disappeared (P<0.05). In all experiments experimental tonic pain decreased the subjective ratings of the perioral laser stimulation (P< 0.001). Experimental tonic pain, either from muscle or from skin, induced bilateral inhibitory effects on the trigeminal laser evoked potentials and brainstem reflex responses and on the subjective ratings of the laser pulses. These effects could be

  12. 5-HT7 Receptors Are Not Involved in Neuropeptide Release in Primary Cultured Rat Trigeminal Ganglion Neurons.

    Science.gov (United States)

    Wang, Xiaojuan; Hu, Rong; Liang, Jianbo; Li, Ze; Sun, Weiwen; Pan, Xiaoping

    2016-06-01

    Migraine is a common but complex neurological disorder. Its precise mechanisms are not fully understood. Increasing indirect evidence indicates that 5-HT7 receptors may be involved; however, their role remains unknown. Our previous in vivo study showed that selective blockade of 5-HT7 receptors caused decreased serum levels of calcitonin gene-related peptide (CGRP) in the external jugular vein following electrical stimulation of the trigeminal ganglion (TG) in an animal model of migraine. In the present study, we used an in vitro model of cultured TG cells to further investigate whether 5-HT7 receptors are directly responsible for the release of CGRP and substance P from TG neurons. We stimulated rat primary cultured TG neurons with capsaicin or potassium chloride (KCl) to mimic neurogenic inflammation, resulting in release of CGRP and substance P. 5-HT7 receptors were abundantly expressed in TG neurons. Greater than 93 % of 5-HT7 receptor-positive neurons co-expressed CGRP and 56 % co-expressed substance P. Both the capsaicin- and KCl-induced release of CGRP and substance P were unaffected by pretreatment of cultured TG cells with the selective 5-HT7 receptor agonist AS19 and antagonist SB269970. This study demonstrates for the first time that 5-HT7 receptors are abundantly co-expressed with CGRP and substance P in rat primary TG neurons and suggests that they are not responsible for the release of CGRP and substance P from cultured TG neurons evoked by capsaicin or KCl.

  13. Assessment of Pain Response in Capsaicin-Induced Dynamic Mechanical Allodynia Using a Novel and Fully Automated Brushing Device

    Directory of Open Access Journals (Sweden)

    Kristian G du Jardin

    2013-01-01

    Full Text Available BACKGROUND: Dynamic mechanical allodynia is traditionally induced by manual brushing of the skin. Brushing force and speed have been shown to influence the intensity of brush-evoked pain. There are still limited data available with respect to the optimal stroke number, length, force, angle and speed. Therefore, an automated brushing device (ABD was developed, for which brushing angle and speed could be controlled to enable quantitative assessment of dynamic mechanical allodynia.

  14. Triggering trigeminal neuralgia.

    Science.gov (United States)

    Di Stefano, Giulia; Maarbjerg, Stine; Nurmikko, Turo; Truini, Andrea; Cruccu, Giorgio

    2017-01-01

    Introduction Although it is widely accepted that facial pain paroxysms triggered by innocuous stimuli constitute a hallmark sign of trigeminal neuralgia, very few studies to date have systematically investigated the role of the triggers involved. In the recently published diagnostic classification, triggered pain is an essential criterion for the diagnosis of trigeminal neuralgia but no study to date has been designed to address this issue directly. In this study, we set out to determine, in patients with trigeminal neuralgia, how frequently triggers are present, which manoeuvres activate them and where cutaneous and mucosal trigger zones are located. Methods Clinical characteristics focusing on trigger factors were collected from 140 patients with trigeminal neuralgia, in a cross-sectional study design. Results Provocation of paroxysmal pain by various trigger manoeuvres was reported by 136 of the 140 patients. The most frequent manoeuvres were gentle touching of the face (79%) and talking (54%). Trigger zones were predominantly reported in the perioral and nasal region. Conclusion This study confirms that in trigeminal neuralgia, paroxysmal pain is associated with triggers in virtually all patients and supports the use of triggers as an essential diagnostic feature of trigeminal neuralgia.

  15. Effect of capsaicin on thermoregulation: an update with new aspects

    Science.gov (United States)

    Szolcsányi, János

    2015-01-01

    Capsaicin, a selective activator of the chemo- and heat-sensitive transient receptor potential (TRP) V1 cation channel, has characteristic feature of causing long-term functional and structural impairment of neural elements supplied by TRPV1/capsaicin receptor. In mammals, systemic application of capsaicin induces complex heat-loss response characteristic for each species and avoidance of warm environment. Capsaicin activates cutaneous warm receptors and polymodal nociceptors but has no effect on cold receptors or mechanoreceptors. In this review, thermoregulatory features of capsaicin-pretreated rodents and TRPV1-mediated neural elements with innocuous heat sensitivity are summarized. Recent data support a novel hypothesis for the role of visceral warmth sensors in monitoring core body temperature. Furthermore, strong evidence suggests that central presynaptic nerve terminals of TRPV1-expressing cutaneous, thoracic and abdominal visceral receptors are activated by innocuous warmth stimuli and capsaicin. These responses are absent in TRPV1 knockout mice. Thermoregulatory disturbance induced by systemic capsaicin pretreatment lasts for months and is characterized by a normal body temperature at cool environment up to a total dose of 150 mg/kg s.c. Upward differential shift of set points for activation vasodilation, other heat-loss effectors and thermopreference develops. Avoidance of warm ambient temperature (35°C, 40°C) is severely impaired but thermopreference at cool ambient temperatures (Tas) are not altered. TRPV1 knockout or knockdown and genetically altered TRPV1, TRPV2 and TRPM8 knockout mice have normal core temperature in thermoneutral or cool environments, but the combined mutant mice have impaired regulation in warm or cold (4°C) environments. Several lines of evidence support that in the preoptic area warmth sensitive neurons are activated and desensitized by capsaicin, but morphological evidence for it is controversial. It is suggested that these

  16. Quantitative sensory testing response patterns to capsaicin- and ultraviolet-B-induced local skin hypersensitization in healthy subjects: a machine-learned analysis.

    Science.gov (United States)

    Lötsch, Jörn; Geisslinger, Gerd; Heinemann, Sarah; Lerch, Florian; Oertel, Bruno G; Ultsch, Alfred

    2017-08-16

    The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat stimulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain). This study provided a 246 × 10-sized data matrix (82 subjects assessed at baseline, following UV-B application, and following capsaicin application) with respect to 10 QST parameters, which we analyzed using machine-learning techniques. We observed statistically significant effects of the hypersensitization treatments in 9 different QST parameters. Supervised machine-learned analysis implemented as random forests followed by ABC analysis pointed to heat pain thresholds as the most relevantly affected QST parameter. However, decision tree analysis indicated that UV-B additionally modulated sensitivity to cold. Unsupervised machine-learning techniques, implemented as emergent self-organizing maps, hinted at subgroups responding to topical application of capsaicin. The distinction among subgroups was based on sensitivity to pressure pain, which could be attributed to sex differences, with women being more sensitive than men. Thus, while UV-B and capsaicin share a major component of heat pain sensitization, they differ in their effects on QST parameter patterns in healthy subjects, suggesting a lack of redundancy between these models.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible

  17. Use of Capsaicin to Treat Pain: Mechanistic and Therapeutic Considerations

    Directory of Open Access Journals (Sweden)

    Man-Kyo Chung

    2016-11-01

    Full Text Available Capsaicin is the pungent ingredient of chili peppers and is approved as a topical treatment of neuropathic pain. The analgesia lasts for several months after a single treatment. Capsaicin selectively activates TRPV1, a Ca2+-permeable cationic ion channel that is enriched in the terminals of certain nociceptors. Activation is followed by a prolonged decreased response to noxious stimuli. Interest also exists in the use of injectable capsaicin as a treatment for focal pain conditions, such as arthritis and other musculoskeletal conditions. Recently injection of capsaicin showed therapeutic efficacy in patients with Morton’s neuroma, a painful foot condition associated with compression of one of the digital nerves. The relief of pain was associated with no change in tactile sensibility. Though injection evokes short term pain, the brief systemic exposure and potential to establish long term analgesia without other sensory changes creates an attractive clinical profile. Short-term and long-term effects arise from both functional and structural changes in nociceptive terminals. In this review, we discuss how local administration of capsaicin may induce ablation of nociceptive terminals and the clinical implications.

  18. Cerebro-afferent vessel and pupillary basal diameter variation induced by stomatognathic trigeminal proprioception: a case report

    Directory of Open Access Journals (Sweden)

    De Cicco Vincenzo

    2012-09-01

    Full Text Available Abstract Introduction A patient affected by asymmetric hemodynamics of cerebro-afferent vessels underwent duplex color scanner investigations in occlusal proprioceptive un- and rebalance conditions. Pupillometric video-oculographic examinations were performed in order to spot connected trigeminal proprioceptive motor patterns able to interfere on sympathetic autonomic activity. The aim of this case report is to verify if involuntary jaw closing during swallowing, executed in unbalance and rebalance myoelectric activity, would be able to modify cerebral hemodynamics. Case presentation A 56-year-old Caucasian Italian woman affected by asymmetric blood flow of cerebro-afferent vessels underwent an electromyographic investigation of her occlusal muscles in order to assess their occlusal functional balance. The extreme asymmetry of myoelectric activity in dental occlusion evidenced by electromyographic values suggested the rebalancing of the functions of occlusal muscles through concurrent transcutaneous stimulation of the trigeminal nerve supra- and submandibular motor branches. The above-mentioned method allowed the detection of a symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch: called orthotic-syntropic bite for its peculiar use of electrostimulation. A few days later, the patient underwent a duplex color scanner investigation and pupillometric video-oculographic examinations in occlusal unbalance and rebalance conditions. Conclusions A comparative data analysis showed that an unbalanced dental occlusal function may represent an interferential pattern on cerebral hemodynamics velocity and pupillometric evaluations have proved useful both in the analysis of locus coeruleus functional modalities and as a diagnostic tool in the assessment of pathologies involving locus coeruleus and autonomic systems. The inclusion of myoelectric masseter examinations can be

  19. Cerebro-afferent vessel and pupillary basal diameter variation induced by stomatognathic trigeminal proprioception: a case report.

    Science.gov (United States)

    De Cicco, Vincenzo

    2012-09-03

    A patient affected by asymmetric hemodynamics of cerebro-afferent vessels underwent duplex color scanner investigations in occlusal proprioceptive un- and rebalance conditions. Pupillometric video-oculographic examinations were performed in order to spot connected trigeminal proprioceptive motor patterns able to interfere on sympathetic autonomic activity. The aim of this case report is to verify if involuntary jaw closing during swallowing, executed in unbalance and rebalance myoelectric activity, would be able to modify cerebral hemodynamics. A 56-year-old Caucasian Italian woman affected by asymmetric blood flow of cerebro-afferent vessels underwent an electromyographic investigation of her occlusal muscles in order to assess their occlusal functional balance. The extreme asymmetry of myoelectric activity in dental occlusion evidenced by electromyographic values suggested the rebalancing of the functions of occlusal muscles through concurrent transcutaneous stimulation of the trigeminal nerve supra- and submandibular motor branches. The above-mentioned method allowed the detection of a symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch: called orthotic-syntropic bite for its peculiar use of electrostimulation. A few days later, the patient underwent a duplex color scanner investigation and pupillometric video-oculographic examinations in occlusal unbalance and rebalance conditions. A comparative data analysis showed that an unbalanced dental occlusal function may represent an interferential pattern on cerebral hemodynamics velocity and pupillometric evaluations have proved useful both in the analysis of locus coeruleus functional modalities and as a diagnostic tool in the assessment of pathologies involving locus coeruleus and autonomic systems. The inclusion of myoelectric masseter examinations can be useful in patients with asymmetric hemodynamics of cerebro

  20. Capsaicin and arterial hypertensive crisis.

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo; La Rosa, Felice Carmelo; La Rocca, Roberto

    2010-10-08

    Chili peppers are rich in capsaicin. The potent vasodilator calcitonin gene-related peptide (CGRP) is stored in a population of C-fiber afferents that are sensitive to capsaicin. CGRP and peptides released from cardiac C fibers have a beneficial effect in myocardial ischemia and reperfusion. It has been reported that capsaicin pretreatment can deplete cardiac C-fiber peptide stores. Furthermore, it has also been reported that capsaicin-treated pigs have significantly increased mean arterial blood pressure compared with controls, and that the decrease in CGRP synthesis and release contributes to the elevated blood pressure. A case has also been reported of an arterial hypertensive crisis in a patient with a large ingestion of peppers and chili peppers the day before. We present a case of an arterial hypertensive crisis in a 19-year-old Italian man with an abundant ingestion of peppers and of chili peppers the preceding day. This case describes an unusual pattern of arterial hypertensive crisis due to capsaicin. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.

  1. Repeated oral administration of capsaicin increases anxiety-like behaviours with prolonged stress-response in rats

    Indian Academy of Sciences (India)

    Y-J Choi; J Y Kim; S B Yoo; J-H Lee; J W Jahng

    2013-09-01

    This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy counts and rostral grooming were significantly increased, and caudal grooming decreased, in capsaicin-treated rats during the ambulatory activity test. In elevated plus maze test, not only the time spent in open arms but also the percent arm entry into open arms was reduced in capsaicin-treated rats compared with control rats. In forced swim test, although swimming duration was decreased, struggling increased in the capsaicin group, immobility duration did not differ between the groups. Repeated oral capsaicin did not affect the basal levels of plasma corticosterone; however, the stress-induced elevation of plasma corticosterone was prolonged in capsaicin treated rats. Oral capsaicin exposure significantly increased c-Fos expression not only in the nucleus tractus of solitarius but also in the paraventricular nucleus. Results suggest that repeated oral exposure to capsaicin increases anxiety-like behaviours in rats, and dysfunction of the hypothalamic-pituitary-adrenal axis may play a role in its pathophysiology.

  2. Ruthenium red inhibits tail skin vasodilatation evoked by intracerebroventricular injection of capsaicin in the rat.

    Science.gov (United States)

    Hajós, M; Jancsó, G; Mari, Z; Obál, F

    1991-04-01

    The effect of Ruthenium red on the tail skin vasodilatation evoked by an intracerebroventricular injection of capsaicin was studied in the anesthetized rat. Injection of capsaicin into the lateral ventricle resulted in a marked elevation of the tail skin temperature, indicative of peripheral vasodilatation. Ruthenium red, given by intracerebroventricular injection, significantly inhibited this response, which is known to be mediated by central warmth-sensitive neuronal structures. The findings suggest that the sensitivity to Ruthenium red, reportedly characteristic of the capsaicin-sensitive neurons in the peripheral nervous system, is also a trait of the capsaicin-sensitive nerve cells in the central nervous system. This is the first evidence indicating that similar molecular mechanisms, presumably involving changes in cellular calcium metabolism, contribute to the capsaicin-induced activation of neurons in both the peripheral and central nervous systems.

  3. New insight into trigeminal neuralgia

    OpenAIRE

    Truini, A.; Galeotti, F; Cruccu, G

    2005-01-01

    Trigeminal neuralgia is universally considered the neuropathic facial pain most and best known in medical practice. We propose a short review on trigeminal neuralgia reporting its main clinical aspects, unsolved problems and highlighting differential diagnosis between classical and symptomatic trigeminal neuralgia.

  4. Inhibitory effects of capsaicin on hepatic stellate cells and liver fibrosis.

    Science.gov (United States)

    Yu, Fu-Xiang; Teng, Yin-Yan; Zhu, Qian-Dong; Zhang, Qi-Yu; Tang, Yin-He

    2014-10-01

    Hepatic stellate cells (HSCs) play an important role in the process of liver fibrosis. In this study, we investigated the inhibitory effects of capsaicin on HSCs and liver fibrosis. Cultured HSCs were incubated with various concentrations of capsaicin. Cell proliferation was examined using a cell counting kit. Production of hydrogen peroxide was determined using a 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay. The mRNA and protein expression of target genes was analyzed by reverse transcription PCR and Western blot analysis, respectively. Cell apoptosis was evaluated by annexin V-FITC and propidium iodide (PI) costaining followed by flow cytometric analysis. A CCl4 rat liver fibrosis model was used to assess in vivo effects of capsaicin by histological examination and measurement of liver fibrosis markers, including hydroxyproline content, serum type III collagen, and hyaluronic acid (HA) levels. Our results show that capsaicin dose-dependently inhibited cell proliferation, suppressed cell activation, and decreased hydrogen peroxide production in cultured HSCs. Capsaicin reduced the mRNA levels of tissue inhibitors of metalloproteinase 1 (TIMP-1) and transforming growth factor-β1 (TGF-β1) in HSCs. Moreover, capsaicin-induced cell apoptosis was associated with increased expression of Bax, cytochrome c (cyt c), and caspase-3, but reduced levels of Bcl-2. The animal studies further revealed that capsaicin efficiently reduced the extent of liver fibrosis, inhibited HSC proliferation, and promoted cell apoptosis. Our findings suggest that capsaicin might inhibit fibrogenesis by inhibiting the activities of HSCs.

  5. Capsaicin- resistant arterial baroreceptors

    Directory of Open Access Journals (Sweden)

    Andresen Michael C

    2006-05-01

    Full Text Available Abstract Background Aortic baroreceptors (BRs comprise a class of cranial afferents arising from major arteries closest to the heart whose axons form the aortic depressor nerve. BRs are mechanoreceptors that are largely devoted to cardiovascular autonomic reflexes. Such cranial afferents have either lightly myelinated (A-type or non-myelinated (C-type axons and share remarkable cellular similarities to spinal primary afferent neurons. Our goal was to test whether vanilloid receptor (TRPV1 agonists, capsaicin (CAP and resiniferatoxin (RTX, altered the pressure-discharge properties of peripheral aortic BRs. Results Periaxonal application of 1 μM CAP decreased the amplitude of the C-wave in the compound action potential conducting at 0.50 but completely inhibited discharge of an irregularly discharging BR (C-type. CAP at high concentrations (10–100 μM depressed BR sensitivity in regularly discharging BRs, an effect attributed to non-specific actions. RTX (≤ 10 μM did not affect the discharge properties of regularly discharging BRs (n = 7, p > 0.18. A CAP-sensitive BR had significantly lower discharge regularity expressed as the coefficient of variation than the CAP-resistant fibers (p Conclusion We conclude that functional TRPV1 channels are present in C-type but not A-type (A-δ myelinated aortic arch BRs. CAP has nonspecific inhibitory actions that are unlikely to be related to TRV1 binding since such effects were absent with the highly specific TRPV1 agonist RTX. Thus, CAP must be used with caution at very high concentrations.

  6. Trigeminal trophic syndrome

    Directory of Open Access Journals (Sweden)

    Parimalam Kumar

    2014-01-01

    Full Text Available Trigeminal trophic syndrome (TTS is a rare cause of facial ulceration, consequent to damage to the trigeminal nerve or its central sensory connections. We reporta case of TTS in a 48-year-old woman with Bell′s palsy following herpes zoster infection. The patient was treated and counseled. There hasnot been any recurrence for 1 year and the patient is being followed-up. The diagnosis of TTS should be suspected when there is unilateral facial ulceration, especially involving the ala nasi associated with sensory impairment.

  7. Trigeminal Neuralgia as the First Clinical Manifestation of Anti-Hu Paraneoplastic Syndrome Induced by a Borderline Ovarian Mucinous Tumor

    Directory of Open Access Journals (Sweden)

    Hossein Kalanie

    2014-01-01

    Full Text Available Paraneoplastic neurologic syndrome (PNS is an uncommon manifestation of cancer that is not caused by the tumor or metastasis. Trigeminal neuralgia (TN is an initial symptom of this disease, but it has rarely been reported in the literature. Here, we report the case of a 76-year-old woman who presented with classic TN, followed by limbic encephalitis due to an underlying ovarian intestinal-type mucinous borderline tumor, with the presence of anti-Hu antibodies. She recovered quickly after removal of the tumor and was essentially free of symptoms 2 weeks after surgery. Because PNS precedes the tumor in approximately 60% of cases, its rapid detection and treatment are crucial. Therefore, we propose that PNS be considered during the management of TN when brain imaging is normal, as it is followed by other central and/or peripheral neurological manifestations as well as the presence of systemic symptoms such as anemia, fatigability, loss of appetite, or weight loss.

  8. Preparation and Evaluation of PLGA-Coated Capsaicin Magnetic Nanoparticles.

    Science.gov (United States)

    Baskaran, Mrudhula; Baskaran, Padmamalini; Arulsamy, Navamoney; Thyagarajan, Baskaran

    2017-06-01

    Drugs used in the treatment of diseases can cause several unwanted systemic side effects. A site-specific drug delivery system can eliminate such consequences by delivering drugs to certain target areas of the body where therapeutic effects are required. Here we present the preparation and evaluation of magnetic nanoparticles of capsaicin, the active ingredient in chili peppers, coated with poly-L-lactide co-glycolide (PLGA), a FDA-approved biodegradable bioavailable polymer. PCMN were prepared by solvent-evaporation/coprecipitation technique and their physicochemical and pharmacological characteristics evaluated in vitro. Further, effective pain/inflammation therapeutics of PCMN in a mouse model of inflammation was also studied. We also prepared and evaluated the subcellular localization of PLGA coated fluorescence magnetic nanoparticle (PFMN) in vitro in HEK293 cells. Transmission electron microscopic images of PCMN showed that the size of the nanoparticles were of the order of 10-20 nm. PCMN showed approximately 9.29% drug loading and 89.15% encapsulation efficiencies. In vitro dissolution studies showed an increased solubility of capsaicin due to the nano-size of the PCMN, while PLGA coating allowed sustained release of capsaicin in vitro. The PCMN also reduced paw edema after injection in mice, and confocal microscopy revealed the successful intracellular localization of PLGA-coated fluorescein magnetic nanoparticles in HEK293 cells. The PCMN provided a sustained release of capsaicin in vitro and inhibited carrageenan-induced inflammatory pain in mouse model in vivo. These data suggest that PLGA coating of capsaicin magnetic nanoparticles have the potential to be amenable for a sustained release of capsaicin to relieve pain.

  9. Anticancer Properties of Capsaicin Against Human Cancer.

    Science.gov (United States)

    Clark, Ruth; Lee, Seong-Ho

    2016-03-01

    There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity. Capsaicin is a bioactive phytochemical abundant in red and chili peppers. While the preponderance of the data strongly indicates significant anticancer benefits of capsaicin, more information to highlight molecular mechanisms of its action is required to improve our knowledge to be able to propose a potential therapeutic strategy for use of capsaicin against cancer. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. In this review article, we highlight multiple molecular targets responsible for the anticancer mechanism of capsaicin. In addition, we deal with the benefits of combinational use of capsaicin with other dietary or chemotherapeutic compounds, focusing on synergistic anticancer activities.

  10. A critical re-evaluation of the specificity of action of perivagal capsaicin.

    Science.gov (United States)

    Browning, K N; Babic, T; Holmes, G M; Swartz, E; Travagli, R A

    2013-03-15

    Perivagal application of capsaicin (1% solution) is considered to cause a selective degeneration of vagal afferent C fibres and has been used extensively to examine the site of action of many gastrointestinal (GI) neuropeptides. The actions of both capsaicin and GI neuropeptides may not be restricted to vagal afferent fibres, however, as other non-sensory neurones have displayed sensitivity to capsaicin and brainstem microinjections of these neuropeptides induce GI effects similar to those obtained upon systemic application. The aim of the present study was to test the hypothesis that perivagal capsaicin induces degeneration of vagal efferents controlling GI functions. Experiments were conducted 7-14 days after 30 min unilateral perivagal application of 0.1-1% capsaicin. Immunohistochemical analyses demonstrated that, as following vagotomy, capsaicin induced dendritic degeneration, decreased choline acetyltransferase but increased nitric oxide synthase immunoreactivity in rat dorsal motor nucleus of the vagus (DMV) neurones. Electrophysiological recordings showed a decreased DMV input resistance and excitability due, in part, to the expression of a large conductance calcium-dependent potassium current and the opening of a transient outward potassium window current at resting potential. Furthermore, the number of DMV neurones excited by thyrotrophin-releasing hormone and the gastric motility response to DMV microinjections of TRH were decreased significantly. Our data indicate that perivagal application of capsaicin induced DMV neuronal degeneration and decreased vagal motor responses. Treatment with perivagal capsaicin cannot therefore be considered selective for vagal afferent C fibres and, consequently, care is needed when using perivagal capsaicin to assess the mechanism of action of GI neuropeptides.

  11. A critical re-evaluation of the specificity of action of perivagal capsaicin

    Science.gov (United States)

    Browning, K N; Babic, T; Holmes, G M; Swartz, E; Travagli, R A

    2013-01-01

    Perivagal application of capsaicin (1% solution) is considered to cause a selective degeneration of vagal afferent C fibres and has been used extensively to examine the site of action of many gastrointestinal (GI) neuropeptides. The actions of both capsaicin and GI neuropeptides may not be restricted to vagal afferent fibres, however, as other non-sensory neurones have displayed sensitivity to capsaicin and brainstem microinjections of these neuropeptides induce GI effects similar to those obtained upon systemic application. The aim of the present study was to test the hypothesis that perivagal capsaicin induces degeneration of vagal efferents controlling GI functions. Experiments were conducted 7–14 days after 30 min unilateral perivagal application of 0.1–1% capsaicin. Immunohistochemical analyses demonstrated that, as following vagotomy, capsaicin induced dendritic degeneration, decreased choline acetyltransferase but increased nitric oxide synthase immunoreactivity in rat dorsal motor nucleus of the vagus (DMV) neurones. Electrophysiological recordings showed a decreased DMV input resistance and excitability due, in part, to the expression of a large conductance calcium-dependent potassium current and the opening of a transient outward potassium window current at resting potential. Furthermore, the number of DMV neurones excited by thyrotrophin-releasing hormone and the gastric motility response to DMV microinjections of TRH were decreased significantly. Our data indicate that perivagal application of capsaicin induced DMV neuronal degeneration and decreased vagal motor responses. Treatment with perivagal capsaicin cannot therefore be considered selective for vagal afferent C fibres and, consequently, care is needed when using perivagal capsaicin to assess the mechanism of action of GI neuropeptides. PMID:23297311

  12. Chemosensory Information Processing between Keratinocytes and Trigeminal Neurons

    Science.gov (United States)

    Sondersorg, Anna Christina; Busse, Daniela; Kyereme, Jessica; Rothermel, Markus; Neufang, Gitta; Gisselmann, Günter; Hatt, Hanns; Conrad, Heike

    2014-01-01

    Trigeminal fibers terminate within the facial mucosa and skin and transmit tactile, proprioceptive, chemical, and nociceptive sensations. Trigeminal sensations can arise from the direct stimulation of intraepithelial free nerve endings or indirectly through information transmission from adjacent cells at the peripheral innervation area. For mechanical and thermal cues, communication processes between skin cells and somatosensory neurons have already been suggested. High concentrations of most odors typically provoke trigeminal sensations in vivo but surprisingly fail to activate trigeminal neuron monocultures. This fact favors the hypothesis that epithelial cells may participate in chemodetection and subsequently transmit signals to neighboring trigeminal fibers. Keratinocytes, the major cell type of the epidermis, express various receptors that enable reactions to multiple environmental stimuli. Here, using a co-culture approach, we show for the first time that exposure to the odorant chemicals induces a chemical communication between human HaCaT keratinocytes and mouse trigeminal neurons. Moreover, a supernatant analysis of stimulated keratinocytes and subsequent blocking experiments with pyrodoxalphosphate-6-azophenyl-2′,4′-disulfonate revealed that ATP serves as the mediating transmitter molecule released from skin cells after odor stimulation. We show that the ATP release resulting from Javanol® stimulation of keratinocytes was mediated by pannexins. Consequently, keratinocytes act as chemosensors linking the environment and the trigeminal system via ATP signaling. PMID:24790106

  13. The role of histamine H1, H2 and H3 receptors of ventral posteromedial nucleus of thalamus in modulation of trigeminal pain.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Erfanparast, Amir; Ghasemi, Hamid; Henareh-Chareh, Farzin; Hadidi, Mansoor; Mirzakhani, Navideh; Seyedin, Sahar; Taati, Mina; Salighedar, Reza; Salimi, Sara; Safaei, Farshad

    2016-11-15

    Histamine receptors are involved in supraspinal modulation of pain. In the present study, we investigated the effects of microinjection of histamine H1, H2 and H3 receptor antagonists and agonists into the ventral posteromedial (VPM) nucleus of the thalamus on two models of trigeminal pain. Right and left sides of VPM were implanted with two guide cannulas. Corneal pain was induced by local corneal surface application of hypertonic saline and the number of eye wipes was recorded. The duration of face rubbing, as an orofacial pain measure, was recorded after subcutaneous (s.c.) injection of capsaicin into the vibrissa pad. 2-pyridylethylamine (2-PEA, a histamine H1 receptor agonist, 4µg/site) and dimaprit (a histamine H2 receptor agonist, 1 and 4µg/site) suppressed corneal and orofacial pains. Mepyramine (a histamine H1 receptor antagonist) and ranitidine (a histamine H2 receptor antagonist) at the similar doses of 0.5, 2 and 8µg/site alone had no effects on trigeminal pain. Prior microinjection of mepyramine and ranitidine at a similar dose of 8µg/site inhibited the antinociceptive effects of 2-PEA (4µg/site) and dimaprit (4µg/site), respectively. Immepip (a histamine H3 receptor agonist, 1 and 4µg/site) increased, and thioperamide (a histamine H3 receptor antagonist, 2 and 8µg/site) attenuated nociceptive responses. Prior microinjection of thioperamide (8µg/site) prevented immepip (4µg/site)-induced nociception. These chemicals did not change locomotor behavior. It is concluded that post-synaptic histamine H2, and to a lesser extent H1, receptors and pre-synaptic histamine H3 receptor may be involved in VPM modulation of trigeminal pain. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Corticofugal projections induce long-lasting effects on somatosensory responses in the trigeminal complex of the rat

    Directory of Open Access Journals (Sweden)

    Angel eNunez

    2014-05-01

    Full Text Available The sensory information flow at subcortical relay stations is controlled by the action of topographic connections from the neocortex. To determinate the functional properties of the somatosensory corticofugal projections to the principal (Pr5 and caudal spinal (Sp5C trigeminal nuclei, we performed unitary recordings in anesthetized rats. To examine the effect of these cortical projections we used tactile stimulation of the whisker and electrical stimulation of somatosensory cortices. Corticofugal anatomical projections to Pr5 and Sp5C nuclei were detected by using retrograde fluorescent tracers. Neurons projecting exclusively to Pr5 were located in the cingulate cortex while neurons projecting to both Sp5C and Pr5 nuclei were located in the somatosensory and insular cortices (>75% of neurons. Physiological results indicated that primary somatosensory cortex produced a short-lasting facilitating or inhibiting effects (< 5 minutes of tactile responses in Pr5 nucleus through activation of NMDA glutamatergic or GABAA receptors since effects were blocked by iontophoretically application of APV and bicuculline, respectively. In contrast, stimulation of secondary somatosensory cortex did not affect most of the Pr5 neurons; however both cortices inhibited the nociceptive responses in the Sp5C nucleus through activation of glycinergic or GABAA receptors because effects were blocked by iontophoretically application of strychnine and bicuculline, respectively. These and anatomical results demonstrated that the somatosensory cortices projects to Pr5 nucleus to modulate tactile responses by excitatory and inhibitory actions, while projections to the Sp5C nucleus control nociceptive sensory transmission by only inhibitory effects. Thus, somatosensory cortices may modulate innocuous and noxious inputs simultaneously, contributing to the perception of specifically tactile or painful sensations.

  15. The capsaicin cough reflex in patients with symptoms elicited by odorous chemicals

    DEFF Research Database (Denmark)

    Holst, H.; Arendt-Nielsen, Lars; Mosbech, H.;

    2010-01-01

    Patients with multiple chemical sensitivity and eczema patients with airway symptoms elicited by odorous chemicals have enhanced cough reflex to capsaicin when applying the tidal breathing method. The aims of the present study were to test whether the capsaicin induced cough reflex was enhanced......'s criteria for multiple chemical sensitivity and 15 eczema patients with airway symptoms elicited by odorous chemicals were compared with 29 age-matched, healthy controls. We measured C5--the capsaicin concentration causing five coughs or more--using the single breath inhalation test. No difference was found...

  16. Cold suppresses agonist-induced activation of TRPV1.

    Science.gov (United States)

    Chung, M-K; Wang, S

    2011-09-01

    Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.

  17. Capsaicin: A novel chemopreventive molecule and its underlying molecular mechanisms of action

    Directory of Open Access Journals (Sweden)

    A A Oyagbemi

    2010-01-01

    Full Text Available Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide is the a principal pungent ingredient of hot red and chili peppers that belong to the plant genus Capsicum (Solanaceae. Capsaicin is a cancer-suppressing agent. It blocks the translocation of nuclear factor kappa B (NF-kB, activator protein 1 (AP-1, and signal transducer and activator of transcription (STAT3 signaling pathway that are required for carcinogenesis. The anti-inflammatory potential of capsaicin is attributed to its inhibitory effect on inducible COX-2 mRNA expression. Cytochrome P4502E1 mediates the activation of xenobiotics such as vinyl carbamate and dimethyl nitrosamine to their toxic metabolites. This metabolic activation of xenobiotics by Cytochrome P4502E1 has been shown to be inhibited by capsaicin. Capsaicin also generates reactive oxygen species in cells with resultant induction of apoptosis and cell cycle arrest, which is beneficial for cancer chemoprevention. Therefore, the use of capsaicin as a chemopreventive agent is of immense benefit for cancer chemoprevention. The search strategy included printed journals, pubmed, and medline, using the terms ′capsaicin′ and ′anticancer′ citations, relevant to anticancer properties of capsaicin.

  18. Novel therapeutics in the field of capsaicin and pain.

    Science.gov (United States)

    Evangelista, Stefano

    2015-01-01

    Capsaicin, a pharmacologically active agent found in chili peppers, causes burning and itching sensation due to binding at the transient receptor potential vanilloid-1 (TRPV-1) receptor, a polymodal receptor critical to the sensing of a variety of stimuli (e.g., noxious heat, bidirectional pH), and subsequent activation of polymodal C and A-δ nociceptive fibers. Acutely, TRPV-1 activation with peripheral capsaicin produces pronociceptive effects, which extends to the development of hyperalgesia and allodynia. However, capsaicin has been reported to display antinociceptive properties as well, largely through TRPV-1-dependent mechanisms. Local application of high concentration of capsaicin is used for neuropathic pain and repeated stimulation of TRPV-1 induced an improvement of epigastric pain in irritable bowel syndrome and dyspepsia patients by desensitization of nociceptive pathways. New TRPV-1 agonists are currently under preclinical study and TRPV-1 antagonists are in early clinical development as analgesics. The TRPV-1 pathway might be a novel target for therapeutics in pain sensitivity.

  19. Neuralgias of the Trigeminal Nerve

    OpenAIRE

    Gordon, Allan S

    2000-01-01

    Practitioners are often presented with patients who complain bitterly of facial pain. The trigeminal nerve is involved in four conditions that are sometimes mixed up. The four conditions - trigeminal neuralgia, trigeminal neuropathic pain, postherpetic neuralgia and atypical facial pain - are discussed under the headings of clinical features, differential diagnosis, cause and treatment. This article should help practitioners to differentiate one from the other and to manage their care.

  20. Neuralgias of the Trigeminal Nerve

    Directory of Open Access Journals (Sweden)

    Allan S Gordon

    2000-01-01

    Full Text Available Practitioners are often presented with patients who complain bitterly of facial pain. The trigeminal nerve is involved in four conditions that are sometimes mixed up. The four conditions - trigeminal neuralgia, trigeminal neuropathic pain, postherpetic neuralgia and atypical facial pain - are discussed under the headings of clinical features, differential diagnosis, cause and treatment. This article should help practitioners to differentiate one from the other and to manage their care.

  1. Gamma Knife® radiosurgery for trigeminal neuralgia.

    Science.gov (United States)

    Yen, Chun-Po; Schlesinger, David; Sheehan, Jason P

    2011-11-01

    Trigeminal neuralgia is characterized by a temporary paroxysmal lancinating facial pain in the trigeminal nerve distribution. The prevalence is four to five per 100,000. Local pressure on nerve fibers from vascular loops results in painful afferent discharge from an injured segment of the fifth cranial nerve. Microvascular decompression addresses the underlying pathophysiology of the disease, making this treatment the gold standard for medically refractory trigeminal neuralgia. In patients who cannot tolerate a surgical procedure, those in whom a vascular etiology cannot be identified, or those unwilling to undergo an open surgery, stereotactic radiosurgery is an appropriate alternative. The majority of patients with typical facial pain will achieve relief following radiosurgical treatment. Long-term follow-up for recurrence as well as for radiation-induced complications is required in all patients undergoing stereotactic radiosurgery for trigeminal neuralgia.

  2. MR imaging of trigeminal neuropathy

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    Kim, Si Yeon; Yoon, Pyeong Ho; Chung, Jin Il; Lee, Seung Ik; Kim, Dong Ik [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    2001-03-01

    The trigeminal nerve is the largest of the cranial nerves and has both sensory and motor functions. It can be divided into proximal (brainstem, preganglionic, gasserian ganglion, and cavernous sinus) and distal (extracranial opthalmic, maxillary, and mandibular) segments. Patients with trigeminal neuropathy present with a wide variety of symptoms, and lesions producing those symptoms may occur anywhere along the protracted course of the trigeminal nerve, from its distal facial branches to its nuclear columns in the brainstem. The purpose of this article is to illustrate the normal anatomy of the trigeminal nerve and associated various pathologic conditions. These are arranged anatomically according to their site of interaction with it.

  3. Quantum dot nanoprobe-based high-content monitoring of notch pathway inhibition of breast cancer stem cell by capsaicin.

    Science.gov (United States)

    Shim, Yumi; Song, Joon Myong

    2015-12-01

    Breast cancer is the major cause of cancer death for women worldwide. Breast cancer patients are treated with chemotherapy and radiotherapy. Although chemotherapy and radiotherapy are applied, some cancer cells still survive. These cells, called cancer stem cell (CSC), exhibit special capabilities, such as drug and radio resistance. The remaining CSC can trigger cancer recurrence. Thus, it is critical to find an effective way to target CSC. Capsaicin has been reported to affect anticancer activity in many cancers. It also has been shown that capsaicin induces apoptosis in the MCF-7 breast cancer cell line. In this study, we demonstrate that capsaicin causes dose-dependent growth disruption in breast CSC and inhibits translocation of notch intracellular membrane domain (NICD) into the nucleus. MCF-7 cells were treated with capsaicin at various concentrations (5 μM, 10 μM, and 20 μM) for 24 h. After capsaicin treatment, it was found that the number of breast CSC (%) decreased as the treatment concentration of capsaicin increased. This result was also confirmed with FACS. NICD translocation to the nucleus and apoptotic cell death of breast CSC were concurrently observed at the single breast CSC level using highly sensitive quantum dot (Qdot)-antibody nanoprobes. The control breast CSCs without the capsaicin treatment were able to translocate NICD into the nucleus. On the other hand, translocation of NICD into the nucleus was not observed in capsaicin-treated cells. In addition, apoptotic cell death was caused when the breast CSC were treated with capsaicin at more than 10 μM. Although many studies have shown that capsaicin produces anticancer activity in cancer cell lines, the present result is the first report to demonstrate that capsaicin is capable of causing breast CSC apoptotic cell death via inhibiting its notch signaling pathway.

  4. Gender differences in pain and secondary hyperalgesia after heat/capsaicin sensitization in healthy volunteers

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Petersen, Karin Lottrup

    2006-01-01

    In most published studies women are more sensitive to experimental pain than men. Enhanced central pain processing in women has been suggested, but psychosocial factors might also have affected the findings. Data from five completed healthy volunteer studies were analyzed to investigate gender...... differences in development of secondary hyperalgesia. Cutaneous hyperalgesia was induced with the heat/capsaicin sensitization model. Outcome measures were areas of secondary hyperalgesia to brush and von Frey hair stimulation after heat and capsaicin sensitization, rating of pain during heat....../capsaicin sensitization, and heat pain detection thresholds. There was a trend toward smaller areas of secondary hyperalgesia in women. After adjusting for estimated gender differences in forearm surface area, areas to brush but not von Frey hair stimulation after capsaicin sensitization were larger in women. Peak pain...

  5. Refined distribution of myelinated trigeminal proprioceptive nerve fibres in Mueller's muscle as the mechanoreceptors to induce involuntary reflexive contraction of the levator and frontalis muscles.

    Science.gov (United States)

    Yuzuriha, Shunsuke; Matsuo, Kiyoshi; Hirasawa, Chihiro; Moriizumi, Tetsuji

    2009-11-01

    Stretching of mechanoreceptors in Mueller's muscle induces reflexive contraction of not only the levator muscle but also the frontalis muscle as two different eyelid-opening muscles. Previously, we reported that fine neural myelinated structures, acting as mechanoreceptors, were found in the proximal Mueller's muscle. Since there is a risk of misunderstanding that the middle and distal Mueller's muscle does not contain mechanoreceptors and can be invalidated or resected, the accurate distribution of myelinated trigeminal proprioceptive nerve fibres as mechanoreceptors in Mueller's muscle was refined horizontally in this study. We explored 10 whole Mueller's muscles between the levator muscle and the tarsus of the upper eyelids obtained from five Japanese cadavers. The specimens were serially sliced along the horizontal plane and stained with HE, S-100 protein to determine the presence of Schwann cells, and smooth muscle actin antibody to determine the presence of Mueller's smooth muscle fibres. Although all myelinated nerve fibres in the intermuscular connective tissues among the sympathetically innervated Mueller's multi-unit smooth muscle fibres may not correspond to the proprioceptive nerve fibres, the nerve bundles consisting of multiple myelinated nerve fibres were well distributed in the proximal Mueller's muscle, and single myelinated nerve fibres were well distributed in the middle and distal Mueller's muscle. We believe that the mechanoreceptors in Mueller's muscle consist of myelinated proprioceptive nerve fibres with nerve endings possibly attached to collagen fibres in the intermuscular connective tissues present among Mueller's smooth muscle fibres. As the myelinated nerve fibres innervate the middle and distal Mueller's muscle to a greater extent than those in the proximal Mueller's muscle, the former may be more important as mechanoreceptors than the latter and should not be invalidated or excised during surgery for treatment of blepharoptosis to

  6. Mechanisms and clinical uses of capsaicin.

    Science.gov (United States)

    Sharma, Surinder Kumar; Vij, Amarjit Singh; Sharma, Mohit

    2013-11-15

    Capsaicin is the active ingredient of chili peppers and gives them the characteristic pungent flavor. Understanding the actions of capsaicin led to the discovery of its receptor, transient receptor potential vanilloid subfamily member 1 (TRPV1). This receptor is found on key sensory afferents, and so the use of capsaicin to selectively activate pain afferents has been studied in animal and human models for various indications. Capsaicin is unique among naturally occurring irritant compounds because the initial neuronal excitation evoked by it is followed by a long-lasting refractory period, during which the previously excited neurons are no longer responsive to a broad range of stimuli. This process known as defunctionalisation has been exploited for therapeutic use of capsaicin in various painful conditions. We reviewed different studies on mechanisms of action of capsaicin and its utility in different clinical conditions. A beneficial role of capsaicin has been reported in obesity, cardiovascular and gastrointestinal conditions, various cancers, neurogenic bladder, and dermatologic conditions. Various theories have been put forth to explain these effects. Interestingly many of these pharmacological actions are TRPV1 independent. This review is aimed at providing an overview of these mechanisms and to also present literature which contradicts the proposed beneficial effects of capsaicin. Most of the literature comes from animal studies and since many of these mechanisms are poorly understood, more investigation is required in human subjects.

  7. Bioconversion of Capsaicin by Aspergillus oryzae.

    Science.gov (United States)

    Lee, Minji; Cho, Jeong-Yong; Lee, Yu Geon; Lee, Hyoung Jae; Lim, Seong-Il; Park, So-Lim; Moon, Jae-Hak

    2015-07-08

    This study identified metabolites of capsaicin bioconverted by Aspergillus oryzae, which is generally used for mass production of gochujang prepared by fermenting red pepper powder in Korea. A. oryzae was incubated with capsaicin in potato dextrose broth. Capsaicin decreased depending on the incubation period, but new metabolites increased. Five capsaicin metabolites purified from the ethyl acetate fraction of the capsaicin culture were identified as N-vanillylcarbamoylbutyric acid, N-vanillyl-9-hydroxy-8-methyloctanamide, ω-hydroxycapsaicin, 8-methyl-N-vanillylcarbamoyl-6(E)-octenoic acid, and 2-methyl-N-vanillylcarbamoyl-6(Z)-octenoic acid by nuclear magnetic resonance (NMR) and mass spectrometry (MS). The capsaicin metabolites in gochujang were confirmed and quantitated by selective multiple reaction monitoring detection after liquid chromatography electrospray ionization MS using the isolated compounds as external standards. On the basis of the structures of the capsaicin metabolites, it is proposed that capsaicin metabolites were converted by A. oryzae by ω-hydroxylation, alcohol oxidation, hydrogenation, isomerization, and α- and/or β-oxidation.

  8. Calcitonin gene-related peptide is released from capsaicin-sensitive nerve fibres and induces vasodilatation of human cerebral arteries concomitant with activation of adenylyl cyclase

    DEFF Research Database (Denmark)

    Jansen-Olesen, I; Mortensen, A; Edvinsson, L

    1996-01-01

    strong and potent relaxation of precontracted circular vessel segments. The Imax (maximum relaxant effect) to human calcitonin was low and the pD2 (concentration for half maximum effect) 7.7 was much lower than that of CGRP. The CGRP-1, antagonist human alpha-CGRP8-37 blocked the response to human alpha......-CGRP but not to human beta-CGRP, while the putative antagonist [Tyr]CGRP28-37 did not. Capsaicin (10(-15)-10(-8)M) caused relaxation of the cerebral arteries by 22% of precontraction. Pre-treatment with 10(-6)M human alpha-CGRP8-37 inhibited this relaxation. Human alpha-CGRP increased the cyclic AMP content of human...... cerebral arteries in a concentration-dependent manner. This increase in adenylyl cyclase activity was blocked by human alpha-CGRP8-37. The results suggest that CGRP-1 receptors coupled to adenylyl cyclase are present in human cerebral arteries....

  9. Capsaicin inhibits the adipogenic differentiation of bone marrow mesenchymal stem cells by regulating cell proliferation, apoptosis, oxidative and nitrosative stress.

    Science.gov (United States)

    Ibrahim, Muhammed; Jang, Mi; Park, Mina; Gobianand, Kuppannan; You, Seungkwon; Yeon, Sung-Heom; Park, Sungkwon; Kim, Min Ji; Lee, Hyun-Jeong

    2015-07-01

    Obesity is a global health problem that requires the utmost attention. Apart from other factors the trans-differentiation of mesenchymal stem cells (MSCs) into adipocytes is an added detrimental factor causing the intensification of obesity. The main objective of this present study is to analyse whether capsaicin is capable of inhibiting the differentiation of BMSCs to adipocytes. Bone marrow mesenchymal stem cells (BMSCs) were obtained and exposed to different concentrations of capsaicin for a period of 6 days following 2 days of adipogenic induction. The capsaicin exposed cells were collected at three different time points (2, 4 and 6 days) and subjected to various analyses. BMSCs after exposure to capsaicin showed dose and time dependent reduction in cell viability and proliferation. Interestingly, capsaicin induced cell cycle arrest at G0-G1 and increased apoptosis by increasing reactive oxygen species (ROS) and reactive nitrogen species (RNS) production. Capsaicin significantly inhibited the early adipogenic differentiation, lipogenesis and maturation of adipocytes with concomitant repression of PPARγ, C/EBPα, FABP4 and SCD-1. Taken together, the results of the present study have clearly emphasized that capsaicin potentially inhibits the adipogenic differentiation of mesenchymal stem cells via many different pathways (anti-proliferative, apoptotic and cell cycle arrest) through the stimulation of ROS and RNS production. Thus, capsaicin not only suppresses the maturation of pre-adipocytes into adipocytes but also inhibits the differentiation of mesenchymal stem cells into adipocytes.

  10. Capsaicin effects on blinking Efectos de la capsaicina en el parpadeo

    Directory of Open Access Journals (Sweden)

    Fidias E. Leon-Sarmiento

    2005-09-01

    Full Text Available Blinking is a normal human phenomenom involving trigeminal and facial patways. To gain understanding on the neurobiology of blinking, five normal subjects were investigated before and after application of transdermal capsaicin at the forehead for two weeks. No effects of topical capsaicin were detected in eye blink rates. However, when capsaicin was applied to a female subject with blepharospasm, she showed a dramatic restoration of her vision subsequent to blinking modification. Deactivation of abnormal A-to-C fibers cross talks at the trigeminal-facial pathways seems to be the most likely mechanism of such improvement.El parpadeo es un fenómeno normal en los humanos que involucra las vías trigéminas faciales. Con el fin de conocer un poco más la neurobiología de este fenómeno estudiamos cinco individuos normales antes y después de aplicar capsaicina trasdérmica en la frente de cada uno de ellos, por dos semanas. La frecuencia de parpadeo no se alteró con la aplicación de capsaicina tópica. Sin embargo, cuando la misma sustancia se aplicó a una paciente con blefaroespasmo hubo dramática restauración de su visión, la cual fue secundaria a la modificación de la actividad muscular palpebral. La desactivación del cruce patológico de información que pasa de las fibras A a las fibras C, pertenecientes a las vías trigémino-faciales, parece ser el mecanismo de acción relacionado con la aplicación de capsaicina, el que estaría directamente relacionado con la recuperación clínica observada en la paciente con blefaroespasmo.

  11. Chemosensory properties of murine nasal and cutaneous trigeminal neurons identified by viral tracing

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    Mettenleiter Thomas C

    2006-06-01

    Full Text Available Abstract Background Somatosensation of the mammalian head is mainly mediated by the trigeminal nerve that provides innervation of diverse tissues like the face skin, the conjunctiva of the eyes, blood vessels and the mucouse membranes of the oral and nasal cavities. Trigeminal perception encompasses thermosensation, touch, and pain. Trigeminal chemosensation from the nasal epithelia mainly evokes stinging, burning, or pungent sensations. In vitro characterization of trigeminal primary sensory neurons derives largely from analysis of complete neuronal populations prepared from sensory ganglia. Thus, functional properties of primary trigeminal afferents depending on the area of innervation remain largely unclear. Results We established a PrV based tracing technique to identify nasal and cutaneous trigeminal neurons in vitro. This approach allowed analysis and comparison of identified primary afferents by means of electrophysiological and imaging measurement techniques. Neurons were challenged with several agonists that were reported to exhibit specificity for known receptors, including TRP channels and purinergic receptors. In addition, TTX sensitivity of sodium currents and IB4 binding was investigated. Compared with cutaneous neurons, a larger fraction of nasal trigeminal neurons showed sensitivity for menthol and capsaicin. These findings pointed to TRPM8 and TRPV1 receptor protein expression largely in nasal neurons whereas for cutaneous neurons these receptors are present only in a smaller fraction. The majority of nasal neurons lacked P2X3 receptor-mediated currents but showed P2X2-mediated responses when stimulated with ATP. Interestingly, cutaneous neurons revealed largely TTX resistant sodium currents. A significantly higher fraction of nasal and cutaneous afferents showed IB4 binding when compared to randomly chosen trigeminal neurons. Conclusion In conclusion, the usability of PrV mediated tracing of primary afferents was demonstrated

  12. Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal chemosensory neurons to ethanol and its flavor components.

    Science.gov (United States)

    Glendinning, John I; Tang, Joyce; Morales Allende, Ana Paula; Bryant, Bruce P; Youngentob, Lisa; Youngentob, Steven L

    2017-08-01

    Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent rats and humans. We asked whether these behavioral changes may be mediated in part by changes in responsiveness of the peripheral taste and oral trigeminal systems. We exposed the experimental rats to ethanol in utero by administering ethanol to dams through a liquid diet; we exposed the control rats to an isocaloric and isonutritive liquid diet. To assess taste responsiveness, we recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess trigeminal responsiveness, we measured changes in calcium levels of isolated trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin, mustard oil, and KCl. Compared with adolescent control rats, the adolescent experimental rats exhibited diminished CT nerve responses to ethanol, quinine, and sucrose and GL nerve responses to quinine and sucrose. The reductions in taste responsiveness persisted into adulthood for quinine but not for any of the other stimuli. Adolescent experimental rats also exhibited reduced TG neuron responses to ethanol, capsaicin, and mustard oil. The lack of change in responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates that FAE altered only a subset of the response pathways within each chemosensory system. We propose that FAE reprograms development of the peripheral taste and trigeminal systems in ways that reduce their responsiveness to ethanol and surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral burning) flavor attributes.NEW & NOTEWORTHY Pregnant mothers are advised to avoid alcohol. This is because even small amounts of alcohol can alter fetal brain development and increase the risk of adolescent alcohol abuse. We asked how fetal alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring responsiveness of taste nerves and trigeminal

  13. Trigeminal autonomic cephalalgias.

    Science.gov (United States)

    Eller, M; Goadsby, P J

    2016-01-01

    The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders characterised by lateralized symptoms: prominent headache and ipsilateral cranial autonomic features, such as conjunctival injection, lacrimation and rhinorrhea. The TACs are: cluster headache (CH), paroxysmal hemicrania (PH), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)/short-lasting neuralgiform headache attacks with cranial autonomic features (SUNA) and hemicrania continua (HC). Their diagnostic criteria are outlined in the International Classification of Headache Disorders, third edition-beta (ICHD-IIIb). These conditions are distinguished by their attack duration and frequency, as well as response to treatment. HC is continuous and by definition responsive to indomethacin. The main differential when considering this headache is chronic migraine. Other TACs are remarkable for their short duration and must be distinguished from other short-lasting painful conditions, such as trigeminal neuralgia and primary stabbing headache. Cluster headache is characterised by exquisitely painful attacks that occur in discrete episodes lasting 15-180 min a few times a day. In comparison, PH occurs more frequently and is of shorter duration, and like HC is responsive to indomethacin. SUNCT/SUNA is the shortest duration and highest frequency TAC; attacks can occur over a hundred times every day.

  14. Radiosurgical management of trigeminal neuralgia.

    Science.gov (United States)

    Chan, Michael D; Shaw, Edward G; Tatter, Stephen B

    2013-10-01

    Over the past several decades, stereotactic radiosurgery has become a viable noninvasive treatment option for patients with trigeminal neuralgia. The scientific literature regarding the radiosurgical treatment of trigeminal neuralgia has evolved to identify factors that predict both efficacy and toxicity. Radiosurgical management has, thus, become complementary to medical management, microvascular decompression, and percutaneous ablative procedures. Thus, effective management often requires multidisciplinary collaboration. The intent of this review is to discuss the role of radiosurgery in the modern management of trigeminal neuralgia and to review radiosurgical outcomes, targeting, and controversies. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Neonatal capsaicin treatment in rats affects TRPV1-related noxious heat sensation and circadian body temperature rhythm.

    Science.gov (United States)

    Jeong, Keun-Yeong; Seong, Jinsil

    2014-06-15

    The transient receptor potential vanilloid 1 (TRPV1) is a cation channel that serves as a polymodal detector of noxious stimuli such as capsaicin. Therefore, capsaicin treatment has been used to investigate the physiological function of TRPV1. Here, we report physiological changes induced by treating neonatal rats with capsaicin. Capsaicin (50mg/kg) (cap-treated) or vehicle (vehicle-treated) was systemically administered to newborn SD rat pups within 48 h after birth. TRPV1 expression, intake volume of capsaicin water, and noxious heat sensation were measured 6 weeks after capsaicin treatment. Circadian body temperature and locomotion were recorded by biotelemetry. Expression of Per1, Per2, Bmal1 and Hsf1 (clock genes) was also investigated. Neonatal capsaicin treatment not only decreased TRPV1 expression but also induced desensitization to noxious heat stimuli. Circadian body temperature of cap-treated rats increased significantly compared with that of vehicle-treated rats. Additionally, the amplitude of the circadian body temperature was reversed in cap-treated rats. Expression of the hypothalamic Hsf1 and liver Per2 clock genes followed a similar trend. Therefore, we suggest that these findings will be useful in studying various physiological mechanisms related to TRPV1.

  16. Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: attenuated by KYNA derivate (SZR72).

    Science.gov (United States)

    Lukács, M; Warfvinge, K; Tajti, J; Fülöp, F; Toldi, J; Vécsei, L; Edvinsson, L

    2017-12-01

    Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund's Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72. Activation in the trigeminal nucleus caudalis (TNC) and the trigeminal tract (Sp5) was achieved by application of CFA onto the dural parietal surface. SZR72 was given intraperitoneally (i.p.), one dose prior CFA deposition and repeatedly daily for 7 days. Immunohistochemical studies were performed for mapping glutamate, c-fos, PACAP, substance P, IL-6, IL-1β and TNFα in the TNC/Sp5 and other regions of the brainstem and at the C1-C2 regions of the spinal cord. We found that CFA increased c-fos and glutamate immunoreactivity in TNC and C1-C2 neurons. This effect was mitigated by SZR72. PACAP positive fibers were detected in the fasciculus cuneatus and gracilis. Substance P, TNFα, IL-6 and IL-1β immunopositivity were detected in fibers of Sp5 and neither of these molecules showed any change in immunoreactivity following CFA administration. This is the first study demonstrating that dural application of CFA increases the expression of c-fos and glutamate in TNC neurons. Treatment with the KYNA analogue prevented this expression.

  17. Triptan-induced enhancement of neuronal nitric oxide synthase in trigeminal ganglion dural afferents underlies increased responsiveness to potential migraine triggers

    OpenAIRE

    De Felice, Milena; Ossipov, Michael H.; Wang, Ruizhong; Dussor, Gregory; Lai, Josephine; Meng, Ian D.; Chichorro, Juliana; Andrews, John S; Rakhit, Suman; Maddaford, Shawn; Dodick, David; Porreca, Frank

    2010-01-01

    Migraine is a common neurological disorder often treated with triptans. Triptan overuse can lead to increased frequency of headache in some patients, a phenomenon termed medication overuse headache. Previous preclinical studies have demonstrated that repeated or sustained triptan administration for several days can elicit persistent neural adaptations in trigeminal ganglion cells innervating the dura, prominently characterized by increased labelling of neuronal profiles for calcitonin gene re...

  18. Trigeminal neuralgia - diagnosis and treatment.

    Science.gov (United States)

    Maarbjerg, Stine; Di Stefano, Giulia; Bendtsen, Lars; Cruccu, Giorgio

    2017-01-01

    Introduction Trigeminal neuralgia (TN) is characterized by touch-evoked unilateral brief shock-like paroxysmal pain in one or more divisions of the trigeminal nerve. In addition to the paroxysmal pain, some patients also have continuous pain. TN is divided into classical TN (CTN) and secondary TN (STN). Etiology and pathophysiology Demyelination of primary sensory trigeminal afferents in the root entry zone is the predominant pathophysiological mechanism. Most likely, demyelination paves the way for generation of ectopic impulses and ephaptic crosstalk. In a significant proportion of the patients, the demyelination is caused by a neurovascular conflict with morphological changes such as compression of the trigeminal root. However, there are also other unknown etiological factors, as only half of the CTN patients have morphological changes. STN is caused by multiple sclerosis or a space-occupying lesion affecting the trigeminal nerve. Differential diagnosis and treatment Important differential diagnoses include trigeminal autonomic cephalalgias, posttraumatic or postherpetic pain and other facial pains. First line treatment is prophylactic medication with sodium channel blockers, and second line treatment is neurosurgical intervention. Future perspectives Future studies should focus on genetics, unexplored etiological factors, sensory function, the neurosurgical outcome and complications, combination and neuromodulation treatment as well as development of new drugs with better tolerability.

  19. Cell bodies of the trigeminal proprioceptive neurons that transmit reflex contraction of the levator muscle are located in the mesencephalic trigeminal nucleus in rats.

    Science.gov (United States)

    Fujita, Kenya; Matsuo, Kiyoshi; Yuzuriha, Shunsuke; Kawagishi, Kyutaro; Moriizumi, Tetsuji

    2012-12-01

    Since the levator and frontalis muscles lack interior muscle spindles despite being antigravity mixed muscles to involuntarily sustain eyelid opening and eyebrow lifting, this study has proposed a hypothetical mechanism to compensate for this anatomical defect. The voluntary contraction of fast-twitch fibres of the levator muscle stretches the mechanoreceptors in Müller's muscle to evoke proprioception, which continuously induces reflex contraction of slow-twitch fibres of the levator and frontalis muscles. This study confirmed the presence of cell bodies of the trigeminal proprioceptive neurons that transmit reflex contraction of the levator and frontalis muscles. After confirming that severing the trigeminal proprioceptive fibres that innervate the mechanoreceptors in Müller's muscle induced ipsilateral eyelid ptosis, Fluorogold was applied as a tracer to the proximal stump of the trigeminal proprioceptive nerve in rats. Fluorogold labelled the cell bodies of the trigeminal proprioceptive neurons, not in any regions of the rat brain including the trigeminal ganglion, but in the ipsilateral mesencephalic trigeminal nucleus neighbouring the locus ceruleus. Some Fluorogold particles accumulated in the area of the locus ceruleus. The trigeminal proprioceptive neurons could be considered centrally displaced ganglion cells to transmit afferent signal from the mechanoreceptors in Müller's muscle to the mesencephalon, where they may be able to make excitatory synaptic connections with both the oculomotor neurons and the frontalis muscle motoneurons for the involuntary coordination of the eyelid and eyebrow activities, and potentially to the locus ceruleus.

  20. Chemical and pharmacological aspects of capsaicin.

    Science.gov (United States)

    Reyes-Escogido, Maria de Lourdes; Gonzalez-Mondragon, Edith G; Vazquez-Tzompantzi, Erika

    2011-01-28

    Capsaicin is a unique alkaloid found primarily in the fruit of the Capsicum genus and is what provides its spicy flavor. Generally extracted directly from fruit, high demand has driven the use of established methods to increase production through extraction and characterization. Over time these methods have improved, usually be applying existing techniques in conjunction. An increasingly wide range of potential applications has increased interest in capsaicin. Especially compelling are the promising results of medical studies showing possible beneficial effects in many diseases. Capsaicin's pungency has limited its use in clinical trials to support its biological activity. Characterization and extraction/ synthesis of non-pungent analogues is in progress. A review is made of capsaicin research focusing mainly on its production, synthesis, characterization and pharmacology, including some of its main potential clinical uses in humans.

  1. Persistent Respiratory Symptoms following Prolonged Capsaicin Exposure

    Directory of Open Access Journals (Sweden)

    S Copeland

    2013-10-01

    Full Text Available Capsaicin causes direct irritation of the eyes, mucous membranes, and respiratory tract. It is used in self-defense, in crowd control, and as a less lethal weapon in police work. Controlled trials suggest that capsaicin has minimal serious acute effects. Herein, we report a woman who had a 20-minute exposure to capsaicin during a jail riot. She subsequently developed episodic dyspnea and cough, and increased sensitivity to scents, perfumes, and cigarette smoke. She has not had wheezes on physical examination or abnormal pulmonary function tests. Her response to inhaled steroids and long-acting beta-agonists has been incomplete. She appears to have developed airway sensory hyperreactivity syndrome after the inhalation of capsaicin, which likely injured sensory nerves and/or caused persistent neurogenic inflammation.

  2. Dietary Capsaicin Improves Glucose Homeostasis and Alters the Gut Microbiota in Obese Diabetic ob/ob Mice

    Directory of Open Access Journals (Sweden)

    Jun-Xian Song

    2017-08-01

    , and IL-6 levels as compared with the normal diet.Conclusions: The beneficial effects of dietary capsaicin on glucose homeostasis are likely associated with the alterations of specific bacteria at the genus level. These alterations in bacteria induced by dietary capsaicin contribute to improved glucose homeostasis through increasing short-chain fatty acids, regulating gastrointestinal hormones and inhibiting pro-inflammatory cytokines. However, our results should be interpreted cautiously due to the lower caloric intake at the initial stage after capsaicin diet administration.

  3. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction

    Science.gov (United States)

    Sun, Fang; Xiong, Shiqiang; Zhu, Zhiming

    2016-01-01

    Chili peppers have a long history of use for flavoring, coloring, and preserving food, as well as for medical purposes. The increased use of chili peppers in food is very popular worldwide. Capsaicin is the major pungent bioactivator in chili peppers. The beneficial effects of capsaicin on cardiovascular function and metabolic regulation have been validated in experimental and population studies. The receptor for capsaicin is called the transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is ubiquitously distributed in the brain, sensory nerves, dorsal root ganglia, bladder, gut, and blood vessels. Activation of TRPV1 leads to increased intracellular calcium signaling and, subsequently, various physiological effects. TRPV1 is well known for its prominent roles in inflammation, oxidation stress, and pain sensation. Recently, TRPV1 was found to play critical roles in cardiovascular function and metabolic homeostasis. Experimental studies demonstrated that activation of TRPV1 by capsaicin could ameliorate obesity, diabetes, and hypertension. Additionally, TRPV1 activation preserved the function of cardiometabolic organs. Furthermore, population studies also confirmed the beneficial effects of capsaicin on human health. The habitual consumption of spicy foods was inversely associated with both total and certain causes of specific mortality after adjustment for other known or potential risk factors. The enjoyment of spicy flavors in food was associated with a lower prevalence of obesity, type 2 diabetes, and cardiovascular diseases. These results suggest that capsaicin and TRPV1 may be potential targets for the management of cardiometabolic vascular diseases and their related target organs dysfunction. PMID:27120617

  4. Antioxidant and antibacterial properties of capsaicine microemulsions

    Directory of Open Access Journals (Sweden)

    CRISTIAN DIMA

    2013-08-01

    Full Text Available The aim of this study was to prepare capsaicin microemulsions and to assess their antioxidant and antibacterial properties. Pseudoternare phase diagrams were made and were highlighted O/W/S/CoS weight ratios corresponding to microemulsion states. The oil phase (O was soybean oil and for the aqueous phase (W was used a mixture of water and glycerol in a ratio of 4:1 (wt/wt. As a surfactant (S was used Tween 40 and cosurfactant (CoS was ethanol in the mass ratio S:CoS = 2:1. Viscosimetric and conductometric analyses revealed the transition state of the O/W, W/O microemulsions and bicontinuous structures. The antioxidant properties of the capsaicin microemulsions were assayed based on the capacity to counteract DPPH (2,2-diphenyl-1-picrylhydrazyl radical. The scavenging capacity of the crude capsaicin was IC50 (DPPH = 2.63±0.34 and for capsaicin microemulsions was IC50 (DPPH = 5.26±0.28, lower than the value BHT (IC50 = 9.21±0.36μg·mL-1 (p<0.5. Antibacterial activity of capsaicin and capsaicin microemulsions were evaluated using Kirby-Bauer disk diffusion susceptibility tests against three common bacteria: Staphylococcus aureus, Salmonela enterica, and Escherichia coli.

  5. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction.

    Science.gov (United States)

    Sun, Fang; Xiong, Shiqiang; Zhu, Zhiming

    2016-04-25

    Chili peppers have a long history of use for flavoring, coloring, and preserving food, as well as for medical purposes. The increased use of chili peppers in food is very popular worldwide. Capsaicin is the major pungent bioactivator in chili peppers. The beneficial effects of capsaicin on cardiovascular function and metabolic regulation have been validated in experimental and population studies. The receptor for capsaicin is called the transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is ubiquitously distributed in the brain, sensory nerves, dorsal root ganglia, bladder, gut, and blood vessels. Activation of TRPV1 leads to increased intracellular calcium signaling and, subsequently, various physiological effects. TRPV1 is well known for its prominent roles in inflammation, oxidation stress, and pain sensation. Recently, TRPV1 was found to play critical roles in cardiovascular function and metabolic homeostasis. Experimental studies demonstrated that activation of TRPV1 by capsaicin could ameliorate obesity, diabetes, and hypertension. Additionally, TRPV1 activation preserved the function of cardiometabolic organs. Furthermore, population studies also confirmed the beneficial effects of capsaicin on human health. The habitual consumption of spicy foods was inversely associated with both total and certain causes of specific mortality after adjustment for other known or potential risk factors. The enjoyment of spicy flavors in food was associated with a lower prevalence of obesity, type 2 diabetes, and cardiovascular diseases. These results suggest that capsaicin and TRPV1 may be potential targets for the management of cardiometabolic vascular diseases and their related target organs dysfunction.

  6. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction

    Directory of Open Access Journals (Sweden)

    Fang Sun

    2016-04-01

    Full Text Available Chili peppers have a long history of use for flavoring, coloring, and preserving food, as well as for medical purposes. The increased use of chili peppers in food is very popular worldwide. Capsaicin is the major pungent bioactivator in chili peppers. The beneficial effects of capsaicin on cardiovascular function and metabolic regulation have been validated in experimental and population studies. The receptor for capsaicin is called the transient receptor potential vanilloid subtype 1 (TRPV1. TRPV1 is ubiquitously distributed in the brain, sensory nerves, dorsal root ganglia, bladder, gut, and blood vessels. Activation of TRPV1 leads to increased intracellular calcium signaling and, subsequently, various physiological effects. TRPV1 is well known for its prominent roles in inflammation, oxidation stress, and pain sensation. Recently, TRPV1 was found to play critical roles in cardiovascular function and metabolic homeostasis. Experimental studies demonstrated that activation of TRPV1 by capsaicin could ameliorate obesity, diabetes, and hypertension. Additionally, TRPV1 activation preserved the function of cardiometabolic organs. Furthermore, population studies also confirmed the beneficial effects of capsaicin on human health. The habitual consumption of spicy foods was inversely associated with both total and certain causes of specific mortality after adjustment for other known or potential risk factors. The enjoyment of spicy flavors in food was associated with a lower prevalence of obesity, type 2 diabetes, and cardiovascular diseases. These results suggest that capsaicin and TRPV1 may be potential targets for the management of cardiometabolic vascular diseases and their related target organs dysfunction.

  7. A hyperexcitability phenotype in mouse trigeminal sensory neurons expressing the R192Q Cacna1a missense mutation of familial hemiplegic migraine type-1.

    Science.gov (United States)

    Hullugundi, S K; Ansuini, A; Ferrari, M D; van den Maagdenberg, A M J M; Nistri, A

    2014-04-25

    Missense mutation R192Q in the CACNA1A gene causes familial hemiplegic migraine type-1 (FHM1), a monogenic subtype of migraine with aura. Using knock-in (KI) gene targeting we introduced this mutation into the mouse gene and generated a transgenic mouse model to investigate basic mechanisms of migraine pathophysiology. While FHM1 R192Q KI trigeminal ganglia were previously shown to exhibit constitutive up-regulation of ATP-gated P2X3 receptors, little is known about the firing properties of trigeminal sensory neurons, which convey nociceptive inputs to higher brain centers. We patch-clamped trigeminal sensory neurons to search for differences in firing properties between wildtype (WT) and KI cells in culture. Although various subclasses of trigeminal neurons were observed with respect to their firing patterns evoked by intracellular current injection, their distribution among WT and KI cells was similar with only small differences in rheobase or input resistance values. However, when neurons were excited by either α,β-methyl-ATP to stimulate P2X3 receptors or capsaicin to activate transient receptor potential vanilloid (TRPV1) receptors, the firing threshold in KI neurons was significantly lowered and followed by a larger number of spikes. Activation by α,β-methyl-ATP was associated with a transient cluster of action potentials, while capsaicin elicited more persistent firing. Using α,β-methyl-ATP or capsaicin, two functional classes of WT or KI neurons were distinguished according to the first spike latency, which suggests that a subgroup of neurons may be indirectly activated, probably via crosstalk between neurons and satellite glial cells. Thus, our results are consistent with reported facilitated trigeminal pain behavior of FHM1 R192Q KI mice. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. MRI of the Trigeminal Nerve in Patients With Trigeminal Neuralgia Secondary to Vascular Compression.

    Science.gov (United States)

    Hughes, Marion A; Frederickson, Andrew M; Branstetter, Barton F; Zhu, Xiao; Sekula, Raymond F

    2016-03-01

    Trigeminal neuralgia is a debilitating facial pain disorder, frequently caused by vascular compression of the trigeminal nerve. Vascular compression that results in trigeminal neuralgia occurs along the cisternal segment of the nerve. Imaging combined with clinical information is critical to correctly identify patients who are candidates for microvascular decompression. The purpose of this article is to review trigeminal nerve anatomy and to provide strategies for radiologists to recognize important MRI findings in patients with trigeminal neuralgia.

  9. Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following intradermal injection of capsaicin

    Directory of Open Access Journals (Sweden)

    Fang Li

    2006-03-01

    Full Text Available Abstract Background Intradermal injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A on the central nociceptive amplification process, which is induced by intradermal injection of capsaicin in rats. Results In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following intradermal injection of capsaicin in rats. Capsaicin injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer. Conclusion These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by intradermal injection of capsaicin in rats, which may have implications in

  10. The addition of GTN to capsaicin cream reduces the discomfort associated with application of capsaicin alone. A volunteer study.

    Science.gov (United States)

    McCleane, G J; McLaughlin, M

    1998-11-01

    In a double blind, placebo controlled trial of 40 volunteers, the burning discomfort associated with application of capsaicin cream (0.025%) was compared to placebo, GTN cream (1.33%) and to the combination of capsaicin cream (0.025%) plus GTN cream 1.33%. Median VAS for burning pain were 0 for the placebo, GTN and GTN + capsaicin groups and 3 for the capsaicin group after single application of each cream at daily intervals. This study demonstrates that after single application the addition of GTN to capsaicin significantly reduces the burning discomfort associated with application of capsaicin alone.

  11. Historical characterization of trigeminal neuralgia.

    Science.gov (United States)

    Eboli, Paula; Stone, James L; Aydin, Sabri; Slavin, Konstantin V

    2009-06-01

    TRIGEMINAL NEURALGIA IS a well known clinical entity characterized by agonizing, paroxysmal, and lancinating facial pain, often triggered by movements of the mouth or eating. Historical reviews of facial pain have attempted to describe this severe pain over the past 2.5 millennia. The ancient Greek physicians Hippocrates, Aretaeus, and Galen, described kephalalgias, but their accounts were vague and did not clearly correspond with what we now term trigeminal neuralgia. The first adequate description of trigeminal neuralgia was given in 1671, followed by a fuller description by physician John Locke in 1677. André described the convulsive-like condition in 1756, and named it tic douloureux; in 1773, Fothergill described it as "a painful affection of the face;" and in 1779, John Hunter more clearly characterized the entity as a form of "nervous disorder" with reference to pain of the teeth, gums, or tongue where the disease "does not reside." One hundred fifty years later, the neurological surgeon Walter Dandy equated neurovascular compression of the trigeminal nerve with trigeminal neuralgia.

  12. Trigeminal neuralgia: a new therapy?

    Science.gov (United States)

    Collet, C; Haen, P; Laversanne, S; Brignol, L; Thiéry, G

    2013-12-01

    Trigeminal neuralgia (TN) is a rare form of neuropathic pain that results in sudden, unilateral and recurrent pains in the distribution of one or more branches of the trigeminal nerve. The aetiology of TN remains unclear and several theories have been proposed. Many medical and surgical methods have been applied with only partial effectiveness and several side effects. New hypotheses and therapeutic methods are urgently needed. Using evidence presented in a literature review and in our own case report, we hypothesize that pain resulting from trigeminal neuralgia can be caused by demyelinating lesions in the trigger zone. These lesions can be repaired through the injection of fat containing Adipose-Derived Stem Cells (ADSC). Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Capsaicin pretreatment prevents disruption of the blood-aqueous barrier in the rabbit eye

    Energy Technology Data Exchange (ETDEWEB)

    Bynke, G.

    1983-06-01

    Capsaicin, the irritating agent of red pepper, produces ocular inflammation through a neurogenic mechanism. The present study is concerned with the long-term effects of capsaicin pretreatment on the capacity of the eye to respond to different inflammatory stimuli. Following retrobulbar injection of capsaicin to rabbits the aqueous flare response induced by subsequent infrared irradiation (IR) of the iris, subcutaneously administered alpha-melanocyte-stimulating hormone (alpha-MSH) and exogenously administered prostaglandin E2 (PGE2) was reduced greatly. In the case of IR and alpha-MSH the reduced responsiveness was manifest for several weeks after capsaicin pretreatment, involving first the capsaicin-treated eye, but later also the contralateral control eye. After 2-3 months the aqueous flare response was normal in both eyes. In the case of PGE2 the responsiveness was reduced for a shorter time; after 3 weeks the response was normal in both eyes. The results indicate that all three stimuli tested are at least partly dependent upon an intact sensory innervation to disrupt the blood-aqueous barrier, but that the mechanism of action of PGE2 is different from that of IR and alpha-MSH.

  14. Capsaicin-mediated denervation of sensory neurons promotes mammary tumor metastasis to lung and heart.

    Science.gov (United States)

    Erin, Nuray; Boyer, Philip J; Bonneau, Robert H; Clawson, Gary A; Welch, Danny R

    2004-01-01

    Capsaicin specifically activates or destroys small diameter nociceptive sensory neurons that contain the capsaicin receptor, also called vanilloid receptor 1. Neurons sensitive to capsaicin mediate inflammatory pain and are important targets for management of chronic pain. These neurons also regulate local tissue homeostasis, inflammation, healing and development, especially under conditions of psychological stress. Stress contributes to increased cancer recurrence and metastasis through as yet undefined mechanisms. Likewise, activity of capsaicin-sensitive neurons is altered by pathological conditions that may lead to metastatic growth (e.g. stress). Therefore, we examined effects of a treatment that induces sensory nerve denervation on breast cancer metastases. Systemic denervation of sensory neurons caused by treatment with 125 mg/kg capsaicin resulted in significantly more lung and cardiac metastases in adult mice injected orthotopically with syngeneic 4T1 mammary carcinoma cells than was observed in vehicle-treated controls. Heart metastases, normally very rare, occurred as pericardial nodules, intra-myocardial nodules, or combined pericardial-myocardial lesions. Since the rate of primary tumor growth was unaffected, effects on metastases appear to be host tissue-specific. Although preliminary, these observations provide one possible explanation for resistance of cardiac tissue to tumor involvement and highlight contributions of host tissue, including sensory neurons, in the efficiency of cancer metastasis.

  15. Evidence for the role of lipid rafts and sphingomyelin in Ca2+-gating of Transient Receptor Potential channels in trigeminal sensory neurons and peripheral nerve terminals.

    Science.gov (United States)

    Sághy, Éva; Szőke, Éva; Payrits, Maja; Helyes, Zsuzsanna; Börzsei, Rita; Erostyák, János; Jánosi, Tibor Zoltán; Sétáló, György; Szolcsányi, János

    2015-10-01

    Transient Receptor Potential (TRP) cation channels, such as TRP Vanilloid 1 and TRP Ankyrin repeat domain 1 (TRPV1 and TRPA1) are nocisensors playing important role to signal pain. Two "melastatin" TRP receptors, like TRPM8 and TRPM3 are also expressed in a subgroup of primary sensory neurons. These channels serve as thermosensors with unique thermal sensitivity ranges and are activated also by several exogenous and endogenous chemical ligands inducing conformational changes from various allosteric ("multisteric") sites. We analysed the role of plasma membrane microdomains of lipid rafts on isolated trigeminal (TRG) neurons and TRPV1-expressing CHO cell line by measuring agonist-induced Ca2+ transients with ratiometric technique. Stimulation-evoked calcitonin gene related peptide (CGRP) release from sensory nerve endings of the isolated rat trachea by radioimmunoassay was also measured. Lipid rafts were disrupted by cleaving sphingomyelin (SM) with sphingomyelinase (SMase), cholesterol depletion with methyl β-cyclodextrin (MCD) and ganglioside breakdown with myriocin. It has been revealed that intracellular Ca2+ increase responses evoked by the TRPV1 agonist capsaicin, the TRPA1 agonsits allyl isothiocyanate (AITC) and formaldehyde as well as the TRPM8 activator icilin were inhibited after SMase, MCD and myriocin incubation but the response to the TRPM3 agonist pregnenolon sulphate was not altered. Extracellular SMase treatment did not influence the thapsigargin-evoked Ca2+-release from intracellular stores. Besides the cell bodies, SMase also inhibited capsaicin- or AITC-evoked CGRP release from peripheral sensory nerve terminals, this provides the first evidence for the importance of lipid raft integrity in TRPV1 and TRPA1 gating on capsaicin-sensitive nerve terminals. SM metabolites, ceramide and sphingosine, did not influence TRPA1 and TRPV1 activation on TRG neurons, TRPV1-expressing CHO cell line, and nerve terminals. We suggest, that the hydrophobic

  16. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Aubuchon, Adam C., E-mail: acaubuchon@gmail.com [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Lovato, James F. [Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Balamucki, Christopher J. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  17. Trigeminal Nerve Root Demyelination Not Seen in Six Horses Diagnosed with Trigeminal-Mediated Headshaking

    Directory of Open Access Journals (Sweden)

    Veronica L. Roberts

    2017-05-01

    Full Text Available Trigeminal-mediated headshaking is an idiopathic neuropathic facial pain syndrome in horses. There are clinical similarities to trigeminal neuralgia, a neuropathic facial pain syndrome in man, which is usually caused by demyelination of trigeminal sensory fibers within either the nerve root or, less commonly, the brainstem. Our hypothesis was that the neuropathological substrate of headshaking in horses is similar to that of trigeminal neuralgia in man. Trigeminal nerves, nerve roots, ganglia, infraorbital, and caudal nasal nerves from horse abattoir specimens and from horses euthanized due to trigeminal-mediated headshaking were removed, fixed, and processed for histological assessment by a veterinary pathologist and a neuropathologist with particular experience of trigeminal neuralgia histology. No histological differences were detected between samples from horses with headshaking and those from normal horses. These results suggest that trigeminal-mediated headshaking may have a different pathological substrate from trigeminal neuralgia in man.

  18. The capsaicin cough reflex in patients with symptoms elicited by odorous chemicals

    DEFF Research Database (Denmark)

    Holst, H; Arendt-Nielsen, L; Mosbech, H;

    2010-01-01

    Patients with multiple chemical sensitivity and eczema patients with airway symptoms elicited by odorous chemicals have enhanced cough reflex to capsaicin when applying the tidal breathing method. The aims of the present study were to test whether the capsaicin induced cough reflex was enhanced...... when applying the single breath inhalation method in similar groups of patients with symptoms related to odorous chemicals e.g. other persons wearing of perfume; and to investigate to what extent the reporting of lower airway symptoms influenced the cough reflex. Sixteen patients fulfilling Cullen......'s criteria for multiple chemical sensitivity and 15 eczema patients with airway symptoms elicited by odorous chemicals were compared with 29 age-matched, healthy controls. We measured C5--the capsaicin concentration causing five coughs or more--using the single breath inhalation test. No difference was found...

  19. Ascending projections of nociceptive neurons from trigeminal subnucleus caudalis: A population approach.

    Science.gov (United States)

    Saito, Hiroto; Katagiri, Ayano; Okada, Shinji; Mikuzuki, Lou; Kubo, Asako; Suzuki, Tatsuro; Ohara, Kinuyo; Lee, Jun; Gionhaku, Nobuhito; Iinuma, Toshimitsu; Bereiter, David A; Iwata, Koichi

    2017-07-01

    Second-order neurons in trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1) are critical for craniofacial pain processing and project rostrally to terminate in: ventral posteromedial thalamic nucleus (VPM), medial thalamic nuclei (MTN) and parabrachial nuclei (PBN). The contribution of each region to trigeminal nociception was assessed by the number of phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons co-labeled with fluorogold (FG). The phenotype of pERK-IR neurons was further defined by the expression of neurokinin 1 receptor (NK1). The retrograde tracer FG was injected into VPM, MTN or PBN of the right hemisphere and after seven days, capsaicin was injected into the left upper lip in male rats. Nearly all pERK-IR neurons were found in superficial laminae of Vc-C1 ipsilateral to the capsaicin injection. Nearly all VPM and MTN FG-labeled neurons in Vc-C1 were found contralateral to the injection site, whereas FG-labeled neurons were found bilaterally after PBN injection. The percentage of FG-pERK-NK1-IR neurons was significantly greater (>10%) for PBN projection neurons than for VPM and MTN projection neurons (NK1-IR VPM projection neurons were found mainly in the middle-Vc, while pERK-NK1-immunoreactive MTN or PBN projection neurons were found in the middle-Vc and caudal Vc-C1. These results suggest that a significant percentage of capsaicin-responsive neurons in superficial laminae of Vc-C1 project directly to PBN, while neurons that project to VPM and MTN are subject to greater modulation by pERK-IR local interneurons. Furthermore, the rostrocaudal distribution differences of FG-pERK-NK1-IR neurons in Vc-C1 may reflect functional differences between these projection areas regarding craniofacial pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Changes in heart rate, blood pressure and renal sympathetic nerve activity induced by microinjection of capsaicin into area postrema in rats%最后区微量注射辣椒素对大鼠血压、心率和肾交感神经放电的影响

    Institute of Scientific and Technical Information of China (English)

    薛保建; 何瑞荣

    2000-01-01

    The effects of capsaicin microinjection into area postrema (AP) on mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were investigated in 36 anesthetized Sprague-Dawley rats. The results obtained are as follows. (1) Following microinjection of capsaicin (10 μmol/L, 50 nl) into the AP, MAP, HR and RSNA were significantly increased from 12.34±0.53 kPa, 328.52±7.54 bpm and 100±0% to 15.17±0.25 kPa (P<0.001), 354.81±8.54 bpm (P<0.001) and 156.95±7.57% (P<0.001), respectively. (2) Ruthenium red (RR, 100 mmol/L, 0.2 ml, iv), a capsaicin receptor antagonist, significantly inhibited these effects of capsaicin. (3) Pretreatment with a NMDA receptor antagonist MK-801 (500 μg/kg, 0.2 ml, iv) also reduced these effects of capsaicin. The above results indicate that microinjection of capsaicin into AP induces excitatory effects on MAP, HR and RSNA, which are mediated by capsaicin receptors with glutamate involvement.%在36只麻醉Sprague-Dawley大鼠, 观察了最后区内微量注射辣椒素(10 μmol/L, 50 nl)对平均动脉压(MAP)、心率(HR)和肾交感神经放电(RSNA)的影响.实验结果如下:(1)最后区内注射辣椒素可引起 MAP、HR 和RSNA明显增加, 分别由12.34±0.53 kPa、 328.52±7.54 bpm 和100±0% 增至15.17±0.25 kPa (P<0.001)、 354.81±8.54 bpm (P<0.001) 和156.95±7.57% (P<0.001);(2) 静脉注射辣椒素受体阻断剂钌红(100 mmol/L, 0.2 ml) 后, 辣椒素的上述效应可被明显抑制;(3) 预先应用NMDA 受体阻断剂MK-801 (500 μg/kg, 0.2 ml, iv)也明显抑制辣椒素的兴奋效应.以上结果提示, 最后区微量注射辣椒素对血压、心率和肾交感神经放电有兴奋作用, 而此作用由辣椒素受体介导并有谷氨酸参与.

  1. Chemical and Pharmacological Aspects of Capsaicin

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Reyes-Escogido

    2011-01-01

    Full Text Available Capsaicin is a unique alkaloid found primarily in the fruit of the Capsicum genus and is what provides its spicy flavor. Generally extracted directly from fruit, high demand has driven the use of established methods to increase production through extraction and characterization. Over time these methods have improved, usually be applying existing techniques in conjunction. An increasingly wide range of potential applications has increased interest in capsaicin. Especially compelling are the promising results of medical studies showing possible beneficial effects in many diseases. Capsaicin’s pungency has limited its use in clinical trials to support its biological activity. Characterization and extraction/ synthesis of non-pungent analogues is in progress. A review is made of capsaicin research focusing mainly on its production, synthesis, characterization and pharmacology, including some of its main potential clinical uses in humans.

  2. Capsaicin-fighting fire with fire

    Directory of Open Access Journals (Sweden)

    Poonam Agarwal

    2009-01-01

    Full Text Available Chronic pain conditions involving the maxillofacial region represent a major health problem and patients with persistent pain are difficult to manage successfully. Most of these conditions are often comorbid with additional health issues. Capsaicin has been studied in various models of pain and neuropathy. Currently, its best known use is as a topical analgesic and anti-inflammatory. Its use as a noxious stimulus offers several benefits and has been used with considerable success in conditions like postherpetic neuralgia, atypical facial pain, musculoskeletal pain etc. Adverse events from capsaicin are mainly at the application site (burning, stinging, erythema, and systemic events are rare. This review highlights the emerging evidence on the use of capsaicin in the commonly encountered orofacial pain conditions.

  3. Microvascular decompression for trigeminal neuralgia.

    Science.gov (United States)

    Sade, Burak; Lee, Joung H

    2014-10-01

    The microvascular decompression procedure has proven to be a safe and effective option in the surgical management of neurovascular compression syndromes in general and trigeminal neuralgia in particular. This article aims to serve as an overview of the decision-making process, application of the surgical technique, and clinical outcome pertaining to this procedure.

  4. Pharmacological treatment of trigeminal neuralgia.

    Science.gov (United States)

    Di Stefano, Giulia; Truini, Andrea

    2017-10-01

    Unique among the different neuropathic pain conditions, trigeminal neuralgia frequently has an excellent response to some selected drugs, which, on the other hand, often entail disabling side effects. Physicians should be therefore acquainted with the management of these drugs and the few alternative options. Areas covered: This article, based on a systematic literature review, describes the pharmacological options, and indicates the future perspectives for treating trigeminal neuralgia. The article therefore provides current, evidence-based knowledge about the pharmacological treatment of trigeminal neuralgia, and suggests a practical approach to the various drugs, including starting dose, titration and side effects. Expert commentary: Carbamazepine and oxcarbazepine are the reference standard drugs for treating patients with trigeminal neuralgia. They are effective in most patients. The undesired effects however cause withdrawal from treatment or a dosage reduction to an insufficient level in many patients. Sodium channel blockers selective for the sodium channel 1.7 (Nav1.7) receptor, currently under development, might be an alternative, better-tolerated pharmacological option in the next future.

  5. CILOSTAZOL INDUCES C-FOS EXPRESSION IN THE TRIGEMINAL NUCLEUS CAUDALIS AND BEHAVIOURAL CHANGES SUGGESTIVE OF HEADACHE WITH MIGRAINE-LIKE MANIFESTATIONS IN RATS

    DEFF Research Database (Denmark)

    Christensen, S. L. T.; Petersen, S.; Sorensen, D. B.;

    2016-01-01

    Introduction: Research in migraine therapeutics is hindered by the lack of knowledge on migraine pathophysiology and suitable predictive animal models. As headache and migraine can be provoked in healthy humans and migraine patients the aim of this study was to see if it can also provoke headache...... in rats. Also, we tested the response to sumatriptan in order to evaluate the predictive properties of the model. Methods: The effect of cilostazol (125 mg/kg p.o.) was evaluated on a range of spontaneous behavioural parameters, light sensitivity and mechanical sensitivity thresholds. To assess headache...... specificity we evaluated the c-fos expression in the trigeminal nucleus caudalis. All experiments were done in female Sprague Dawley rats and the oestrous cycle was included in the analyses. Results: We found that cilostazol increased the light sensitivity and grooming behaviour of the rats and decreased...

  6. Effect of highly purified capsaicin on articular cartilage and rotator cuff tendon healing: An in vivo rabbit study.

    Science.gov (United States)

    Friel, Nicole A; McNickle, Allison G; DeFranco, Michael J; Wang, FanChia; Shewman, Elizabeth F; Verma, Nikhil N; Cole, Brian J; Bach, Bernard R; Chubinskaya, Susan; Kramer, Susan M; Wang, Vincent M

    2015-12-01

    Highly purified capsaicin has emerged as a promising injectable compound capable of providing sustained pain relief following a single localized treatment during orthopedic surgical procedures. To further assess its reliability for clinical use, the potential effect of highly purified capsaicin on articular cartilage metabolism as well as tendon structure and function warrants clarification. In the current study, rabbits received unilateral supraspinatus transection and repair with a single 1 ml injection of capsaicin (R+C), PEG-only placebo (R+P), or saline (R+S) into the glenohumeral joint (GHJ). An additional group received 1 ml capsaicin onto an intact rotator cuff (I+C). At 18 weeks post-op, cartilage proteoglycan (PG) synthesis and content as well as cell viability were similar (p>0.05) across treatment groups. Biomechanical testing revealed no differences (p>0.05) among tendon repair treatment groups. Similarly, histologic features of both cartilage and repaired tendons showed minimal differences across groups. Hence, in this rabbit model, a single injection of highly purified capsaicin into the GHJ does not induce a deleterious response with regard to cartilage matrix metabolism and cell viability, or rotator cuff healing. These data provide further evidence supporting the use of injectable, highly purified capsaicin as a safe alternative for management of postoperative pain following GHJ surgery.

  7. The Effect of Capsaicin on Salivary Gland Dysfunction

    Directory of Open Access Journals (Sweden)

    Yong-Hwan Shin

    2016-06-01

    Full Text Available Capsaicin (trans-8-methyl-N-vanilyl-6-nonenamide is a unique alkaloid isolated from hot chili peppers of the capsicum family. Capsaicin is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1, which is expressed in nociceptive sensory neurons and a range of secretory epithelia, including salivary glands. Capsaicin has analgesic and anti-inflammatory properties in sensory neurons. Recently, increasing evidence has indicated that capsaicin also affects saliva secretion and inflammation in salivary glands. Applying capsaicin increases salivary secretion in human and animal models. Capsaicin appears to increase salivation mainly by modulating the paracellular pathway in salivary glands. Capsaicin activates TRPV1, which modulates the permeability of tight junctions (TJ by regulating the expression and function of putative intercellular adhesion molecules in an ERK (extracelluar signal-regulated kinase -dependent manner. Capsaicin also improved dysfunction in transplanted salivary glands. Aside from the secretory effects of capsaicin, it has anti-inflammatory effects in salivary glands. The anti-inflammatory effect of capsaicin is, however, not mediated by TRPV1, but by inhibition of the NF-κB pathway. In conclusion, capsaicin might be a potential drug for alleviating dry mouth symptoms and inflammation of salivary glands.

  8. Spontaneous trigeminal allodynia in rats: a model of primary headache.

    Science.gov (United States)

    Oshinsky, Michael L; Sanghvi, Menka M; Maxwell, Christina R; Gonzalez, Dorian; Spangenberg, Rebecca J; Cooper, Marnie; Silberstein, Stephen D

    2012-10-01

    Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment.

  9. Antilithogenic influence of dietary capsaicin and curcumin during experimental induction of cholesterol gallstone in mice.

    Science.gov (United States)

    Shubha, Malenahalli C; Reddy, Raghunatha R L; Srinivasan, Krishnapura

    2011-04-01

    Spice bioactive compounds, capsaicin and curcumin, were both individually and in combination examined for antilithogenic potential during experimental induction of cholesterol gallstones in mice. Cholesterol gallstones were induced by feeding mice a high-cholesterol (0.5%) diet for 10 weeks. Groups of mice were maintained on a lithogenic diet that was supplemented with 0.015% capsaicin/0.2% curcumin/0.015% capsaicin + 0.2% curcumin. The lithogenic diet that contained capsaicin, curcumin, or their combination reduced the incidence of cholesterol gallstones by 50%, 66%, and 56%, respectively, compared with lithogenic control. This was accompanied by reduced biliary cholesterol and a marginal increase in phospholipid in these spice-fed groups. Increased cholesterol saturation index and cholesterol : phospholipid ratio in the bile caused by the lithogenic diet was countered by the dietary spice compounds. The antilithogenic influence of spice compounds was attributable to the cholesterol-lowering effect of these dietary spices in blood and liver, as well as a moderate increase in phospholipids. Decreased activities of hepatic glutathione reductase and glutathione-S-transferase caused by the lithogenic diet were countered by the combination of capsaicin and curcumin. The increased lipid peroxidation and the decreased concentration of ascorbic acid in the liver that was caused by the lithogenic diet was countered by the dietary spice compounds, individually or in combination. Thus, while the capsaicin and curcumin combination did not have an additive influence in reducing the incidence of cholesterol gallstones in mice, their combination nevertheless was more beneficial in enhancing the activity of hepatic antioxidant enzyme ─ glutathione reductase in the lithogenic situation. The antioxidant effects of dietary spice compounds are consistent with the observed reduction in cholesterol gallstones formed under lithogenic condition.

  10. Capsaicin facilitates carotid sinus baroreflex in anesthetized rats.

    Science.gov (United States)

    Zhang, Hao; Liu, Yi-Xian; Wu, Yu-Ming; Wang, Sheng; He, Rui-Rong

    2004-04-25

    The effects of capsaicin (CAP) on the carotid sinus baroreflex were studied in 30 anaesthetized rats with perfused isolated carotid sinus. The results are as follows. (1) By perfusing the isolated carotid sinus with CAP (1 micromol/L), the functional curve of the baroreflex was shifted to the left and downward, with a peak slope (PS) increasing from 0.34+/-0.01 to 0.42+/-0.01 (PPS and RD induced by capsaicin were dose-dependent. (2) By pretreatment with ruthenium red (RR, 100 micromol/L), an antagonist of vanilloid receptor subtype 1 (VR(1)), the above effects of CAP on carotid baroreflex were abolished. (3) The CAP-induced change in the baroreflex was also eliminated by pretreatment with glibenclamide (20 microm ol/L), a K(ATP) channel blocker. On the basis of the results, it is concluded that CAP facilitates the carotid baroreflex, an effect of which may be resulted from the opening of K(ATP) channels mediated by VR(1).

  11. Topical ethosomal capsaicin attenuates edema and nociception in arthritic rats.

    Science.gov (United States)

    Kumar Sarwa, Khomendra; Rudrapal, Mithun; Mazumder, Bhaskar

    2015-12-01

    In this study, topical ethosomal formulation of capsaicin was prepared and evaluated for bio-efficacy in arthritic rats. Physical and biological characterizations of prepared capsaicin-loaded nano vesicular systems were also carried out. Ethosomal capsaicin showed significant reduction of rat paw edema along with promising antinociceptive action. The topical antiarthritic efficacy of prepared formulation of capsaicin was found more than that of Thermagel, a marketed gel of capsaicin. From toxicological study, no predictable signs of toxicity such as skin irritation (of experimental rats) were observed. Based on this finding, ethosomal capsaicin could be proposed as an effective as well as a safe topical delivery system for the long-term treatment of arthritis and associated inflammo-musculoskeletal disorders. Such exciting result would eventually enlighten the analgesic and anti-inflammatory potential of capsaicin for topical remedy.

  12. Capsaicin patch (Qutenza) for postherpetic neuralgia.

    Science.gov (United States)

    2011-05-30

    The FDA has approved a topical 8% patch formulation of capsaicin (Qutenza-NeurogesX), available only by prescription, for local treatment of postherpetic neuralgia. Postherpetic neuralgia occurs after herpes zoster in about one third of patients ≥60 years old and can persist for months or even years.

  13. Evaluation of surgical procedures for trigeminal neuralgia.

    OpenAIRE

    Ong, K. S.; Keng, S. B.

    2003-01-01

    Trigeminal neuralgia is a type of facial pain that is difficult to treat. The pain can be excruciating and debilitating. The wide range of treatments currently used for trigeminal neuralgia is ample evidence that there is no simple answer to how it should be managed. This review will evaluate the current surgical procedures used for the treatment of trigeminal neuralgia. A critical analysis of the evidence-based studies to date was done to evaluate and compare the efficacy of the different su...

  14. The enhanced anti-obesity effect and reduced gastric mucosa irritation of capsaicin-loaded nanoemulsions.

    Science.gov (United States)

    Lu, Muwen; Cao, Yong; Ho, Chi-Tang; Huang, Qingrong

    2017-05-24

    Capsaicin (CAP), the major active component of chili peppers, is known to have thermogenic and weight-loss potential. The aim of this study was to investigate the anti-obesity effects of capsaicin-loaded nanoemulsions (C-NE) on male Sprague Dawley (SD) rats treated with a high-fat diet (HFD). The food grade C-NE was prepared using capsaicin, medium chain triacylglycerols (MCT) (Neobee 1053), sucrose stearate S-370, Tween 80 and distilled water with an emulsion droplet size of 168 nm and a capsaicin loading of 80.4 mg mL(-1). Results showed that C-NE effectively decreased body weight gain and hypercholesterolemia induced by HFD in a dose-dependent manner. Histological evaluations of the liver and adipose tissue confirmed that C-NE had significant effects on inhibiting diet-induced hepatic steatosis, reducing epididymal adipocyte size and tissue mass. A gastric mucosa irritation test demonstrated that C-NE was effective in alleviating the gastric inflammation caused by free unformulated CAP crystals.

  15. Trigeminal Neuralgia and Radiofrequency Lesioning

    Directory of Open Access Journals (Sweden)

    Andy R. Eugene

    2015-12-01

    Full Text Available Trigeminal Neuralgia is a disorder that is characterized with electrical-type shocking pain in the face and jaw. This pain may either present as sharp unbearable pain unilateral or bilaterally. There is no definite etiology for this condition. There are various treatment methods that are currently being used to relieve the pain. One of the pharmacological treatments is Carbamazepine and the most prevalent surgical treatments include Gamma Knife Surgery (GKS, Microvascular Decompression (MVD and Radiofrequency Lesioning (RFL. Although, MVD is the most used surgical method it is not an option for all the patients due to the intensity of the procedure. RFL is used when MVD is not suitable. In this paper we present the various treatments and Monte-Carlo based pharmacokinetic simulations of Carbamazepine in treatment of Trigeminal Neuralgia.

  16. Transient receptor potential channels encode volatile chemicals sensed by rat trigeminal ganglion neurons.

    Directory of Open Access Journals (Sweden)

    Matthias Lübbert

    Full Text Available Primary sensory afferents of the dorsal root and trigeminal ganglia constantly transmit sensory information depicting the individual's physical and chemical environment to higher brain regions. Beyond the typical trigeminal stimuli (e.g. irritants, environmental stimuli comprise a plethora of volatile chemicals with olfactory components (odorants. In spite of a complete loss of their sense of smell, anosmic patients may retain the ability to roughly discriminate between different volatile compounds. While the detailed mechanisms remain elusive, sensory structures belonging to the trigeminal system seem to be responsible for this phenomenon. In order to gain a better understanding of the mechanisms underlying the activation of the trigeminal system by volatile chemicals, we investigated odorant-induced membrane potential changes in cultured rat trigeminal neurons induced by the odorants vanillin, heliotropyl acetone, helional, and geraniol. We observed the dose-dependent depolarization of trigeminal neurons upon application of these substances occurring in a stimulus-specific manner and could show that distinct neuronal populations respond to different odorants. Using specific antagonists, we found evidence that TRPA1, TRPM8, and/or TRPV1 contribute to the activation. In order to further test this hypothesis, we used recombinantly expressed rat and human variants of these channels to investigate whether they are indeed activated by the odorants tested. We additionally found that the odorants dose-dependently inhibit two-pore potassium channels TASK1 and TASK3 heterologously expressed In Xenopus laevis oocytes. We suggest that the capability of various odorants to activate different TRP channels and to inhibit potassium channels causes neuronal depolarization and activation of distinct subpopulations of trigeminal sensory neurons, forming the basis for a specific representation of volatile chemicals in the trigeminal ganglia.

  17. Multimodality Management of Trigeminal Schwannomas.

    Science.gov (United States)

    Niranjan, Ajay; Barnett, Samuel; Anand, Vijay; Agazzi, Siviero

    2016-08-01

    Patients presenting with trigeminal schwannomas require multimodality management by a skull base surgical team that can offer expertise in both transcranial and transnasal approaches as well as radiosurgical and microsurgical strategies. Improvement in neurologic symptoms, preservation of cranial nerve function, and control of mass effect are the primary goals of management for trigeminal schwannomas. Complete surgical resection is the treatment of choice but may not be possible in all cases. Radiosurgery is an option as primary management for small- to moderate-sized tumors and can be used for postoperative residuals or recurrences. Planned surgical resection followed by SRS for residual tumor is an effective option for larger trigeminal schwannomas. The endoscopic resection is an excellent approach for patients with an extradural tumor or tumors isolated to the Meckel cave. A detailed analysis of a tumor and its surroundings based on high-quality imaging can help better estimate the expected outcome from each treatment. An expert skull base team should be able to provide precise counseling for each patient's situation for selecting the best option.

  18. Transient receptor potential vanilloid 1 activation by dietary capsaicin promotes urinary sodium excretion by inhibiting epithelial sodium channel α subunit-mediated sodium reabsorption.

    Science.gov (United States)

    Li, Li; Wang, Fei; Wei, Xing; Liang, Yi; Cui, Yuanting; Gao, Feng; Zhong, Jian; Pu, Yunfei; Zhao, Yu; Yan, Zhencheng; Arendshorst, William J; Nilius, Bernd; Chen, Jing; Liu, Daoyan; Zhu, Zhiming

    2014-08-01

    High salt (HS) intake contributes to the development of hypertension. Epithelial sodium channels play crucial roles in regulating renal sodium reabsorption and blood pressure. The renal transient receptor potential vanilloid 1 (TRPV1) cation channel can be activated by its agonist capsaicin. However, it is unknown whether dietary factors can act on urinary sodium excretion and renal epithelial sodium channel (ENaC) function. Here, we report that TRPV1 activation by dietary capsaicin increased urinary sodium excretion through reducing sodium reabsorption in wild-type (WT) mice on a HS diet but not in TRPV1(-/-) mice. The effect of capsaicin on urinary sodium excretion was involved in inhibiting αENaC and its related with-no-lysine kinase 1/serum- and glucocorticoid-inducible protein kinase 1 pathway in renal cortical collecting ducts of WT mice. Dietary capsaicin further reduced the increased αENaC activity in WT mice attributed to the HS diet. In contrast, this capsaicin effect was absent in TRPV1(-/-) mice. Immunoprecipitation study indicated αENaC specifically coexpressed and functionally interact with TRPV1 in renal cortical collecting ducts of WT mice. Additionally, ENaC activity and expression were suppressed by capsaicin-mediated TRPV1 activation in cultured M1-cortical collecting duct cells. Long-term dietary capsaicin prevented the development of high blood pressure in WT mice on a HS diet. It concludes that TRPV1 activation in the cortical collecting ducts by capsaicin increases urinary sodium excretion and avoids HS diet-induced hypertension through antagonizing αENaC-mediated urinary sodium reabsorption. Dietary capsaicin may represent a promising lifestyle intervention in populations exposed to a high dietary salt intake.

  19. Establishment of a rat model of trigeminal neuralgia induced by photochemical nerve injury%一种光化学损伤诱导的三叉神经痛大鼠模型的建立

    Institute of Scientific and Technical Information of China (English)

    崔悦; 王丹巧; 高天乐; 徐晓军; 赵佳; 王晔; 孙丹丹; 张莹; 刘洋; 赵小亮; 牛晓红; 张美玉

    2014-01-01

    Aim To investigate the behavioral changes of the pain related neuromodulation and neurotransmission in peripheral and central nervous systems in rats with trigeminal neuralgia (TN)and provide a disease relevant animal model for mecha-nism study of TN.Methods The male SD rats were randomly divided into sham operation group and TN surgical group.The latter group was further divided into model group and gabapentin group (100 mg · kg-1 ). TN was induced by intravenous erythrosine B injection and laser irradiation.The pain behavior of rats was evaluated using mechanical pain threshold measured with Von Frey hairs.Fluorescence quantitative PCR technique was deployed to study the change of Tac1 mRNA expressions in trigeminal ganglia.Utilizing microdialysis technique followed by high performance liquid chromatography fluorescence detection (HPLC-FLD),the extracellular striatum fluid was collected and glutamate(Glu)concentration was determined.Results In the model group,the average mechanical pain threshold in facial ar-ea innervated by the trigeminal nerve remained below 4g after 7 days post surgery.The mechanical threshold of the model group (1.63 ±1.27)g was significantly lower (P<0.01)than the control group (24.17 ±4.49)g on day10 post surgery.In gen-eral,the mechanical withdraw threshold was decreased from the preoperative value of 26g to the postoperative value of (1.60 ± 1.74)g (P<0.01),and maintained stable at (0.71 ±1.24) g during the whole dynamic monitoring period from day7 to day60.The successful rate of this model was 63%.After sur-gery,Tac1 mRNA expression in trigeminal ganglia and extracel-lular Glu levels in striatum were significantly up-regulated (P<0.05 ) in the model group. Animals receiving Gabapentin showed significant improvement in pain symptoms,as well as re-ductions of Tac1 mRNA expression in trigeminal ganglia and ex-tracellular Glu concentration in striatum (P<0.05 ).Conclu-sions The above described photochemically induced TN rat model can

  20. MR findings of trigeminal neurinoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hong Suk; Han, Moon Hee; Chang, Kee Hyun; Yoo, In Kyu; Kim, Sam Soo; Lee, Kyoung Won; Jung, Hee Won; Yeon, Kyung Mo [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-08-01

    To describe the MRI findings of trigeminal neurinoma. We retrospectively analyzed the MRI findings of 19 patients with trigeminal neurinomas proven by surgery and pathologic examination. Axial T1- and T2-weighted MR images in all patients and gadolinium-enhanced T1-weighted images in 14 patients were obtained at 2.0T(8 cases), 1.5T(6 cases) or 0.5T(5 cases). These were analyzed in terms of tumor size, signal intensity, degree of contrast enhancement, the presence or absence of cystic change and denervation atrophy of the masticator muscles. Clinical manifestations included sensory abnormality or pain(n=12), headache(n=10), impaired visual acuity or diplopia(n=6), hearing loss or tinnitus(n=3), weakness of masticator muscles(n=2), and mass or nasal obstruction(n=2). On MR images, tumor size was seen to average 4.2(range 1.5-6)cm;tumors were located in the posterior cranial fossa(n=8), middle cranial fossa(n=4), ophthalmic nerve(n=2), maxillary nerve(n=1), and mandibular nerve(n=1), and in three cases were dumbbell-shaped and extended into both the middle and posterior cranial fossa. On T1-weighted images, signals were isointense with cortical grey matter, in ten cases(53%), and of low intensity in nine (47%);on T2-weighted images, signals were of high intensity in 15cases(79%) and were isointense in four (21%). Cystic change was seen in 12 cases(63%). After enhancement, all (14/14) the tumors enhanced. Denervation atrophy was seen in nine cases(47%) and all of these involved the trigeminal ganglion or mandibular nerve. A trigeminal neurinoma shows similar signal intensity and enhancement to other cranial neurinomas with a higher incidence of cystic degeneration. Its location and shape are characteristic, and where there is involvement of the trigeminal ganglion or mandibular nerve, denervation atrophy may be seen.

  1. Bioavailability of capsaicin and its implications for drug delivery.

    Science.gov (United States)

    Rollyson, William D; Stover, Cody A; Brown, Kathleen C; Perry, Haley E; Stevenson, Cathryn D; McNees, Christopher A; Ball, John G; Valentovic, Monica A; Dasgupta, Piyali

    2014-12-28

    The dietary compound capsaicin is responsible for the "hot and spicy" taste of chili peppers and pepper extracts. It is a valuable pharmacological agent with several therapeutic applications in controlling pain and inflammation. Emerging studies show that it displays potent anti-tumor activity in several human cancers. On a more basic research level, capsaicin has been used as a ligand to activate several types of ion-channel receptors. The pharmacological activity of capsaicin-like compounds is dependent on several factors like the dose, the route of administration and most importantly on its concentration at target tissues. The present review describes the current knowledge involving the metabolism and bioavailability of capsaicinoids in rodents and humans. Novel drug delivery strategies used to improve the bioavailability and therapeutic index of capsaicin are discussed in detail. The generation of novel capsaicin-mimetics and improved drug delivery methods will foster the hope of innovative applications of capsaicin in human disease.

  2. The sensory response to capsaicin during repeated topical exposures: differential effects on sensations of itching and pungency.

    Science.gov (United States)

    Green, B G; Shaffer, G S

    1993-06-01

    Changes in sensory irritation were measured during repeated topical exposures to capsaicin over 2 days. The perceived intensities of itching and pungent sensations, predominantly burning and stinging/pricking, were assessed every 60 sec during 5 applications of capsaicin at inter-stimulus intervals (ISI) of 90 min (Exp. 1) or 15 min (Exp. 2) and in follow-up tests 24 h later. Psychophysical measurements were obtained with a hand-held dynamometer in conjunction with the method of magnitude production. When the ISI was 90 min, itching and pungency were both significantly reduced (i.e., desensitization occurred) by the fifth exposure; however, the reduction occurred more rapidly and dramatically for itching. After 24 h, desensitization remained significant only for itching. When the ISI was 15 min, the sensations on day 1 first intensified in a manner consistent with sensitization, then declined in a manner consistent with desensitization; compared to pungency, itch exhibited less sensitization and more desensitization. On day 2, overall intensity was less for both categories of sensation, primarily because of a reduction in sensitization. Marked individual differences were observed in the overall sensitivity to capsaicin, the time course of sensation, the susceptibility to capsaicin-induced itch, and the rate and duration of sensitization and desensitization. The results are discussed in terms of current hypotheses about the sensory mechanisms that underlie chemically induced itch and the use of capsaicin as a topical analgesic and antipruritic.

  3. Neuronal plasticity of trigeminal ganglia in mice following nerve injury

    Science.gov (United States)

    Lynds, Randi; Lyu, Chuang; Lyu, Gong-Wei; Shi, Xie-Qi; Rosén, Annika; Mustafa, Kamal; Shi, Tie-Jun Sten

    2017-01-01

    Background Nerve injury may induce neuropathic pain. In studying the mechanisms of orofacial neuropathic pain, attention has been paid to the plastic changes that occur in the trigeminal ganglia (TGs) and nucleus in response to an injury of the trigeminal nerve branches. Previous studies have explored the impact of sciatic nerve injury on dorsal root ganglia (DRGs) and it has shown dramatic changes in the expression of multiple biomarkers. In large, the changes in biomarker expression in TGs after trigeminal nerve injury are similar to that in DRGs after sciatic nerve injury. However, important differences exist. Therefore, there is a need to study the plasticity of biomarkers in TGs after nerve injury in the context of the development of neuropathic pain-like behaviors. Aim The aim of this study was to investigate the plasticity of biomarkers associated with chronic persistent pain in TGs after trigeminal nerve injury. Materials and methods To mimic the chronic nature of the disorder, we used an intraoral procedure to access the infraorbital nerve (ION) and induced a nerve injury in mice. Immunohistochemistry and quantification were used for revealing the expression level of each biomarker in TGs after nerve injury. Results Two weeks after partial ION injury, immunohistochemistry results showed strongly upregulated expressions of activating transcription factor 3 and neuropeptide Y (NPY) in the ipsilateral TGs. Microglial cells were also activated after nerve injury. In regard to positive neuronal profile counting, however, no significant difference in expression was observed in galanin, substance P, calcitonin gene-related peptide, neuronal nitric oxide synthase, phosphorylated AKT, or P2X3 in ipsilateral TGs when compared to contralateral TGs. Conclusion In this study, the expression and regulation of biomarkers in TGs have been observed in response to trigeminal nerve injury. Our results suggest that NPY and Iba1 might play crucial roles in the pathogenesis of

  4. In Vitro and Sensory Evaluation of Capsaicin-Loaded Nanoformulations

    OpenAIRE

    Mathias Kaiser; Benedikt Kirsch; Hannah Hauser; Désirée Schneider; Ingrid Seuß-Baum; Francisco M Goycoolea

    2015-01-01

    Capsaicin has known health beneficial and therapeutic properties. It is also able to enhance the permeability of drugs across epithelial tissues. Unfortunately, due to its pungency the oral administration of capsaicin is limited. To this end, we assessed the effect of nanoencapsulation of capsaicin, under the hypothesis that this would reduce its pungency. Core-shell nanocapsules with an oily core and stabilized with phospholipids were used. This system was used with or without chitosan coati...

  5. In Vitro and Sensory Evaluation of Capsaicin-Loaded Nanoformulations

    OpenAIRE

    Kaiser, M.; Kirsch, B.; Hauser, H; Schneider, D; Seuß-Baum, I. (Ingrid); Goycoolea, F. M.

    2016-01-01

    Capsaicin has known health beneficial and therapeutic properties. It is also able to enhance the permeability of drugs across epithelial tissues. Unfortunately, due to its pungency the oral administration of capsaicin is limited. To this end, we assessed the effect of nanoencapsulation of capsaicin, under the hypothesis that this would reduce its pungency. Core-shell nanocapsules with an oily core and stabilized with phospholipids were used. This system was used with or without chitosan coati...

  6. Trigeminal Neuropathy in Sjogren′s Syndrome

    Directory of Open Access Journals (Sweden)

    Pinheiro L

    1999-01-01

    Full Text Available Trigeminal neuropathy is the most common CNS disorder in Sjogren′s syndrome. It is believed to be caused by vasculitis. Unless this is recognised, a diagnosis of trigeminal neuralgia is often made. The therapeutic response to steroids is unpredictable. There are two subgroups - those with associated collagen disorders and those only with the sicca syndrome.

  7. Trigeminal neuralgia in an HIV patient

    Directory of Open Access Journals (Sweden)

    Mohammad A Hashmi

    2010-01-01

    Full Text Available Trigeminal neuralgia is a painful condition affecting face. Its commonest cause is the tortuous vessels in prepontine cistern. There are other causes also, like brainstem lesions and mass lesions, as well as inflammatory causes. We present a case of an HIV patient with marked involvement of trigeminal nerves, which is a unique finding in immunocompromised patients.

  8. Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism.

    Science.gov (United States)

    Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

    2015-01-01

    Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands

  9. Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism.

    Directory of Open Access Journals (Sweden)

    Kiyoshi Matsuo

    Full Text Available Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically

  10. TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor.

    Science.gov (United States)

    Chen, Yong; Kanju, Patrick; Fang, Quan; Lee, Suk Hee; Parekh, Puja K; Lee, Whasil; Moore, Carlene; Brenner, Daniel; Gereau, Robert W; Wang, Fan; Liedtke, Wolfgang

    2014-12-01

    Detection of external irritants by head nociceptor neurons has deep evolutionary roots. Irritant-induced aversive behavior is a popular pain model in laboratory animals. It is used widely in the formalin model, where formaldehyde is injected into the rodent paw, eliciting quantifiable nocifensive behavior that has a direct, tissue-injury-evoked phase, and a subsequent tonic phase caused by neural maladaptation. The formalin model has elucidated many antipain compounds and pain-modulating signaling pathways. We have adopted this model to trigeminally innervated territories in mice. In addition, we examined the involvement of TRPV4 channels in formalin-evoked trigeminal pain behavior because TRPV4 is abundantly expressed in trigeminal ganglion (TG) sensory neurons, and because we have recently defined TRPV4's role in response to airborne irritants and in a model for temporomandibular joint pain. We found TRPV4 to be important for trigeminal nocifensive behavior evoked by formalin whisker pad injections. This conclusion is supported by studies with Trpv4(-/-) mice and TRPV4-specific antagonists. Our results imply TRPV4 in MEK-ERK activation in TG sensory neurons. Furthermore, cellular studies in primary TG neurons and in heterologous TRPV4-expressing cells suggest that TRPV4 can be activated directly by formalin to gate Ca(2+). Using TRPA1-blocker and Trpa1(-/-) mice, we found that both TRP channels co-contribute to the formalin trigeminal pain response. These results imply TRPV4 as an important signaling molecule in irritation-evoked trigeminal pain. TRPV4-antagonistic therapies can therefore be envisioned as novel analgesics, possibly for specific targeting of trigeminal pain disorders, such as migraine, headaches, temporomandibular joint, facial, and dental pain, and irritation of trigeminally innervated surface epithelia.

  11. Effect of inhaled procaterol on cough receptor sensitivity to capsaicin in patients with asthma or chronic bronchitis and in normal subjects.

    OpenAIRE

    Fujimura, M; Sakamoto, S.; Kamio, Y.; Bando, T.; Kurashima, K.; T. Matsuda

    1993-01-01

    BACKGROUND--To evaluate the effect of inhaled beta 2 adrenergic agonists on the sensitivity of airway cough receptors, the effect of inhaled procaterol on cough induced by aerosolised capsaicin, a stimulant of C fibres, was studied in patients with asthma or chronic bronchitis and in normal subjects. METHOD--Eleven patients with asthma and 10 with chronic bronchitis and 14 normal subjects participated. Increasing concentrations of capsaicin solution were inhaled for 15 seconds by tidal breath...

  12. Trigeminal neuralgia and facial pain imaging.

    Science.gov (United States)

    Graff-Radford, Steven; Gordon, Rachael; Ganal, John; Tetradis, Sotirois

    2015-06-01

    The trigeminal nerve or fifth cranial nerve has an extensive distribution in the head and face. It is the source for pain conduction and thereby is often implicated in a variety of disorders including inflammatory and neoplastic diseases. To determine the disease source, understanding the trigeminal nerve anatomy is essential, and further being able to image the trigeminal nerve provides insight into the location and type of pathology. The best approach to imaging is to consider the nerve in segments. The nerve segments may be divided into the brainstem, cisternal, Meckel's cave, cavernous sinus, and peripheral divisions. This review utilizes these segments to explore imaging options to help understand trigeminal neuralgia and pain in the trigeminal nerve distribution.

  13. Characterization of capsaicin synthase and identification of its gene (csy1) for pungency factor capsaicin in pepper (Capsicum sp.).

    Science.gov (United States)

    Prasad, B C Narasimha; Kumar, Vinod; Gururaj, H B; Parimalan, R; Giridhar, P; Ravishankar, G A

    2006-09-05

    Capsaicin is a unique alkaloid of the plant kingdom restricted to the genus Capsicum. Capsaicin is the pungency factor, a bioactive molecule of food and of medicinal importance. Capsaicin is useful as a counterirritant, antiarthritic, analgesic, antioxidant, and anticancer agent. Capsaicin biosynthesis involves condensation of vanillylamine and 8-methyl nonenoic acid, brought about by capsaicin synthase (CS). We found that CS activity correlated with genotype-specific capsaicin levels. We purified and characterized CS ( approximately 35 kDa). Immunolocalization studies confirmed that CS is specifically localized to the placental tissues of Capsicum fruits. Western blot analysis revealed concomitant enhancement of CS levels and capsaicin accumulation during fruit development. We determined the N-terminal amino acid sequence of purified CS, cloned the CS gene (csy1) and sequenced full-length cDNA (981 bp). The deduced amino acid sequence of CS from full-length cDNA was 38 kDa. Functionality of csy1 through heterologous expression in recombinant Escherichia coli was also demonstrated. Here we report the gene responsible for capsaicin biosynthesis, which is unique to Capsicum spp. With this information on the CS gene, speculation on the gene for pungency is unequivocally resolved. Our findings have implications in the regulation of capsaicin levels in Capsicum genotypes.

  14. Reciprocal effects of capsaicin and menthol on thermosensation through regulated activities of TRPV1 and TRPM8.

    Science.gov (United States)

    Takaishi, Masayuki; Uchida, Kunitoshi; Suzuki, Yoshiro; Matsui, Hiroshi; Shimada, Tadashi; Fujita, Fumitaka; Tominaga, Makoto

    2016-03-01

    Transient receptor potential vanilloid 1 (TRPV1) is activated by elevated temperature (>42 °C), and it has been reported that cold temperature decreases capsaicin-induced TRPV1 activity. In contrast, transient receptor potential melastatin 8 (TRPM8) is activated by low temperatures and menthol, and heat stimulation suppresses menthol-evoked TRPM8 currents. These findings suggest that the effects of specific agents on TRPV1 and TRPM8 channels are intricately interrelated. We examined the effects of menthol on human (h)TRPV1 and of capsaicin on hTRPM8. hTRPV1 currents activated by heat and capsaicin were inhibited by menthol, whereas hTRPM8 currents activated by cold and menthol were similarly inhibited by capsaicin. An in vivo sensory irritation test showed that menthol conferred an analgesic effect on the sensory irritation evoked by a capsaicin analogue. These results indicate that in our study the agonists of TRPV1 and TRPM8 interacted with both of these channels and suggest that the anti-nociceptive effects of menthol can be partially explained by this phenomenon.

  15. Transient activation of specific neurons in mice by selective expression of the capsaicin receptor

    Science.gov (United States)

    Güler, Ali D.; Rainwater, Aundrea; Parker, Jones G.; Jones, Graham L.; Argilli, Emanuela; Arenkiel, Benjamin R.; Ehlers, Michael D.; Bonci, Antonello; Zweifel, Larry s.; Palmiter, Richard D.

    2013-01-01

    The ability to control the electrical activity of a neuronal subtype is a valuable tool in deciphering the role of discreet cell populations in complex neural circuits. Recent techniques that allow remote control of neurons are either labor intensive and invasive or indirectly coupled to neural electrical potential with low temporal resolution. Here we show the rapid, reversible and direct activation of genetically identified neuronal subpopulations by generating two inducible transgenic mouse models. Confined expression of the capsaicin receptor, TRPV1, allows cell-specific activation after peripheral or oral delivery of ligand in freely moving mice. Capsaicin-induced activation of dopaminergic or serotonergic neurons reversibly alters both physiological and behavioural responses within minutes, and lasts ~10 min. These models showcase a robust and remotely controllable genetic tool that modulates a distinct cell population without the need for invasive and labour-intensive approaches. PMID:22434189

  16. Capsaicin failed in suppressing cortical processing of CO2 laser pain in migraine patients.

    Science.gov (United States)

    de Tommaso, Marina; Losito, Luciana; Difruscolo, Olimpia; Sardaro, Michele; Libro, Giuseppe; Guido, Marco; Lamberti, Paolo; Livrea, Paolo

    The aim of this study was to compare the properties of the nociceptive system in eight migraine without aura patients in the pain-free phase with 10 healthy controls, by evaluating the topography and the source of the CO2 laser-evoked potentials (LEPs) obtained by the right supraorbital skin, during and after capsaicin topical application. In healthy subjects the acute cutaneous pain induced by capsaicin reduced the amplitude of the vertex LEPs and induced a posterior shifting of the P2 wave dipolar source within the anterior cingulate cortex. These functional changes seemed significantly reduced in migraine patients, for a disturbed pattern of pain modulation at the cortical level, which may subtend the onset and persistence of migraine.

  17. Antimicrobial and anti-virulence activity of capsaicin against erythromycin-resistant, cell-invasive Group A streptococci

    Directory of Open Access Journals (Sweden)

    Emanuela eMarini

    2015-11-01

    Full Text Available Capsaicin (8-methyl-N-vanillyl-6-nonenamide is the active component of Capsicum plants (chilli peppers, which are grown as food and for medicinal purposes since ancient times, and is responsible for the pungency of their fruit. Besides its multiple pharmacological and physiological properties (pain relief, cancer prevention, and beneficial cardiovascular, and gastrointestinal effects capsaicin has recently attracted considerable attention because of its antimicrobial and anti-virulence activity. This is the first study of its in vitro antibacterial and anti-virulence activity against Streptococcus pyogenes [Group A streptococci (GAS], a major human pathogen. The test strains were previously characterized, erythromycin-susceptible (n=5 and erythromycin-resistant (n=27, cell-invasive pharyngeal isolates. The MICs of capsaicin were 64-128 μg/mL (the most common MIC was 128 µg/mL. The action of capsaicin was bactericidal, as suggested by MBC values that were equal or close to the MICs, and by early detection of dead cells in the live/dead assay. No capsaicin-resistant mutants were obtained in single-step resistance selection studies. Interestingly, growth in presence of sublethal capsaicin concentrations induced an increase in biofilm production (p ≤ 0.05 and in the number of bacteria adhering to A549 monolayers, and a reduction in cell-invasiveness and haemolytic activity (both p ≤ 0.05. Cell invasiveness fell so dramatically that a highly invasive strain became non-invasive. The dose-response relationship, characterized by opposite effects of low and high capsaicin doses, suggests a hormetic response. The present study documents that capsaicin has promising bactericidal activity against erythromycin-resistant, cell-invasive pharyngeal GAS isolates. The fact that sublethal concentrations inhibited cell invasion and reduced haemolytic activity, two important virulence traits of GAS, is also interesting, considering that cell

  18. In Vitro and Sensory Evaluation of Capsaicin-Loaded Nanoformulations.

    Directory of Open Access Journals (Sweden)

    Mathias Kaiser

    Full Text Available Capsaicin has known health beneficial and therapeutic properties. It is also able to enhance the permeability of drugs across epithelial tissues. Unfortunately, due to its pungency the oral administration of capsaicin is limited. To this end, we assessed the effect of nanoencapsulation of capsaicin, under the hypothesis that this would reduce its pungency. Core-shell nanocapsules with an oily core and stabilized with phospholipids were used. This system was used with or without chitosan coating. In this work, we investigated the in vitro release behavior of capsaicin-loaded formulations in different physiological media (including simulated saliva fluid. We also evaluated the influence of encapsulation of capsaicin on the cell viability of buccal cells (TR146. To study the changes in pungency after encapsulation we carried out a sensory analysis with a trained panel of 24 students. The in vitro release study showed that the systems discharged capsaicin slowly in a monotonic manner and that the chitosan coating had an effect on the release profile. The cytotoxic response of TR146 cells to capsaicin at a concentration of 500 μM, which was evident for the free compound, was reduced following its encapsulation. The sensory study revealed that a chitosan coating results in a lower threshold of perception of the formulation. The nanoencapsulation of capsaicin resulted in attenuation of the sensation of pungency significantly. However, the presence of a chitosan shell around the nanoformulations did not mask the pungency, when compared with uncoated systems.

  19. In Vitro and Sensory Evaluation of Capsaicin-Loaded Nanoformulations.

    Science.gov (United States)

    Kaiser, Mathias; Kirsch, Benedikt; Hauser, Hannah; Schneider, Désirée; Seuß-Baum, Ingrid; Goycoolea, Francisco M

    2015-01-01

    Capsaicin has known health beneficial and therapeutic properties. It is also able to enhance the permeability of drugs across epithelial tissues. Unfortunately, due to its pungency the oral administration of capsaicin is limited. To this end, we assessed the effect of nanoencapsulation of capsaicin, under the hypothesis that this would reduce its pungency. Core-shell nanocapsules with an oily core and stabilized with phospholipids were used. This system was used with or without chitosan coating. In this work, we investigated the in vitro release behavior of capsaicin-loaded formulations in different physiological media (including simulated saliva fluid). We also evaluated the influence of encapsulation of capsaicin on the cell viability of buccal cells (TR146). To study the changes in pungency after encapsulation we carried out a sensory analysis with a trained panel of 24 students. The in vitro release study showed that the systems discharged capsaicin slowly in a monotonic manner and that the chitosan coating had an effect on the release profile. The cytotoxic response of TR146 cells to capsaicin at a concentration of 500 μM, which was evident for the free compound, was reduced following its encapsulation. The sensory study revealed that a chitosan coating results in a lower threshold of perception of the formulation. The nanoencapsulation of capsaicin resulted in attenuation of the sensation of pungency significantly. However, the presence of a chitosan shell around the nanoformulations did not mask the pungency, when compared with uncoated systems.

  20. Glial involvement in trigeminal central sensitization

    Institute of Scientific and Technical Information of China (English)

    Yu-feng XIE

    2008-01-01

    Recent studies have indicated that trigeminal neurons exhibit central sensitization, an increase in the excitability of neurons within the central nervous system to the extent that a normally innocuous stimulus begins to produce pain after inflamma-tion or injury, and that glial activities play a vital role in this central sensitization. The involvement of glial cells in trigeminal central sensitization contains multiple mechanisms, including interaction with glutamatergic and purinergic receptors. A better understanding of the trigeminal central sensitization mediated by glial cells will help to find potential therapeutic targets and lead to developing new analge-sics for orofacial-specific pain with higher efficiency and fewer side-effects.

  1. Trigeminal neuromas: Assessment of MRI and CT

    Energy Technology Data Exchange (ETDEWEB)

    Beges, C.; Revel, M.P.; Gaston, A.; Brugieres, P. (Dept. of Neuroradiology, Hopital Henri Mondor, Creteil (France)); Meder, J.F. (Dept. of Neuroradiology, Hopital Sainte Anne, Paris (France)); Martin, N. (Dept. of Neuroradiology, Hopital de la Pitie-Salpetriere, Paris (France))

    1992-06-01

    We report four cases of trigeminal neuroma. One of the patients had von Recklinghausen's neurofibromatosis with plexiform neurofibromas of the branches of the trigeminal nerve. MRI provided more information than CT as regards the spread of tumor: extension to the mandibular and maxillary division of the trigeminal nerve was well demonstrated on sagittal and coronal sections. This examination yielded an accurate census of the intraocular plexiform neurofibromas and allowed a correct preoperative diagnosis to be obtained. With Gd-DOTA, better definition of the outline of the tumours and of cystic components was obtained. However, CT was better for demonstration of bone erosions. (orig.).

  2. Overview and History of Trigeminal Neuralgia.

    Science.gov (United States)

    Patel, Smruti K; Liu, James K

    2016-07-01

    Although the symptoms associated with trigeminal neuralgia have been well documented, the root cause of this disease initially eluded most surgeons. Although early remedies were haphazard because of a lack of understanding about the condition, near the 20th century both medical and procedural therapies were established for the treatment of trigeminal neuralgia. These treatments include a variety of medications, chemoneurolysis, radiofrequency lesioning, percutaneous ablative procedures, stereotactic radiosurgery, and open rhizotomy and microvascular decompression. This report recounts the history of trigeminal neuralgia, from its earliest descriptions to the historical evolution of nonsurgical and surgical therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Separation of capsaicin from capsaicinoids by macroporous resin adsorption chromatography.

    Science.gov (United States)

    Liu, Changxia; Liu, Ruican; Zhang, Peng; Chen, Yiming; Xu, Tao; Wang, Fang; Tan, Tianwei; Liu, Chunqiao

    2015-12-01

    The aim of present study is to develop an efficient and low-cost method for capsaicin production isolated from capsaicinoids by macroporous resin adsorption chromatography. HZ816 resin has shown the best adsorption and desorption capacities for capsaicin among other resins. To optimize the operating parameters for separation, initial concentration, diameter-to-height ratio, mobile phase ratio, and crystallization method were investigated. When capsaicinoids solution (5 g/L) was loaded onto the column (diameter-to-height ratio = 1:12) with ethanol/1% w/w NaOH (4:6, v/v) as the mobile phase, capsaicin was purified most effectively. By using acid neutralization as the crystallization method, the purity of capsaicin improved from 90.3 to 99.5% with 82.3% yield. In conclusion, this study provides a simple and low-cost method for the industrial-scale production of high-purity capsaicin.

  4. TRIGEMINAL UPTAKE AND CLEARANCE OF INHALED MANGANESECHLORIDE IN RATS AND MICE

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, J; Bench, G; Myers, O; Tinner, B; Staines, W; Barr, E; Divine, K K; Barrington, W; Karlsson, J

    2003-12-09

    Inhaled manganese (Mn) can enter the olfactory bulbs via the olfactory epithelium, and can then be further transported trans-synaptically to deeper brain structures. In addition to olfactory neurons, the nasal cavity is innervated by the maxillary division of the trigeminal nerve that projects to the spinal trigeminal nucleus. Direct uptake and transport of inhaled metal particles in the trigeminal system has not been investigated previously. We studied the uptake, deposition, and clearance of soluble Mn in the trigeminal system following nose-only inhalation of environmentally relevant concentrations. Rats and mice were exposed for 10 days (6 hours/day, 5 days/week) to air or MnCl2 aerosols containing 2.3 {+-} 1.3mg Mn/m{sup 3} with mass median aerodynamic diameter (MMAD) of 3.1 {+-} 1.4 {micro}m for rats and 2.0 {+-} 0.09 mg Mn/m{sup 3} MnCl{sup 2} with MMAD of 1.98 {+-} 0.12 {micro}m for mice. Mn concentrations in the trigeminal ganglia and spinal trigeminal nucleus were measured 2 hours (0 day), 7, 14, or 30 days post-exposure using Proton Induced X-ray Emission (PIXE). Manganese-exposed rats and mice showed statistically elevated levels of Mn in trigeminal ganglia 0, 7 and 14 days after the 10 day exposure period when compared to control animals. The Mn concentration gradually decreased over time with a clearance rate (t{sub 1/2}) of 7-8 days. Rats and mice were similar in both average accumulated Mn levels in trigeminal ganglia and in rates of clearance. We also found a small but significant elevation of Mn in the spinal trigeminal nucleus of mice 7 days post-exposure and in rats 0 and 7 days post-exposure. Our data demonstrate that the trigeminal nerve can serve as a pathway for entry of inhaled Mn to the brain in rodents following nose-only exposure and raise the question of whether entry of toxicants via this pathway may contribute to development of neurodegenerative diseases.

  5. [Aural Stimulation with Capsaicin Ointment Improved the Swallowing Function in Patients with Dysphagia: Evaluation by the SMRC Scale].

    Science.gov (United States)

    Kondo, Eiji; Jinnouchi, Osamu; Ohnishi, Hiroki; Kawata, Ikuji; Takeda, Noriaki

    2015-11-01

    Cough and swallowing reflexes are important airway-protective mechanisms against aspiration. Angiotensin-converting enzyme (ACE) inhibitors, one of the side effects of which is cough, have been reported to reduce the incidence of aspiration pneumonia in hypertensive patients with stroke. ACE inhibitors have also been reported to improve the swallowing function in post-stroke patients. On the other hand, stimulation of the Arnold nerve, the auricular branch of the vagus, triggers the cough reflex (Arnold's ear-cough reflex). Capsaicin, an agonist of Transient Receptor Potential Vanilloid 1 (TRPV1), has been shown to activate the peripheral sensory C-fibers. Stimulation of the sensory branches of the vagus in the laryngotracheal mucosa with capsaicin induces the cough reflex and has been reported to improve the swallowing function in patients with dysphagia. In our previous study, we showed that aural stimulation of the Arnold nerve with 0.025% capsaicin ointment improved the swallowing function, as evaluated by the endoscopic swallowing score, in 26 patients with dysphagia. In the present study, the video images of swallowing recorded in the previous study were re-evaluated using the SMRC scale by an independent otolaryngologist who was blinded to the information about the patients and the endoscopic swallowing score. The SMRC scale is used to evaluate four aspects of the swallowing function: 1) Sensory: the initiation of the swallowing reflex as assessed by the white-out timing; 2) Motion: the ability to hold blue-dyed water in the oral cavity and induce laryngeal elevation; 3) Reflex: glottal closure and the cough reflex induced by touching the epiglottis or arytenoid with the endoscope; 4) Clearance: pharyngeal clearance of the blue-dyed water after swallowing. Accordingly, we demonstrated that a single application of capsaicin ointment to the external auditory canal of patients with dysphagia significantly improved the R, but not the S, M or C scores, and this

  6. Central effect of histamine in a rat model of acute trigeminal pain.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Khalilzadeh, Emad; Hamzeh-Gooshchi, Nasrin; Seiednejhad-Yamchi, Sona

    2008-01-01

    In conscious rats implanted with an intracerebroventricular (icv) cannula, effect of icv injections of histamine, chlorpheniramine (H(1)-receptor antagonist) and ranitidine (H(2)-receptor blocker) was investigated in a rat model of acute trigeminal pain. Acute trigeminal pain was induced by putting a drop of 5 M NaCl solution on the corneal surface of the eye and the numbers of eye wipes were counted during the first 30 s. Histamine (20, 40 microg) and chlorpheniramine (80 microg) significantly decreased the numbers of eye wipes. Ranitidine alone had no effect. Pretreatment with chlorpheniramine did not change the histamine-induced analgesia, whereas the histamine effect on pain was inhibited with ranitidine pretreatment. These results indicate that the brain histamine, through central H(2) receptors, may be involved in the modulation of the acute trigeminal pain in rats.

  7. Chemosensory properties of the trigeminal system.

    Science.gov (United States)

    Viana, Félix

    2011-01-19

    The capacity of cutaneous, including trigeminal endings, to detect chemicals is known as chemesthesis or cutaneous chemosensation. This sensory function involves the activation of nociceptor and thermoreceptor endings and has a protective or defensive function, as many of these substances are irritants or poisonous. However, humans have also developed a liking for the distinct sharpness or pungency of many foods, beverages, and spices following activation of the same sensory afferents. Our understanding of the cellular and molecular mechanisms of chemosensation in the trigeminal system has experienced enormous progress in the past decade, following the cloning and functional characterization of several ion channels activated by physical and chemical stimuli. This brief review attempts to summarize our current knowledge in this field, including a functional description of various sensory channels, especially TRP channels, involved in trigeminal chemosensitivy. Finally, some of these new findings are discussed in the context of the pathophysiology of trigeminal chemosensation, including pain, pruritus, migraine, cough, airway inflammation, and ophthalmic diseases.

  8. Trigeminal neuralgia: report of 3 cases

    Energy Technology Data Exchange (ETDEWEB)

    Park, Geum Mee; Ki, Joo Yeon; Cho, Bong Hae; Nah, Kyung Soo [College of Dentistry, Pusan National University, Pusan (Korea, Republic of)

    2002-03-15

    Orofacial pain can be caused by intracranial disorders or can be musculoskeletal, vascular, internal derangemental, and neurologic in origin. The neurologic pain is derived from structural and functional disorders of nerve, and the trigeminal neuralgia is the typical manifestation. Trigeminal neuralgia is known from centuries ago, and is one of the most common pains in human. We present our experience with three patients who have trigeminal neuralgia. The first case is a 50-year-old female who had no specific evidence radiographically. Second is a 50-year-old male with microvascular compression on right trigeminal nerve. The third case is a 60-year-old female who had a neoplasm in cerebellopontine angle with associated mass effect.

  9. Stereotactic Radiosurgery for Classical Trigeminal Neuralgia

    Directory of Open Access Journals (Sweden)

    Henry Kodrat

    2016-04-01

    Full Text Available Trigeminal neuralgia is a debilitating pain syndrome with a distinct symptom mainly excruciating facial pain that tends to come and go unpredictably in sudden shock-like attacks. Medical management remains the primary treatment for classical trigeminal neuralgia. When medical therapy failed, surgery with microvascular decompression can be performed. Radiosurgery can be offered for classical trigeminal neuralgia patients who are not surgical candidate or surgery refusal and they should not in acute pain condition. Radiosurgery is widely used because of good therapeutic result and low complication rate. Weakness of this technique is a latency period, which is time required for pain relief. It usually ranges from 1 to 2 months. This review enlightens the important role of radiosurgery in the treatment of classical trigeminal neuralgia.

  10. Trigeminal trophic syndrome: A rare entity

    Directory of Open Access Journals (Sweden)

    Sunil N Mishra

    2011-01-01

    Full Text Available Trigeminal trophic syndrome is a rare condition resulting from self-manipulation of the skin after a peripheral or central injury to the trigeminal system. The syndrome consists of a classic triad of anaesthesia, paraesthesia, and a secondary persistent or recurrent facial ulceration. We describe a 60 year-old woman who developed this syndrome as a sequel to the gasserian ganglion block for trigeminal neuralgia. She had also developed melasma within 1 year. A remarkable benefit was achieved by proper patient education and topical antibiotics which led to the healing of all ulcerations within 4 weeks. In the case reported here, the diagnosis of the trigeminal trophic syndrome was made primarily as a result of the physician′s experience with the syndrome previously.

  11. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch

    Science.gov (United States)

    Anand, P.; Bley, K.

    2011-01-01

    Summary Topical capsaicin formulations are used for pain management. Safety and modest efficacy of low-concentration capsaicin formulations, which require repeated daily self-administration, are supported by meta-analyses of numerous studies. A high-concentration capsaicin 8% patch (Qutenza™) was recently approved in the EU and USA. A single 60-min application in patients with neuropathic pain produced effective pain relief for up to 12 weeks. Advantages of the high-concentration capsaicin patch include longer duration of effect, patient compliance, and low risk for systemic effects or drug–drug interactions. The mechanism of action of topical capsaicin has been ascribed to depletion of substance P. However, experimental and clinical studies show that depletion of substance P from nociceptors is only a correlate of capsaicin treatment and has little, if any, causative role in pain relief. Rather, topical capsaicin acts in the skin to attenuate cutaneous hypersensitivity and reduce pain by a process best described as ‘defunctionalization’ of nociceptor fibres. Defunctionalization is due to a number of effects that include temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fibre terminals. Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms, including altered expression of the capsaicin receptor TRPV1 or other key ion channels in affected or intact adjacent peripheral nociceptive nerve fibres, aberrant re-innervation, and collateral sprouting, all of which are defunctionalized by topical capsaicin. Evidence suggests that the utility of topical capsaicin may extend beyond painful peripheral neuropathies. PMID:21852280

  12. Trigemino-cardiac reflex during microvascular trigeminal decompression in cases of trigeminal neuralgia.

    Science.gov (United States)

    Schaller, Bernhard

    2005-01-01

    The trigemino-cardiac reflex (TCR) is a well-recognized phenomenon consisting of bradycardia, arterial hypotension, apnea, and gastric hypermotility during ocular surgery or other manipulations in and around the orbit. Thus far, it could bee shown that central stimulation of the trigeminal nerve during transsphenoidal surgery and surgery for tumors in the cerebellopontine angle can lead to TCR. In cases of microvascular trigeminal decompression for trigeminal neuralgia, no data of the possible occurrence of TCR are available. TCR was defined as a drop in mean arterial blood pressure (MABP) and the heart rate (HR) of more than 20% to the baseline values before the stimulus and coinciding with the manipulation of the trigeminal nerve. Electronic anesthetic recorded perioperative HR and MABP values were reviewed retrospectively in 28 patients who received microvascular trigeminal decompression in cases of trigeminal neuralgia and were divided into two subgroups on the basis of occurrence of TCR during surgery. Of the 28 patients, 5 (18%) showed evidence of TCR during manipulation at the trigeminal radix by separation from microvascular structures. Their HR fell 46% and their MABP 57% during operative procedures near the trigeminal nerve as compared with levels immediately before the stimulus. After cessation of manipulation, HR and MABP returned (spontaneously) to levels before the stimulus. Risk factors of TCR were compared with results from the literature. In conclusion, the present results give evidence of TCR during manipulation of the central part of the trigeminal nerve during microvascular trigeminal decompression in cases of trigeminal neuralgia under a standardized anesthetic protocol.

  13. Aging of the trigeminal blink system.

    Science.gov (United States)

    Peshori, K R; Schicatano, E J; Gopalaswamy, R; Sahay, E; Evinger, C

    2001-02-01

    This study characterizes trigeminal blinks in normal human subjects between 20 and 80 years of age, 60-year-old Parkinson's disease patients, and young and old guinea pigs. In normal humans over 60 years of age, lid-closing duration, and the excitability and latency of the trigeminal reflex blink increase significantly relative to younger subjects. Aged guinea pigs appear to display similar increases in reflex blink duration and latency. Reflex blink amplitude, however, does not change consistently with age. For subjects less than 70 years of age, a unilateral trigeminal stimulus evokes a 37% larger blink in the eyelid ipsilateral to the stimulus than in the contralateral eyelid, but 70-year-olds exhibit blinks of equal amplitude. In all cases, blink duration is identical for the two eyelids. If normal, age-related loss of dopamine neurons explains these trigeminal blink modifications, then Parkinson's disease should exaggerate age-related changes in these blink parameters. Preliminary data show that Parkinson's disease increases blink duration and excitability relative to age-matched control subjects. Thus, it seems likely that normal, age-related loss of dopamine neurons accounts for increases in trigeminal blink excitability and duration. A previously uncharacterized type of trigeminally evoked blink appears after age 40 in humans and in aged guinea pigs. In subjects less than 40 years old, a single trigeminal stimulus elicits a single reflex blink. In subjects over age 40, however, a single stimulus frequently evokes a reflex blink and additional blinks that occur at a fixed interval relative to the preceding blink. These "blink oscillations" may arise from oscillatory processes within trigeminal reflex blink circuits. The presence of exaggerated blink oscillations in subjects with dry eye and benign essential blepharospasm suggests that an alteration of blink oscillation mechanisms plays a critical role in these disorders.

  14. Sleep in trigeminal autonomic cephalagias

    DEFF Research Database (Denmark)

    Barløse, Mads; Lund, Nunu; Jensen, Rigmor Højland

    2014-01-01

    PURPOSE OF REVIEW: Sleep and cluster headache (CH) are believed to be interconnected but the precise relation to the other trigeminal autonomic cephalalgias (TACs) is uncertain and complex. A better understanding of these relations may eventually lead to a clarification of the underlying mechanisms...... and eventually to more effective therapeutic regimens. This review aims to evaluate the existing literature on the subject of TACs and sleep. An association between episodic CH and distinct macrostructural sleep phases, especially the relation to rapid eye movement (REM) sleep, has been described in some older...... studies but could not be confirmed in other, more recent studies. Investigations into the microstructure of sleep in these patients are lacking. Only a few case reports exist on the relation between sleep and other TACs. SUMMARY: Recent studies do not find an association between CH and REM sleep. One...

  15. Treatment options in trigeminal neuralgia

    Science.gov (United States)

    Obermann, Mark

    2010-01-01

    The incidence of trigeminal neuralgia (TN) is 4.3 per 100,000 persons per year, with a slightly higher incidence for women (5.9/100,000) compared with men (3.4/100,000). There is a lack of certainty regarding the aetiology and pathophysiology of TN. The treatment of TN can be very challenging despite the numerous options patients and physicians can choose from. This multitude of treatment options poses the question as to which treatment fits which patient best. The preferred medical treatment for TN consists of anticonvulsant drugs, muscle relaxants and neuroleptic agents. Large-scale placebo-controlled clinical trials are scarce. For patients refractory to medical therapy, Gasserian ganglion percutaneous techniques, gamma knife surgery and microvascular decompression are the most promising invasive treatment options. PMID:21179603

  16. An exploration of the estrogen receptor transcription activity of capsaicin analogues via an integrated approach based on in silico prediction and in vitro assays.

    Science.gov (United States)

    Li, Juan; Ma, Duo; Lin, Yuan; Fu, Jianjie; Zhang, Aiqian

    2014-06-16

    Capsaicin has been considered as an alternative template of dichlorodiphenyl trichloroethane (DDT) in antifouling paint. However, information regarding the estrogenic activity of capsaicin analogues is rather limited in comparison to that of DDT analogues and their metabolites. We here explore the ER transcription activity of selected capsaicin analogues via an integrated approach based on in silico prediction and in vitro assays. Molecular simulation and the agonist/antagonist differential-docking screening identified 6-iodonordihydrocapsaicin (6-I-CPS) as a weak ERα agonist, while anti-estrogenicity was expected for N-arachidonoyldopamine, capsazepine, dihydrocapsaicin, trichostatin A, and capsaicin. On the contrary, the large volume of analogues, such as phorbol 12-phenylacetate 13-acetate 20-homovanillate and phorbol 12,13-dinonanoate 20-homovanillate, cannot fit well with the ER cavity. The result of MVLN assay was in accord with the in silico prediction. 6-I-CPS was demonstrated to induce luciferase gene expression, while the other analogues of relatively small molecular volume reduced luciferase gene expression in MVLN cells, both in the absence and presence of estradiol. This finding suggested that the ER transcription activity of capsaicin analogues is generated at least partly through the ERα-mediated pathway. Moreover, receptor polymorphism analysis indicated that capsaicin analogues may exhibit diverse species selectivity for human beings and marine species.

  17. Percutaneous microballoon compression for trigeminal neuralgia

    Institute of Scientific and Technical Information of China (English)

    LIU Hong-bing; MA Yi; ZOU Jian-jun; LI Xin-gang

    2007-01-01

    Background Percutaneous microballoon compression (PMC) for trigeminal neuralgia is an important therapeutic method. The aim of this study was to review the effects of PMC for trigeminal neuralgia in 276 patients.Methods From December 2000 to May 2003, 276 patients with trigeminal neuralgia were treated with PMC. The course of the disease ranged from 3 months to 38 years. Under the guidance of C-arm X-ray, 14# needle was placed into the foramen ovale using the classical Hakanson's technique. Fogarty balloon catheter was navigated into the Meckel's cave tenderly. A small amount of Omnipaque was slowly injected to inflate the balloon and compress the trigeminal ganglion for 3 to10 minutes.Results A total of 290 PMC were performed on the 276 patients. Among them, 252 had immediate relief from pain. The patients were followed up for a mean of 18.7 months (range, 4 to 32), 14 of them had a recurrence. Of the 14 patients, 12 were re-operated with PMC, and the pain was all controlled successfully.Conclusions PMC is an effective and technically simple method for trigeminal neuralgia. For older patients with trigeminal neuralgia, it may be the first choice.

  18. Capsaicin and menthol in the treatment of itch and pain: recently cloned receptors provide the key

    OpenAIRE

    Anand, P.

    2003-01-01

    Topical capsaicin is reported to be an effective treatment for idiopathic intractable pruritis ani. While both capsaicin and menthol application produce a transient perianal burning sensation, only capsaicin relieves itching. Classical observations on functional desensitisation of nociceptors by capsaicin may explain the beneficial effects but the recent discovery of a range of receptors which respond to capsaicin, menthol, and temperature, and their expression in subsets of sensory nerve fib...

  19. Capsaicin 8 % Patch: A Review in Peripheral Neuropathic Pain.

    Science.gov (United States)

    Burness, Celeste B; McCormack, Paul L

    2016-01-01

    The capsaicin 8 % patch (QUTENZA®) is an adhesive patch containing a high concentration (8 % w/w) of synthetic capsaicin, a selective agonist of transient receptor potential vanilloid 1 channel. It is approved for treatment of peripheral neuropathic pain in adults either alone or in combination with other medicinal products for pain in the EU; it is only approved to treat postherpetic neuralgia (PHN) in the USA. In patients with painful diabetic peripheral neuropathy (PDPN), a single 30-min application of the capsaicin 8 % patch significantly improved pain relief and sleep quality compared with placebo in a 12-week double-blind trial. In a 52-week, randomized trial, up to seven consecutive 30-min treatments with the capsaicin 8 % patch (≤7 treatments each at least 8 weeks apart) plus standard of care therapy was associated with sustained pain relief and no negative neurological safety consequences compared with standard of care. In two randomized trials, a single 60-min application of the capsaicin 8 % patch reduced pain scores significantly more than a low-concentration (0.04 %) capsaicin control patch in patients with PHN. Capsaicin 8 % patch treatment was noninferior to pregabalin (optimized dosage) in a randomized trial in patients with nondiabetic peripheral neuropathic pain. Results in two trials in patients with HIV-AN were equivocal, with a significant improvement in pain intensity observed in one trial, but not in the other. The capsaicin 8 % patch was associated with expected, transient, capsaicin-related application-site adverse events such as erythema and pain.

  20. Antagonistic and Synergistic Activation of Cardiovascular Vagal and Sympathetic Motor Outflows in Trigeminal Reflexes.

    Science.gov (United States)

    Buchholz, Bruno; Kelly, Jazmín; Bernatene, Eduardo A; Méndez Diodati, Nahuel; Gelpi, Ricardo J

    2017-01-01

    The trigeminal nerve and heart are strongly related through somato-autonomic nervous reflexes that induce rapid changes in cardiovascular function. Several trigeminal reflexes have been described, but the diving and trigeminocardiac reflexes are the most studied. The heart is a target organ dually innervated by the sympathetic and parasympathetic systems. Thus, how cardiac function is regulated during the trigeminal reflexes is the result of the combination of an increased parasympathetic response and increased, decreased, or unaltered sympathetic activity. Various hemodynamic changes occur as a consequence of these alterations in autonomic tone. Often in the oxygen-conserving physiological reflexes such as the diving reflex, sympathetic/parasympathetic co-activation reduces the heart rate and either maintains or increases blood pressure. Conversely, in the trigeminocardiac reflex, bradycardia and hypotension due to parasympathetic activation and sympathetic inactivation tend to be observed. These sudden cardiac innervation disturbances may promote the generation of arrhythmias or myocardial ischemia during surgeries in the trigeminal territory. However, the function and mechanisms involved in the trigeminal reflexes remain to be fully elucidated. The current review provides a brief update and analysis of the features of these reflexes, with special focus on how the autonomic nervous system interacts with cardiovascular function.

  1. Trigeminal cardiac reflex and cerebral blood flow regulation

    Directory of Open Access Journals (Sweden)

    Dominga Lapi

    2016-10-01

    Full Text Available The stimulation of some facial regions is known to trigger the trigemino-cardiac reflex: the main stimulus is represented by the contact of the face with water. This phenomenon called diving reflex induces a set of reactions in the cardiovascular and respiratory systems occurring in all mammals, especially marine (whales, seals. During the immersion of the face in the water, the main responses are aimed at reducing the oxygen consumption of the organism. Accordingly reduction in heart rate, peripheral vasoconstriction, blood pooling in certain organs, especially the heart and brain, and an increase in blood pressure have been reported. Moreover, the speed and intensity of the reflex is inversely proportional to the temperature of the water: more cold the water, more reactions as described are strong. In the case of deep diving an additional effect, such as blood deviation, has been reported: the blood is requested within the lungs, to compensate for the increase in the external pressure, preventing them from collapsing.The trigeminal-cardiac reflex is not just confined to the diving reflex; recently it has been shown that a brief proprioceptive stimulation (10 min by jaw extension in rats produces interesting effects both at systemic and cerebral level, reducing the arterial blood pressure and vasodilating the pial arterioles. The arteriolar dilation is associated with rhythmic diameter changes characterized by an increase in the endothelial activity. Fascinating the stimulation of trigeminal nerve is able to activated the nitric oxide release by vascular endothelial. Therefore the aim of this review was to highlight the effects due to trigeminal cardiac reflex induced by a simple mandibular extension, because produced opposite effects compared to those elicited by the diving reflex as it induces hypotension and modulation of cerebral arteriolar tone.

  2. RNA sequencing of trigeminal ganglia in Rattus Norvegicus after glyceryl trinitrate infusion with relevance to migraine

    DEFF Research Database (Denmark)

    Pedersen, Sara Hougaard; Sørensen, Lasse Maretty; Ramachandran, Roshni

    2016-01-01

    transcriptional responses to GTN-infusion in the rat trigeminal ganglia. METHODS: Rats were infused with GTN or vehicle and trigeminal ganglia were isolated either 30 or 90 minutes post infusion. RNA sequencing was used to investigate transcriptomic changes in response to the treatment. Furthermore, we developed......INTRODUCTION: Infusion of glyceryl trinitrate (GTN), a donor of nitric oxide, induces immediate headache in humans that in migraineurs is followed by a delayed migraine attack. In order to achieve increased knowledge of mechanisms activated during GTN-infusion this present study aims to investigate...

  3. The selective target of capsaicin on FASN expression and de novo fatty acid synthesis mediated through ROS generation triggers apoptosis in HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Hathaichanok Impheng

    Full Text Available The inhibition of the mammalian de novo synthesis of long-chain saturated fatty acids (LCFAs by blocking the fatty acid synthase (FASN enzyme activity in tumor cells that overexpress FASN can promote apoptosis, without apparent cytotoxic to non-tumor cells. The present study aimed to focus on the potent inhibitory effect of capsaicin on the fatty acid synthesis pathway inducing apoptosis of capsaicin in HepG2 cells. The use of capsaicin as a source for a new FASN inhibitor will provide new insight into its possible application as a selective anti-cancer therapy. The present findings showed that capsaicin promoted apoptosis as well as cell cycle arrest in the G0/G1 phase. The onset of apoptosis was correlated with a dissipation of mitochondrial membrane potential (ΔΨm. Apoptotic induction by capsaicin was mediated by inhibition of FASN protein expression which was accompanied by decreasing its activity on the de novo fatty acid synthesis. The expression of FASN was higher in HepG2 cells than in normal hepatocytes that were resistant to undergoing apoptosis following capsaicin administration. Moreover, the inhibitory effect of capsaicin on FASN expression and activity was found to be mediated by an increase of intracellular reactive oxygen species (ROS generation. Treatment of HepG2 cells with capsaicin failed to alter ACC and ACLY protein expression, suggesting ACC and ACLY might not be the specific targets of capsaicin to induce apoptosis. An accumulation of malonyl-CoA level following FASN inhibition represented a major cause of mitochondrial-dependent apoptotic induction instead of deprivation of fatty acid per se. Here, we also obtained similar results with C75 that exhibited apoptosis induction by reducing the levels of fatty acid without any change in the abundance of FASN expression along with increasing ROS production. Collectively, our results provide novel evidence that capsaicin exhibits a potent anti-cancer property by targeting

  4. The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells

    Science.gov (United States)

    Impheng, Hathaichanok; Pongcharoen, Sutatip; Richert, Lysiane; Pekthong, Dumrongsak; Srisawang, Piyarat

    2014-01-01

    The inhibition of the mammalian de novo synthesis of long-chain saturated fatty acids (LCFAs) by blocking the fatty acid synthase (FASN) enzyme activity in tumor cells that overexpress FASN can promote apoptosis, without apparent cytotoxic to non-tumor cells. The present study aimed to focus on the potent inhibitory effect of capsaicin on the fatty acid synthesis pathway inducing apoptosis of capsaicin in HepG2 cells. The use of capsaicin as a source for a new FASN inhibitor will provide new insight into its possible application as a selective anti-cancer therapy. The present findings showed that capsaicin promoted apoptosis as well as cell cycle arrest in the G0/G1 phase. The onset of apoptosis was correlated with a dissipation of mitochondrial membrane potential (ΔΨm). Apoptotic induction by capsaicin was mediated by inhibition of FASN protein expression which was accompanied by decreasing its activity on the de novo fatty acid synthesis. The expression of FASN was higher in HepG2 cells than in normal hepatocytes that were resistant to undergoing apoptosis following capsaicin administration. Moreover, the inhibitory effect of capsaicin on FASN expression and activity was found to be mediated by an increase of intracellular reactive oxygen species (ROS) generation. Treatment of HepG2 cells with capsaicin failed to alter ACC and ACLY protein expression, suggesting ACC and ACLY might not be the specific targets of capsaicin to induce apoptosis. An accumulation of malonyl-CoA level following FASN inhibition represented a major cause of mitochondrial-dependent apoptotic induction instead of deprivation of fatty acid per se. Here, we also obtained similar results with C75 that exhibited apoptosis induction by reducing the levels of fatty acid without any change in the abundance of FASN expression along with increasing ROS production. Collectively, our results provide novel evidence that capsaicin exhibits a potent anti-cancer property by targeting FASN protein in Hep

  5. Dissociation and trafficking of rat GABAB receptor heterodimer upon chronic capsaicin stimulation.

    Science.gov (United States)

    Laffray, Sophie; Tan, Kelly; Dulluc, Josette; Bouali-Benazzouz, Rabia; Calver, Andrew R; Nagy, Frédéric; Landry, Marc

    2007-03-01

    Gamma-aminobutyric acid type B receptors (GABAB) are G-protein-coupled receptors that mediate GABAergic inhibition in the brain. Their functional expression is dependent upon the formation of heterodimers between GABAB1 and GABAB2 subunits, a process that occurs within the endoplasmic reticulum. However, the mechanisms that regulate GABAB receptor oligomerization at the plasma membrane remain largely unknown. We first characterized the functional cytoarchitecture of an organotypic co-culture model of rat dorsal root ganglia and spinal cord. Subsequently, we studied the interactions between GABAB subunits after chronic stimulation of sensory fibres with capsaicin. Surface labelling of recombinant proteins showed a decrease in subunit co-localization and GABAB2 labelling, after capsaicin treatment. In these conditions, fluorescence lifetime imaging measurements further demonstrated a loss of interactions between green fluorescent protein-GABAB1b and t-dimer discosoma sp red fluorescent protein-GABAB2 subunits. Finally, we established that the GABAB receptor undergoes clathrin-dependent internalization and rapid recycling to the plasma membrane following activation with baclofen, a GABAB agonist. However, in cultures chronically stimulated with capsaicin, the agonist-induced endocytosis was decreased, reflecting changes in the dimeric state of the receptor. Taken together, our results indicate that the chronic stimulation of sensory fibres can dissociate the GABAB heterodimer and alters its responsiveness to the endogenous ligand. Chronic stimulation thus modulates receptor oligomerization, providing additional levels of control of signalling.

  6. Nanomechanical analysis of insulinoma cells after glucose and capsaicin stimulation using atomic force microscopy

    Institute of Scientific and Technical Information of China (English)

    Rui-guo YANG; Ning XI; King Wai-chiu LAI; Bei-hua ZHONG; Carmen Kar-man Fung; Chen-geng QU; Donna H Wang

    2011-01-01

    Aim: Glucose stimulates insulin secretion from pancreatic islet β cells by altering ion channel activity and membrane potential in the β cells. TRPV1 channel is expressed in the β cells and capsaicin induces insulin secretion similarly to glucose. This study aims to investigate the biophysical properties of the β ceils upon stimulation of membrane channels using an atomic force microscopic (AFM)nanoindentation system.Methods: ATCC insulinoma cell line was used. Cell stiffness, a marker of reorganization of cell membrane and cytoskeleton due to ion channel activation, was measured in real time using an integrated AFM nanoindentation system. Cell height that represented structural changes was simultaneously recorded along with cell stiffness.Results: After administration of glucose (16,20,and 40 mmol/L), the cell stiffness was markedly increased in a dose-dependent manner, whereas cell height was changed in an opposite way. Lower concentrations of capsaicin (1.67×10-9 and 1.67×10-8 mol/L)increased the cell stiffness without altering cell height. In contrast, higher concentrations of capsaicin (1.67×10-6 and 1.67×10-7mol/L) had no effect on the cell physical properties.Conclusion: A unique bio-nanomechanical signature was identified for characterizing biophysical properties of insulinoma cells upon general or specific activation of membrane channels. This study may deepen our understanding of stimulus-secretion coupling of pancreatic islet cells that leads to insulin secretion.

  7. Neonatal capsaicin causes compensatory adjustments to energy homeostasis in rats

    NARCIS (Netherlands)

    van de Wall, E. H. E. M.; Wielinga, P. Y.; Strubbe, J. H.; van Dijk, G.

    2006-01-01

    Several mechanisms involved in ingestive behavior and neuroendocrine activity rely on vagal afferent neuronal signaling. Seemingly contradictory to this idea are observations that vagal afferent neuronal ablation by neonatal capsaicin (CAP) treatment has relatively small effects on glucose homeostas

  8. Neonatal capsaicin causes compensatory adjustments to energy homeostasis in rats

    NARCIS (Netherlands)

    van de Wall, E. H. E. M.; Wielinga, P. Y.; Strubbe, J. H.; van Dijk, G.

    2006-01-01

    Several mechanisms involved in ingestive behavior and neuroendocrine activity rely on vagal afferent neuronal signaling. Seemingly contradictory to this idea are observations that vagal afferent neuronal ablation by neonatal capsaicin (CAP) treatment has relatively small effects on glucose homeostas

  9. EFFECT OF CAPSAICIN ON SUBSTANCE P IN PSORIASIS VULGARIS

    Institute of Scientific and Technical Information of China (English)

    王万卷; 谭升顺

    2003-01-01

    Objective To the investigate the mechanism of capsaicin in psoriasis vulgaris. Methods Substance P(SP) in psoriatic lesions before and 6 weeks after the treatment with capsaicin was detedted by radioimmunoassary. Results After 3 weeks and 6 weeks treatment with capsaicin, SP in psoriatic lesions was decreased (P<0.05), while it in the self-control group was not decreased; Overall the efficient incidence in therapeutic group was 78.8% , while it in the control group was 36.8%. There was significant difference between them (χ2=16.30, P<0.001). Conclusion Capsaicin inhibits dermal inflammatory responses and proliferation of keratinocytes by decreasing the expression of SP in psoriasis vulgaris.

  10. Trigeminal Cardiac Reflex and Cerebral Blood Flow Regulation

    Science.gov (United States)

    Lapi, Dominga; Scuri, Rossana; Colantuoni, Antonio

    2016-01-01

    The stimulation of some facial regions is known to trigger the trigemino-cardiac reflex: the main stimulus is represented by the contact of the face with water. This phenomenon called diving reflex induces a set of reactions in the cardiovascular and respiratory systems occurring in all mammals, especially marine (whales, seals). During the immersion of the face in the water, the main responses are aimed at reducing the oxygen consumption of the organism. Accordingly reduction in heart rate, peripheral vasoconstriction, blood pooling in certain organs, especially the heart, and brain and an increase in blood pressure have been reported. Moreover, the speed and intensity of the reflex is inversely proportional to the temperature of the water: more cold the water, more reactions as described are strong. In the case of deep diving an additional effect, such as blood deviation, has been reported: the blood is sequestered within the lungs, to compensate for the increase in the external pressure, preventing them from collapsing. The trigeminal-cardiac reflex is not just confined to the diving reflex; recently it has been shown that a brief proprioceptive stimulation (10 min) by jaw extension in rats produces interesting effects both at systemic and cerebral levels, reducing the arterial blood pressure, and vasodilating the pial arterioles. The arteriolar dilation is associated with rhythmic diameter changes characterized by an increase in the endothelial activity. Fascinating the stimulation of trigeminal nerve is able to activate the nitric oxide release by vascular endothelial cells. Therefore, the aim of this review was to highlight the effects due to trigeminal cardiac reflex induced by a simple mandibular extension. Opposite effects, such as hypotension, and modulation of cerebral arteriolar tone, were observed, when these responses were compared to those elicited by the diving reflex. PMID:27812317

  11. Dissecting the role of TRPV1 in detecting multiple trigeminal irritants in three behavioral assays for sensory irritation [v1; ref status: indexed, http://f1000r.es/p8

    Directory of Open Access Journals (Sweden)

    CJ Saunders

    2013-03-01

    Full Text Available Polymodal neurons of the trigeminal nerve innervate the nasal cavity, nasopharynx, oral cavity and cornea. Trigeminal nociceptive fibers express a diverse collection of receptors and are stimulated by a wide variety of chemicals. However, the mechanism of stimulation is known only for relatively few of these compounds. Capsaicin, for example, activates transient receptor potential vanilloid 1 (TRPV1 channels. In the present study, wildtype (C57Bl/6J and TRPV1 knockout mice were tested in three behavioral assays for irritation to determine if TRPV1 is necessary to detect trigeminal irritants in addition to capsaicin. In one assay mice were presented with a chemical via a cotton swab and their response scored on a 5 level scale. In another assay, a modified two bottle preference test, which avoids the confound of mixing irritants with the animal’s drinking water, was used to assess aversion. In the final assay, an air dilution olfactometer was used to administer volatile compounds to mice restrained in a double-chambered plethysmograph where respiratory reflexes were monitored. TRPV1 knockouts showed deficiencies in the detection of benzaldehyde, cyclohexanone and eugenol in at least one assay. However, cyclohexanone was the only substance tested that appears to act solely through TRPV1.

  12. Capsaicin facilitates carotid sinus baroreceptor activity in anesthetized rats

    Institute of Scientific and Technical Information of China (English)

    HaoZHANG; Yi-xianLIU; Yu-mingWU; Ze-minWANG; Rui-rongHE

    2004-01-01

    AIM: To study the effect of capsaicin on carotid sinus baroreceptor activity (CBA). METHODS: The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid sinus baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized rats with perfused isolated carotid sinus. RESULTS: Low-concentration of capsaicin (0.2μmol/L) had no significant effect on CBA, while perfusion of the isolated carotid sinus with middle-concentration of capsaicin (1μmol/L) could shift FCCB to the left and upward,with peak slope (PS) increased from (2.47%±0.14%)/mmHg to (2.88%±0.10%)/mmHg (P<0.05) and peak integral value of carotid sinus nerve discharge (PIV) enhanced from 211%±5% to 238%±6% (P<0.01). The threshold pressure (TP) and saturation pressure (SP) were significantly decreased from 68.0±1.1 to 62.7±1.0mmHg (P<0.01) and from 171.0±1.6 to 165.0±0.6 mmHg (P<0.01). By perfusing with high-concentration of capsaicin (5μmol/L), FCCB was shifted to the left and upward further and the changes of the functional parameters such as PS, TP, and SP were concentration-dependent. Pretreatment with ruthenium red (100μmol/L), an antagonist of vanilloid receptor subtype 1 (VR1), blocked the effect of capsaicin on CBA. Preperfusion with glibenclamide(20μmol/L), a KATP channel blocker, could eliminate the effect of capsaicin on CBA. CONCLUSION: Capsaicin exerts a facilitatory role on the isolated carotid baroreceptor in a concentration-dependent manner. The facilitatory action of capsaicin may be attributed to the opening of KATP channels mediated by VR1.

  13. Capsaicin facilitates carotid sinus baroreceptor activity in anesthetized rats

    Institute of Scientific and Technical Information of China (English)

    Hao ZHANG; Yi-xian LIU; Yu-ming WU; Ze-min WANG; Rui-rong HE

    2004-01-01

    AIM: To study the effect of capsaicin on carotid sinus baroreceptor activity (CBA). METHODS: The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid sinus baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized rats with perfused isolated carotid sinus.RESULTS: Low-concentration of capsaicin (0.2 μmol/L) had no significant effect on CBA, while perfusion of the isolated carotid sinus with middle-concentration of capsaicin (1 μmol/L) could shift FCCB to the left and upward,with peak slope (PS) increased from (2.47 %±0.14 %)/mmHg to (2.88 %±0.10 %)/mmHg (P<0.05) and peak integral value of carotid sinus nerve discharge (PIV) enhanced from 211%±5 % to 238 %±6 % (P<0.01). The threshold pressure (TP) and saturation pressure (SP) were significantly decreased from 68.0±1.1 to 62.7±1.0mmHg (P<0.01) and from 171.0±1.6 to 165.0±0.6 mmHg (P<0.01). By perfusing with high-concentration of capsaicin (5 μmol/L), FCCB was shifted to the left and upward further and the changes of the functional parameters such as PS, TP, and SP were concentration-dependent. Pretreatment with ruthenium red (100 μmol/L), an antagonist of vanilloid receptor subtype 1 (VR1), blocked the effect of capsaicin on CBA. Preperfusion with glibenclamide(20 μmol/L), a KATp channel blocker, could eliminate the effect of capsaicin on CBA. CONCLUSION: Capsaicin exerts a facilitatory role on the isolated carotid baroreceptor in a concentration-dependent manner. The facilitatory action of capsaicin may be attributed to the opening of KATP channels mediated by VR1.

  14. Management of trigeminal neuralgia in sclerosteosis.

    Science.gov (United States)

    de Andrade, Emerson Magno; Beer-Furlan, André; Duarte, Kleber Paiva; Fonoff, Erich Talamoni; Teixeira, Manoel Jacobsen

    2013-01-01

    Sclerosteosis is a rare bone disorder characterized by a progressive craniotubular hyperostosis. The diagnosis of sclerosteosis is based on characteristic clinical and radiographic features and a family history consistent with autosomal recessive inheritance. The skull overgrowth may lead to lethal elevation of intracranial pressure, distortion of the face, and entrapment of cranial nerves, resulting in recurrent facial palsy or secondary trigeminal neuralgia. The authors reported cases of two siblings who were diagnosed with familial sclerosteosis and presented with secondary trigeminal neuralgia. The patients were 28 and 40-year-old and presented with pain in the right V2-V3 and V3 distributions, respectively. The facial pain was resistant to medications and was treated with percutaneous techniques. The foramen ovale puncture was complicated initially and the difficulty increased over the years due to stenosis of the foramen. The treatment of the trigeminal neuralgia secondary to hyperostosis and resistant to medications presents a dilemma. The narrowing of the foramen oval and difficulty in the identifying and approaching of the foramen makes the percutaneous technique a challenge for the neurosurgeon in patients harboring sclerosteosis. Microvascular decompression should not be considered since the primary cause of the trigeminal neuralgia is the nerve entrapment by the narrowing of neurovascular foramina and not the neurovascular conflict related to essential trigeminal neuralgia. Stereotactic radiosurgery may be a good treatment option, but there is a lack of published data supporting the use of this method in cranial hyperostosis.

  15. Gastrointestinal absorption and metabolism of capsaicin and dihydrocapsaicin in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kawada, T.; Suzuki, T.; Takahashi, M.; Iwai, K.

    1984-03-15

    Gastrointestinal absorption of capsaicin and dihydrocapsaicin was studied in rats in vivo and in situ. Rapid absorption of capsaicin or dihydrocapsaicin from stomach and small intestine occurred in vivo. About 85% of the dose was absorbed in the gastrointestinal tract within 3 hr. In situ, within 60 min after the administration of capsaicin and dihydrocapsaicin into stomach, jejunum, and ileum, about 50, 80, and 70% of the respective dose had disappeared from the lumen. When 2,4-dinitrophenol or NaCN was added, no significant reduction in uptake of (/sup 3/H)dihydrocapsaicin was observed in the jejunum. These results suggested that capsaicin and its analogs were absorbed by a nonactive process in jejunum. (/sup 3/H)Dihydrocapsaicin was mainly absorbed via the portal system but not a mesenteric lymphangial one. The radioactivity in the portal blood was composed of 85% of (/sup 3/H)dihydrocapsaicin and 15% of its metabolite (8-methyl nonanoic acid) bound to the albumin fraction. Dihydrocapsaicin-hydrolyzing enzyme activity was found in jejunal tissue. These results suggest that capsaicin and its analogs partly received a first-pass effect, i.e., metabolism of a compound following first absorption in the gastrointestinal tract. It is concluded that capsaicin and its analogs are readily transported to the portal vein through the gastrointestinal tract by a nonactive process and partly metabolized during absorption.

  16. Tractography delineates microstructural changes in the trigeminal nerve after focal radiosurgery for trigeminal neuralgia.

    Directory of Open Access Journals (Sweden)

    Mojgan Hodaie

    Full Text Available PURPOSE: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN, a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. Since diffusion tensor imaging (DTI provides information on white matter microstructure, we explored the feasibility of trigeminal nerve tractography and assessment of DTI parameters to study microstructural changes after treatment. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Changes in specific diffusivities may provide insight into the mechanism of action of radiosurgery on the trigeminal nerve. METHODS AND MATERIALS: Five TN patients (4 females, 1 male, average age 67 years treated with Gamma Knife radiosurgery, 80 Gy/100% isodose line underwent 3Tesla MR trigeminal nerve tractography before and sequentially up to fourteen months after treatment. Fractional anisotropy (FA, radial (RD and axial (AD diffusivities were calculated for the radiosurgical target area defined as the region-of-interest. Areas outside target and the contralateral nerve served as controls. RESULTS: Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, demonstrating highly focal changes after treatment. RD but not AD changed markedly, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive than conventional gadolinium-enhanced post-treatment MR, since FA changes were detected regardless of trigeminal nerve enhancement. In subjects with long term follow-up, recovery of FA/RD correlated with pain recurrence. CONCLUSIONS: DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an

  17. Diet-Induced Obesity Enhances TRPV1-Mediated Neurovascular Reactions in the Dura Mater.

    Science.gov (United States)

    Marics, Balázs; Peitl, Barna; Pázmándi, Kitti; Bácsi, Attila; Németh, József; Oszlács, Orsolya; Jancsó, Gábor; Dux, Mária

    2017-03-01

    Exploring the pathophysiological changes in transient receptor potential vanilloid 1 (TRPV1) receptor of the trigeminovascular system in high-fat, high-sucrose (HFHS) diet-induced obesity of experimental animals. Clinical and experimental observations suggest a link between obesity and migraine. Accumulating evidence indicates that metabolic and immunological alterations associated with obesity may potentially modulate trigeminovascular functions. A possible target for obesity-induced pathophysiological changes is the TRPV1/capsaicin receptor which is implicated in the pathomechanism of headaches in a complex way. Male Sprague-Dawley rats were fed a regular (n = 25) or HFHS diet (n = 26) for 20 weeks. At the end of the dietary period, body weight of the animals was normally distributed in both groups and it was significantly higher in animals on HFHS diet. Therefore, experimental groups were regarded as control and HFHS diet-induced obese groups. Capsaicin-induced changes in meningeal blood flow and release of calcitonin gene-related peptide (CGRP) from dural trigeminal afferents were measured in control and obese rats. The distribution of TRPV1- and CGRP-immunoreactive meningeal sensory nerves was also compared in whole mount preparations of the dura mater. Metabolic parameters of the animals were assessed by examining glucose and insulin homeostasis as well as plasma cytokine concentrations. HFHS diet was accompanied by reduced food consumption and greater fluid and energy intakes in addition to increased body weight of the animals. HFHS diet increased fasting blood glucose and insulin concentrations as well as levels of circulating proinflammatory cytokines interleukin-1β and interleukin-6. In obese animals, dural application of the archetypal TRPV1 agonist capsaicin resulted in significantly augmented vasodilatory and vasoconstrictor responses as compared to controls. Diet-induced obesity was also associated with enhanced basal and capsaicin-induced

  18. Sensitization of voltage activated calcium channel currents for capsaicin in nociceptive neurons by tumor-necrosis-factor-alpha.

    Science.gov (United States)

    Hagenacker, T; Czeschik, J C; Schäfers, M; Büsselberg, D

    2010-01-15

    It is known that application of tumor-necrosis-factor-alpha (TNF-alpha) sensitizes neuronal calcium channels for heat stimuli in rat models of neuropathic pain. This study examines whether TNF-alpha modulates the capsaicin-induced effects after transient receptor potential vanilloid (TRPV)-1 receptor activation on voltage activated calcium channel currents (I(Ca(V))). TRPV-1 receptors are activated by heat and play an important role in the pathogenesis of thermal hyperalgesia in neuropathic pain syndromes, while voltage activated channels are essential for transmission of neuronal signals. Eliciting I(Ca(V)) in DRG neurons of rats by a depolarization from the resting potential to 0 mV, TNF-alpha (100 ng/ml) reduces I(Ca(V)) by 16.9+/-2.2%, while capsaicin (0.1 microM) decreases currents by 27+/-4.3%. Pre-application of TNF-alpha (100 ng/ml) for 24h results in a sensitization of I(Ca(V)) to capsaicin (0.1 microM) with a reduction of 42.8+/-4.4% mediated by TRPV-1. While L-type (36.6+/-5.2%) and P/Q-type currents (35.6+/-4.1%) are also sensitized by TRPV-1 activation, N-type channel currents are most sensitive (74.5+/-7.3%). The capsaicin-induced shift towards the hyperpolarizing voltage range does not occur when TNF-alpha is applied. Summarizing, TNF-alpha sensitizes nociceptive neurons for capsaicin.

  19. Small-fiber dysfunction in trigeminal neuralgia

    DEFF Research Database (Denmark)

    Cruccu, G.; Leandri, M.; Iannetti, G. D.

    2001-01-01

    Background: In patients with trigeminal neuralgia, results of clinical examination of sensory function are normal. Reflex and evoked potential studies have already provided information on large-afferent (non-nociceptive) function. Using laser-evoked potentials (LEP), the authors sought information...... on small-afferent (nociceptive) function. Methods: The brain potentials evoked by CO2-laser pulses directed to the perioral and supraorbital regions were studied in 67 patients with idiopathic or symptomatic trigeminal neuralgia and 30 normal subjects. Of the 67 patients, 49 were receiving carbamazepine....... Results: All patients with symptomatic and 51% of those with idiopathic trigeminal neuralgia had frankly abnormal LEP on the painful side. The mean latency was significantly higher and mean amplitude lower on the painful than the nonpainful side. However, even on the nonpainful side, the mean latency...

  20. Trigeminal neuralgia treatment dosimetry of the Cyberknife

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Anthony [Department of Radiation Oncology, Stanford University, Stanford, CA (United States); Lo, Anthony T., E-mail: tonyho22003@yahoo.com [Department of Radiation Oncology, Stanford University, Stanford, CA (United States); Dieterich, Sonja; Soltys, Scott G.; Gibbs, Iris C. [Department of Radiation Oncology, Stanford University, Stanford, CA (United States); Chang, Steve G.; Adler, John R. [Department of Neurosurgery, Stanford University, Stanford, CA (United States)

    2012-04-01

    There are 2 Cyberknife units at Stanford University. The robot of 1 Cyberknife is positioned on the patient's right, whereas the second is on the patient's left. The present study examines whether there is any difference in dosimetry when we are treating patients with trigeminal neuralgia when the target is on the right side or the left side of the patient. In addition, we also study whether Monte Carlo dose calculation has any effect on the dosimetry. We concluded that the clinical and dosimetric outcomes of CyberKnife treatment for trigeminal neuralgia are independent of the robot position. Monte Carlo calculation algorithm may be useful in deriving the dose necessary for trigeminal neuralgia treatments.

  1. [Update on the management of trigeminal neuralgia].

    Science.gov (United States)

    Alcántara Montero, A; Sánchez Carnerero, C I

    2016-01-01

    Trigeminal neuralgia is one of the most severe facial pain syndromes. The annual incidence varies between 4-13% and has a significant effect on patient quality of life. The initial treatment of trigeminal neuralgia is pharmacological, and although other drugs have demonstrated efficacy, albeit in more limited form, carbamazepine is the only drug with sufficient level of evidence. When medical treatment fails, surgery should be considered and can opt for open surgery or minimally invasive percutaneous techniques. This paper reviews the medical and surgical therapeutic options for the treatment of trigeminal neuralgia, based on current available evidence. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Substance MCS-18 isolated from Helleborus purpurascens is a potent antagonist of the capsaicin receptor, TRPV1, in rat cultured sensory neurons.

    Science.gov (United States)

    Neacsu, C; Ciobanu, C; Barbu, I; Toader, O; Szegli, G; Kerek, F; Babes, A

    2010-01-01

    Extracts of Helleborus roots were traditionally used in the Balkan area for their analgesic action. We report that the pure natural product MCS-18 isolated from this source is a potent, specific and reversible antagonist of the capsaicin receptor, TRPV1, expressed in rat dorsal root ganglion (DRG) neurons. TRPV1 is a non-selective cation channel expressed in a subset of cutaneous and visceral sensory nerve endings and activated by noxious heat, acidity and fatty acid metabolites of arachidonic acid, with a decisive role in inflammatory heat hyperalgesia. MCS-18 inhibited the increase in intracellular calcium concentration evoked in DRG neurons by capsaicin (300 nM) and low pH (5.5) but not by heat (43 degrees C). The substance had no effect on the responses mediated by acid-sensing ion channels (ASICs) or the irritant receptor TRPA1. Whole-cell patch-clamp was used to confirm the inhibition of capsaicin-induced currents by MCS-18 which was dose-dependent. The mechanism of inhibition does not require an intact cell, as capsaicin-induced currents were also inhibited in the excised outside-out configuration. The antagonism of the capsaicin and proton action on native TRPV1 by MCS-18 may be of interest for pain therapy.

  3. Assessment of the biological similarity of three capsaicin analogs (Capsinoids) found in non-pungent chili pepper (CH-19 Sweet) fruits.

    Science.gov (United States)

    Sasahara, Ikuko; Furuhata, Yasufumi; Iwasaki, Yusaku; Inoue, Naohiko; Sato, Hitoshi; Watanabe, Tatsuo; Takahashi, Michio

    2010-01-01

    CH-19 Sweet is a newly found chili pepper breed bearing much less pungent fruits. Because CH-19 Sweet fruits were found to contain three analogs (capsinoids) of capsaicin, a major component of pungency of hot peppers (the analogs are capsiate or CST, dihydrocapsiate or DCT, and nordihydrocapsiate or NDCT), we assessed in this study the bio-potencies of these three capsinoids by comparing them with capsaicin. The three capsinoids bound to transient potential vanilloid 1 (TRPV1) receptors expressed in cultured cells and activated Ca(2+) influx in a concentration-dependent manner with similar magnitudes. In contrast to capsaicin, capsinoids at the same concentration induced virtually no nociceptive responses when applied to the eyes or the oral cavities of mice. Intravenous administration of capsaicin or 20-fold increased doses of each capsinoid to rats induced significant increases in plasma catecholamine levels. Orally administered, each capsinoid enhanced oxygen consumption in mice. Based on the present results, capsaicin and these three capsinoids should have similar bio-potency, though capsinoids do not generate pungency or sensory irritation.

  4. The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

    Science.gov (United States)

    Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

    2016-01-01

    Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin

  5. Non-pungent long chain capsaicin-analogs arvanil and olvanil display better anti-invasive activity than capsaicin in human small cell lung cancers.

    Science.gov (United States)

    Hurley, John D; Akers, Austin T; Friedman, Jamie R; Nolan, Nicholas A; Brown, Kathleen C; Dasgupta, Piyali

    2017-01-02

    The nutritional compound capsaicin inhibits the invasion of many types of human cancers. The clinical development of capsaicin as an anti-cancer drug is limited due to its unfavorable side effects like burning sensation, stomach cramps, gut pain and nausea. This study compared the anti-invasive activity of capsaicin to non-pungent long chain capsaicin analogs, namely arvanil and olvanil, in human small cell lung cancer cells. Boyden chamber invasion assays revealed that arvanil and olvanil displayed improved anti-invasive activity relative to capsaicin in human SCLC cells. The results of the Boyden chamber assay were confirmed by the spherical invasion assay, and similar results were obtained. The anti-invasive activity of arvanil, olvanil and capsaicin were independent of TRPV and CB1 receptors. Furthermore, the anti-invasive activity of arvanil, olvanil and capsaicin was mediated by the AMPK pathway. Depletion of AMPK levels by siRNA methodology abrogated the anti-invasive activity of arvanil, olvanil and capsaicin. The non-pungent capsaicin analogs arvanil and olvanil display improved anti-invasive activity relative to capsaicin in human SCLC cells. These agents may represent the second generation of capsaicin-like compounds which are more potent than the parent molecule and have a better side effect profile.

  6. [Malignant lymphoma in a perineural spreading along trigeminal nerve, which developed as trigeminal neuralgia].

    Science.gov (United States)

    Mano, Tomoo; Matsuo, Koji; Kobayashi, Yosuke; Kobayashi, Yasushi; Ozawa, Hiroaki; Arakawa, Toshinao

    2014-01-01

    A rare cause of trigeminal neuralgia is malignant lymphoma which spread along the trigeminal nerve. We report a 79-year-old male presented with 4-month history of neuralgic pain in right cheek. He was diagnosed as classical trigeminal neuralgia. It had improved through medication of carbamazepine. Four months later, the dull pain unlike neuralgia complicated on the right cheeks, it was ineffective with the medication. Furthermore, diplopia and facial palsy as the other cranial nerve symptoms appeared. Gadolinium-enhanced magnetic resonance imaging (MRI) revealed contrast-enhanced mass lesion extend both external pterygoid muscle and brainstem through the swelling trigeminal nerve. The patient was pathological diagnosed of diffuse large B cell lymphoma by biopsy. Malignant lymphoma should be considered in the different diagnosis of cases with a minimal single cranial nerve symptom.

  7. Structural magnetic resonance imaging can identify trigeminal system abnormalities in classical trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Danielle DeSouza

    2016-10-01

    Full Text Available Classical trigeminal neuralgia (TN is a chronic pain disorder that has been described as one ofthe most severe pains one can suffer. The most prevalent theory of TN etiology is that the trigeminal nerve is compressed at the root entry zone (REZ by blood vessels. However, there is significant evidence showing a lack of neurovascular compression (NVC for many cases of classical TN. Furthermore, a considerable number of patients who are asymptomatic have MR evidence of NVC. Since there is no validated animal model that reproduces the clinical features of TN, our understanding of TN pathology mainly comes from biopsy studies that have limitations. Sophisticated structural MRI techniques including diffusion tensor imaging provide new opportunities to assess the trigeminal nerves and CNS to provide insight into TN etiology and pathogenesis. Specifically, studies have used high-resolution structural MRI methods to visualize patterns of trigeminal nerve-vessel relationships and to detect subtle pathological features at the trigeminal REZ. Structural MRI has also identified CNS abnormalities in cortical and subcortical gray matter and white matter and demonstrated that effective neurosurgical treatment for TN is associated with a reversal of specific nerve and brain abnormalities. In conclusion, this review highlights the advanced structural neuroimaging methods that are valuable tools to assess the trigeminal system in TN and may inform our current understanding of TN pathology. These methods may in the future have clinical utility for the development of neuroimaging-based biomarkers of TN.

  8. Structural Magnetic Resonance Imaging Can Identify Trigeminal System Abnormalities in Classical Trigeminal Neuralgia

    Science.gov (United States)

    DeSouza, Danielle D.; Hodaie, Mojgan; Davis, Karen D.

    2016-01-01

    Classical trigeminal neuralgia (TN) is a chronic pain disorder that has been described as one of the most severe pains one can suffer. The most prevalent theory of TN etiology is that the trigeminal nerve is compressed at the root entry zone (REZ) by blood vessels. However, there is significant evidence showing a lack of neurovascular compression (NVC) for many cases of classical TN. Furthermore, a considerable number of patients who are asymptomatic have MR evidence of NVC. Since there is no validated animal model that reproduces the clinical features of TN, our understanding of TN pathology mainly comes from biopsy studies that have limitations. Sophisticated structural MRI techniques including diffusion tensor imaging provide new opportunities to assess the trigeminal nerves and CNS to provide insight into TN etiology and pathogenesis. Specifically, studies have used high-resolution structural MRI methods to visualize patterns of trigeminal nerve-vessel relationships and to detect subtle pathological features at the trigeminal REZ. Structural MRI has also identified CNS abnormalities in cortical and subcortical gray matter and white matter and demonstrated that effective neurosurgical treatment for TN is associated with a reversal of specific nerve and brain abnormalities. In conclusion, this review highlights the advanced structural neuroimaging methods that are valuable tools to assess the trigeminal system in TN and may inform our current understanding of TN pathology. These methods may in the future have clinical utility for the development of neuroimaging-based biomarkers of TN. PMID:27807409

  9. [Orofacial pain - Trigeminal neuralgia and posttraumatic trigeminal neuropathy: Common features and differences].

    Science.gov (United States)

    Thieme, V

    2016-02-01

    Neuropathic pain is the result of a lesion or disease of the somatosensory system in the peripheral or central nervous system. Classical trigeminal neuralgia and posttraumatic trigeminal neuropathy are pain disorders which oral and maxillofacial surgeons and dentists are confronted with in the differential diagnostics in routine daily practice. The etiopathogenesis of classical trigeminal neuralgia is attributable to pathological blood vessel-nerve contact in the trigeminal nerve root entry zone to the brain stem. The typical pain symptoms are characterized by sudden stabbing pain attacks. The pharmaceutical prophylaxis is based on the individually titrated administration of anticonvulsant drugs. The indications for interventional treatment are dependent on the course, response to drug treatment, resilience and wishes of the patient. The neuropathic mechanism of posttraumatic trigeminal neuropathy originates from nerve damage, which leads to peripheral and central sensitization with lowering of the pain threshold and multiple somatosensory disorders. The prophylaxis consists of avoidance of excessive acute and long-lasting pain stimuli. Against the background of the biopsychosocial pain model, the treatment of posttraumatic trigeminal neuropathy necessitates a multimodal, interdisciplinary concept.

  10. The Anticancer Role of Capsaicin in Experimentallyinduced Lung Carcinogenesis.

    Science.gov (United States)

    Anandakumar, Pandi; Kamaraj, Sattu; Jagan, Sundaram; Ramakrishnan, Gopalakrishnan; Asokkumar, Selvamani; Naveenkumar, Chandrashekar; Raghunandhakumar, Subramanian; Vanitha, Manickam Kalappan; Devaki, Thiruvengadam

    2015-06-01

    Capsaicin (CAP) is the chief pungent principle found in the hot red peppers and the chili peppers that have long been used as spices, food additives and drugs. This study investigated the anticancer potential of CAP through its ability to modify extracellular matrix components and proteases during mice lung carcinogenesis. Swiss albino mice were treated with benzo(a) pyrene (50 mg/kg body weight dissolved in olive oil) orally twice a week for four successive weeks to induce lung cancer at the end of 14(th) week. CAP was administrated (10 mg/kg body weight dissolved in olive oil) intraperitoneally. Extracellular matrix components were assayed; Masson's trichome staining of lung tissues was performed. Western blot analyses of matrix metalloproteases 2 and 9 were also carried out. In comparison with the control animals, animals in which benzo(a)pyrene had induced lung cancer showed significant increases in extracellular matrix components such as collagen (hydroxy proline), elastin, uronic acid and hexosamine and in glycosaminoglycans such as hyaluronate, chondroitin sulfate, keratan sulfate and dermatan sulfate. The above alterations in extracellular matrix components were effectively counteracted in benzo(a)pyrene along with CAP supplemented animals when compared to benzo(a) pyrene alone supplemented animals. The results of Masson's trichome staining for collagen and of, immunoblotting analyses of matrix metalloproteases 2 and 9 further supported the biochemical findings. The apparent potential of CAP in modulating extracellular matrix components and proteases suggests that CAP plays a chemomodulatory and anti- cancer role working against experimentally induced lung carcinogenesis.

  11. The Anticancer Role of Capsaicin in Experimentallyinduced Lung Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Pandi Anandakumar

    2015-06-01

    Full Text Available Objectives: Capsaicin (CAP is the chief pungent principle found in the hot red peppers and the chili peppers that have long been used as spices, food additives and drugs. This study investigated the anticancer potential of CAP through its ability to modify extracellular matrix components and proteases during mice lung carcinogenesis. Methods: Swiss albino mice were treated with benzo(a pyrene (50 mg/kg body weight dissolved in olive oil orally twice a week for four successive weeks to induce lung cancer at the end of 14th week. CAP was administrated (10 mg/kg body weight dissolved in olive oil intraperitoneally. Extracellular matrix components were assayed; Masson’s trichome staining of lung tissues was performed. Western blot analyses of matrix metalloproteases 2 and 9 were also carried out. Results: In comparison with the control animals, animals in which benzo(apyrene had induced lung cancer showed significant increases in extracellular matrix components such as collagen (hydroxy proline, elastin, uronic acid and hexosamine and in glycosaminoglycans such as hyaluronate, chondroitin sulfate, keratan sulfate and dermatan sulfate. The above alterations in extracellular matrix components were effectively counteracted in benzo(apyrene along with CAP supplemented animals when compared to benzo(a pyrene alone supplemented animals. The results of Masson’s trichome staining for collagen and of, immunoblotting analyses of matrix metalloproteases 2 and 9 further supported the biochemical findings. Conclusion: The apparent potential of CAP in modulating extracellular matrix components and proteases suggests that CAP plays a chemomodulatory and anti- cancer role working against experimentally induced lung carcinogenesis.

  12. Trigeminal Neuralgia due to Vertebrobasilar Dolichoectasia

    Directory of Open Access Journals (Sweden)

    Wuilker Knoner Campos

    2012-01-01

    Full Text Available We presented a case of drug-resistant trigeminal neuralgia attributed to vertebrobasilar dolichoectasia, a rare condition characterized by enlargement, tortuosity, or elongation of intracranial arteries. Dolichoectatic vessels can cause dysfunction of cranial nerves through direct vascular compression. The relationships of vertebrobasilar dolichoectasia with the particularities of neurovascular conflict and images findings are discussed.

  13. Trigeminal nerve: Anatomic correlation with MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, D.L.; Pech, P.; Pojunas, K.W.; Kilgore, D.P.; Williams, A.L.; Haughton, V.M.

    1986-06-01

    Through correlation with cryomicrotic sections, the appearance of the trigeminal nerve and its branches on magnetic resonance images is described in healthy individuals and in patients with tumors involving this nerve. Coronal images are best for defining the different parts of the nerve and for making a side-to-side comparison. Sagittal images are useful to demonstrate tumors involving the Gasserian ganglion.

  14. Gamma-knife radiosurgery for trigeminal neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Kannan, V.; Deopujari, C.E.; Misra, B.K.; Shetty, P.G.; Shroff, M.M.; Pendse, A.M. [PD Hinduja National Hospital and Medical Research Centre, Mumbai, (India)

    1999-08-01

    Gamma knife was installed at the PD Hinduja National Hospital and Medical Research Centre, Mumbai, India, in January 1997. In the first year of gamma-knife radiosurgery to January 1998, we treated 110 patients, of whom six had medically refractory trigeminal neuralgia. Seven treatments were administered to this group of six patients (one had bilateral neuralgia). This report evaluates the effectiveness of radiosurgery treatment in these patients. The median age of the patients was 56 years and there were five males and one female. Following Leksell stereotactic frame fixation, a magnetic resonance imaging scan was done in all. The Leksell gamma plan was used for planning. A radiosurgery dose of 70-80 Gy was delivered to the trigeminal root entry zone, 2-4 mm anterior to the junction of the pons and trigeminal nerve with a single 4 mm collimator helmet. Complete pain relief was achieved in four patients. Two had partial relief. No patient developed any radiosurgery related morbidity during the follow-up period of 5-16 months. Radiosurgery seems to be an effective approach for medically or surgically refractory trigeminal neuralgia. Copyright (1999) Blackwell Science Pty Ltd 10 refs., 2 figs.

  15. Idiopathic trigeminal neuropathy in a poodle

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Aparicio

    2010-12-01

    Full Text Available A seven years old, male poodle is examined presenting acute mandible paralysis (dropped jaw, drooling and difficulty for the apprehension and chewing; not evidence of an other alteration of cranial nerves. The muscular biopsy rules out a myositisof masticatory muscles. The disorder is resolved completely in 3 weeks confirming diagnosis of idiopathic trigeminal neuropathy.

  16. Potential of capsaicin-loaded transfersomes in arthritic rats.

    Science.gov (United States)

    Sarwa, Khomendra Kumar; Mazumder, Bhaskar; Rudrapal, Mithun; Verma, Vinod Kumar

    2015-01-01

    In the present study, the biopotential of capsaicin (an active principle of capsicum) as a topical antiarthritic agent was studied in arthritic rats. Transfersomal vesicular system was employed for the topical administration of capsaicin in experimental rats. The characterization of prepared capsaicin-loaded transfersomes reveals their nano size (94 nm) with negative surface charge (-14.5 mV) and sufficient structural flexibility, which resulted in 60.34% entrapment efficacy, penetration across the biomembrane (220 µm) and 76.76% of drug release from vesicular system in 24 h in their intact form as evident from confocal laser scanning micrographic study. Results of transfersomal nanoformulation (capsaicin loaded, test) were compared with that of conventional gel formulation available in the market (Thermagel, standard), with an aim to assess the antiarthritic efficacy of our prepared capsaicin-loaded transfersomal formulation. In vivo antiarthritic activity study shows that our formulation possesses superior inhibitory activity than the marketed Thermagel formulation at the same dosage level, which could probably be due to the lesser permeability of Thermagel across the dermal barriers compared to our specially designed transfersomal delivery system. Moreover, the better tolerance of prepared vesicular formulation in biological system further enlightens the suitability of the transfersomal vesicle to be used as a novel carrier system for the topical administration of such highly irritant substance.

  17. Capsaicin inhalation in man and the effects of sodium cromoglycate.

    Science.gov (United States)

    Collier, J. G.; Fuller, R. W.

    1984-01-01

    The inhalation of capsaicin for 1 min, delivered as an aerosol by nebulising solutions of capsaicin at concentrations of 2-65 mumol 1(-1), caused dose-dependent coughing in normal volunteers and subjects with mild asthma. Capsaicin did not cause a feeling of breathlessness, and had no effect on forced expiratory volume in 1 s (FEV1) measured at the 1st, 5th and 9th min after the challenge was completed. Coughing started within seconds of applying the face mask, continued throughout the minute of capsaicin inhalation, and stopped within seconds of the mask being removed. In any one subject the number of coughs was reproducible when repeated on the same day or after an interval of several days. Experiments using local anaesthesia applied to the buccal mucosa or larynx indicated that the cough was caused by the stimulation of capsaicin-sensitive nerve terminals situated in the larynx. Cough response was not altered by the prior inhalation of sodium cromoglycate. PMID:6423016

  18. Putrescine facilitated enhancement of capsaicin production in cell suspension cultures of Capsicum frutescens.

    Science.gov (United States)

    Sudha, Govindaswamy; Ravishankar, Gokare A

    2003-04-01

    Putrescine treatment (0.1 mmol/L) influenced enhancement of growth and capsaicin production in the cell suspension cultures of C. frutescens. The administration of polyamine inhibitor DFMA (alpha-DL-difluoromethylarginine) resulted in a reduction of the growth, capsaicin content and the endogenous titres of polyamines (PAs). The capsaicin synthase activity was also higher in the putrescine (Put) treated cultures. Ethylene levels were lower in the cultures treated with putrescine. This study suggested that Put facilitates growth and capsaicin production.

  19. Sensory effects of capsaicin congeners. Part II: Importance of chemical structure and pungency in desensitizing activity of capsaicin-type compounds.

    Science.gov (United States)

    Szolcsányi, J; Jancsó-Gábor, A

    1976-01-01

    The characteristic insensitivity of sensory nerve endings to chemically induced pain brought about by capsaicin could be reproduced on the rat's eye by pungent vanillylamides, homovanilloyl-alkylamides and piperine, while homovanilloyl-cycloalkylamides, -azacycloalkylamides, - alkylesters, -alkyl-homovanillylamides, undecenoyl-3-aminopropranololand zingerone were practically ineffective in this respect. Desensitizing potency was not parallel with the stimulating effect of the compounds, e.g. the strongly pungent homovanilloyl-octylester failed to desensitize the receptors, while the less pungent homovanilloyl-dodecylamide proved to be a more potent desensitizing agent than capsaicin itself. It is concluded that the inverse position of the acylamide linkage does not modify, while its replacement by an esteric group completely abolishes the desensitizing activity. In contrast to the stimulating effect, in desensitizing action the presence of an alkyl chain is essential and its optimal length corresponds to 10-12 C atoms. On the basis of these results the possible molecular interactions at the site of action are discussed.

  20. 40 CFR 180.1165 - Capsaicin; exemption from the requirement of a tolerance.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Capsaicin; exemption from the requirement of a tolerance. 180.1165 Section 180.1165 Protection of Environment ENVIRONMENTAL PROTECTION... Exemptions From Tolerances § 180.1165 Capsaicin; exemption from the requirement of a tolerance. Capsaicin...

  1. Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis.

    Science.gov (United States)

    Borbély, Éva; Botz, Bálint; Bölcskei, Kata; Kenyér, Tibor; Kereskai, László; Kiss, Tamás; Szolcsányi, János; Pintér, Erika; Csepregi, Janka Zsófia; Mócsai, Attila; Helyes, Zsuzsanna

    2015-03-01

    The K/BxN serum-transfer arthritis is a widely-used translational mouse model of rheumatoid arthritis, in which the immunological components have thoroughly been investigated. In contrast, little is known about the role of sensory neural factors and the complexity of neuro-immune interactions. Therefore, we analyzed the involvement of capsaicin-sensitive peptidergic sensory nerves in autoantibody-induced arthritis with integrative methodology. Arthritogenic K/BxN or control serum was injected to non-pretreated mice or resiniferatoxin (RTX)-pretreated animals where capsaicin-sensitive nerves were inactivated. Edema, touch sensitivity, noxious heat threshold, joint function, body weight and clinical arthritis severity scores were determined repeatedly throughout two weeks. Micro-CT and in vivo optical imaging to determine matrix-metalloproteinase (MMP) and neutrophil-derived myeloperoxidase (MPO) activities, semiquantitative histopathological scoring and radioimmunoassay to measure somatostatin in the joint homogenates were also performed. In RTX-pretreated mice, the autoantibody-induced joint swelling, arthritis severity score, MMP and MPO activities, as well as histopathological alterations were significantly greater compared to non-pretreated animals. Self-control quantification of the bone mass revealed decreased values in intact female mice, but significantly greater arthritis-induced pathological bone formation after RTX-pretreatment. In contrast, mechanical hyperalgesia from day 10 was smaller after inactivating capsaicin-sensitive afferents. Although thermal hyperalgesia did not develop, noxious heat threshold was significantly higher following RTX pretreatment. Somatostatin-like immunoreactivity elevated in the tibiotarsal joints in non-pretreated, which was significantly less in RTX-pretreated mice. Although capsaicin-sensitive sensory nerves mediate mechanical hyperalgesia in the later phase of autoantibody-induced chronic arthritis, they play important

  2. IL-1β stimulates COX-2 dependent PGE₂ synthesis and CGRP release in rat trigeminal ganglia cells.

    Directory of Open Access Journals (Sweden)

    Lars Neeb

    Full Text Available OBJECTIVE: Pro-inflammatory cytokines like Interleukin-1 beta (IL-1β have been implicated in the pathophysiology of migraine and inflammatory pain. The trigeminal ganglion and calcitonin gene-related peptide (CGRP are crucial components in the pathophysiology of primary headaches. 5-HT1B/D receptor agonists, which reduce CGRP release, and cyclooxygenase (COX inhibitors can abort trigeminally mediated pain. However, the cellular source of COX and the interplay between COX and CGRP within the trigeminal ganglion have not been clearly identified. METHODS AND RESULTS: 1. We used primary cultured rat trigeminal ganglia cells to assess whether IL-1β can induce the expression of COX-2 and which cells express COX-2. Stimulation with IL-1β caused a dose and time dependent induction of COX-2 but not COX-1 mRNA. Immunohistochemistry revealed expression of COX-2 protein in neuronal and glial cells. 2. Functional significance was demonstrated by prostaglandin E2 (PGE(2 release 4 hours after stimulation with IL-1β, which could be aborted by a selective COX-2 (parecoxib and a non-selective COX-inhibitor (indomethacin. 3. Induction of CGRP release, indicating functional neuronal activation, was seen 1 hour after PGE(2 and 24 hours after IL-1β stimulation. Immunohistochemistry showed trigeminal neurons as the source of CGRP. IL-1β induced CGRP release was blocked by parecoxib and indomethacin, but the 5-HT1B/D receptor agonist sumatriptan had no effect. CONCLUSION: We identified a COX-2 dependent pathway of cytokine induced CGRP release in trigeminal ganglia neurons that is not affected by 5-HT1B/D receptor activation. Activation of neuronal and glial cells in the trigeminal ganglion by IL-β leads to an elevated expression of COX-2 in these cells. Newly synthesized PGE(2 (by COX-2 in turn activates trigeminal neurons to release CGRP. These findings support a glia-neuron interaction in the trigeminal ganglion and demonstrate a sequential link between COX-2

  3. Hot Chili Peppers: Extraction, Cleanup, and Measurement of Capsaicin

    Science.gov (United States)

    Huang, Jiping; Mabury, Scott A.; Sagebiel, John C.

    2000-12-01

    Capsaicin, the pungent ingredient of the red pepper or Capsicum annuum, is widely used in food preparation. The purpose of this experiment was to acquaint students with the active ingredients of hot chili pepper (capsaicin and dihydrocapsaicin), the extraction, cleanup, and analysis of these chemicals, as a fun and informative analytical exercise. Fresh peppers were prepared and extracted with acetonitrile, removing plant co-extractives by addition to a C-18 solid-phase extraction cartridge. Elution of the capsaicinoids was accomplished with a methanol-acetic acid solution. Analysis was completed by reverse-phase HPLC with diode-array or variable wavelength detection and calibration with external standards. Levels of capsaicin and dihydrocapsaicin were typically found to correlate with literature values for a specific hot pepper variety. Students particularly enjoyed relating concentrations of capsaicinoids to their perceived valuation of "hotness".

  4. Progesterone produces antinociceptive and neuroprotective effects in rats with microinjected lysophosphatidic acid in the trigeminal nerve root

    Directory of Open Access Journals (Sweden)

    Kim Min

    2012-03-01

    Full Text Available Abstract Background In our present study, we studied the role of demyelination of the trigeminal nerve root in the development of prolonged nociceptive behavior in the trigeminal territory. Results Under anesthesia, the Sprague-Dawley rats were mounted onto a stereotaxic frame and 3 μL of lysophosphatidic acid (LPA, 1 nmol was injected into the trigeminal nerve root to produce demyelination. This treatment decreased the air-puff thresholds, persisted until postoperative day 130, and then returned to the preoperative levels 160 days after LPA injection. The LPA-treated rats also showed a significant hyper-responsiveness to pin-prick stimulation. We further investigated the antinociceptive and neuroprotective effects of progesterone in rats undergoing demyelination of the trigeminal nerve root. Progesterone (8, 16 mg/kg/day was administered subcutaneously, beginning on the operative day, for five consecutive days in the LPA-treated rats. Treatment with progesterone produced significant early anti-allodynic effects and delayed prolonged anti-allodynic effects. The expression of protein zero (P0 and peripheral myelin protein 22 (PMP22 were significantly down-regulated in the trigeminal nerve root on postoperative day 5 following LPA injection. This down-regulation of the P0 and PMP22 levels was blocked by progesterone treatment. Conclusions These results suggest that progesterone produces antinociceptive effects through neuroprotective action in animals with LPA-induced trigeminal neuropathic pain. Moreover, progesterone has potential utility as a novel therapy for trigeminal neuropathic pain relief at an appropriate managed dose and is therefore a possible future treatment strategy for improving the recovery from injury.

  5. ETB receptor activation as a mechanism of modulation of inflammatory pain and neurogenic inflammation in the temporomandibular joint of capsaicin-treated rats

    Directory of Open Access Journals (Sweden)

    Thiago E. V. Lemos

    2013-06-01

    Full Text Available Background: Endothelin (ET, a peptide best known for its vascular effects, also evokes pain and hyperalgesia, independently of its vascular actions. Data suggest that ET can have nociceptive effects, acting directly on receptors expressed in sensory neurons. As such, the aim this study was to investigate the direct effect of ET on hyperalgesia and edema, induced by carrageenan, on the temporomandibular joint (TMJ of capsaicin-treated rats. Methods: Capsaicin was administered by subcutaneous injection to newborn, male Wistar rats. Inflammation was induced 60 days later by a single intra-articular injection of carrageenan into the left TMJ (control group received sterile saline. Inflammatory parameters, such as plasma extravasation, leukocyte influx and mechanical allodynia (measured as the head-withdrawal force threshold were evaluated 4 h after edematogenic stimulus. ET-1 and ET-3, and the ET-B receptor (ETBR antagonist were administered 3 min before edematogenic stimulus. ET and transient receptor potential vanilloid (TRPV1 mRNA expression was assessed by reverse-transcription polymerase chain reaction (RT-PCR. Edema formation was evaluated by measurement of the extravascular accumulation of injected 125I-human serum albumin into the TMJ soft tissues of anesthetized rats. Results: Capsaicin neonatal treatment significantly reduced edema formation, leukocyte influx and mechanical allodynia in TMJ, when compared to the control group, while the ETBR antagonist increased plasma extravasation and hyperalgesia in the capsaicin-treated group. ET-1 treatment reduced both plasma extravasation and myeloperoxidase activity. Capsular mRNA for ET-1 was significantly augmented in the TMJ of capsaicin-treated rats, when compared to controls. Conclusions: Our results suggest, for the first time, that ET-1, via ETBR activation, reduces plasma extravasation, leukocyte influx and inflammatory pain in the temporomandibular joint of capsaicin-treated rats. [J Exp

  6. Experimental study of the inhibitory effect of capsaicin on PGE2 concentration of IL-1βinduced NCI-H460 cells by downregulating COX-2 and mPGES-1%辣椒素通过下调 COX-2和 mPGES-1抑制 IL-1β诱导的NCI-H460细胞 PGE2含量的实验研究

    Institute of Scientific and Technical Information of China (English)

    任公平; 那辉; 佟雷; 李华洋

    2016-01-01

    目的:观察辣椒素对 IL-1β诱导的人肺腺癌 NCI-H460细胞 PGE2含量的影响,并且进一步观察其对 COX-2和mPGES-1的影响,探讨其抗非小细胞肺癌(NSCLC)的可能机制。方法体外培养 NCI-H460细胞,采用 MTT 比色分析法,观察辣椒素对 NCI-H460细胞增殖抑制作用,计算 IC50;采用 IL-1β刺激的方法构建炎症模型,ELISA 法检测辣椒素对 NCI-H460细胞 PGE2含量和 COX-2活性的影响;Western blot 法检测辣椒素对 NCI-H460细胞 COX-2、mPGES-1蛋白表达的影响;Real-time PCR 法检测辣椒素对 NCI-H460细胞 COX-2 mRNA 和 mPGES-1 mRNA 表达的影响。结果MTT 比色分析结果表明,辣椒素对 NCI-H460细胞增殖具有明显抑制作用,与对照组比较,差异具有统计学意义(P <0.05或 P <0.01)。辣椒素明显降低 NCI-H460细胞 COX-2活性和 PGE2浓度,而且明显降低 NCI-H460细胞 COX-2、mPGES-1蛋白及其 mRNA 的表达,且呈剂量依赖性,与模型组比较,差异具有统计学意义(P <0.05)。结论辣椒素通过降低 NCI-H460细胞 COX-2和 mPGES-1 mRNA 表达从而抑制 PGE2释放,可能是其抗NSCLC 的机制之一。%Objective To observe the effects of capsaicin on PGE2 concentration of IL-1β-induced human large cell carcinoma NCI-H460 cells,and further observe its effect on COX-2 and mPGES-1 so as to explore the possible mechanisms against non-small cell lung cancer.Methods NCI-H460 cells were cultured in vitro ;the effect of capsaicin in inhibiting NCI-H460 cells proliferation was observed.The 50% inhibitory concentration (IC50 ) was measured by MTT assay.IL-1βstimulation method was used to construct inflammation model,and the effects of capsaicin on COX-2 activity and PGE2 concentration in NCI-H460 cells were measured by ELISA.The effects of capsaicin on COX-2 and mPGES-1 protein level in NCI-H460 cells were analyzed by Western blot;the effects of capsaicin on COX-2 mRNA and mPGES-1 mRNA expressions in NCI-H460 cells were analyzed by Real

  7. Differences in individual susceptibility affect the development of trigeminal neuralgia

    Institute of Scientific and Technical Information of China (English)

    Yusuf Kurtulu(s) Duransoy; Mesut Mete; Emrah Ak(c)ay; Mehmet Sel(c)uki1

    2013-01-01

    Trigeminal neuralgia is a syndrome due to dysfunctional hyperactivity of the trigeminal nerve, and is characterized by a sudden, usually unilateral, recurrent lancinating pain arising from one or more divisions of the nerve. The most accepted pathogenetic mechanism for trigeminal neuralgia is compression of the nerve at its dorsal root entry zone or in its distal course. In this paper, we report four cases with trigeminal neuralgia due to an unknown mechanism after an intracranial intervention. The onset of trigeminal neuralgia after surgical interventions that are unrelated to the trigeminal nerve suggests that in patients with greater individual susceptibility, nerve contact with the vascular structure due to postoperative pressure and changes in cerebrospinal fluid flow may cause the onset of pain.

  8. Radiology of trigeminal neuralgia; With special reference to CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Shunichi; Kishikawa, Takashi; Kudo, Sho (Saga Medical School, Saga (Japan)) (and others)

    1990-05-01

    CT findings in ninty-nine patients with trigeminal neuralgia were reviewed. Brain tumors including three trigeminal neurinomas, three meningiomas, one epidermoid, one acoustic neurinoma, were found in eight cases as a cause of symptomatic trigeminal neuralgia. Among seventy-nine patients with idiopathic trigeminal neuralgia, four cases had vascular decompression surgery because of the tortuous, ectatic or anomalous vertebrobasilar artery. Among the other seventy-five non-surgical cases, seventeen cases showed the tortuous and/or ectatic vertebrobasilar artery on CT, and this group of patients showed slightly higher recurrence rate of trigeminal neuralgia after nerve block or medication compared with other non-surgical patients. CT is thought to be a useful screening imaging modality for evaluation of patients with trigeminal neuralgia, and angiography is required for precise evaluation of the compressing vessels when surgical treatment is contemplated. (author).

  9. Case series: non vascular considerations in trigeminal neuralgia.

    Science.gov (United States)

    Balasundram, Sathesh; Cotrufo, Stefano; Liew, Colin

    2012-02-01

    An abnormal vascular course of the superior cerebellar artery is often cited as the cause for trigeminal neuralgia. However, among patients with TN-like symptoms, 6% to 16% are variously reported to have intracranial tumours. Aneurysms, tumours, or other lesions may impinge or irritate the trigeminal nerve along its course. Uncommonly, an area of demyelination from multiple sclerosis may be the precipitant. We would like to present a series of unusual lesions, all of which initially presented with neuralgic-like symptoms and were refractory to treatment. Collated case series with photographs and imaging are reviewed in this paper. Discussion of case presentation and management are done for evaluation. A wide range of other compressive lesions can cause trigeminal neuralgia. This paper illustrates the clinical presentation of atypical trigeminal neuralgia and emphasises the value of diagnostic imaging in trigeminal neuralgia patient. Suggested algorithm for management of trigeminal neuralgia.

  10. Acute effects of capsaicin on energy expenditure and fat oxidation in negative energy balance.

    Directory of Open Access Journals (Sweden)

    Pilou L H R Janssens

    Full Text Available BACKGROUND: Addition of capsaicin (CAPS to the diet has been shown to increase energy expenditure; therefore capsaicin is an interesting target for anti-obesity therapy. AIM: We investigated the 24 h effects of CAPS on energy expenditure, substrate oxidation and blood pressure during 25% negative energy balance. METHODS: Subjects underwent four 36 h sessions in a respiration chamber for measurements of energy expenditure, substrate oxidation and blood pressure. They received 100% or 75% of their daily energy requirements in the conditions '100%CAPS', '100%Control', '75%CAPS' and '75%Control'. CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units (SHU with every meal. RESULTS: An induced negative energy balance of 25% was effectively a 20.5% negative energy balance due to adapting mechanisms. Diet-induced thermogenesis (DIT and resting energy expenditure (REE at 75%CAPS did not differ from DIT and REE at 100%Control, while at 75%Control these tended to be or were lower than at 100%Control (p = 0.05 and p = 0.02 respectively. Sleeping metabolic rate (SMR at 75%CAPS did not differ from SMR at 100%CAPS, while SMR at 75%Control was lower than at 100%CAPS (p = 0.04. Fat oxidation at 75%CAPS was higher than at 100%Control (p = 0.03, while with 75%Control it did not differ from 100%Control. Respiratory quotient (RQ was more decreased at 75%CAPS (p = 0.04 than at 75%Control (p = 0.05 when compared with 100%Control. Blood pressure did not differ between the four conditions. CONCLUSION: In an effectively 20.5% negative energy balance, consumption of 2.56 mg capsaicin per meal supports negative energy balance by counteracting the unfavorable negative energy balance effect of decrease in components of energy expenditure. Moreover, consumption of 2.56 mg capsaicin per meal promotes fat oxidation in negative energy balance and does not increase blood pressure significantly. TRIAL REGISTRATION

  11. Peripheral nerve field stimulation for trigeminal neuralgia, trigeminal neuropathic pain, and persistent idiopathic facial pain.

    Science.gov (United States)

    Klein, Johann; Sandi-Gahun, Sahr; Schackert, Gabriele; Juratli, Tareq A

    2016-04-01

    Peripheral nerve field stimulation (PNFS) is a promising modality for treatment of intractable facial pain. However, evidence is sparse. We are therefore presenting our experience with this technique in a small patient cohort. Records of 10 patients (five men, five women) with intractable facial pain who underwent implantation of one or several subcutaneous electrodes for trigeminal nerve field stimulation were retrospectively analyzed. Patients' data, including pain location, etiology, duration, previous treatments, long-term effects and complications, were evaluated. Four patients suffered from recurrent classical trigeminal neuralgia, one had classical trigeminal neuralgia and was medically unfit for microvascular decompression. Two patients suffered from trigeminal neuropathy attributed to multiple sclerosis, one from post-herpetic neuropathy, one from trigeminal neuropathy following radiation therapy and one from persistent idiopathic facial pain. Average patient age was 74.2 years (range 57-87), and average symptom duration was 10.6 years (range 2-17). Eight patients proceeded to implantation after successful trial. Average follow-up after implantation was 11.3 months (range 5-28). Using the visual analog scale, average pain intensity was 9.3 (range 7-10) preoperatively and 0.75 (range 0-3) postoperatively. Six patients reported absence of pain with stimulation; two had only slight constant pain without attacks. PNFS may be an effective treatment for refractory facial pain and yields high patient satisfaction. © International Headache Society 2015.

  12. KCNQ channels in nociceptive cold-sensing trigeminal ganglion neurons as therapeutic targets for treating orofacial cold hyperalgesia.

    Science.gov (United States)

    Abd-Elsayed, Alaa A; Ikeda, Ryo; Jia, Zhanfeng; Ling, Jennifer; Zuo, Xiaozhuo; Li, Min; Gu, Jianguo G

    2015-07-31

    Hyperexcitability of nociceptive afferent fibers is an underlying mechanism of neuropathic pain and ion channels involved in neuronal excitability are potentially therapeutic targets. KCNQ channels, a subfamily of voltage-gated K(+) channels mediating M-currents, play a key role in neuronal excitability. It is unknown whether KCNQ channels are involved in the excitability of nociceptive cold-sensing trigeminal afferent fibers and if so, whether they are therapeutic targets for orofacial cold hyperalgesia, an intractable trigeminal neuropathic pain. Patch-clamp recording technique was used to study M-currents and neuronal excitability of cold-sensing trigeminal ganglion neurons. Orofacial operant behavioral assessment was performed in animals with trigeminal neuropathic pain induced by oxaliplatin or by infraorbital nerve chronic constrictive injury. We showed that KCNQ channels were expressed on and mediated M-currents in rat nociceptive cold-sensing trigeminal ganglion (TG) neurons. The channels were involved in setting both resting membrane potentials and rheobase for firing action potentials in these cold-sensing TG neurons. Inhibition of KCNQ channels by linopirdine significantly decreased resting membrane potentials and the rheobase of these TG neurons. Linopirdine directly induced orofacial cold hyperalgesia when the KCNQ inhibitor was subcutaneously injected into rat orofacial regions. On the other hand, retigabine, a KCNQ channel potentiator, suppressed the excitability of nociceptive cold-sensing TG neurons. We further determined whether KCNQ channel could be a therapeutic target for orofacial cold hyperalgesia. Orofacial cold hyperalgesia was induced in rats either by the administration of oxaliplatin or by infraorbital nerve chronic constrictive injury. Using the orofacial operant test, we showed that retigabine dose-dependently alleviated orofacial cold hyperalgesia in both animal models. Taken together, these findings indicate that KCNQ channel plays a

  13. Neural tube derived Wnt signals cooperate with FGF signaling in the formation and differentiation of the trigeminal placodes

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    Graham Anthony

    2008-12-01

    Full Text Available Abstract Background Neurogenic placodes are focal thickenings of the embryonic ectoderm that form in the vertebrate head. It is within these structures that the precursors of the majority of the sensory neurons of the cranial ganglia are specified. The trigeminal placodes, the ophthalmic and maxillomandibular, form close to the midbrain-hindbrain boundary and many lines of evidence have shown that signals emanating from this level of the neuraxis are important for the development of the ophthalmic placode. Results Here, we provide the first evidence that both the ophthalmic and maxillomandibular placodes form under the influence of isthmic Wnt and FGF signals. Activated Wnt signals direct development of the Pax3 expressing ophthalmic placodal field and induce premature differentiation of both the ophthalmic and the maxillomandibular placodes. Similarly, overexpression of Fgf8 directs premature differentiation of the trigeminal placodes. Wnt signals require FGF receptor activity to initiate Pax3 expression and, subsequently, the expression of neural markers, such as Brn3a, within the cranial ectoderm. Furthermore, fibroblast growth factor signaling via the mitogen activated protein kinase pathway is required to maintain early neuronal differentiation within the trigeminal placodes. Conclusion We demonstrate the identity of inductive signals that are necessary for trigeminal ganglion formation. This is the first report that describes how isthmic derived Wnt signals act in concert with fibroblast growth factor signaling. Together, both are necessary and sufficient for the establishment and differentiation of the ophthalmic and maxillomandibular placodes and, consequently, the trigeminal ganglion.

  14. Rare cause of trigeminal neuralgia: Meckel's cave meningocele.

    Science.gov (United States)

    Alobaid, Abdullah; Schaeffer, Todd; Virojanapa, Justin; Dehdashti, Amir R

    2015-07-01

    The most common etiology of classic trigeminal neuralgia is vascular compression. However, other causes must be excluded. It is very unlikely that a meningocele presents with symptomatic trigeminal neuralgia. We present a rare case of a patient presenting with left trigeminal neuralgia. Thin-slice CT and MRI showed a transclival Meckel's cave meningocele. The patient underwent endoscopic repair of the meningocele, which resulted in complete resolution of her symptoms. Meckel's cave meningocele or encephalocele should be considered among the differential diagnoses of trigeminal neuralgia. Meningocele repair should be suggested as the first treatment option in this rare situation.

  15. Late results of bulbar trigeminal tractotomy

    Science.gov (United States)

    Moffie, D.

    1971-01-01

    Re-examination of eight patients in whom bulbar trigeminal tractotomy had been performed 13 to 15 years previously showed that four had no complaints, and the other four had only very slight complaints about pain. In two patients a Spiller-Frazier operation had been performed after tractotomy, in two patients exairesis of the infraorbital or supraorbital nerve had been done. As bulbar trigeminal tractotomy is a major operation and the risk of recurrence is substantial, the indications for this type of operation have to remain very restricted. Theories to explain the recovery of sensation are discussed. It is possible that regeneration of transected fibres is responsible for the loss of analgesia. Images PMID:5571314

  16. Trigeminal perineural spread of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hornik, Alejandro; Rosenblum, Jordan; Biller, Jose [Stritch School of Medicine, Loyola University Medical Center, Chicago (United States)

    2012-07-01

    A 55-year-old man had a five-day history of 'pins and needles' sensation on the left chin. Examination showed decreased pinprick sensation on the territory of the left mandibular branch of the trigeminal nerve. Brain magnetic resonance imaging (MRI) with gadolinium showed enhancement involving the left mandibular branch. Computed tomography (CT) of the chest, abdomen, and pelvis showed a left kidney mass diagnosed as renal carcinoma following nephrectomy. The 'numb-chin' syndrome heralds or accompanies systemic malignancies. Trigeminal perineural spread has been well-documented in head and neck neoplasms, however, to our knowledge, it has not been reported in renal neoplasms. (author)

  17. Trigeminal Neuralgia — A Debilitating Facial Pain

    Science.gov (United States)

    2011-01-01

    Trigeminal neuralgia (TN) is characterised by sudden usually unilateral severe, brief, stabbing, recurrent episodes of pain in the distribution of one or more branches of the trigeminal nerve. Diagnosis is largely based on clinical history due to the current lack of objective investigations. MRI can identify those patients who have TN secondary to an underlying pathology such as multiple sclerosis. The first line medical management remains carbamazepine, with oxcarbazepine being the second choice medication. Both percutaneous techniques targeting the Gasserian ganglion and microvascular decompression can be considered effective in the management of TN. Microvascular decompression is considered to provide on average, the longest pain free period post surgery. There are a number of TN associations and support groups which provide a valued service to patients and clinicians. Due to a dearth of high quality studies in many aspects of the condition, TN requires further research to be conducted. PMID:26527120

  18. Gastro-protective action of lafutidine mediated by capsaicin-sensitive afferent neurons without interaction with TRPV1 and involvement of endogenous prostaglandins

    Institute of Scientific and Technical Information of China (English)

    Kazuhiro Fukushima; Yoko Aoi; Shinichi Kato; Koji Takeuchi

    2006-01-01

    AIM: Lafutidine, a histamine H2 receptor antagonist,exhibits gastro-protective action mediated by capsaicinsensitive afferent neurons (CSN). We compared the effect between lafutidine and capsaicin, with respect to the interaction with endogenous prostaglandins (PG), nitric oxide (NO) and the afferent neurons, including transient receptor potential vanilloid subtype 1 (TRPV1).METHODS: Male SD rats and C57BL/6 mice, both wildtype and prostacyclin IP receptor knockout animals, were used after 18 h of fasting. Gastric lesions were induced by the po administration of HCI/ethanol (60% in 150 mmol/L HCI) in a volume of 1 mL for rats or 0.3 mL for mice.RESULTS: Both lafutidine and capsaicin (1-10 mg/kg,po) afforded dose-dependent protection against HCI/ethanol in rats and mice. The effects were attenuated by both the ablation of CSN and pretreatment with NG-nitroL-arginine methyl ester, yet only the effect of capsaicin was mitigated by prior administration of capsazepine, the TRPV1 antagonist, as well as indomethacin. Lafutidine protected the stomach against HCI/ethanol in IP receptor knockout mice, similar to wild-type animals, while capsaicin failed to afford protection in the animals lacking IP receptors. Neither of these agents affected the mucosal PGE2 or 6-keto PGF1α contents in rat stomachs. Capsaicin evoked an increase in [Ca2+]i in rat TRPV1-transfected HEK293 cells while lafutidine did not.CONCLUSION: These results suggest that although both lafutidine and capsaicin exhibit gastro-protective action mediated by CSN, the mode of their effects differs regarding the dependency on endogenous PGs/IP receptors and TRPV1. It is assumed that lafutidine interacts with CSN at yet unidentified sites other than TRPV1.

  19. Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX and Sirtuin1 (SIRT1

    Directory of Open Access Journals (Sweden)

    Ming-Hung Lin

    2016-06-01

    Full Text Available Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1 in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression.

  20. Effects of Capsaicin on Adipogenic Differentiation in Bovine Bone Marrow Mesenchymal Stem Cell

    Directory of Open Access Journals (Sweden)

    Jin Young Jeong

    2014-12-01

    Full Text Available Capsaicin is a major constituent of hot chili peppers that influences lipid metabolism in animals. In this study, we explored the effects of capsaicin on adipogenic differentiation of bovine bone marrow mesenchymal stem cells (BMSCs in a dose- and time-dependent manner. The BMSCs were treated with various concentrations of capsaicin (0, 0.1, 1, 5, and 10 μM for 2, 4, and 6 days. Capsaicin suppressed fat deposition significantly during adipogenic differentiation. Peroxisome proliferator-activated receptor gamma, cytosine-cytosine-adenosine-adenosine-thymidine/enhancer binding protein alpha, fatty acid binding protein 4, and stearoyl-CoA desaturase expression decreased after capsaicin treatment. We showed that the number of apoptotic cells increased in dose- and time-dependent manners. Furthermore, we found that capsaicin increased the expression levels of apoptotic genes, such as B-cell lymphoma 2-associated X protein and caspase 3. Overall, capsaicin inhibits fat deposition by triggering apoptosis.

  1. Comparison of Trigeminal and Postherpetic Neuralgia

    OpenAIRE

    Watson, C. Peter N.

    1996-01-01

    Although postherpetic neuralgia and trigeminal neuralgia (tic douloureux) are common causes of facial pain, they have very little in common aside from lancinating pain (other qualities of pain in each disorder are different). Each disorder affects different areas of the face and the treatment of each is quite dissimilar. The pathogenesis of these two disorders quite likely involves different mechanisms. This report reviews aspects of these two difficult pain problems, particularly with refere...

  2. Trigeminal Trophic Syndrome – Case Report

    Directory of Open Access Journals (Sweden)

    Boštjan Matos

    2015-05-01

    Full Text Available 1024x768 Trigeminal trophic syndrome is a rare condition resulting from compulsive self-manipulation of the skin after a peripheral or central injury to the trigeminal system. The classic triad consists of trigeminal anesthesia, facial paresthesias, and crescentric lateral nasal alar erosion and ulceration. Although the symptoms are visibly clear, the diagnosis is not easy to establish. The appearance of the ulcers mimics many other disease entities such as neoplasm, infection, granulomatous disease, vasculitis and factitial dermatitis. Trigeminal trophic syndrome should be considered with a positive neurologic history and when laboratory and biopsy workup is inconclusive. Once diagnosis is confirmed, treatment is complicated and often multidisciplinary. We report a case of a woman who developed a strictly unilateral crescent ulcer of the ala nasi after resection of an statoacoustic neurinoma. A clinician who is faced with a patient with nasal ulceration should consider this diagnosis.     Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  3. Can pontine trigeminal T2-hyperintensity suggest herpetic etiology of trigeminal neuralgia?

    Science.gov (United States)

    Russo, Carmela; Ugga, Lorenzo; Mazio, Federica; Capone, Elisa; D’Arco, Felice; Mankad, Kshitij; Caranci, Ferdinando; Marano, Enrico; Brunetti, Arturo

    2016-01-01

    Background Trigeminal neuralgia (TN) is usually classified into two different categories: idiopathic and secondary. We have investigated the frequency of brainstem pontine lesions in patients with idiopathic TN without multiple sclerosis (MS) or stroke, and their association with herpes zoster (HZ) infection. Methods Brain magnetic resonance imaging (MRI) studies of 28 patients with TN were retrospectively reviewed. Results We found seven patients with clinical suspicion of HZ infection and pontine T2 hyperintense lesions, associated with nerve atrophy in one case. Fifteen patients had a neurovascular conflict (NVC) without brainstem involvement, two of them associated with trigeminal atrophy, while four patients had only volumetric reduction of the nerve. In all patients MRI findings were ipsilateral to the side of TN. Conclusions Pontine T2 hyperintensities could be considered as a MRI sign of TN in patients without NVCs. This “trigeminal pontine sign” (TPS) is frequently found in association with herpetic infections. PMID:27942467

  4. Topical capsaicin for pain in osteoarthritis: A literature review.

    Science.gov (United States)

    Guedes, Vânia; Castro, João Paulo; Brito, Iva

    2016-08-26

    Osteoarthritis is the most common joint disorder worldwide. The predominant symptom, pain, is usually treated with acetaminophen or oral non-steroidal anti-inflammatory drugs, although they are associated with a significant risk of side effects. Topical capsaicin may represent an effective and safe alternative. The aim of this review is to examine the evidence for the efficacy and safety profile of topical capsaicin in the management of pain caused by osteoarthritis. Databases were searched for articles published between 2004 and 2016, in Portuguese, English or Spanish, using the search terms "capsaicin" and "osteoarthritis". When compared to placebo, it was found that topical capsaicin has a good safety profile and efficacy in reducing osteoarthritis pain of the hand, knee, hip or shoulder. However, the studies have significant limitations, the most important the difficulty of blinding. It is attributed to this review the strength of recommendation B. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  5. Natural Capsaicin in Capsicum chinense: Concentration vs. Origin

    Science.gov (United States)

    Capsaicin [N-vanillyl-8-methyl-6-(E) noneamide] is the most pungent of the group of compounds known as capsaicinoids in chili peppers. A survey was conducted to screen fruits of 307 hot pepper accessions of Capsicum chinense selected from the USDA germplasm collection for their major capsaicinoids c...

  6. Dietary grape seed polyphenols repress neuron and glia activation in trigeminal ganglion and trigeminal nucleus caudalis

    Directory of Open Access Journals (Sweden)

    Durham Paul L

    2010-12-01

    Full Text Available Abstract Background Inflammation and pain associated with temporomandibular joint disorder, a chronic disease that affects 15% of the adult population, involves activation of trigeminal ganglion nerves and development of peripheral and central sensitization. Natural products represent an underutilized resource in the pursuit of safe and effective ways to treat chronic inflammatory diseases. The goal of this study was to investigate effects of grape seed extract on neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis in response to persistent temporomandibular joint inflammation. Sprague Dawley rats were pretreated with 200 mg/kg/d MegaNatural-BP grape seed extract for 14 days prior to bilateral injections of complete Freund's adjuvant into the temporomandibular joint capsule. Results In response to grape seed extract, basal expression of mitogen-activated protein kinase phosphatase 1 was elevated in neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis, and expression of the glutamate aspartate transporter was increased in spinal glia. Rats on a normal diet injected with adjuvant exhibited greater basal levels of phosphorylated-p38 in trigeminal ganglia neurons and spinal neurons and microglia. Similarly, immunoreactive levels of OX-42 in microglia and glial fibrillary acidic protein in astrocytes were greatly increased in response to adjuvant. However, adjuvant-stimulated levels of phosphorylated-p38, OX-42, and glial fibrillary acidic protein were significantly repressed in extract treated animals. Furthermore, grape seed extract suppressed basal expression of the neuropeptide calcitonin gene-related peptide in spinal neurons. Conclusions Results from our study provide evidence that grape seed extract may be beneficial as a natural therapeutic option for temporomandibular joint disorders by suppressing development of peripheral and central sensitization.

  7. Involvement of trigeminal transition zone and laminated subnucleus caudalis in masseter muscle hypersensitivity associated with tooth inflammation.

    Directory of Open Access Journals (Sweden)

    Kohei Shimizu

    Full Text Available A rat model of pulpitis/periapical periodontitis was used to study mechanisms underlying extraterritorial enhancement of masseter response associated with tooth inflammation. Periapical bone loss gradually increased and peaked at 6 weeks after complete Freund's adjuvant (CFA application to the upper molar tooth pulp (M1. On day 3, the number of Fos-immunoreactive (IR cells was significantly larger in M1 CFA rats compared with M1 vehicle (veh rats in the trigeminal subnucleus interpolaris/caudalis transition zone (Vi/Vc. The number of Fos-IR cells was significantly larger in M1 CFA and masseter (Mass capsaicin applied (M1 CFA/Mass cap rats compared with M1 veh/Mass veh rats in the contralateral Vc and Vi/Vc. The number of phosphorylated extracellular signal-regulated kinase (pERK-IR cells was significantly larger in M1 CFA/Mass cap and M1 veh/Mass cap rats compared to Mass-vehicle applied rats with M1 vehicle or CFA in the Vi/Vc. Pulpal CFA application caused significant increase in the number of Fos-IR cells in the Vi/Vc but not Vc on week 6. The number of pERK-IR cells was significantly lager in the rats with capsaicin application to the Mass compared to Mass-vehicle treated rats after pulpal CFA- or vehicle-application. However, capsaicin application to the Mass did not further affect the number of Fos-IR cells in the Vi/Vc in pulpal CFA-applied rats. The digastric electromyographic (d-EMG activity after Mass-capsaicin application was significantly increased on day 3 and lasted longer at 6 weeks after pulpal CFA application, and these increase and duration were significantly attenuated by i.t. PD98059, a MEK1 inhibitor. These findings suggest that Vi/Vc and Vc neuronal excitation is involved in the facilitation of extraterritorial hyperalgesia for Mass primed with periapical periodontitis or acute pulpal-inflammation. Furthermore, phosphorylation of ERK in the Vi/Vc and Vc play pivotal roles in masseter hyperalgesia after pulpitis or

  8. Meckel's cave epidermoid with trigeminal neuralgia: CT findings.

    Science.gov (United States)

    Kapila, A; Steinbaum, S; Chakeres, D W

    1984-12-01

    An epidermoid tumor of Meckel's cave was found in a middle-aged woman with trigeminal neuralgia. On CT the lesion had negative attenuation numbers of fat and extended from an expanded Meckel's cave through the porous trigeminus into the ambient and cerebellopontine angle cisterns. Surgical excision provided relief of the patient's trigeminal neuralgia.

  9. Effect of tetrandrine on nitroglycerin induced activation of satellite cells in trigeminal ganglia%粉防己碱对硝酸甘油致三叉神经节卫星胶质细胞激活的影响

    Institute of Scientific and Technical Information of China (English)

    崔智威; 熊新; 陈力学; 秦光成; 陈连连; 周冀英

    2011-01-01

    Objective;To evaluate the effect of tetrandrine (Tet) on nitroglycerin ( GTN ) - induced activation of the satellite cells released inflammatory cytokines and to explore its mechanism. Method: Neonatal rat satellite cells of trigeminal ganglia were cultured and separated into three groups. Group CON: the cells were normal cultured; Group TGN: the cells were cultured with 0. 55 mmol·L" GTN; Group Tet: the cells were treated with 0. 55 mmol·L-1 GTN and 1 x 10 mol·L-1 Tet respectively. Cell viability after GTN and Tet was detected by AlamarBlue assay. The concentration change of intracellular Ca2 + ( [ Ca2 + ]I) in single satellite cell loaded with Fluo-3/AM was determined by laser scanning confocal microscopy. NF-kB and IL-1β mRNA levels were determined by FQ-PCR. Through double-immunofluorescent staining identifies satellite cells and determines the expression of NF-kB protein. Result: Satellite cells activities decreased with GTN stimulating, but according to the viability and modality of the cells, 1 x 10 mol·L-1Tet was the suitable prophylaxis. Tet can inhibit the elevation of cytosolic free calcium of rat satellite cell and decrease the mRNA and protein levels of NF-kB and the mRNA levels of IL-1β. Conclusion; Via preventing Ca2+ influxion, Tet inhibited NF-kB activation of satellite cell which decreased IL-1β expression.%目的:探讨粉防己碱(Tet)对硝酸甘油(GTN)激活的三叉神经节卫星胶质细胞释放的炎性因子的影响及其机制.方法:体外纯化培养新生大鼠三叉神经节卫星胶质细胞;实验分正常对照组、GTN组和Tet治疗组;GTN组和Tet治疗组利用0.55 mmol·L-1 GTN诱导卫星胶质细胞激活,Tet治疗组同时给予1×10-7 mol·L-1 Tet进行干预.应用AlamarBlue检测细胞存活情况;利用Fluo-3/AM探针负载后,激光共聚焦显微镜观测各实验组细胞内Ca2+浓度([Ca2+]i)的变化;FQ-PCR检测NF-κB,IL-1β mRNA的表达情况;利用双重免疫荧光技术同时对卫星胶

  10. Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review.

    Science.gov (United States)

    Srinivasan, Krishnapura

    2016-07-03

    Capsaicin, the pungent alkaloid of red pepper (Capsicum annuum) has been extensively studied for its biological effects which are of pharmacological relevance. These include: cardio protective influence, antilithogenic effect, antiinflammatory, and analgesia, thermogenic influence, and beneficial effects on gastrointestinal system. Therefore, capsaicinoids may have the potential clinical value for pain relief, cancer prevention and weight loss. It has been shown that capsaicinoids are potential agonists of capsaicin receptor (TRPV1). They could exert the effects not only through the receptor-dependent pathway but also through the receptor-independent one. The involvement of neuropeptide Substance P, serotonin, and somatostatin in the pharmacological actions of capsaicin has been extensively investigated. Topical application of capsaicin is proved to alleviate pain in arthritis, postoperative neuralgia, diabetic neuropathy, psoriasis, etc. Toxicological studies on capsaicin administered by different routes are documented. Capsaicin inhibits acid secretion, stimulates alkali and mucus secretion and particularly gastric mucosal blood flow which helps in prevention and healing of gastric ulcers. Antioxidant and antiinflammatory properties of capsaicin are established in a number of studies. Chemopreventive potential of capsaicin is evidenced in cell line studies. The health beneficial hypocholesterolemic influence of capsaicin besides being cardio protective has other implications, viz., prevention of cholesterol gallstones and protection of the structural integrity of erythrocytes under conditions of hypercholesterolemia. Beneficial influences of capsaicin on gastrointestinal system include digestive stimulant action and modulation of intestinal ultrastructure so as to enhance permeability to micronutrients.

  11. Anti-hyperalgesic effects of anti-serotonergic compounds on serotonin- and capsaicin-evoked thermal hyperalgesia in the rat.

    Science.gov (United States)

    Loyd, D R; Chen, P B; Hargreaves, K M

    2012-02-17

    The peripheral serotonergic system has been implicated in the modulation of an array of pain states, from migraine to fibromyalgia; however, the mechanism by which serotonin (5HT) induces pain is unclear. Peripherally released 5HT induces thermal hyperalgesia, possibly via modulation of the transient receptor potential V1 (TRPV1) channel, which is gated by various noxious stimuli, including capsaicin. We previously reported in vitro that 5HT increases calcium accumulation in the capsaicin-sensitive population of sensory neurons with a corresponding increase in proinflammatory neuropeptide release, and both are antagonized by pretreatment with 5HT(2A) and 5HT(3) antagonists, as well as the anti-migraine drug sumatriptan. In the current study, we extended these findings in vivo using the rat hind paw thermal assay to test the hypothesis that peripheral 5HT enhances TRPV1-evoked thermal hyperalgesia that can be attenuated with 5HT(2A) and 5HT(3) receptor antagonists, as well as sumatriptan. Thermal hyperalgesia and edema were established by 5HT injection (0.1-10 nmol/100 μl) into the rat hind paw, and the latency to paw withdrawal (PWL) from noxious heat was determined. Rats were then pretreated with either 5HT before capsaicin (3 nmol/10 μl), the 5HT(2A) receptor antagonist ketanserin or the 5HT(3) receptor antagonist granisetron (0.0001-0.1 nmol/100 μl) before 5HT and/or capsaicin, or the 5HT(1B/1D) receptor agonist sumatriptan (0.01-1 nmol/100 μl) before capsaicin, and PWL was determined. We report that 5HT pretreatment enhances TRPV1-evoked thermal hyperalgesia, which is attenuated with local pretreatment with ketanserin, granisetron, or sumatriptan. We also report that peripheral 5HT induced a similar magnitude of thermal hyperalgesia in male and female rats. Overall, our results provide in vivo evidence supporting an enhancing role of 5HT on TRPV1-evoked thermal hyperalgesia, which can be attenuated by peripheral serotonergic intervention.

  12. Significance of neurovascular contact in classical trigeminal neuralgia

    DEFF Research Database (Denmark)

    Maarbjerg, Stine; Wolfram, Frauke; Gozalov, Aydin

    2015-01-01

    Neurovascular contact is considered a frequent cause of classical trigeminal neuralgia and microvascular decompression with transposition of a blood vessel is preferred over other surgical options in medically refractory patients with classical trigeminal neuralgia. However, the prevalence...... of neurovascular contact has not been investigated in a representative cohort of patients with classical trigeminal neuralgia based in a neurological setting and using high-quality neuroimaging and blinded evaluation. We aimed to investigate whether presence and degree of neurovascular contact are correlated...... to pain side in classical trigeminal neuralgia. Consecutive classical trigeminal neuralgia patients with unilateral symptoms were referred to 3.0 T magnetic resonance imaging and included in a cross-sectional study. Magnetic resonance imaging scans were evaluated blindly and graded according to presence...

  13. Magnetic resonance tomographic angiography: diagnostic value in trigeminal neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Umehara, F. [Third Dept. of Internal Medicine, Faculty of Medicine, Kagoshima Univ. (Japan); Kamishima, K. [Div. of Diagnostic Neuroradiology, Kagoshima Univ. (Japan); Kashio, N. [Third Dept. of Internal Medicine, Faculty of Medicine, Kagoshima Univ. (Japan); Yamaguchi, K. [Div. of Diagnostic Neuroradiology, Kagoshima Univ. (Japan); Sakimoto, T.; Osame, M. [Third Dept. of Internal Medicine, Faculty of Medicine, Kagoshima Univ. (Japan)

    1995-07-01

    A combination of MRI, MR angiography and MR tomographic angiography (MRTA) was used to study the relationship of the root exit zone of the trigeminal nerve to surrounding vascular structures in seven patients with trigeminal neuralgia (TN) and ten patients with no evidence at a lesion in this region. MRTA is the technique for showing the relationship between vessels, cranial nerves and brain stem. MRTA clearly demonstrated the presence of a vessel at the root exit zone of the trigeminal nerve in all patients with TN. In the ten other patients, examination of 20 trigeminal nerves revealed that only one nerve (5%) was in contact with a vessel at the root exit zone. This study supports vascular compression of trigeminal nerves as a cause of TN, and demonstrates the value of MRTA as noninvasive technique for demonstrating compression. (orig.)

  14. Linear accelerator radiosurgery for trigeminal neuralgia: case report

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Hyong Geun [Dongguk University International Hospital, Goyang (Korea, Republic of)

    2006-06-15

    Trigeminal neuralgia is defined as an episodic electrical shock-like sensation in a dermatomal distribution of the trigeminal nerve. When medications fail to control pain, various procedures are used to attempt to control refractory pain. Of available procedures, stereotactic radiosurgery is the least invasive procedure and has been demonstrated to produce significant pain relief with minimal side effects. Recently, linear accelerators were introduced as a tool for radiosurgery of trigeminal neuralgia beneath the already accepted gamma unit. Author have experienced one case with trigeminal neuralgia treated with linear accelerator. The patient was treated with 85 Gy by means of 5 mm collimator directed to trigeminal nerve root entry zone. The patient obtained pain free without medication at 20 days after the procedure and remain pain free at 6 months after the procedure. He didn't experience facial numbness or other side effects.

  15. RNA Sequencing of Trigeminal Ganglia in Rattus Norvegicus after Glyceryl Trinitrate Infusion with Relevance to Migraine

    DEFF Research Database (Denmark)

    Hougaard Pedersen, Sara; Maretty, Lasse; Ramachandran, Roshni;

    2016-01-01

    INTRODUCTION: Infusion of glyceryl trinitrate (GTN), a donor of nitric oxide, induces immediate headache in humans that in migraineurs is followed by a delayed migraine attack. In order to achieve increased knowledge of mechanisms activated during GTN-infusion this present study aims to investigate...... transcriptional responses to GTN-infusion in the rat trigeminal ganglia. METHODS: Rats were infused with GTN or vehicle and trigeminal ganglia were isolated either 30 or 90 minutes post infusion. RNA sequencing was used to investigate transcriptomic changes in response to the treatment. Furthermore, we developed...... a novel method for Gene Set Analysis Of Variance (GSANOVA) to identify gene sets associated with transcriptional changes across time. RESULTS: 15 genes displayed significant changes in transcription levels in response to GTN-infusion. Ten of these genes showed either sustained up- or down...

  16. Persistent trigeminal artery associated with trigeminal neuralgia: hypothesis of neurovascular compression

    Energy Technology Data Exchange (ETDEWEB)

    Bondt, Bert-Jan de [University Hospital Maastricht, Department of Radiology, Maastricht (Netherlands); Stokroos, Robert [University Hospital Maastricht, Department of Otorhinolaryngology-Head and Neck Surgery, Maastricht (Netherlands); Casselman, Jan [AZ St. Jan, Department of Radiology, Bruges (Belgium)

    2007-01-15

    The aim of this study was to determine the prevalence of persistent trigeminal artery (PTA) associated with trigeminal neuralgia (TN). From January 1998 to January 2004, 288 MRI scans of patients examined for trigeminal deficits were retrospectively evaluated. MRI was performed at 1.5 T. Scan protocols included cerebral TSE T2-weighted imaging, contrast enhanced SE T1-weighted imaging and thin-section 3D T2-weighted imaging of the temporal bones, 3D TOF pre- and postcontrast MR angiography. TN was defined as episodes of intense stabbing, electric shock-like pain in areas of the face supplied by the trigeminal branches. Neurovascular compression (NVC) was assumed to be present if the patient showed clinical features of TN, if there was contact between an artery and the trigeminal nerve on the affected side, and if other pathology had been excluded. The prevalence and confidence intervals were calculated (95% CI of the prevalence was based on the exact binomial distribution). Of 288 patients, 136 matched the criteria for TN. In this series a PTA was detected in three patients, which in all patients was on the same side as the TN. The prevalence of a PTA in patients presenting with TN was 2.2% (CI 0.005-0.06). Previous studies have shown PTA as an incidental finding in 0.1-0.6% of cerebral angiograms. The prevalence of a PTA in patients with TN was 2.2%. With respect to the clinical significance, a PTA has to be considered in TN and the diagnosis of a PTA can easily be made using MR imaging/angiography. (orig.)

  17. CT-Guided Trigeminal Neuralgia in MS

    Directory of Open Access Journals (Sweden)

    Jalal Jalal Shokouhi

    2011-05-01

    Full Text Available Background/Objective: Multiple sclerosis has nonspecific"nsigns in MR images and clinic and also has pain,"none of the pain syndromes in MS cases is trigeminal"nneuralgia. 12 patients of our 38 trigeminal neuralgic"npatients etiology were known as MS cases. All of them"nwere young (20-40 years old."nIntroduction: Multiple sclerosis diagnosis is by clinic,"nMRI, CSF electrophoresis and evocked potensial tests."nImaging diagnostis is not suggestive and specific but in"nthis article we show imaging help not only in diagnosis"nalso in treatment of complications. Trigeminal neuralgia"nis the worse clinical condition in M.S patients and may"npush them to addiction or suicide."nMaterials and Methods: X-ray CT machine is used for"nguidance of L.P or coaxial 10cm needle with 22G, local"nanesthesia and ethanol injection. One time treatment"nmade for all patients and they were pain free after"ninterventional drug injection. 5-6 cc bupivicain 0.5%"nand 3-4cc ethanol 96% are used for treatment."nResults: All patients were pain free and very happy"nafter treatment. One of them had pain for 12 years"nand had tried all the other treatments with no good"nresponse. No complication was seen in our treatments."n15 to 20 minutes time is needed for each examination"nor treatment."nConclusion: Despite known MS cases and relative"ndrug therapies for patients it is not possible to treat"ntrigeminal paint except using interventional therapy"nand CT-guidance is exactive and easy. There was"nno complication except irritation in the middle ear"nbecause of Eustachian tube compression by injected"nvolume of drugs

  18. Diagnosis and behavior in autonomic trigeminal headaches

    Directory of Open Access Journals (Sweden)

    Erélido Hernández Valero

    2008-04-01

    Full Text Available Autonomic trigeminal headaches are primary headaches which include: cluster headaches, paroxistical hemicranea, and syndrome of unilateral headache in a neuralgic way, of short duration, accompanied by cojunctival injection and tearing and the continuous hemicranea. It is also accompanied by autonomic manifestations such as: palpebrate ptosis, tearing, nasal congestion, rhinorrhea, Horner syndrome (palpebrate ptosis, miosis, and enophthalmos and changes in the coloration of the periocular skin and in the cheek. In this paper we propose the most likely diagnosis and therapeutic to this nosologic entity

  19. Comparison of Trigeminal and Postherpetic Neuralgia

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    C Peter N Watson

    1996-01-01

    Full Text Available Although postherpetic neuralgia and trigeminal neuralgia (tic douloureux are common causes of facial pain, they have very little in common aside from lancinating pain (other qualities of pain in each disorder are different. Each disorder affects different areas of the face and the treatment of each is quite dissimilar. The pathogenesis of these two disorders quite likely involves different mechanisms. This report reviews aspects of these two difficult pain problems, particularly with reference to the work of the late Gerhard Fromm, to whom this is dedicated.

  20. Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain

    Directory of Open Access Journals (Sweden)

    Zhang Zhi-Jun

    2012-07-01

    Full Text Available Abstract Background Neuropathic pain in the trigeminal system is frequently observed in clinic, but the mechanisms involved are largely unknown. In addition, the function of immune cells and related chemicals in the mechanism of pain has been recognized, whereas few studies have addressed the potential role of chemokines in the trigeminal system in chronic pain. The present study was undertaken to test the hypothesis that chemokine C-C motif ligand 2 (CCL2-chemokine C-C motif receptor 2 (CCR2 signaling in the trigeminal nucleus is involved in the maintenance of trigeminal neuropathic pain. Methods The inferior alveolar nerve and mental nerve transection (IAMNT was used to induce trigeminal neuropathic pain. The expression of ATF3, CCL2, glial fibrillary acidic protein (GFAP, and CCR2 were detected by immunofluorescence histochemical staining and western blot. The cellular localization of CCL2 and CCR2 were examined by immunofluorescence double staining. The effect of a selective CCR2 antagonist, RS504393 on pain hypersensitivity was checked by behavioral testing. Results IAMNT induced persistent (>21 days heat hyperalgesia of the orofacial region and ATF3 expression in the mandibular division of the trigeminal ganglion. Meanwhile, CCL2 expression was increased in the medullary dorsal horn (MDH from 3 days to 21 days after IAMNT. The induced CCL2 was colocalized with astroglial marker GFAP, but not with neuronal marker NeuN or microglial marker OX-42. Astrocytes activation was also found in the MDH and it started at 3 days, peaked at 10 days and maintained at 21 days after IAMNT. In addition, CCR2 was upregulated by IAMNT in the ipsilateral medulla and lasted for more than 21 days. CCR2 was mainly colocalized with NeuN and few cells were colocalized with GFAP. Finally, intracisternal injection of CCR2 antagonist, RS504393 (1, 10 μg significantly attenuated IAMNT-induced heat hyperalgesia. Conclusion The data suggest that CCL2-CCR

  1. Spermatogonial stem cell sensitivity to capsaicin: An in vitro study

    Directory of Open Access Journals (Sweden)

    Ozer Aytekin

    2008-11-01

    Full Text Available Abstract Background Conflicting reports have been published on the sensitivity of spermatogenesis to capsaicin (CAP, the pungent ingredient of hot chili peppers. Here, the effect of CAP on germ cell survival was investigated by using two testis germ cell lines as a model. As CAP is a potent agonist of the transient receptor potential vanilloid receptor 1 (TRPV1 and no information was available of its expression in germ cells, we also studied the presence of TRPV1 in the cultured cells and in germ cells in situ. Methods The rat spermatogonial stem cell lines Gc-5spg and Gc-6spg were used to study the effects of different concentrations of CAP during 24 and 48 h. The response to CAP was first monitored by phase-contrast microscopy. As germ cells appear to undergo apoptosis in the presence of CAP, the activation of caspase 3 was studied using an anti activated caspase 3 antibody or by quantifying the amount of cells with DNA fragmentation using flow cytometry. Immunolocalization was done with an anti-TRPV1 antibody either with the use of confocal microscopy to follow live cell labeling (germ cells or on Bouin fixed paraffin embedded testicular tissues. The expression of TRPV1 by the cell lines and germ cells was confirmed by Western blots. Results Initial morphological observations indicated that CAP at concentrations ranging from 150 uM to 250 uM and after 24 and 48 h of exposure, had deleterious apoptotic-like effects on both cell lines: A large population of the CAP treated cell cultures showed signs of DNA fragmentation and caspase 3 activation. Quantification of the effect demonstrated a significant effect of CAP with doses of 150 uM in the Gc-5spg cell line and 200 uM in the Gc-6spg cell line, after 24 h of exposure. The effect was dose and time dependent in both cell lines. TRPV1, the receptor for CAP, was found to be expressed by the spermatogonial stem cells in vitro and also by premeiotic germ cells in situ. Conclusion CAP adversely

  2. Capsaicin: a potent inhibitor of carbonic anhydrase isoenzymes.

    Science.gov (United States)

    Arabaci, Betul; Gulcin, Ilhami; Alwasel, Saleh

    2014-07-10

    Carbonic anhydrase (CA, EC 4.2.1.1) is a zinc containing metalloenzyme that catalyzes the rapid and reversible conversion of carbon dioxide (CO2) and water (H2O) into a proton (H+) and bicarbonate (HCO3-) ion. On the other hand, capsaicin is the main component in hot chili peppers and is used extensively used in spices, food additives and drugs; it is responsible for their spicy flavor and pungent taste. There are sixteen known CA isoforms in humans. Human CA isoenzymes I, and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. In this study, the inhibition properties of capsaicin against the slow cytosolic isoform hCA I, and the ubiquitous and dominant rapid cytosolic isozymes hCA II were studied. Both CA isozymes were inhibited by capsaicin in the micromolar range. This naturally bioactive compound has a Ki of 696.15 µM against hCA I, and of 208.37 µM against hCA II.

  3. Capsaicin: A Potent Inhibitor of Carbonic Anhydrase Isoenzymes

    Directory of Open Access Journals (Sweden)

    Betul Arabaci

    2014-07-01

    Full Text Available Carbonic anhydrase (CA, EC 4.2.1.1 is a zinc containing metalloenzyme that catalyzes the rapid and reversible conversion of carbon dioxide (CO2 and water (H2O into a proton (H+ and bicarbonate (HCO3– ion. On the other hand, capsaicin is the main component in hot chili peppers and is used extensively used in spices, food additives and drugs; it is responsible for their spicy flavor and pungent taste. There are sixteen known CA isoforms in humans. Human CA isoenzymes I, and II (hCA I and hCA II are ubiquitous cytosolic isoforms. In this study, the inhibition properties of capsaicin against the slow cytosolic isoform hCA I, and the ubiquitous and dominant rapid cytosolic isozymes hCA II were studied. Both CA isozymes were inhibited by capsaicin in the micromolar range. This naturally bioactive compound has a Ki of 696.15 µM against hCA I, and of 208.37 µM against hCA II.

  4. Environmental risk assessment on capsaicin used as active substance for antifouling system on ships.

    Science.gov (United States)

    Wang, Jianbing; Shi, Ting; Yang, Xiaoling; Han, Wenya; Zhou, Yunrui

    2014-06-01

    Biodegradation experiments were carried out with capsaicin to evaluate its degradability. The results show that capsaicin was readily biodegradable under aerobic conditions. The values of Kow and the calculated bioconcentration factor indicate that capsaicin have a low potential for bioconcentration. The fish acute toxicity tests conducted with Brachydanio rerio show LC50 for capsaicin was 5.98 mg L(-1). The tests of alga growth inhibition conducted with Selenastrum capricornutum suggest EC50 for capsaicin was 114 mg L(-1). The calculated PNEC (Predicted No Effect Concentration) was 4.9×10(-4) mg L(-1). The average PEC (Predicted Environmental Concentration) for OECD-EU commercial harbor and marina were 3.99×10(-6) and 2.49×10(-5) mg L(-1), respectively. These indicate that the PEC was much less than the PNEC for capsaicin. The low Kp value of capsaicin suggests the data about the risk of capsaicin to sediment organisms can be waived. According to the results from the analysis of the degradation, bioaccumulation, toxicity and accumulation in sediment, it can be concluded that capsaicin used as active substance for antifouling system on ships poses relatively low risk to marine environment.

  5. The effects of Hot Pepper Extract and Capsaicin on Adipocyte Metabolism

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    Ching Sheng, Chu

    2008-03-01

    Full Text Available Objectives : The purpose of this study is to investigate the effects of hot pepper extract and capsaicin on the adipogenesis in 3T3-L1 cells, lipolysis in rat epididymal adipocytes and histological changes in porcine adipose tissue. Methods : Inhibiton of preadipocyte differentiation and/or stimulation of lipolysis play important roles in reducing obesity. 3T3-L1 preadipocytes were differentiated with adipogenic reagents by incubating for 3 days in the absence or presence of hot pepper extract or capsaicin ranging from 0.01 to 1㎎/㎖. The effects of hot pepper extract and capsaicin on adipogenesis were examined by measuring GPDH activity and by Oil Red O staining. Mature adipocytes from rat epididymal fat pad was incubated with hot pepper extract or capsaicin ranging from 0.01 to 1㎎/㎖ for 3 hrs. The effects of hot pepper extract and capsaicin on lipolysis were examined by measuring free glycerol released. Fat tissue from pig skin was injected with hot pepper extract or capsaicinCFP ranging from 0.1 to 10㎎/㎖ to examine the effects of hot pepper extract and capsaicin on histological changes under light microscopy. Results : The following results were obtained from present study on adipogenesis of preadipocytes, lipolysis of adipocytes and histological changes in fat tissue. 1. Hot pepper extract and capsaicin inhibited adipogenic differentiation at the concentration of 0.1 and 0.01㎎/㎖, respectively, indicating that capsaicin was more effective in inhibiting adipogenesis than hot pepper extract. 2. Hot pepper extract and capsaicin decreased the activity of glycerol-3-phosphate dehydrogenase(GPDH at the concentration of 0.1 and 0.01㎎/㎖, respectively, indicating that capsaicin was more effective in inhibiting adipogenic differentiation than hot pepper extract. 3. Hot pepper extract and capsaicin increased glycerol release at the concentration of 0.1㎎/㎖. There was no difference in lipolytic activity between hot pepper extract and

  6. Some like it hot: The emerging role of spicy food (capsaicin) in autoimmune diseases.

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    Deng, Yaxiong; Huang, Xin; Wu, Haijing; Zhao, Ming; Lu, Qianjin; Israeli, Eitan; Dahan, Shani; Blank, Miri; Shoenfeld, Yehuda

    2016-05-01

    Autoimmune diseases refer to a spectrum of diseases characterized by an active immune response against the host, which frequently involves increased autoantibody production. The pathogenesis of autoimmune diseases is multifactorial and the exploitation of novel effective treatment is urgent. Capsaicin is a nutritional factor, the active component of chili peppers, which is responsible for the pungent component of chili pepper. As a stimuli, capsaicin selectively activate transient receptor potential vanilloid subfamily 1(TRPV1) and exert various biological effects. This review discusses the effect of capsaicin through its receptor on the development and modulation of autoimmune diseases, which may shed light upon potential therapies in capsaicin-targeted approaches.

  7. Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases

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    Shaherin Basith

    2016-07-01

    Full Text Available Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neuro-protective functions. Moreover, emerging data indicate its clinical significance in treating vascular-related diseases, metabolic syndrome, and gastro-protective effects. The dearth of potent drugs for management of such disorders necessitates the urge for further research into the pharmacological aspects of capsaicin. This review summarizes the historical background, source, structure and analogues of capsaicin, and capsaicin-triggered TRPV1 signaling and desensitization processes. In particular, we will focus on the therapeutic roles of capsaicin and its analogues in both normal and pathophysiological conditions.

  8. Influence of topical capsaicin on facial sensitivity in response to experimental pain.

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    Lee, Y-S; Kho, H-S; Kim, Y-K; Chung, S-C

    2007-01-01

    Capsaicin, the pungent component of the red pepper, has been used as an analgesic in a variety of pain conditions, but sensory impairment after long-term treatment has been concerned. This study investigated the influence of topical capsaicin on various types of sensations including pain in the facial areas innervated by the mental nerve, and also evaluated whether the measurement of cutaneous current perception threshold (CPT) is reliable for the quantification of sensory change following capsaicin application. Twenty healthy subjects were given topical capsaicin cream (0.075%), which was applied to the mental area unilaterally, four times daily for 2 weeks. Burning sensation after capsaicin application gradually decreased with repeated applications. Repeated topical capsaicin resulted in reduced sensation to mechanical, heat and cold pain without changing non-painful tactile sensation. It also resulted in increased CPTs at 5 Hz and 250 Hz stimuli but no change in the CPTs at 2000 Hz from the first evaluation after capsaicin treatment and throughout the treatment period. This study demonstrated that topical capsaicin treatment for the management of chronic localized pain can be safely applied to the face without affecting non-painful normal sensations, and that CPT testing is a clinically useful tool for the quantification of sensory changes following capsaicin application.

  9. Gastric Lymphoma with Secondary Trigeminal Nerve Lymphoma: A Case Report

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    Warissara Rongthong

    2017-05-01

    Full Text Available Data supporting the role of radiotherapy in secondary trigeminal nerve lymphoma is scarce. Here, I report the case of 64-year-old Thai male diagnosed as gastric diffuse large B cell lymphoma with secondary trigeminal nerve lymphoma. He had previously received one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, followed by five cycles of rituximab plus CHOP (R-CHOP with intrathecal methotrexate (MTX and cytarabine (Ara-C. One month after the last cycle of R-CHOP, he developed a headache and numbness on the left side of his face. MRI revealed thickening of the left trigeminal nerve. He received one intrathecal injection of MTX and Ara-C, followed by systemic chemotherapy. After receiving intrathecal chemotherapy, his symptoms disappeared. Clinical response and MRI studies suggested secondary trigeminal nerve lymphoma. Two months later, our patient’s secondary trigeminal nerve lymphoma had progressed. Salvage whole brain irradiation (36 Gy with boost dose (50 Gy along the left trigeminal nerve was given. Unfortunately, our patient developed heart failure and expired during the radiotherapy session. In conclusion and specific to secondary central nervous system lymphoma (SCNSL, radiotherapy may benefit patients who fail to respond to systemic chemotherapy and palliative treatment. The results this report fail to support the role of radiotherapy in secondary trigeminal nerve lymphoma.

  10. Histopathological effects of radiosurgery on a human trigeminal nerve

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    Al-Otaibi, Faisal; Alhindi, Hindi; Alhebshi, Adnan; Albloushi, Monirah; Baeesa, Saleh; Hodaie, Mojgan

    2013-01-01

    Background: Radiosurgery is a well-established treatment modality for medically refractory trigeminal neuralgia. The exact mechanism of pain relief after radiosurgery is not clearly understood. Histopathology examination of the trigeminal nerve in humans after radiosurgery is rarely performed and has produced controversial results. Case Description: We report on a 45-year-old female who received radiosurgery treatment for trigeminal neuralgia by Cyberknife. A 6-mm portion of the cisternal segment of trigeminal nerve received a dose of 60 Gy. The clinical benefit started 10 days after therapy and continued for 8 months prior to a recurrence of her previous symptoms associated with mild background pain. She underwent microvascular decompression and partial sensory root sectioning. Atrophied trigeminal nerve rootlets were grossly noted intraoperatively under surgical microscope associated with changes in trigeminal nerve color to gray. A biopsy from the inferolateral surface of the nerve proximal to the midcisternal segment showed histological changes in the form of fibrosis and axonal degeneration. Conclusion: This case study supports the evidence of histological damage of the trigeminal nerve fibers after radiosurgery therapy. Whether or not the presence and degree of nerve damage correlate with the degree of clinical benefit and side effects are not revealed by this study and need to be explored in future studies. PMID:24605252

  11. The usual treatment of trigeminal autonomic cephalalgias.

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    Pareja, Juan A; Álvarez, Mónica

    2013-10-01

    Trigeminal autonomic cephalalgias include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, and rhinorrhea (SUNCT). Conventional pharmacological therapy can be successful in the majority of trigeminal autonomic cephalalgias patients. Most cluster headache attacks respond to 100% oxygen inhalation, or 6 mg subcutaneous sumatriptan. Nasal spray of sumatriptan (20 mg) or zolmitriptan (5 mg) are recommended as second choice. The bouts can be brought under control by a short course of corticosteroids (oral prednisone: 60-100 mg/day, or intravenous methylprednisolone: 250-500 mg/day, for 5 days, followed by tapering off the dosage), or by long-term prophylaxis with verapamil (at least 240 mg/day). Alternative long-term preventive medications include lithium carbonate (800-1600 mg/day), methylergonovine (0.4-1.2 mg/day), and topiramate (100-200 mg/day). As a rule, paroxysmal hemicrania responds to preventive treatment with indomethacin (75-150 mg/day). A short course of intravenous lidocaine (1-4 mg/kg/hour) can reduce the flow of attacks during exacerbations of SUNCT. Lamotrigine (100-300 mg/day) is the preventive drug of choice for SUNCT. Gabapentin (800-2700 mg/day), topiramate (50-300 mg/day), and carbamazepine (200-1600 mg/day) may be of help. © 2013 American Headache Society.

  12. Giant Trigeminal Schwannoma Presenting with Obstructive Hydrocephalus

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    Martinez-Gutierrez, Juan Carlos; Elder, Benjamin D; Olivi, Alessandro

    2015-01-01

    Trigeminal schwannomas represent between 0.07% and 0.36% of all intracranial tumors and 0.8% to 8% of intracranial schwannomas. Selection of the appropriate management strategy requires an understanding of the tumor’s natural history and treatment outcomes. This report describes the case of a 36-year-old male who presented with a three-month history of progressive headaches, dizziness, loss of balance, decreased sleep, and cognitive decline. Magnetic resonance imaging revealed a large enhancing lesion centered around the left Meckel’s cave and extending into both the middle and the posterior fossa with obstructive hydrocephalus secondary to compression of the fourth ventricle. Resection of the posterior fossa component of the tumor was performed in order to relieve the mass effect upon the brainstem without attempting a radical removal of the middle fossa component and a potential risk of further cognitive impairment. The pathological exam confirmed the diagnosis of a trigeminal schwannoma. The residual tumor showed progressive spontaneous volumetric shrinkage after a subtotal surgical resection. This case shows the value of a planned conservative surgery in complex schwannomas and highlights the challenges in interpreting the treatment responses in these benign tumors, whether approached surgically or with stereotactic radiation techniques. PMID:26719829

  13. Trigeminal neuralgia and persistent idiopathic facial pain.

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    Obermann, Mark; Holle, Dagny; Katsarava, Zaza

    2011-11-01

    Trigeminal neuralgia (TN) and persistent idiopathic facial pain (PIFP) are two of the most puzzling orofacial pain conditions and affected patients are often very difficult to treat. TN is characterized by paroxysms of brief but severe pain followed by asymptomatic periods without pain. In some patients a constant dull background pain may persist. This constant dull pain sometimes makes the distinction from PIFP difficult. PIFP is defined as continuous facial pain, typically localized in a circumscribed area of the face, which is not accompanied by any neurological or other lesion identified by clinical examination or clinical investigations. The pain usually does not stay within the usual anatomic boundaries of the trigeminal nerve distribution and is a diagnosis of exclusion. Epidemiologic evidence on TN, and even more so on PIFP, is quite scarce, but generally both conditions are considered to be rare diseases. The etiology and underlying pathophysiology of TN, and more so PIFP, remain unknown. Treatment is based on only few randomized controlled clinical trials and insufficiently evaluated surgical procedures.

  14. Trigeminal neuralgia: unilateral episodic facial pain.

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    Zakrzewska, Joanna M

    2015-06-01

    Trigeminal neuralgia is a rare cause of episodic unilateral facial pain and often in the initial presentation dental causes need to be eliminated, as it frequently presents in the lower trigeminal divisions. The pain description is characteristic of electric shock-like pain that is light-touch provoked, paroxysmal, and occurring daily; the condition can go into remission for weeks or months, however. The first-line drug is either carbamazepine or oxcarbazepine and has to be started in low doses. Over 70% of patients will initially obtain immediate relief. If efficacy or tolerability becomes a problem, then referral to a secondary care specialist should be made. Magnetic resonance imaging (MRI) scans can determine if there is a symptomatic cause and whether surgery is indicated. Surgical options provide longest pain relief periods. Patients need to be given information about all treatment options so they can make a decision about treatment. This report is adapted from paineurope 2014; Issue 4, © Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be viewed via the Web site: www.paineurope.com , at which health professionals can find links to the original articles and request copies of the quarterly publication and access additional pain education and pain management resources.

  15. Hemicrania continua. Unquestionably a trigeminal autonomic cephalalgia.

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    Vincent, Maurice B

    2013-05-01

    Hemicrania continua (HC) is a well-known primary headache. The present version of the International Classification of Headache Disorders lists HC in the "other primary headaches" group. However, evidence has emerged demonstrating that HC is a phenotype that belongs to the trigeminal autonomic cephalalgias together with cluster headache, paroxysmal hemicrania (PH), and short-lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing. This is supported by a common general clinical picture - paroxysmal, fluctuating, unilateral, side-locked headaches located to the ocular, frontal, and/or temporal regions, accompanied by ipsilateral autonomic dysfunctions including for example, tearing and conjunctival injection. Apart from the remarkable clinical similarities, the absolute and incomparable effect of indomethacin in HC parallels the effect of this drug in PH, suggesting a shared core pathogenesis. Finally, neuroimage findings demonstrate a posterior hypothalamic activation in HC similarly to cluster headache, PH, and short-lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing. Taken together, data indicate that HC is certainly a type of trigeminal autonomic cephalalgia that should no longer be placed in a group of miscellaneous primary headache disorders.

  16. The influence of repetitive painful stimulation on peripheral and trigeminal pain thresholds.

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    Dirkwinkel, Monika; Gralow, Ingrid; Colak-Ekici, Reyhan; Wolowski, Anne; Marziniak, Martin; Evers, Stefan

    2008-10-15

    We were interested in how continuous painful stimulation which is performed as inurement exercises in some Asian martial arts influences sensory and pain perception. Therefore, we examined 15 Kung Fu disciples before and after a 14 day period with repetitive inurement exercises and measured sensory and pain thresholds and intensities in both the trigeminal and the peripheral (peroneal nerve) region. The results of the probands were compared to those of 15 healthy control subjects who were performing sports without painful stimulation during this period. The probands showed a significantly decreased trigeminal pain intensity after repetitive electrical stimulation whereas the control subjects did not show any changes of sensory or pain perception during the study period. This suggests a change of central sensitisation and inhibitory control mechanisms in the nociceptive spinal or cerebral pathways by inurement exercises. In addition, pain thresholds showed an (not significant) increase after the study period whereas the control subjects showed a significant decrease of pain thresholds. In summary, our pilot study suggests that inurement exercises, i.e. repetitive painful stimulation, over a period of 14 days might induce changes of pain perception resulting in trigeminal pain habituation and higher pain thresholds.

  17. Endoscope-assisted retrosigmoid intradural suprameatal approach for surgical treatment of trigeminal schwannomas.

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    Samii, Madjid; Alimohamadi, Maysam; Gerganov, Venelin

    2014-12-01

    Trigeminal schwannomas are the most common intracranial nonvestibular schwannomas, and the dumbbell-shaped subtype is the most challenging. To evaluate the efficiency and safety of the endoscope-assisted retrosigmoid intradural suprameatal approach (EA-RISA) for dumbbell trigeminal schwannomas and to compare EA-RISA with classic RISA. A retrospective study of all patients with trigeminal schwannomas was performed with a focus on dumbbell tumors. Tumors were classified according to a modified Samii classification. Extent of tumor removal, outcome, and morbidity rates in the 2 subgroups were compared. Twenty patients were enrolled: 8 had dumbbell-shaped tumors (type C1), 8 had middle fossa tumors (A1-3), 3 had extracranial extension (D2), and 1 had posterior fossa tumor. Gross total resection was achieved in 15 and near-total resection in 5 patients. In 4 patients with dumbbell tumors, the classic RISA (Samii approach) was used; EA-RISA was used in the other 4 patients. The extent of petrous apex drilling was determined individually on the basis of the anatomic variability of suprameatal tubercle and degree of tumor-induced petrous apex erosion; in 2 patients, only minimal drilling was needed. The endoscope was applied after microsurgical tumor removal and in 3 of 4 patients revealed a significant unrecognized tumor remnant in the anterolateral and superolateral aspects of the Meckel cave. Thus, the EA-RISA technique allowed gross total resection of the tumor. The EA-RISA enlarges the exposure obtained with the classic RISA. Its judicious use can help achieve safe and radical removal of dumbbell-shaped trigeminal schwannomas (C1 type).

  18. Trigeminal neuralgia secondary to basilar impression: A case report

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    de Almeida Holanda, Maurus Marques; Pereira Neto, Normando Guedes; de Moura Peixoto, Gustavo; Pinheiro Santos, Rayan Haquim

    2015-01-01

    We report a rare case of trigeminal neuralgia. A 23-year-old woman with a history of 1 year of typical trigeminal neuralgia manifested the characteristics of basilar impression. Magnetic resonance imaging (MRI) demonstrated basilar impression, deformity of the posterior fossa with asymmetry of petrous bone, and compression of medulla oblongata in the topography of the odontoid apophysis. The operation was performed through a suboccipital craniectomy. The neuralgia disappeared after surgery and remains completely resolved until today. This is the second reported case of trigeminal neuralgia in a patient with basilar impression in Brazil. PMID:25972713

  19. Peripheral neuromodulation for the treatment of refractory trigeminal neuralgia

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    Naum Shaparin

    2015-01-01

    Full Text Available Trigeminal neuralgia is a type of orofacial pain that is diagnosed in 150,000 individuals each year, with an incidence of 12.6 per 100,000 person-years and a prevalence of 155 cases per 1,000,000 in the United States. Trigeminal neuralgia pain is characterized by sudden, severe, brief, stabbing or lancinating, recurrent episodes of pain in the distribution of one or more branches of the trigeminal nerve, which can cause significant suffering for the affected patient population.

  20. The μ opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway

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    Roberts-Thomson Sarah J

    2006-07-01

    Full Text Available Abstract Background The vanilloid receptor 1 (TRPV1 is critical in the development of inflammatory hyperalgesia. Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA pathway to potentiate TRPV1-mediated capsaicin responses. Such regulation may have significance in inflammatory pain. However, few functional receptor interactions that inhibit PKA-mediated potentiation of TRPV1 responses have been described. Results In the present studies we investigated the hypothesis that the μ opioid receptor (MOP agonist morphine can modulate forskolin-potentiated capsaicin responses through a cAMP-dependent PKA pathway. HEK293 cells were stably transfected with TRPV1 and MOP, and calcium (Ca2+ responses to injection of the TRPV1 agonist capsaicin were monitored in Fluo-3-loaded cells. Pre-treatment with morphine did not inhibit unpotentiated capsaicin-induced Ca2+ responses but significantly altered capsaicin responses potentiated by forskolin. TRPV1-mediated Ca2+ responses potentiated by the direct PKA activator 8-Br-cAMP and the PKC activator Phorbol-12-myristate-13-acetatewere not modulated by morphine. Immunohistochemical studies confirmed that the TRPV1 and MOP are co-expressed on cultured Dorsal Root Ganglion neurones, pointing towards the existence of a functional relationship between the G-protein coupled MOP and nociceptive TRPV1. Conclusion The results presented here indicate that the opioid receptor agonist morphine acts via inhibition of adenylate cyclase to inhibit PKA-potentiated TRPV1 responses. Targeting of peripheral opioid receptors may therefore have therapeutic potential as an intervention to prevent potentiation of TRPV1 responses through the PKA pathway in inflammation.

  1. RPF151, a novel capsaicin-like analogue: in vitro studies and in vivo preclinical antitumor evaluation in a breast cancer model.

    Science.gov (United States)

    Ferreira, Adilson Kleber; Tavares, Maurício Temotheo; Pasqualoto, Kerly Fernanda Mesquita; de Azevedo, Ricardo Alexandre; Teixeira, Sarah Fernandes; Ferreira-Junior, Wilson Alves; Bertin, Ariane Matiello; de-Sá-Junior, Paulo Luiz; Barbuto, José Alexandre Marzagão; Figueiredo, Carlos Rogério; Cury, Yara; Damião, Mariana Celestina Frojuello Costa Bernstorff; Parise-Filho, Roberto

    2015-09-01

    Capsaicin, the primary pungent component of the chili pepper, has antitumor activity. Herein, we describe the activity of RPF151, an alkyl sulfonamide analogue of capsaicin, against MDA-MB-231 breast cancer cells. RPF151 was synthetized, and molecular modeling was used to compare capsaicin and RPF151. Cytotoxicity of RPF151 on MDA-MB-231 was also evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis, by flow cytometry, and Western blot analysis of cycle-related proteins were used to evaluate the antiproliferative mechanisms. Apoptosis was evaluated by phosphatidyl-serine externalization, cleavage of Ac-YVAD-AMC, and Bcl-2 expression. The production of reactive oxygen species was evaluated by flow cytometry. RPF151 in vivo antitumor effects were investigated in murine MDA-MB-231 model. This study shows that RPF151 downregulated p21 and cyclins A, D1, and D3, leading to S-phase arrest and apoptosis. Although RPF151 has induced the activation of TRPV-1 and TRAIL-R1/DR4 and TRAIL-2/DR5 on the surface of MDA-MB-231 cells, its in vivo antitumor activity was TRPV-1-independent, thus suggesting that RPF151 should not have the same pungency-based limitation of capsaicin. In silico analysis corroborated the biological findings, showing that RPF151 has physicochemical improvements over capsaicin. Overall, the activity of RPF151 against MDA-MB-231 and its lower pungency suggest that it may have a relevant role in cancer therapy.

  2. Capsaicin and nitric oxide synthase inhibitor interact to evoke a hypothermic synergy.

    Science.gov (United States)

    Ding, Zhe; Cowan, Alan; Tallarida, Ronald; Rawls, Scott M

    2006-11-27

    The present study investigated the effect of a drug combination of capsaicin and L-NAME on hypothermia in rats. Capsaicin administration (0.1, 0.25, 0.5, 1 and 2mg/kg, i.m.) caused a significant hypothermia. L-NAME (50mg/kg, i.p.), a nonspecific nitric oxide synthase (NOS) inhibitor, was ineffective. For combined administration, progressively increasing doses of capsaicin (0.1, 0.25, 0.5, 1 and 2mg/kg, i.p.) were given with a non-hypothermic dose of L-NAME (50mg/kg, i.p.). Experiments revealed that L-NAME (50mg/kg, i.p.) enhanced the hypothermic response to capsaicin (0.25, 0.5, 1, and 2mg/kg, i.m.). Comparison of the graded dose-effect curves for capsaicin alone and capsaicin plus L-NAME revealed a significant difference (P<0.05), thus indicating synergy for the drug interaction. To determine if L-NAME acted centrally, a fixed dose of L-NAME (1mg/rat, i.c.v.) was given with graded doses of capsaicin (0.25, 0.5, 1, and 2mg/kg, i.m.). L-NAME (1mg/rat, i.c.v.) only enhanced the hypothermia at a single dose of capsaicin (0.5mg/kg, i.m.). The super-additive hypothermia produced by the concurrent administration of capsaicin and L-NAME (50mg/kg, i.p.) is the first evidence of synergy for a drug combination of capsaicin and a NOS inhibitor. The synergy is apparent only when L-NAME is given systemically, thus indicating that the inhibition of peripheral NO production enhances the hypothermic response to capsaicin.

  3. Eugenol inhibits the GABAA current in trigeminal ganglion neurons.

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    Lee, Sang Hoon; Moon, Jee Youn; Jung, Sung Jun; Kang, Jin Gu; Choi, Seung Pyo; Jang, Jun Ho

    2015-01-01

    Eugenol has sedative, antioxidant, anti-inflammatory, and analgesic effects, but also serves as an irritant through the regulation of a different set of ion channels. Activation of gamma aminobutyric acid (GABA) receptors on sensory neurons leads to the stabilization of neuronal excitability but contributes to formalin-induced inflammatory pain. In this study, we examined the effect of eugenol on the GABA-induced current in rat trigeminal ganglia (TG) neurons and in human embryonic kidney (HEK) 293 cells expressing the GABAA receptor α1β2γ2 subtype using the whole-cell patch clamp technique. RT-PCR and Western blot analysis were used to confirm the expression of GABAA receptor γ2 subunit mRNA and protein in the TG and hippocampus. Eugenol decreased the amplitude ratio of the GABA-induced current to 27.5 ± 3.2% (p eugenol inhibited GABA-induced currents in a dose-dependent manner. Application of eugenol also decreased the GABA response in the presence of a G-protein blocker. Eugenol pretreatment with different concentrations of GABA resulted in similar inhibition of the GABA-induced current in a non-competitive manner. In conclusion, eugenol inhibits the GABA-induced current in TG neurons and HEK 293 cells expressing the GABAA receptor in a reversible, dose-dependent, and non-competitive manner, but not via the G-protein pathway. We suggest that the GABAA receptor could be a molecular target for eugenol in the modulation of nociceptive information.

  4. Local administration of resveratrol inhibits excitability of nociceptive wide-dynamic range neurons in rat trigeminal spinal nucleus caudalis.

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    Shimazu, Yoshihito; Shibuya, Eri; Takehana, Shiori; Sekiguchi, Kenta; Oshima, Katsuo; Kamata, Hiroaki; Karibe, Hiroyuki; Takeda, Mamoru

    2016-06-01

    Although we recently reported that intravenous administration of resveratrol suppresses trigeminal nociception, the precise peripheral effect of resveratrol on nociceptive and non-nociceptive mechanical stimulation-induced trigeminal neuron activity in vivo remains to be determined. The aim of the present study was to investigate whether local subcutaneous administration of resveratrol attenuates mechanical stimulation-induced excitability of trigeminal spinal nucleus caudalis (SpVc) neuron activity in rats, in vivo. Extracellular single-unit recordings were made of SpVc wide-dynamic range (WDR) neuron activity in response to orofacial mechanical stimulation in pentobarbital-anesthetized rats. Neurons responded to non-noxious and noxious mechanical stimulation applied to the orofacial skin. Local subcutaneous administration of resveratrol (1-10mM) into the orofacial skin dose dependently and significantly reduced the mean number of SpVc WDR neurons firing in response to both non-noxious and noxious mechanical stimuli, with the maximal inhibition of discharge frequency in response to both stimuli being seen within 5min. These inhibitory effects were no longer evident after approximately 20min. The mean magnitude of inhibition by resveratrol (10mM) of SpVc neuron discharge frequency was almost equal to that of the local anesthetic 1% lidocaine (37mM). These results suggest that local injection of resveratrol into the peripheral receptive field suppresses the excitability of SpVc neurons, possibly via inhibition of Na(+) channels in the nociceptive nerve terminals of trigeminal ganglion neurons. Therefore, local subcutaneous administration of resveratrol may provide relief of trigeminal nociceptive pain, without side effects, thus contributing to the suite of complementary and alternative medicines used as local anesthetic agents.

  5. Comparison of P2X and TRPV1 receptors in ganglia or primary culture of trigeminal neurons and their modulation by NGF or serotonin

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    Giniatullin Rashid

    2006-03-01

    Full Text Available Abstract Background Cultured sensory neurons are a common experimental model to elucidate the molecular mechanisms of pain transduction typically involving activation of ATP-sensitive P2X or capsaicin-sensitive TRPV1 receptors. This applies also to trigeminal ganglion neurons that convey pain inputs from head tissues. Little is, however, known about the plasticity of these receptors on trigeminal neurons in culture, grown without adding the neurotrophin NGF which per se is a powerful algogen. The characteristics of such receptors after short-term culture were compared with those of ganglia. Furthermore, their modulation by chronically-applied serotonin or NGF was investigated. Results Rat or mouse neurons in culture mainly belonged to small and medium diameter neurons as observed in sections of trigeminal ganglia. Real time RT-PCR, Western blot analysis and immunocytochemistry showed upregulation of P2X3 and TRPV1 receptors after 1–4 days in culture (together with their more frequent co-localization, while P2X2 ones were unchanged. TRPV1 immunoreactivity was, however, lower in mouse ganglia and cultures. Intracellular Ca2+ imaging and whole-cell patch clamping showed functional P2X and TRPV1 receptors. Neurons exhibited a range of responses to the P2X agonist α, β-methylene-adenosine-5'-triphosphate indicating the presence of homomeric P2X3 receptors (selectively antagonized by A-317491 and heteromeric P2X2/3 receptors. The latter were observed in 16 % mouse neurons only. Despite upregulation of receptors in culture, neurons retained the potential for further enhancement of P2X3 receptors by 24 h NGF treatment. At this time point TRPV1 receptors had lost the facilitation observed after acute NGF application. Conversely, chronically-applied serotonin selectively upregulated TRPV1 receptors rather than P2X3 receptors. Conclusion Comparing ganglia and cultures offered the advantage of understanding early adaptive changes of nociception

  6. The effects of Tween-80 on the integrity of solutions of capsaicin: useful information for performing tussigenic challenges

    OpenAIRE

    Kopec, Scott E; Irwin, Richard S; DeBellis, Ronald J; Bohlke, Mark B; Maher, Timothy J

    2008-01-01

    Background Because variable results of capsaicin challenges may be due to the incomplete solubility of capsaicin, we sought to determine if the use of Tween-80 in solutions of capsaicin improves actual concentrations of freshly prepared and stored solutions. Methods Capsaicin solutions ranging from 0.5–128 μM were mixed with and without Tween-80. Samples of various concentrations were then stored under 4 environmental conditions: 4°C, protected from light; room temperature, protected from lig...

  7. Clinical outcome following micro-vascular decompression for trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Godugu Bhaskar Rao

    2015-07-01

    Conclusion: Micro-vascular decompression is safe and effective in producing good pain relief over a long term in patients with Trigeminal neuralgias refractive to medical treatment. [Int J Res Med Sci 2015; 3(7.000: 1741-1744

  8. Update on neuropathic pain treatment for trigeminal neuralgia

    Science.gov (United States)

    Al-Quliti, Khalid W.

    2015-01-01

    Trigeminal neuralgia is a syndrome of unilateral, paroxysmal, stabbing facial pain, originating from the trigeminal nerve. Careful history of typical symptoms is crucial for diagnosis. Most cases are caused by vascular compression of the trigeminal root adjacent to the pons leading to focal demyelination and ephaptic axonal transmission. Brain imaging is required to exclude secondary causes. Many medical and surgical treatments are available. Most patients respond well to pharmacotherapy; carbamazepine and oxcarbazepine are first line therapy, while lamotrigine and baclofen are considered second line treatments. Other drugs such as topiramate, levetiracetam, gabapentin, pregabalin, and botulinum toxin-A are alternative treatments. Surgical options are available if medications are no longer effective or tolerated. Microvascular decompression, gamma knife radiosurgery, and percutaneous rhizotomies are most promising surgical alternatives. This paper reviews the medical and surgical therapeutic options for the treatment of trigeminal neuralgia, based on available evidence and guidelines. PMID:25864062

  9. Reproducibility of the heat/capsaicin skin sensitization model in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Cavallone LF

    2013-11-01

    Full Text Available Laura F Cavallone,1 Karen Frey,1 Michael C Montana,1 Jeremy Joyal,1 Karen J Regina,1 Karin L Petersen,2 Robert W Gereau IV11Department of Anesthesiology, Washington University in St Louis, School of Medicine, St Louis, MO, USA; 2California Pacific Medical Center Research Institute, San Francisco, CA, USAIntroduction: Heat/capsaicin skin sensitization is a well-characterized human experimental model to induce hyperalgesia and allodynia. Using this model, gabapentin, among other drugs, was shown to significantly reduce cutaneous hyperalgesia compared to placebo. Since the larger thermal probes used in the original studies to produce heat sensitization are now commercially unavailable, we decided to assess whether previous findings could be replicated with a currently available smaller probe (heated area 9 cm2 versus 12.5–15.7 cm2.Study design and methods: After Institutional Review Board approval, 15 adult healthy volunteers participated in two study sessions, scheduled 1 week apart (Part A. In both sessions, subjects were exposed to the heat/capsaicin cutaneous sensitization model. Areas of hypersensitivity to brush stroke and von Frey (VF filament stimulation were measured at baseline and after rekindling of skin sensitization. Another group of 15 volunteers was exposed to an identical schedule and set of sensitization procedures, but, in each session, received either gabapentin or placebo (Part B.Results: Unlike previous reports, a similar reduction of areas of hyperalgesia was observed in all groups/sessions. Fading of areas of hyperalgesia over time was observed in Part A. In Part B, there was no difference in area reduction after gabapentin compared to placebo.Conclusion: When using smaller thermal probes than originally proposed, modifications of other parameters of sensitization and/or rekindling process may be needed to allow the heat/capsaicin sensitization protocol to be used as initially intended. Standardization and validation of

  10. Update of Diagnostic and Treatment of Trigeminal Neuralgia

    OpenAIRE

    Chumpitaz Cerrate, Víctor; Profesor Auxiliar del Departamento de Ciencias Básicas de la Facultad de Odontología UNMSM.; Sayán Sánchez, Cristian; Bachiller en Odontología de la Facultad de Odontología UNMSM.; Ruíz Ramírez, Eliberto; Bachiller en Odontología de la Facultad de Odontología UNMSM.; Franco Quino, César; Estudiante de Odontología de la Facultad de Odontología UNMSM.; Eche Herrera, Juan; Estudiante de Odontología de la Facultad de Odontología UNMSM.; Caldas Cueva, Victoria; Estudiante de Odontología de la Facultad de Odontología UNMSM.; Castro Rodríguez, Yuri; Estudiante de Odontología de la Facultad de Odontología UNMSM.; Erazo Paredes, Carlos; Bachiller en Odontología de la Facultad de Odontología UNMSM.

    2014-01-01

    Trigeminal neuralgia (TN) is a painful neuropathic condition that involves one or more branches of the trigeminal nerve. The pain produced for the TN is described as a very intense acute pain, stabbing or shooting, as an electric shock that usually occurs of form unilateral and that goes all the way of the nerve involved. It is important to make the opportune diagnosis of the condition of TN for adequately differentiate of some odontogenic painful conditions and to prevent that the patient re...

  11. Pain in trigeminal neuralgia: neurophysiology and measurement: a comprehensive review

    OpenAIRE

    Rastogi, S; S. Kumar; Mahendra, P.; Bansal, M; L. Chandra

    2013-01-01

    Abstract Trigeminal neuralgia (TN) is defined as sudden, usually unilateral, severe, brief, stabbing recurrent episodes of pain within the distribution of one or more branches of the trigeminal nerve. It is the most frequent cranial neuralgia, the incidence being 1 per 1,000,00 persons per year. Pain attacks start abruptly and last several seconds but may persist 1 to 2 minutes. The attacks are initiated by non painful physical stimulation of specific areas (trigger points or zones) that are ...

  12. Trigeminal small-fibre dysfunction in patients with diabetes mellitus

    DEFF Research Database (Denmark)

    Agostino, R.; Cruccu, G.; Iannetti, G. D.

    2000-01-01

    Objective: To investigate trigeminal small-fibre function in patients with diabetes mellitus. Methods: In 52 diabetic patients we studied the trigeminal laser evoked potentials after stimulation of the skin bordering the lower lip. In the 21 patients with the severest peripheral nerve damage we...... also studied the electrically evoked corneal reflex, Both responses are mediated by small myelinated afferents. Results: Laser evoked potentials had a longer mean latency and lower amplitude in diabetic patients than in normal subjects (P

  13. Wallenberg’s syndrome and symptomatic trigeminal neuralgia

    OpenAIRE

    Ordás, Carlos M.; Cuadrado, María L.; Simal, Patricia; Barahona, Raúl; Casas, Javier; Matías-Guiu Antem, Jordi; Porta-Etessam, Jesús

    2011-01-01

    Symptomatic trigeminal neuralgia due to a brainstem infarction is said to be rare. However, facial pain is not uncommon in Wallenberg’s syndrome. Facial pain related to a Wallenberg’s syndrome may be either persistent of intermittent, and occasionally occurs in brief attacks. Here, we report a patient with a right lateral medullary infarction who started having first division trigeminal neuralgia 1 month after the stroke. The pain paroxysms were suppressed with gabapentin.

  14. CCK enhances response to gastric distension by acting on capsaicin-insensitive vagal afferents

    NARCIS (Netherlands)

    van de Wall, EHEM; Duffy, P; Ritter, RC

    2005-01-01

    Capsaicin treatment destroys vagal afferent C fibers and markedly attenuates reduction of food intake and induction of hindbrain Fos expression by CCK. However, both anatomical and electrophysiological data indicate that some gastric vagal afferents are not destroyed by capsaicin. Because CCK enhanc

  15. In vitro percutaneous penetration of topically applied capsaicin in relation to in vivo sensation responses.

    Science.gov (United States)

    Magnusson, B M; Koskinen, L D

    2000-02-15

    Capsaicin, the primary pungent element in several spices, elicits a variety of physiological effects which are due to neurogenic responses. The aim of the study was to explore the in vivo sensation responses of capsaicin and to compare the results with the in vitro percutaneous absorption of the substance. The overall objectives were to determining an in vitro-in vivo correlation for capsaicin. Capsaicin was applied in a chamber on the volar forearm of twelve volunteers and in a flow-through diffusion chamber on excised human epidermal membranes. Topical administration of capsaicin produced a complex cutaneous sensation that changed in intensity and quality as a function of time and was characterized by sting, prick, burn and pain. Percutaneous steady-state penetrations of capsaicin with a receptor fluid consisting either of 4% bovine serum albumin in phosphate buffered saline or 50% ethanol in water were 28.2+/-2.7 and 29.6+/-2.9 microg/cm(2) per h, respectively. The corresponding cumulative penetrated amounts of capsaicin after 30 min were 14. 7+/-1.7 and 19.2+/-2.1 microg/cm(2), respectively. The present investigation indicates that there is a good correlation between in vivo physiological responses and in vitro percutaneous penetration of topically applied capsaicin.

  16. Identification of a Potential Target of Capsaicin by Computational Target Fishing

    Directory of Open Access Journals (Sweden)

    Xuan-yi Ye

    2015-01-01

    Full Text Available Capsaicin, the component responsible for the pungency of chili peppers, shows beneficial effects in many diseases, although the underlying mechanisms remain unclear. In the present study, the potential targets of capsaicin were predicted using PharmMapper and confirmed via chemical-protein interactome (CPI and molecular docking. Carbonic anhydrase 2 was identified as the main disease-related target, with the pharmacophore model matching well with the molecular features of capsaicin. The relation was confirmed by CPI and molecular docking and supported by previous research showing that capsaicin is a potent inhibitor of carbonic anhydrase isoenzymes. The present study provides a basis for understanding the mechanisms of action of capsaicin or those of other natural compounds.

  17. Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen?

    Science.gov (United States)

    Surh, Y J; Lee, S S

    1996-03-01

    Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent ingredient of the Capsicum fruits such as hot green and red peppers. Besides its use as a food additive in various spicy cuisines, capsaicin is currently utilized for therapeutic purposes to treat various peripheral painful conditions such as rheumatoid arthritis and diabetic neuropathy. Considering consumption of capsaicin as a food additive and its current medicinal application in humans, correct evaluation and precise assessment of any harmful effects of this compound are essential from the public health standpoint. Numerous investigations have been conducted to determine the potential mutagenic and carcinogenic activity of capsaicin and chili pepper, but results are discordant. This review briefly examines findings in the literature of studies testing mutagenicity and tumorigenicity of capsaicin and presents a possible mechanistic basis for the dual effects exerted by the compound.

  18. [Teflon granuloma after microvascular decompression of the trigeminal nerve root in a patient with recurrent trigeminal neuralgia].

    Science.gov (United States)

    Rzaev, D A; Kulikova, E V; Moysak, G I; Voronina, E I; Ageeva, T A

    2016-01-01

    The use of a Teflon implant for Jannetta surgery in patients with trigeminal neuralgia is complicated in rare cases by the development of a Teflon granuloma and can cause recurrent facial pain. The article presents a clinical case of a Teflon granuloma developed after microvascular decompression of the trigeminal nerve root, describes the surgical findings and histological picture, and analyzes the literature, causes of granuloma development, and recommendations for treatment of these patients.

  19. Exposure to Allergen Causes Changes in NTS Neural Activities after Intratracheal Capsaicin Application, in Endocannabinoid Levels and in the Glia Morphology of NTS.

    Science.gov (United States)

    Spaziano, Giuseppe; Luongo, Livio; Guida, Francesca; Petrosino, Stefania; Matteis, Maria; Palazzo, Enza; Sullo, Nikol; de Novellis, Vito; Di Marzo, Vincenzo; Rossi, Francesco; Maione, Sabatino; D'Agostino, Bruno

    2015-01-01

    Allergen exposure may induce changes in the brainstem secondary neurons, with neural sensitization of the nucleus solitary tract (NTS), which in turn can be considered one of the causes of the airway hyperresponsiveness, a characteristic feature of asthma. We evaluated neurofunctional, morphological, and biochemical changes in the NTS of naive or sensitized rats. To evaluate the cell firing activity of NTS, in vivo electrophysiological experiments were performed before and after capsaicin challenge in sensitized or naive rats. Immunohistochemical studies, endocannabinoid, and palmitoylethanolamide quantification in the NTS were also performed. This study provides evidence that allergen sensitization in the NTS induced: (1) increase in the neural firing response to intratracheal capsaicin application, (2) increase of endocannabinoid anandamide and palmitoylethanolamide, a reduction of 2-arachidonoylglycerol levels in the NTS, (3) glial cell activation, and (4) prevention by a Group III metabotropic glutamate receptor activation of neural firing response to intratracheal application of capsaicin in both naïve and sensitized rats. Therefore, normalization of ovalbumin-induced NTS neural sensitization could open up the prospect of new treatments based on the recovery of specific brain nuclei function and for extensive studies on acute or long-term efficacy of selective mGlu ligand, in models of bronchial hyperreactivity.

  20. Phenylpyrazolone derivatives inhibit gastric emptying in rats by a capsaicin-sensitive afferent pathway

    Directory of Open Access Journals (Sweden)

    A.M. Vinagre

    2009-11-01

    Full Text Available Dipyrone (Dp, 4-aminoantipyrine (AA and antipyrine (At administered iv and Dp administered icv delay gastric emptying (GE in rats. The participation of capsaicin (Cps-sensitive afferent fibers in this phenomenon was evaluated. Male Wistar rats were pretreated sc with Cps (50 mg/kg or vehicle between the first and second day of life and both groups were submitted to the eye-wiping test. GE was determined in these animals at the age of 8/9 weeks (weight: 200-300 g. Ten minutes before the study, the animals of both groups were treated iv with Dp, AA or At (240 μmol/kg, or saline; or treated icv with Dp (4 μmol/animal or saline. GE was determined 10 min after treatment by measuring % gastric retention (GR of saline labeled with phenol red 10 min after orogastric administration. Percent GR (mean ± SEM, N = 8 in animals pretreated with Cps and treated with Dp, AA or At (35.8 ± 3.2, 35.4 ± 2.2, and 35.6 ± 2%, respectively did not differ from the GR of saline-treated animals pretreated with vehicle (36.8 ± 2.8% and was significantly lower than in animals pretreated with vehicle and treated with the drugs (52.1 ± 2.8, 66.2 ± 4, and 55.8 ± 3%, respectively. The effect of icv administration of Dp (N = 6 was not modified by pretreatment with Cps (63.3 ± 5.7% compared to Dp-treated animals pretreated with vehicle (62.3 ± 2.4%. The results suggest the participation of capsaicin-sensitive afferent fibers in the delayed GE induced by iv administration of Dp, AA and At, but not of icv Dp.

  1. Acidification of rat TRPV1 alters the kinetics of capsaicin responses

    Directory of Open Access Journals (Sweden)

    Faltynek Connie R

    2005-09-01

    Full Text Available Abstract TRPV1 (vanilloid receptor 1 receptors are activated by a variety of ligands such as capsaicin, as well as by acidic conditions and temperatures above 42°C. These activators can enhance the potency of one another, shifting the activation curve for TRPV1 to the left. In this study, for example, we observed an approximately 10-fold shift in the capsaicin EC50 (640 nM to 45 nM for rat TRPV1 receptors expressed in HEK-293 cells when the pH was lowered from 7.4 to 5.5. To investigate potential causes for this shift in capsaicin potency, the rates of current activation and deactivation of whole-cell currents were measured in individual cells exposed to treatments of pH 5.5, 1 μM capsaicin or in combination. Acidic pH was found to both increase the activation rate and decrease the deactivation rate of capsaicin-activated currents providing a possible mechanism for the enhanced potency of capsaicin under acidic conditions. Utilizing a paired-pulse protocol, acidic pH slowed the capsaicin deactivation rate and was readily reversible. Moreover, the effect could occur under modestly acidic conditions (pH 6.5 that did not directly activate TRPV1. When TRPV1 was maximally activated by capsaicin and acidic pH, the apparent affinity of the novel and selective capsaicin-site competitive TRPV1 antagonist, A-425619, was reduced ~35 fold. This shift was overcome by reducing the capsaicin concentration co-applied with acidic pH. Since inflammation is associated with tissue acidosis, these findings enhance understanding of TRPV1 receptor responses in inflammatory pain where tissue acidosis is prevalent.

  2. Using Diffusion Tensor Imaging to Evaluate Microstructural Changes and Outcomes after Radiofrequency Rhizotomy of Trigeminal Nerves in Patients with Trigeminal Neuralgia.

    Science.gov (United States)

    Chen, Shu-Tian; Yang, Jen-Tsung; Yeh, Mei-Yu; Weng, Hsu-Huei; Chen, Chih-Feng; Tsai, Yuan-Hsiung

    2016-01-01

    Trigeminal neuralgia is characterized by facial pain that may be sudden, intense, and recurrent. Our aim was to investigate microstructural tissue changes of the trigeminal nerve in patients with trigeminal neuralgia resulting from neurovascular compression by diffusion tensor imaging, and to test the predictive value of diffusion tensor imaging for determining outcomes after radiofrequency rhizotomy. Forty-three patients with trigeminal neuralgia were recruited, and diffusion tensor imaging was performed before radiofrequency rhizotomy. By selecting the cisternal segment of the trigeminal nerve manually, we measured the volume of trigeminal nerve, fractional anisotropy, apparent diffusion coefficient, axial diffusivity, and radial diffusivity. The apparent diffusion coefficient and mean value of fractional anisotropy, axial diffusivity, and radial diffusivity were compared between the affected and normal side in the same patient, and were correlated with pre-rhizotomy and post-rhizotomy visual analogue scale pain scores. The results showed the affected side had significantly decreased fractional anisotropy, increased apparent diffusion coefficient and radial diffusivity, and no significant change of axial diffusivity. The volume of the trigeminal nerve on affected side was also significantly smaller. There was a trend of fractional anisotropy reduction and visual analogue scale pain score reduction (P = 0.072). The results suggest that demyelination without axonal injury, and decreased size of the trigeminal nerve, are the microstructural abnormalities of the trigeminal nerve in patients with trigeminal neuralgia caused by neurovascular compression. The application of diffusion tensor imaging in understanding the pathophysiology of trigeminal neuralgia, and predicting the treatment effect has potential and warrants further study.

  3. 面部炎症痛诱发大鼠三叉神经节神经元中辣椒素受体表达的改变%Facial pain induces the alteration of transient receptor potential vanilloid receptor 1 expression in rat trigeminal ganglion

    Institute of Scientific and Technical Information of China (English)

    裴磊; 林传友; 戴甲培; 殷光甫

    2007-01-01

    Objective To investigate the involvement of transient receptor potential vanilloid receptor 1 (TRPV1) in the facial inflammatory pain in relation to thermal hyperalgesia and cold pain sensation. Methods Facial inflammatory pain model was developed by subcutaneous injection of turpentine oil (TO) into rat facial area. Head withdrawal thermal latency (HWTL) and head withdrawal cold latency (HWCL) were measured once a day for 21 d after TO treatment using thermal and cold measurement apparatus. The immunohistochemical staining, cell-size frequency analysis and the survey of average optical density (OD) value were used to observe the changes of TRPV1 expression in the neurons of the trigeminal ganglion (TG), peripheral nerve fibers in the vibrissal pad, and central projection processes in the trigeminal sensory nuclei caudalis (Vc) on day 3, 5, 7, 14, and 21 after TO injection. Results HWTL and HWCL decreased significantly from day 1 to day 14 after TO injection with the lowest value on day 5 and day 3, respectively, and both recovered on day 21. The number of TRPVl-labeled neurons increased remarkably from day 1 to day 14 with a peak on day 7, and returned back to the normal level on day 21. In control rats, only small and medium-sized TG neurons were immunoreactive (IR) to TRPV1,and the TRPV1-IR terminals were abundant in both the vibrissal pad and the Vc. Within 2 weeks of inflammation, the expression of TRPV1 in small and medium-sized TG neurons increased obviously. Also the TRPV 1 stained terminals and fibers appeared more frequent and denser in both the vibrissal pad skin and throughout laminae I and the outer zone of laminae Ⅱ (Ⅱo) of Vc. Conclusion Facial inflammatory pain could induce hyperalgesia to noxious heat and cold stimuli,and result in increase of the numbers of TRPV1 positive TG neurons and the peripheral and central terminals of TG. These results suggest that the phenotypic changes of TRPV1 expression in small and medium-sized TG neurons and

  4. Gene expression microarray analysis of the spinal trigeminal nucleus in a rat model of migraine with aura

    Institute of Scientific and Technical Information of China (English)

    Ruozhuo Liu; Shengyuan Yu; Fengpeng Li; Enchao Qiu

    2012-01-01

    Cortical spreading depression can trigger migraine with aura and activate the trigeminal vascular system. To examine gene expression profiles in the spinal trigeminal nucleus in rats following cortical spreading depression-induced migraine with aura, a rat model was established by injection of 1 M potassium chloride, which induced cortical spreading depression. DNA microarray analysis revealed that, compared with the control group, the cortical spreading depression group showed seven upregulated genes-myosin heavy chain 1/2, myosin light chain 1, myosin light chain (phosphorylatable, fast skeletal muscle), actin alpha 1, homeobox B8, carbonic anhydrase 3 and an unknown gene. Two genes were downregulated-RGD1563441 and an unknown gene. Real-time quantitative reverse transcription-PCR and bioinformatics analysis indicated that these genes are involved in motility, cell migration, CO2 /nitric oxide homeostasis and signal transduction.

  5. Modulation of inflammatory mediators in the trigeminal ganglion by botulinum neurotoxin type A

    DEFF Research Database (Denmark)

    Edvinsson, Jacob; Warfvinge, Karin; Edvinsson, Lars

    2015-01-01

    BACKGROUND: Onabotulinumtoxin type A (BoNT-A) has been found to reduce pain in chronic migraine. The aim of the present study was to ask if BoNT-A can interact directly on sensory mechanisms in the trigeminal ganglion (TG) using an organ culture method. METHODS: To induce inflammation, rat TGs were...... that treatment with corticosteroids will reduce the symptoms of chronic migraine; however this remedy is associated with long-term side effects. Understanding the mechanisms involved in the expressional alterations may suggest novel ways to modify the changes and indicate novel therapeutics. The results...

  6. NEURAL PATHWAYS OF TRIGEMINAL PROPRIOCEPTIVE AFFERENTS COORDINATE ORAL MOTOR BEHAVIORS

    Institute of Scientific and Technical Information of China (English)

    Luo Pifu; Zhang Jingdong; Li Jishuo

    2003-01-01

    Neural pathways and synaptic connections from the trigeminal mesencephalic nucleus (Vme) neurons to the cranial motor nuclei were studied in the rat using double labelling methodologies of intracellular Neurobiotin staining combined with retrograde horseradish peroxidase (HRP) transport, anterograde biotinylated dextran amine (BDA) tracing combined with retrograde HRP transport, and a dual fluorescent labelling of BDA anterograde combined tracing with Cholera Toxin B (CTB) retrograde transport. Direct projections and synapses were demonstrated from Vme neuronal boutons to motoneurons (MNs) of the trigeminal motor nucleus (Vmo), the hypoglossal nucleus (Ⅻ) and the ambiguus nucleus (Amb). Indirect projections and pathways from Vme neurons to the cranial motor nuclei including Vmo, Ⅻ, the facial nucleus (Ⅶ) and the cervical spinal cord (C1~5) were seen to relay on their premotor neurons. The premotor neurons of above cranial motor nuclei were overlapped in bilateral premotor neuronal pool including the parvocellular reticular formation (PCRt) and its alpha division (PCRtA), the dorsomedial part of the spinal trigeminal nucleus oralis (Vodm), and interpolaris (Vidm), the medullary reticular nucleus dorsal division (MdD), the supratrigeminal region (Vsup) and the dorsomedial part of the principal trigeminal sensory nucleus (Vpdm).Synapses between Vme neuronal boutons and Vmo and Ⅻ MNs and Ⅻ premotor neurons were predominantly asymmetric.There were four types of synaptic organizations, i.e. synaptic convergence; synaptic divergence presynaptic inhibition and afferent feedforward inhibition seen between Vme boutons and Vmno, Ⅻ MNs and between Vme boutons and Ⅻ premotor neurons.The results of present studies have demonstrated direct pathways from the trigeminal proprioceptive afferents to Vmo, Ⅻ and Amb MNs, and indirect pathways from the trigeminal proprioceptive afferents to bilateral Vmno, Ⅻ, Ⅶ and C1~s via their premotor neurons. It provides

  7. Olfactory deficits decrease the time resolution for trigeminal lateralization.

    Science.gov (United States)

    Oleszkiewicz, A; Meusel, T; Güpfert, M; Westermann, B; Hummel, T; Welge-Lüssen, A

    2017-09-15

    To date the temporal resolution of the detection of almost simultaneously applied intranasal trigeminal stimuli is unknown. The aim of our study was to examine this temporal resolution in an/hyposmic subjects, who are known to have reduced trigeminal sensitivity and compare it with healthy controls. Participants were 20 posttraumatic an/hyposmic patients, and 23 healthy controls (matched with regard to sex and age). Olfactory function was tested psychophysically using the Sniffin´ Sticks test battery. Bilateral trigeminal stimulation was carried out using a birhinal high-precision olfactometer. The trigeminal stimulus used was CO₂ 60% v/v, the interstimulus interval ranged from 28 to 32s, stimulus duration was 200ms. Time-lags tested between right and left side of stimulation were at 40, 80, 120, 160 and 200ms. Subjects raised their left or right hand to indicate the side on which the stimulus had been perceived first. In both groups the accuracy in the trigeminal lateralization task increased with the time-lag but normosmic subjects significantly outperformed an/hyposmics in the 200ms time-lag condition. Normosmics significantly exceeded 50% chance level at the time-lag of 80ms, whereas an/hyposmics were only able to score above chance starting from 120ms time-lag. Lateralization scores significantly decreased with age. At a time lag of 200ms intranasal trigeminal stimuli can be lateralized. The reduced trigeminal sensitivity in patients with anosmia or hyposmia leads to an increased time lag required for correct perception of intranasal, almost simultaneously, applied stimuli. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Acute onset of trigeminal neuralgia, facial paresis and dysphagia after mild head injury.

    Science.gov (United States)

    Gkekas, Nikolaos; Primikiris, Panagiotis; Georgakoulias, Nikolaos

    2014-01-01

    The authors report the rare and first documented case of concomitant microvascular decompression of trigeminal, facial and glossopharyngeal nerves for the management of intractable to medical therapy acute onset of trigeminal neuralgia, facial paresis and dysphagia after mild head injury.

  9. Electrochemical impedance spectroscopy versus cyclic voltammetry for the electroanalytical sensing of capsaicin utilising screen printed carbon nanotube electrodes.

    Science.gov (United States)

    Randviir, Edward P; Metters, Jonathan P; Stainton, John; Banks, Craig E

    2013-05-21

    Screen printed carbon nanotube electrodes (SPEs) are explored as electroanalytical sensing platforms for the detection of capsaicin in both synthetic capsaicin solutions and capsaicin extracted from chillies and chilli sauces utilising both cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). It is found that the technique which is most applicable to the electroanalytical detection of capsaicin depends upon the analyte concentration: for the case of low capsaicin concentrations, CV is a more appropriate method as capsaicin exhibits characteristic voltammetric waves of peak heights relevant to the capsaicin concentration; but for the case of high capsaicin concentrations where the voltammetric waves merge and migrate out of the potential window, EIS is shown to be a more appropriate technique, owing to the observed linear increases in R(ct) with increasing concentration. Furthermore, we explore different types of screen printed carbon nanotube electrodes, namely single- and multi- walled carbon nanotubes, finding that they are technique-specific: for the case of low capsaicin concentrations, single-walled carbon nanotube SPEs are preferable (SW-SPE); yet for the case of EIS at high capsaicin concentrations, multi-walled carbon nanotube SPEs (MW-SPE) are preferred, based upon analytical responses. The analytical performance of CV and EIS is applied to the sensing of capsaicin in grown chillies and chilli sauces and is critically compared to 'gold standard' HPLC analysis.

  10. The capsaicin receptor TRPV1 is a crucial mediator of the noxious effects of mustard oil.

    Science.gov (United States)

    Everaerts, Wouter; Gees, Maarten; Alpizar, Yeranddy A; Farre, Ricard; Leten, Cindy; Apetrei, Aurelia; Dewachter, Ilse; van Leuven, Fred; Vennekens, Rudi; De Ridder, Dirk; Nilius, Bernd; Voets, Thomas; Talavera, Karel

    2011-02-22

    Mustard oil (MO) is a plant-derived irritant that has been extensively used in experimental models to induce pain and inflammation. The noxious effects of MO are currently ascribed to specific activation of the cation channel TRPA1 in nociceptive neurons. In contrast to this view, we show here that the capsaicin receptor TRPV1 has a surprisingly large contribution to aversive and pain responses and visceral irritation induced by MO. Furthermore, we found that this can be explained by previously unknown properties of this compound. First, MO has a bimodal effect on TRPA1, producing current inhibition at millimolar concentrations. Second, it directly and stably activates mouse and human recombinant TRPV1, as well as TRPV1 channels in mouse sensory neurons. Finally, physiological temperatures enhance MO-induced TRPV1 stimulation. Our results refute the dogma that TRPA1 is the sole nocisensor for MO and motivate a revision of the putative roles of these channels in models of MO-induced pain and inflammation. We propose that TRPV1 has a generalized role in the detection of irritant botanical defensive traits and in the coevolution of multiple mammalian and plant species.

  11. Antioxidant and iron-binding properties of curcumin, capsaicin, and S-allylcysteine reduce oxidative stress in rat brain homogenate.

    Science.gov (United States)

    Dairam, Amichand; Fogel, Ronen; Daya, Santy; Limson, Janice L

    2008-05-14

    Research demonstrates that antioxidants and metal chelators may be of beneficial use in the treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). This study investigated the antioxidant and metal-binding properties of curcumin, capsaicin, and S-allylcysteine, which are major components found in commonly used dietary spice ingredients turmeric, chilli, and garlic, respectively. The DPPH assay demonstrates that these compounds readily scavenge free radicals. These compounds significantly curtail iron- (Fe2+) and quinolinic acid (QA)-induced lipid peroxidation and potently scavenge the superoxide anion generated by 1 mM cyanide in rat brain homogenate. The ferrozine assay was used to measure the extent of Fe2+ chelation, and electrochemistry was employed to measure the Fe3+ binding activity of curcumin, capsaicin, and S-allylcysteine. Both assays demonstrate that these compounds bind Fe2+ and Fe3+ and prevent the redox cycling of iron, suggesting that this may be an additional method through which these agents reduce Fe2+-induced lipid peroxidation. This study demonstrates the antioxidant and metal-binding properties of these spice ingredients, and it is hereby postulate that these compounds have important implications in the prevention or treatment of neurodegenerative diseases such as AD.

  12. Effects of percutaneous trigeminal nerve electrical stimulation on behavior and the ability of learning and memory of epileptic rats induced by Pilocarpine%经皮三叉神经电刺激对匹罗卡品诱导的癫痫大鼠的行为及学习记忆能力的影响

    Institute of Scientific and Technical Information of China (English)

    王倩倩; 刘益民; 钟平; 张雷; 王玉

    2015-01-01

    Objective To observe the effects of percutaneous trigeminal nerve electrical stimulation on behavior and the ability of learning and memory of epileptic rats induced by Pilocarpine.Methods Thirty healthy male rats were randomly divided into normal control group, epilepsy model group and trigeminal nerve stimulation group ( TNS group) .Pilocarpine was used to inducestatus epileptics ( SE) in rats.TNS group rats were treated with percutaneous trigeminal nerve stimulation consecutive for 4 weeks.At 2 weeks after SE model established, video monitor were employed to record the frequency of spontaneous recurrence seizures ( SRS) , the intensity and duration of seizures. At 4 weeks after SE model established, rats in each group were taken Morris water maze test.The incubation period of rats finding underwater platform in the acquired training was recorded.The percentage of time and distance of rats searching target quadrant and the number of times through the platform were also recorded.Results Rats in control group didn''t show abnormal behavior throughout this experiment.During the process of animal model making, a rat died in epilepsy model group while 2 in TNS group.During-EEG monitoring, 2 rats in epilepsy model group died. Compared with epilepsy model group, the frequency of spontaneous recurrence seizure and the intensity of seizure significantly decreased, the average time of seizure significantly shortened in TNS group ( P<0.05 -0.01 ) in 2 weeks.In acquired training experiment, with the number of training increased, the average escape latent of experimental animals gradually reduced, the escape latent of rats in epilepsy model group were significantly prolonged compared with control group rats at each time-point ( all P<0.01 ) , while the average escape latency was significantly reduced in TNS group rats than epilepsy model group (P<0.05-0.01).Compared to control group, the percentage of time search and the percentage of navigation distance in the target

  13. Role of capsaicin-sensitive nerve fibers in uterine contractility in the rat.

    Science.gov (United States)

    Klukovits, Anna; Gaspar, Robert; Santha, Peter; Jancso, Gabor; Falkay, George

    2004-01-01

    The possible participation of capsaicin-sensitive sensory nerves in the modulation of neurogenic contractions was studied in nonpregnant and term pregnant rat uteri. Neurogenic contractions were elicited by electric field stimulation (40 V, 1-70 Hz, 0.6 msec) in intact uteri and uteri that were previously exposed to capsaicin in vitro. In capsaicin pretreated preparations obtained both from nonpregnant and term pregnant rats, a dose-dependent increase in the amplitude of uterine contractions was detected. Prior systemic treatment of the rats with capsaicin (130 mg/kg, s.c.) abolished the effect of in vitro capsaicin administration on the amplitude of neurogenic contractions. Use of a specific antagonist of calcitonin gene-related peptide revealed that depletion of this peptide, which normally elicits uterine smooth muscle relaxation, may be responsible for the increased responsiveness of the uterus to low-frequency stimulation. Experiments on the localization of calcitonin gene-related peptide in uterine tissue specimens exposed to capsaicin revealed dose-dependent depletion of calcitonin-gene related peptide-immunoreactive nerves innervating blood vessels and the myometrium. The findings indicate that capsaicin-sensitive afferent nerves, by the release of sensory neuropeptides, significantly contribute to the modulation of uterine contractility both in nonpregnant and term pregnant rats. It is suggested that uterine sensory nerve activation may be part of a trigger mechanism leading to preterm contractions evoked by, for example, inflammation.

  14. Novel Approaches to Extraction Methods in Recovery of Capsaicin from Habanero Pepper (CNPH 15.192).

    Science.gov (United States)

    Martins, Frederico S; Borges, Leonardo L; Ribeiro, Claudia S C; Reifschneider, Francisco J B; Conceição, Edemilson C

    2017-07-01

    The objective of this study was to compare three capsaicin extraction methods: Shoxlet, Ultrasound-assisted Extraction (UAE), and Shaker-assisted Extraction (SAE) from Habanero pepper, CNPH 15.192. The different parameters evaluated were alcohol degree, time extraction, and solid-solvent ratio using response surface methodology (RSM). The three parameters found significant (p extraction time for SAE. The optimum conditions for the capsaicin UAE and SAE were similar 95% alcohol degree, 30 minutes and solid-liquid ratio 2 mg/mL. The Soxhlet increased the extraction in 10-25%; however, long extraction times (45 minutes) degraded 2% capsaicin. The extraction of capsaicin was influenced by extraction method and by the operating conditions chosen. The optimized conditions provided savings of time, solvent, and herbal material. Prudent choice of the extraction method is essential to ensure optimal yield of extract, thereby making the study relevant and the knowledge gained useful for further exploitation and application of this resource. Habanero pepper, line CNPH 15.192, possess capsaicin in higher levels when compared with others speciesHigher levels of ethanolic strength are more suitable to obtain a higher levels of capsaicinBox-Behnken design indicates to be useful to explore the best conditions of ultrasound assisted extraction of capsaicin. Abbreviations used: Nomenclature UAE: Ultrasound-assisted Extraction; SAE: Shaker-assisted Extraction.

  15. Capsaicin and dihydrocapsaicin determination in chili pepper genotypes using ultra-fast liquid chromatography.

    Science.gov (United States)

    Usman, Magaji G; Rafii, Mohd Y; Ismail, Mohd R; Malek, Md Abdul; Latif, Mohammad Abdul

    2014-05-21

    Research was carried out to estimate the levels of capsaicin and dihydrocapsaicin that may be found in some heat tolerant chili pepper genotypes and to determine the degree of pungency as well as percentage capsaicin content of each of the analyzed peppers. A sensitive, precise, and specific ultra fast liquid chromatographic (UFLC) system was used for the separation, identification and quantitation of the capsaicinoids and the extraction solvent was acetonitrile. The method validation parameters, including linearity, precision, accuracy and recovery, yielded good results. Thus, the limit of detection was 0.045 µg/kg and 0.151 µg/kg for capsaicin and dihydrocapsaicin, respectively, whereas the limit of quantitation was 0.11 µg/kg and 0.368 µg/kg for capsaicin and dihydrocapsaicin. The calibration graph was linear from 0.05 to 0.50 µg/g for UFLC analysis. The inter- and intra-day precisions (relative standard deviation) were chili peppers studied except AVPP9703, AVPP0512, AVPP0307, AVPP0803 and AVPP0102 could serve as potential sources of capsaicin. On the other hand, only genotypes AVPP0506, AVPP0104, AVPP0002, C05573 and AVPP0805 gave a % capsaicin content that falls within the pungency limit that could make them recommendable as potential sources of capsaicin for the pharmaceutical industry.

  16. Capsaicin Modulates the Immune Cross Talk Between Human Mononuclears and Cells from Two Colon Carcinoma Lines.

    Science.gov (United States)

    Bessler, Hanna; Djaldetti, Meir

    2017-01-01

    Capsaicin, the pungent alkaloid of the chili peppers, has gained a worldwide reputation. In addition to its culinary assets, capsaicin possesses analgesic, anti-inflammatory, antimicrobial, and even carcinopreventive properties. Considering the linkage between chronic inflammation and tumorigenesis, the aim of the study was to evaluate the role of capsaicin in the immune interplay between human peripheral blood mononuclear cells (PBMCs) and HT-29 or RKO cells from human colon carcinoma lines. PBMCs were incubated for 24 hours with either HT-29 or RKO cells and concentrations of capsaicin ranging between 10 and 200 µM. Subsequently, the generation of the following cytokines was examined: tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ, IL-1ra, and IL-10. Capsaicin caused a concentration-dependent inhibition of colon cancer cells proliferation but had no effect on PBMC viability. 200 µM of capsaicin suppressed the production of all cytokines tested. At lower concentrations, the secretion of TNF-α, IL-1β, IFN-γ, IL-10, and IL-1ra was inhibited concentration-dependently, whereas that of IL-6 was stimulated. Capsaicin causes a concentration-dependent alteration of the immune balance between PBMC and colon carcinoma cells expressed as an inhibited generation of inflammatory cytokines. These findings indicate the existence of an additional immunomodulatory mechanism by which this alkaloid may prevent tumor development.

  17. Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus

    Directory of Open Access Journals (Sweden)

    Jasmin Luc

    2010-12-01

    Full Text Available Abstract Background Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS. Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in animal models of trigeminal sensitization. Therefore, in the present study, we evaluated glial cell activation in the trigeminal-spinal system following injection of the Complete Freund's Adjuvant (CFA into the temporomandibular joint, which generates inflammatory pain and trigeminal hypersensitivity. Results CFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the trigeminal ganglion by a strong increase in the number of GFAP-positive satellite glial cells encircling neurons and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity, but no signs of reactive astrogliosis were detected in the same areas. Since the purinergic system has been implicated in the activation of microglial cells during neuropathic pain, we have also evaluated the expression of the microglial-specific P2Y12 receptor subtype. No upregulation of this receptor was detected following induction of TMJ inflammation, suggesting that any possible role of P2Y12 in this paradigm of inflammatory pain does not involve changes in receptor expression. Conclusions Our data indicate that specific glial cell populations become activated in both the trigeminal ganglia and the CNS following induction of temporomandibular joint inflammation, and suggest that they might represent innovative targets for controlling pain during trigeminal nerve sensitization.

  18. [Transformation of trigeminal nerve tumor into malignant peripheral nerve sheath tumor (MPNST)].

    Science.gov (United States)

    Nenashev, E A; Cherekaev, V A; Kadasheva, A B; Kozlov, A V; Rotin, D L; Stepanian, M A

    2012-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare entity with only 18 cases of trigeminal nerve MPNST described by now and only one report of malignant transformation of trigeminal nerve tumor into MPNST published up to date. One more case of malignant transformation of trigeminal nerve (1st division) tumor into MPNST is demonstrated.

  19. Treatment of atypical trigeminal neuralgia with microvascular decompression

    Directory of Open Access Journals (Sweden)

    Hai Jian

    2006-01-01

    Full Text Available Aim: To explore the methods for achieving pain relief in patients with atypical trigeminal neuralgia (TN using microvascular decompression (MVD. Study Design and Settings: Retrospective study of 26 patients treated during the years 2000 to 2004. Materials and Methods: Twenty-six patients in whom vascular compression of the trigeminal nerve was identified by high definition magnetic resonance tomographic angiography (MRTA were treated with MVD for atypical TN in our department. Clinical presentations, surgical findings and clinical outcomes were analyzed retrospectively. Results: In this study, single trigeminal division was involved in only 2 patients (8% and two or three divisions in the other 24 patients (92%. Of prime importance is the fact that in 46.2% of the patients, several conflicting vessels were found in association. Location of the conflicts around the circumference of the trigeminal root was supero-medial to the root in 53.5%, supero-lateral in 30.8% and inferior in 15.7%. MVD for atypical TN resulted in complete pain relief in 50% of the patients with complete decompression, partial pain relief in 30.8% and poor pain relief or pain recurrence in 19.2% of the patients without complete decompression postoperatively. Conclusions: Complete decompression of the entire trigeminal root plays an important role in achieving pain relief in patients with atypical TN with MVD.

  20. MRI volumetry for the preoperative diagnosis of trigeminal neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Kress, Bodo; Schindler, Markus; Haehnel, Stefan; Sartor, Klaus; Stippich, Christoph [University of Heidelberg, Division of Neuroradiology, Department of Neurology, Medical Center, 69120 Heidelberg (Germany); Rasche, Dirk; Tronnier, Volker [University of Heidelberg, Department of Neurosurgery, Medical Center, 69120 Heidelberg (Germany)

    2005-07-01

    To assess whether quantitative measuring methods can help improve the reliability of MRI-based evaluations of the pathological role of a neurovascular conflict between an artery and the trigeminal nerve. In a prospective study, magnetic resonance images were obtained from 62 patients with unilateral facial pain and 50 healthy test subjects. In coronal T1- and T2-weighted sequences volume measurements were performed by regions of interest and compared intraindividually (healthy versus affected side in the patient populations and right versus left side in the group of test subjects) and on the basis of the different clinical pictures (t test for dependent and independent samples, p<0.05). In patients with trigeminal neuralgia, the affected nerve showed a smaller volume than the trigeminal nerve on the healthy side (p<0.001). Such a volume difference was noted neither in the other patients nor in the healthy test subjects. Quantitative MRI measurements allow a pathological neurovascular conflict to be distinguished from a nonpathological condition where an artery is in close proximity to the trigeminal nerve. The measured volume difference between the healthy and the affected nerve in patients with neuralgia is indicative of trigeminal nerve atrophy resulting from damage to the nerve. (orig.)

  1. Radiosurgery for the management of refractory trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Ajay Niranjan

    2016-01-01

    Full Text Available Gamma Knife stereotactic radiosurgery (SRS is a minimally invasive surgical approach for managing medically refractory trigeminal neuralgia (TN. The goal of trigeminal neuralgia SRS is to eliminate or reduce the facial pain in order to improve the quality of life. Over the past 28 years, 1250 patients have undergone gamma knife SRS for TN at our institution. In our retrospective review of 503 patients who underwent SRS for management of refractory TN, 449 patients (89% experienced initial pain relief at a median latency of 1 month. At the one year mark, 73% patients were pain free (with or without medications and 80% had pain control. Repeat radiosurgery was performed for 193 patients (43%. At the one year mark, 26% of these patients were completely pain free and 78% were pain free with or without medications. The role of gamma Knife SRS in the management of medically refractory trigeminal neuralgia has evolved over the past two decades. SRS is a minimally invasive procedure and is associated with 60-90% rate of pain relief in patents with medical refractory trigeminal neuralgia. Early intervention with SRS as the initial surgical procedure for management of refractory trigeminal neuralgia is associated with faster, better, and longer pain relief. As SRS is the least invasive procedure for TN, it is a good treatment option for patients with other high-risk medical conditions. SRS is an attractive alternative especially to those who do not want to accept the greater risk associated with other surgical procedures.

  2. Efficacy, safety and tolerability of duloxetine in idiopathic trigeminal neuralgia.

    Science.gov (United States)

    Anand, K S; Dhikav, V; Prasad, A; Shewtengna

    2011-04-01

    Trigeminal neuralgia (TN) is the most common type of neuralgia affecting facial region and is considered to be one of the most painful conditions. Treatment is often unsatisfactory. Newer treatment modalities are therefore being tried. Duloxetine is FDA approved drug for painful diabetic neuropathy and has been used in painful symptoms of depression as well. Safety and efficacy of duloxetine was evaluated in patients with trigeminal neuralgia; another chronically painful condition, in an open label manner. A total of 15 patients who fulfilled the diagnostic criteria of International Headache Society for Trigeminal Neuralgia were administered duloxetine 40 mg daily. The efficacy of the drug was evaluated by face scale and Likert's numerical scale. Statistically significant pain relief was reported in 9 out of 15 patients of trigeminal neuralgia. The pain relief was reported as early as in one week and was maintained for 16 weeks. The drug was well tolerated and side-effects reported were mild and reversible. No adverse drug reaction requiring hospitalisation or drug discontinuation was reported in the present study. Duloxetine showed statistically significant pain relief in trigeminal neuralgia. Double-blind, placebo-controlled studies are needed to confirm findings at a large scale.

  3. Treatment of trigeminal neuralgia: role of radiofrequency ablation

    Directory of Open Access Journals (Sweden)

    Dessy R Emril

    2010-12-01

    Full Text Available Dessy R Emril1 Kok-Yuen Ho21Neurology Department, Syiah Kuala University/Dr Zainoel Abidin Hospital, Banda Aceh, Indonesia; 2Pain Management Centre, Raffles Hospital, SingaporeAbstract: Trigeminal neuralgia (TN is a neuropathic pain condition affecting the face. It has a significant impact on the quality of life and physical function of patients. Evidence suggests that the likely etiology is vascular compression of the trigeminal nerve leading to focal demyelination and aberrant neural discharge. Secondary causes such as multiple sclerosis or brain tumors can also produce symptomatic TN. Treatment must be individualized to each patient. Carbamazepine remains the drug of choice in the first-line treatment of TN. Minimally invasive interventional pain therapies and surgery are possible options when drug therapy fails. Younger patients may benefit from microvascular decompression. Elderly patients with poor surgical risk may be more suitable for percutaneous trigeminal nerve rhizolysis. The technique of radiofrequency rhizolysis of the trigeminal nerve is described in detail in this review.Keywords: interventional treatment, minimally invasive, pain management, radiofrequency rhizolysis, trigeminal neuralgia 

  4. Peripheral neuromodulation for the treatment of refractory trigeminal neuralgia.

    Science.gov (United States)

    Shaparin, Naum; Gritsenko, Karina; Garcia-Roves, Diego Fernandez; Shah, Ushma; Schultz, Todd; DeLeon-Casasola, Oscar

    2015-01-01

    Trigeminal neuralgia is a type of orofacial pain that is diagnosed in 150,000 individuals each year, with an incidence of 12.6 per 100,000 person-years and a prevalence of 155 cases per 1,000,000 in the United States. Trigeminal neuralgia pain is characterized by sudden, severe, brief, stabbing or lancinating, recurrent episodes of pain in the distribution of one or more branches of the trigeminal nerve, which can cause significant suffering for the affected patient population. In many patients, a combination of medication and interventional treatments can be therapeutic, but is not always successful. Peripheral nerve stimulation has gained popularity as a simple and effective neuromodulation technique for the treatment of many pain conditions, including chronic headache disorders. Specifically in trigeminal neuralgia, neurostimulation of the supraorbital and infraorbital nerves may serve to provide relief of neuropathic pain by targeting the distal nerves that supply sensation to the areas of the face where the pain attacks occur, producing a field of paresthesia within the peripheral distribution of pain through the creation of an electric field in the vicinity of the leads. The purpose of the present case report is to introduce a new, less-invasive interventional technique, and to describe the authors' first experience with supraorbital and infraorbital neurostimulation therapy for the treatment of trigeminal neuralgia in a patient who had failed previous conservative management.

  5. Classification issues related to neuropathic trigeminal pain.

    Science.gov (United States)

    Zakrzewska, Joanna M

    2004-01-01

    The goal of a classification system of medical conditions is to facilitate accurate communication, to ensure that each condition is described uniformly and universally and that all data banks for the storage and retrieval of research and clinical data related to the conditions are consistent. Classification entails deciding which kinds of diagnostic entities should be recognized and how to order them in a meaningful way. Currently there are 3 major pain classification systems of relevance to orofacial pain: The International Association for the Study of Pain classification system, the International Headache Society classification system, and the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). All use different methodologies, and only the RDC/TMD take into account social and psychologic factors in the classification of conditions. Classification systems need to be reliable, valid, comprehensive, generalizable, and flexible, and they need to be tested using consensus views of experts as well as the available literature. There is an urgent need for a robust classification system for neuropathic trigeminal pain.

  6. Trigeminal neuralgia and facial nerve paralysis

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [IPOFG, Department of Radiology, Lisbon (Portugal)

    2005-03-01

    The trigeminal nerve is the largest of the cranial nerves. It provides sensory input from the face and motor innervation to the muscles of mastication. The facial nerve is the cranial nerve with the longest extracranial course, and its main functions include motor innervation to the muscles of facial expression, sensory control of lacrimation and salivation, control of the stapedial reflex and to carry taste sensation from the anterior two-thirds of the tongue. In order to be able adequately to image and follow the course of these cranial nerves and their main branches, a detailed knowledge of neuroanatomy is required. As we are dealing with very small anatomic structures, high resolution dedicated imaging studies are required to pick up normal and pathologic nerves. Whereas CT is best suited to demonstrate bony neurovascular foramina and canals, MRI is preferred to directly visualize the nerve. It is also the single technique able to detect pathologic processes afflicting the nerve without causing considerable expansion such as is usually the case in certain inflammatory/infectious conditions, perineural spread of malignancies and in very small intrinsic tumours. Because a long course from the brainstem nuclei to the peripheral branches is seen, it is useful to subdivide the nerve in several segments and then tailor the imaging modality and the imaging study to that specific segment. This is particularly true in cases where topographic diagnosis can be used to locate a lesion in the course of these nerves. (orig.)

  7. The acute effects of a lunch containing capsaicin on energy and substrate utilisation, hormones, and satiety

    OpenAIRE

    Smeets, Astrid J.; Westerterp-Plantenga, Margriet S.

    2009-01-01

    Background Addition of capsaicin to the diet has been shown to increase satiety and thermogenesis. The effects of capsaicin on ghrelin, peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), in relation to changes in hunger and satiety are unknown. Aim To test the acute effects of a lunch containing capsaicin on gut derived hormones (GLP-1, ghrelin, and PYY), energy expenditure (EE), substrate oxidation and satiety at lunch in the postprandial state. Methods Thirty subjects (age: 31 ± 14 years...

  8. Trigeminal nerve deficit in large and compressive acoustic neuromas and its correlation with MRI findings.

    Science.gov (United States)

    Karkas, Alexandre; Lamblin, Eléa; Meyer, Mikael; Gay, Emmanuel; Ternier, Jessica; Schmerber, Sébastien

    2014-10-01

    Evaluate the prevalence of preoperative trigeminal nerve deficit in large/compressive acoustic neuromas and try to find a correlation between pre/postoperative magnetic resonance imaging (MRI) findings and pre/postoperative trigeminal nerve deficit. Case series with chart review. University medical center. Retrospective study (1994-2009) including patients with stage 4 or 5 acoustic neuromas (Zini-Magnan classification). All patients underwent surgical resection. Pre- and postoperative trigeminal symptoms were sought. Imaging criteria were sought on pre- and 3-month postoperative MRI scans. Pearson χ(2) statistical test was used. Fifty-three patients (27 females, mean 51 years) were operated on. Preoperatively, 3 patients (5.7%) had trigeminal neuralgia, 1 (1.9%) trigeminal anesthesia, and 28 (52.8%) trigeminal hypoesthesia. Sixteen patients (30.2%) had no corneal reflex (ophthalmic branch); keratitis occurred in 1 patient (1.9%). Postoperatively, 2 patients (3.8%) had trigeminal neuralgia, 1 (1.9%) trigeminal anesthesia, and 24 (45.3%) trigeminal hypoesthesia. Twenty-six patients (49%) had no corneal reflex; keratitis occurred in 11 patients (20.7%). Preoperative trigeminal hypoesthesia was statistically correlated with impaction of the tumor on cerebellar peduncles on preoperative MRI. Postoperative trigeminal hypoesthesia was statistically correlated with nonvisibility of the trigeminal nerve on postoperative MRI. In large/compressive acoustic neuromas, trigeminal nerve deficit has to be sought to avoid corneal complications in particular. Trigeminal hypoesthesia occurs preoperatively in about half of the cases. It remains relatively stable after tumor removal, but there appears to be an increased rate of absent corneal reflex and keratitis postoperatively. We were able to correlate pre/postoperative trigeminal hypoesthesia with pre/postoperative MRI findings. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  9. Acupuncture for episodic cluster headache: a trigeminal approach.

    Science.gov (United States)

    Hayhoe, Simon

    2015-09-10

    Following evidence that acupuncture is clinically feasible and cost-effective in the treatment of headache, the UK National Institute for Health and Care Excellence recommends acupuncture as prophylactic treatment for migraine and tension headache. There has thus been expectation that other forms of headache should benefit also. Unfortunately, acupuncture has not generally been successful for cluster headache. This may be due to acupuncturists approaching the problem as one of severe migraine. In fact, cluster headache is classed as a trigeminal autonomic cephalgia. In this case report, episodic cluster headache is treated in the same way as has been shown effective for trigeminal neuralgia. Acupuncture is applied to the contralateral side at points appropriate for stimulating branches of the trigeminal nerve. Thus, ST2 is used for the infraorbital nerve, BL2 and Yuyao for the supratrochlear and supraorbital nerves, and Taiyang for the temporal branch of the zygomatic nerve.

  10. [Four cases of extracranial trigeminal benign neurogenic tumors].

    Science.gov (United States)

    Mada, Yusuke; Ueki, Yuji; Konno, Akiyoshi

    2014-11-01

    Extracranial trigeminal schwannomas are rare tumors accounting for about 10% of all trigeminal schwannomas. We report herein on four cases of extracranial trigeminal benign neurogenic tumors. The patients were aged between 39 and 75 years; they consisted of one male and three females. The origins of the schwannomas consisted of the maxillary nerve in two cases and the mandibular nerve in two cases. All cases were surgically treated using a transmaxillary approach in three cases, and a combination of the transcervical-parotid approach with a midline mandibulotomy in one case. In two cases, the schwannomas located in the pterygopalatine fossa were removed using a transmaxillary approach with the endoscope and the surgical microscope. Two patients underwent selective intravascular embolization of the feeding artery to reduce intraoperative bleeding, and they were less invasively treated via the transmaxillary approach.

  11. Trigeminal neuralgia: An overview of the clinical entity

    Directory of Open Access Journals (Sweden)

    Nargis Qayoom

    2015-01-01

    Full Text Available Trigeminal neuralgia (TN is a rare neurological disease that causes sudden, severe, brief, stabbing recurrent episodes of facial pain in one or more branches of the trigeminal nerve. Over the last few decades, there is evidence that TN may be a result of compression of the trigeminal nerve root at or near the dorsal root entry zone by a blood vessel. TN is treated on an outpatient basis, unless neurosurgical intervention is required. Treatment can be subdivided into pharmacologic therapy, percutaneous procedures, surgery, and radiosurgery. Medical therapy is often sufficient and effective, allowing surgical consideration only if pharmacological treatment fails. Medical therapy alone is an adequate treatment for 75% of patients.

  12. Rhabdomyomatous mesenchymal hamartoma of the face causing trigeminal neuralgia.

    Science.gov (United States)

    White, Leon R; Agrawal, Vaidehi; Sutton, Lisa; Balbosa, Aiysha C

    2015-06-03

    Rhabdomyomatous mesenchymal hamartoma (RMH) is a benign, potentially pigmented lesion that occurs in the head and neck region. It generally consists of haphazardly arranged skeletal muscle with adipose tissue, blood vessels, collagen and nerve fibers and is largely asymptomatic. Trigeminal neuralgia is pain due to compression of the trigeminal nerve. TN may be idiopathic or associated with lesion-mediated compression. We describe the case of a 14-year-old female presenting with trigeminal neuralgia (TN) associated with RMH. On initial consultation, the patient presented with a history of right-sided lower facial swelling, numbness, and pain. Evaluation by various specialists confirmed TN. Surgical resection of the lesion resolved the condition and pathology confirmed RMH. This is the first case report demonstrating RMH-mediated TN. Surgical resection of the RMH is a safe management approach for this diagnosis.

  13. A potent and selective calcitonin gene-related peptide (CGRP) receptor antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation: Role of CGRP in orofacial pain.

    Science.gov (United States)

    Romero-Reyes, Marcela; Pardi, Vanessa; Akerman, Simon

    2015-09-01

    Temporomandibular disorders (TMDs) are orofacial pains within the trigeminal distribution, which involve the masticatory musculature, the temporomandibular joint or both. Their pathophysiology remains unclear, as inflammatory mediators are thought to be involved, and clinically TMD presents pain and sometimes limitation of function, but often appears without gross indications of local inflammation, such as visible edema, redness and increase in temperature. Calcitonin gene-related peptide (CGRP) has been implicated in other pain disorders with trigeminal distribution, such as migraine, of which TMD shares a significant co-morbidity. CGRP causes activation and sensitization of trigeminal primary afferent neurons, independent of any inflammatory mechanisms, and thus may also be involved in TMD. Here we used a small molecule, selective CGRP receptor antagonist, MK-8825, to dissect the role of CGRP in inducing spontaneous nociceptive facial grooming behaviors, neuronal activation in the trigeminal nucleus, and systemic release of pro-inflammatory cytokines, in a mouse model of acute orofacial masseteric muscle pain that we have developed, as a surrogate of acute TMD. We show that CFA masseteric injection causes significant spontaneous orofacial pain behaviors, neuronal activation in the trigeminal nucleus, and release of interleukin-6 (IL-6). In mice pre-treated with MK-8825 there is a significant reduction in these spontaneous orofacial pain behaviors. Also, at 2 and 24h after CFA injection the level of Fos immunoreactivity in the trigeminal nucleus, used as a marker of neuronal activation, was much lower on both ipsilateral and contralateral sides after pre-treatment with MK-8825. There was no effect of MK-8825 on the release of IL-6. These data suggest that CGRP may be involved in TMD pathophysiology, but not via inflammatory mechanisms, at least in the acute stage. Furthermore, CGRP receptor antagonists may have therapeutic efficacy in the treatment of TMD, as they

  14. [A case of combined glossopharyngeal and trigeminal neuralgia].

    Science.gov (United States)

    Katoh, Masahito; Aida, Toshimitsu; Moriwaki, Takuya; Yoshino, Masami; Aoki, Takeshi; Abumiya, Takeo; Imamura, Hiroyuki; Ogata, Akihiko

    2012-06-01

    It is well-known that idiopathic neuralgias of the trigeminal and glossopharyngeal nerves are caused by vascular compression at the root entry zone of the cranial nerves. Because they are functional diseases, initial treatment is medical, especially with carbamazepine. However, if medical therapy fails to adequately manage the pain, microvascular decompression (MVD) is prescribed. Glossopharyngeal neuralgia is rare, and combined trigeminal and glossopharyngeal neuralgia is an extremely rare disorder. A 70-year-old woman presented herself to Hokkaido Neurosurgical Memorial Hospital because of paroxysms of lancinating pain in her left pharynx and another lancinating pain in her left cheek. Carbamazepine, which was prescribed at another hospital, favorably relieved the pain; however, drug eruption compelled her to discontinue the medication. The multi-volume method revealed that a root entry zone of the left glossopharyngeal nerve was compressed by the left posterior inferior cerebellar artery, and the left trigeminal artery was compressed by the left superior cerebellar artery. MVD for both nerves was performed employing a left lateral suboccipital craniotomy. She experienced complete relief of pain immediately after MVD. Combined trigeminal and glossopharyngeal neuralgia is extremely rare, but some groups noted a relatively high incidence of concurrent trigeminal neuralgia in patients with glossopharyngeal neuralgia up until the 1970's. Glossopharyngeal neuralgia includes pain near the gonion; therefore, there is an overlap of symptoms between glossopharyngeal and trigeminal neuralgias. By virtue of recent progress in imaging technology, minute preoperative evaluations of microvascular compression are possible. Until the 1970's, there might have been some misunderstanding regarding the overlap of symptoms because of lack of the concept of microvascular compression as a cause of neuralgia and rudimentary imaging technology. Minute evaluations of both symptoms and

  15. Stereotactic radiosurgery for trigeminal neuralgia: outcomes and complications.

    Science.gov (United States)

    Loescher, Alison R; Radatz, Matthias; Kemeny, Andras; Rowe, Jeremy

    2012-02-01

    Stereotactic radiosurgery is one of a number of recognised treatments for the management of trigeminal neuralgia refractory to drug therapy. The reported success of stereotactic radiosurgery in managing patients with trigeminal neuralgia varies in different units from 22 to 75%. This paper reports the outcomes of patients with trigeminal neuralgia who were treated at the National Centre for Stereotactic Radiosurgery in Sheffield, UK. The study reports the outcome of 72 patients treated consecutively between October 2004 and May 2008. Data were collected prospectively by a postal questionnaire sent to patients at 6, 12 and 24 months after treatment. The median age was 65.6 years (39 males: 33 females). Fourteen patients had secondary trigeminal neuralgia (eight multiple sclerosis). Fifteen of the patients included in the study were receiving a second treatment (an initial treatment having improved their pain significantly for at least 6 months). All radiosurgical procedures were performed using a single 4 mm collimator isocenter covering the region of the dorsal root entry zone with a maximal radiation dose of 80 Gy. The percentage of patients defined as having an excellent outcome (pain free without medication) was 39% after 6 months, 36% after 12 months and 64% after 24 months. The percentage of patients who reported being very satisfied with treatment was 71% after 6 months, 57% after 12 months and 53% after 24 months. Half the patients with secondary trigeminal neuralgia were pain free without medication after treatment, and 60% of patients who underwent a second treatment were pain free. A new trigeminal sensory deficit was reported by 31% of patients after radiosurgical treatment.

  16. Percutaneous Procedures for the Treatment of Trigeminal Neuralgia.

    Science.gov (United States)

    Bender, Matthew T; Bettegowda, Chetan

    2016-07-01

    Three major percutaneous procedures are currently used to treat trigeminal neuralgia (TN). Percutaneous balloon compression, glycerol rhizotomy, and radiofrequency thermocoagulation interrupt afferent pain fibers by injury to the trigeminal nerve root or ganglion. Each is capable of offering immediate and durable pain relief. Each is associated with relatively low, but variable rates of complications. Patient heterogeneity, technical variation, and nonstandard outcomes plague the existing outcomes literature and limit comparisons of treatments. Rendering treatment selection a function of individual physician preference and practice patterns. Randomized, prospective trials are needed; in the meantime, percutaneous rhizotomy remains an excellent treatment for selected patients.

  17. Intraoperative visualisation of the trigeminal cistern. Intraoperative Darstellung der Trigeminuszisterne

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    Bockermann, V.; Dieckmann, G. (Goettingen Univ. (Germany). Abt. Funktionelle Neurochirurgie)

    1991-07-01

    Percutaneous retrogassarian glycerol rhizotomy has passed the test of time as an immediately effective and reliable method for the treatment of trigeminal neuralgia. X-ray-assisted puncture of the trigeminal cistern and contrast-enhanced intraoperative visualisation techniques are absolute requirements of this surgical measure and invariably precede any further steps taken by the surgeon. The use of state-of-the-art fluoroscopic methods ensures that ample information is even obtained from the images of the base-of-scull region. (orig.).

  18. Trigeminal hypoplasia due to vertebrobasilar dolichoectasia: A new entity

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    Abhishek Jha

    2015-01-01

    Full Text Available The term "vertebrobasilar dolichoectasia" refers to anomalous dilatation of the intracranial arteries associated with elongation or tortuosity of the affected vessels. The etiology of the disease is unknown and is usually detected incidentally. The predominant clinical manifestations arise due to the mass effect of the dilated vessels and may include cranial nerve compression, extrinsic aqueductal compression, motor and sensory disturbances. Trigeminal hypoplasia is a very uncommon condition, usually described in association with Goldenhar-Gorlin syndrome and has not yet been attributed to vertebrobasilar dolichoectasia. The current case report highlights this rare association of trigeminal nerve hypoplasia and vertebrobasilar dolichoectasia, leading to hemifacial and corneal anesthesia.

  19. Measurement of Trigeminal Neuralgia Pain: Penn Facial Pain Scale.

    Science.gov (United States)

    Lee, John Y K

    2016-07-01

    Pain is a subjective experience that cannot be directly measured. Therefore, patient-reported outcome is one of the currently accepted methods to capture pain intensity and its impact on activities of daily living. This article focuses on five patient-reported outcomes that have been used to measure trigeminal neuralgia pain-Visual Analog Scale, numeric rating scale, Barrow Neurological Institute Pain Intensity Score, McGill Pain Questionnaire, and Penn Facial Pain Scale. Each scale is evaluated for its practicality, applicability, comprehensiveness, reliability, validity, and sensitivity to measuring trigeminal neuralgia pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Capsaicin, arterial hypertensive crisis and acute myocardial infarction associated with high levels of thyroid stimulating hormone.

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo; Di Bella, Gianluca; Cerrito, Marco; Coglitore, Sebastiano

    2009-05-01

    Chili peppers are rich in capsaicin. The potent vasodilator calcitonin gene-related peptide (CGRP) is stored in a population of C-fiber afferents that are sensitive to capsaicin. CGRP and peptides released from cardiac C fibers have a beneficial effect in myocardial ischemia and reperfusion. It has been reported that capsaicin pretreatment deplete cardiac C-fiber peptide stores. Furthermore, it has also been reported that capsaicin-treated pigs significantly increase mean arterial blood pressure compared with controls and that the decrease in CGRP synthesis and release contributes to the elevated blood pressure. It has also been reported that sub-clinical hypothyroidism is associated with a significant risk of coronary heart disease (CHD). We present a case of arterial hypertensive crisis and acute myocardial infarction in a 59-year-old Italian man with high levels of thyroid stimulating hormone and with an abundant ingestion of peppers and of chili peppers which occurred the day before.

  1. Capsaicin and Dihydrocapsaicin Determination in Chili Pepper Genotypes Using Ultra-Fast Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Magaji G. Usman

    2014-05-01

    Full Text Available Research was carried out to estimate the levels of capsaicin and dihydrocapsaicin that may be found in some heat tolerant chili pepper genotypes and to determine the degree of pungency as well as percentage capsaicin content of each of the analyzed peppers. A sensitive, precise, and specific ultra fast liquid chromatographic (UFLC system was used for the separation, identification and quantitation of the capsaicinoids and the extraction solvent was acetonitrile. The method validation parameters, including linearity, precision, accuracy and recovery, yielded good results. Thus, the limit of detection was 0.045 µg/kg and 0.151 µg/kg for capsaicin and dihydrocapsaicin, respectively, whereas the limit of quantitation was 0.11 µg/kg and 0.368 µg/kg for capsaicin and dihydrocapsaicin. The calibration graph was linear from 0.05 to 0.50 µg/g for UFLC analysis. The inter- and intra-day precisions (relative standard deviation were <5.0% for capsaicin and <9.9% for dihydrocapsaicin while the average recoveries obtained were quantitative (89.4%–90.1% for capsaicin, 92.4%–95.2% for dihydrocapsaicin, indicating good accuracy of the UFLC method. AVPP0705, AVPP0506, AVPP0104, AVPP0002, C05573 and AVPP0805 showed the highest concentration of capsaicin (12,776, 5,828, 4,393, 4,760, 3,764 and 4,120 µg/kg and the highest pungency level, whereas AVPP9703, AVPP0512, AVPP0307, AVPP0803 and AVPP0102 recorded no detection of capsaicin and hence were non-pungent. All chili peppers studied except AVPP9703, AVPP0512, AVPP0307, AVPP0803 and AVPP0102 could serve as potential sources of capsaicin. On the other hand, only genotypes AVPP0506, AVPP0104, AVPP0002, C05573 and AVPP0805 gave a % capsaicin content that falls within the pungency limit that could make them recommendable as potential sources of capsaicin for the pharmaceutical industry.

  2. Chemokine CXCL13 mediates orofacial neuropathic pain via CXCR5/ERK pathway in the trigeminal ganglion of mice.

    Science.gov (United States)

    Zhang, Qian; Cao, De-Li; Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

    2016-07-11

    Trigeminal nerve damage-induced neuropathic pain is a severely debilitating chronic orofacial pain syndrome. Spinal chemokine CXCL13 and its receptor CXCR5 were recently demonstrated to play a pivotal role in the pathogenesis of spinal nerve ligation-induced neuropathic pain. Whether and how CXCL13/CXCR5 in the trigeminal ganglion (TG) mediates orofacial pain are unknown. The partial infraorbital nerve ligation (pIONL) was used to induce trigeminal neuropathic pain in mice. The expression of ATF3, CXCL13, CXCR5, and phosphorylated extracellular signal-regulated kinase (pERK) in the TG was detected by immunofluorescence staining and western blot. The effect of shRNA targeting on CXCL13 or CXCR5 on pain hypersensitivity was checked by behavioral testing. pIONL induced persistent mechanical allodynia and increased the expression of ATF3, CXCL13, and CXCR5 in the TG. Inhibition of CXCL13 or CXCR5 by shRNA lentivirus attenuated pIONL-induced mechanical allodynia. Additionally, pIONL-induced neuropathic pain and the activation of ERK in the TG were reduced in Cxcr5 (-/-) mice. Furthermore, MEK inhibitor (PD98059) attenuated mechanical allodynia and reduced TNF-α and IL-1β upregulation induced by pIONL. TNF-α inhibitor (Etanercept) and IL-1β inhibitor (Diacerein) attenuated pIONL-induced orofacial pain. Finally, intra-TG injection of CXCL13 induced mechanical allodynia, increased the activation of ERK and the production of TNF-α and IL-1β in the TG of WT mice, but not in Cxcr5 (-/-) mice. Pretreatment with PD98059, Etanercept, or Diacerein partially blocked CXCL13-induced mechanical allodynia, and PD98059 also reduced CXCL13-induced TNF-α and IL-1β upregulation. CXCL13 and CXCR5 contribute to orofacial pain via ERK-mediated proinflammatory cytokines production. Targeting CXCL13/CXCR5/ERK/TNF-α and IL-1β pathway in the trigeminal ganglion may offer effective treatment for orofacial neuropathic pain.

  3. Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin.

    Science.gov (United States)

    2007-01-01

    , gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein

  4. Determination of Capsaicin and Dihydrocapsaicin in Capsicum Fruit Samples using High Performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Ayman Abdel Ghafar

    2011-10-01

    Full Text Available The aim of the present study was to determine the content of capsaicin and dihydrocapsaicin in Capsicum samples collected from city markets in Riyadh (Saudi Arabia, calculate their pungency in Scoville heat units (SHU and evaluate the average daily intake of capsaicin for the population of Riyadh. The investigated samples consisted of hot chillies, red chillies, green chillies, green peppers, red peppers and yellow peppers. Extraction of capsaicinoids was done using ethanol as solvent, while high performance liquid chromatography (HPLC was used for separation, identification and quantitation of the components. The limit of detection (LOD of the method was 0.09 and 0.10 µg/g for capsaicin and dihydrocapsaicin, respectively, while the limit of quantification (LOQ was 0.30 and 0.36 µg/g for capsaicin and dihydrocapsaicin, respectively. Hot chillies showed the highest concentration of capsaicin (4249.0 ± 190.3 µg/g and the highest pungency level (67984.60 SHU, whereas green peppers had the lowest detected concentration (1.0 ± 0.9 µg/g; green peppers, red peppers and yellow peppers were non pungent. The mean consumption of peppers for Riyadh city population was determined to be 15.5 g/person/day while the daily capsaicin intake was 7.584 mg/person/day.

  5. Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour.

    Science.gov (United States)

    Newson, Penny N; van den Buuse, Maarten; Martin, Sally; Lynch-Frame, Ann; Chahl, Loris A

    2014-10-01

    Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioural responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5-7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16-18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.

  6. Characterization of cubosomes as a targeted and sustained transdermal delivery system for capsaicin.

    Science.gov (United States)

    Peng, Xinsheng; Zhou, Yanfang; Han, Ke; Qin, Lingzhen; Dian, Linghui; Li, Ge; Pan, Xin; Wu, Chuanbin

    2015-01-01

    Phytantriol- and glycerol monooleate-based cubosomes were produced and characterized as a targeted and sustained transdermal delivery system for capsaicin. The cubosomes were prepared by emulsification and homogenization of phytantriol (F1), glycerol monooleate (F2), and poloxamer dispersions, characterized for morphology and particle size distribution by transmission electron microscope and photon correlation spectroscopy. Their Im3m crystallographic space group was confirmed by small-angle X-ray scattering. An in vitro release study showed that the cubosomes provided a sustained release system for capsaicin. An in vitro diffusion study conducted using Franz diffusion cells indicated that the skin retention of capsaicin from cubosomes in the stratum corneum was much higher (2.75±0.22 μg versus 4.32±0.13 μg, respectively) than that of capsaicin cream (0.72±0.13 μg). The stress testing showed that the cubosome formulations were stable under strong light and high temperature for up to 10 days. After multiapplications on mouse skin, the irritation of capsaicin cubosomes and cream was light with the least amount of side effects. Overall, the present study demonstrated that cubosomes may be a suitable skin-targeted and sustained delivery system for the transdermal administration of capsaicin.

  7. Development of a HPLC Method for the Quantitative Determination of Capsaicin in Collagen Sponge

    Directory of Open Access Journals (Sweden)

    Chun-Lian Guo

    2015-01-01

    Full Text Available Controlling the concentration of drugs in pharmaceutical products is essential to patient’s safety. In this study, a simple and sensitive HPLC method is developed to quantitatively analyze capsaicin in collagen sponge. The capsaicin from sponge was extracted for 30 min with ultrasonic wave extraction technique and methanol was used as solvent. The chromatographic method was performed by using isocratic system composed of acetonitrile-water (70 : 30 with a flow rate of 1 mL/min and the detection wavelength was at 280 nm. Capsaicin can be successfully separated with good linearity (the regression equation is A = 9.7182C + 0.8547; R2 = 1.0 and perfect recovery (99.72%. The mean capsaicin concentration in collagen sponge was 49.32 mg/g (RSD = 1.30%; n = 3. In conclusion, the ultrasonic wave extraction method is simple and the extracting efficiency is high. The HPLC assay has excellent sensitivity and specificity and is a convenient method for capsaicin detection in collagen sponge. This paper firstly discusses the quantitative analysis of capsaicin in collagen sponge.

  8. The capsaicin cough reflex in eczema patients with respiratory symptoms elicited by perfume.

    Science.gov (United States)

    Elberling, Jesper; Dirksen, Asger; Johansen, Jeanne Duus; Mosbech, Holger

    2006-03-01

    Respiratory symptoms elicited by perfume are common in the population but have unclear pathophysiology. Increased capsaicin cough responsiveness has been associated with the symptoms, but it is unknown whether the site of the symptoms in the airways influences this association. The aim of this study was to investigate the association between the site of airway symptoms elicited by perfume and cough responsiveness to bronchial challenge with capsaicin. 21 eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case control study. The participants completed a symptom questionnaire and underwent a bronchial challenge with capsaicin. Lower, but not upper, respiratory symptoms elicited by perfume were associated with increased capsaicin cough responsiveness. Having severe symptoms to perfume (n=11) did not relate to the site of the symptoms in the airways and was not associated with increased capsaicin cough responsiveness. In conclusion, respiratory symptoms elicited by perfume may reflect local hyperreactivity related to defensive reflexes in the airways, and measurements of the capsaicin cough reflex are relevant when patients with lower respiratory symptoms related to environmental perfume exposures are investigated.

  9. Determination of capsaicin and dihydrocapsaicin in Capsicum fruit samples using high performance liquid chromatography.

    Science.gov (United States)

    Al Othman, Zeid Abdullah; Ahmed, Yacine Badjah Hadj; Habila, Mohamed Abdelaty; Ghafar, Ayman Abdel

    2011-10-24

    The aim of the present study was to determine the content of capsaicin and dihydrocapsaicin in Capsicum samples collected from city markets in Riyadh (Saudi Arabia), calculate their pungency in Scoville heat units (SHU) and evaluate the average daily intake of capsaicin for the population of Riyadh. The investigated samples consisted of hot chillies, red chillies, green chillies, green peppers, red peppers and yellow peppers. Extraction of capsaicinoids was done using ethanol as solvent, while high performance liquid chromatography (HPLC) was used for separation, identification and quantitation of the components. The limit of detection (LOD) of the method was 0.09 and 0.10 µg/g for capsaicin and dihydrocapsaicin, respectively, while the limit of quantification (LOQ) was 0.30 and 0.36 µg/g for capsaicin and dihydrocapsaicin, respectively. Hot chillies showed the highest concentration of capsaicin (4249.0 ± 190.3 µg/g) and the highest pungency level (67984.60 SHU), whereas green peppers had the lowest detected concentration (1.0 ± 0.9 µg/g); green peppers, red peppers and yellow peppers were non pungent. The mean consumption of peppers for Riyadh city population was determined to be 15.5 g/person/day while the daily capsaicin intake was 7.584 mg/person/day.

  10. Microstructural abnormalities in the trigeminal nerves of patients with trigeminal neuralgia revealed by multiple diffusion metrics

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yaou [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Beijing Key laboratory of MRI and Brain Informatics, Beijing (China); Li, Jiping [Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Butzkueven, Helmut [Department of Medicine, University of Melbourne, Parkville 3010 (Australia); Duan, Yunyun; Zhang, Mo [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shu, Ni [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Li, Yongjie [Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhang, Yuqing, E-mail: yuqzhang@sohu.com [Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2013-05-15

    Objective: To investigate microstructural tissue changes of trigeminal nerve (TGN) in patients with unilateral trigeminal neuralgia (TN) by multiple diffusion metrics, and correlate the diffusion indexes with the clinical variables. Methods: 16 patients with TN and 6 healthy controls (HC) were recruited into our study. All participants were imaged with a 3.0 T system with three-dimension time-of-flight (TOF) magnetic resonance angiography and fluid attenuated inversion recovery (FLAIR) DTI-sequence. We placed regions of interest over the root entry zone of the TGN and measured fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). The mean values of FA, MD, AD and RD were compared between the affected and unaffected sides in the same patient, and to HC values. The correlation between the side-to-side diffusion metric difference and clinical variables (disease duration and visual analogy scale, VAS) was further explored. Results: Compared with the unaffected side and HC, the affected side showed significantly decreased FA and increased RD; however, no significant changes of AD were found. A trend toward significantly increased MD was identified on the affected side comparing with the unaffected side. We also found the significant correlation between the FA reduction and VAS of pain (r = −0.55, p = 0.03). Conclusion: DTI can quantitatively assess the microstructural abnormalities of the affected TGN in patients with TN. Our results suggest demyelination without significant axonal injury is the essential pathological basis of the affected TGN by multiple diffusion metrics. The correlation between FA reduction and VAS suggests FA as a potential objective MRI biomarker to correlate with clinical severity.

  11. Does the capsaicin-sensitive local neural circuit constitutively regulate vagally evoked esophageal striated muscle contraction in rats?

    Science.gov (United States)

    Shima, Takeshi; Shiina, Takahiko; Naitou, Kiyotada; Nakamori, Hiroyuki; Sano, Yuuki; Shimizu, Yasutake

    2016-03-01

    To determine whether a capsaicin-sensitive local neural circuit constitutively modulates vagal neuromuscular transmission in the esophageal striated muscle or whether the neural circuit operates in a stimulus-dependent manner, we compared the motility of esophageal preparations isolated from intact rats with those in which capsaicin-sensitive neurons had been destroyed. Electrical stimulation of the vagus nerve trunk evoked contractile responses in the esophagus isolated from a capsaicin-treated rat in a manner similar to those in the esophagus from a control rat. No obvious differences were observed in the inhibitory effects of D-tubocurarine on intact and capsaicin-treated rat esophageal motility. Destruction of the capsaicin-sensitive neurons did not significantly affect latency, time to peak and duration of a vagally evoked twitch-like contraction. These findings indicate that the capsaicin-sensitive neural circuit does not operate constitutively but rather is activated in response to an applied stimulus.

  12. Trigeminal branch stimulation for the treatment of intractable craniofacial pain.

    Science.gov (United States)

    Ellis, Jason A; Mejia Munne, Juan C; Winfree, Christopher J

    2015-07-01

    OBJECT Trigeminal branch stimulation has been used in the treatment of craniofacial pain syndromes. The risks and benefits of such an approach have not been clearly delineated in large studies, however. The authors report their experience in treating craniofacial pain with trigeminal branch stimulation and share the lessons they have learned after 93 consecutive electrode placements. METHODS A retrospective review of all patients who underwent trigeminal branch electrode placement by the senior author (C.J.W.) for the treatment of craniofacial pain was performed. RESULTS Thirty-five patients underwent implantation of a total of 93 trial and permanent electrodes between 2006 and 2013. Fifteen patients who experienced improved pain control after trial stimulation underwent implantation of permanent stimulators and were followed for an average of 15 months. At last follow-up 73% of patients had improvement in pain control, whereas only 27% of patients had no pain improvement. No serious complications were seen during the course of this study. CONCLUSIONS Trigeminal branch stimulation is a safe and effective treatment for a subset of patients with intractable craniofacial pain.

  13. Update on the challenges of treating trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Obermann M

    2015-04-01

    Full Text Available Mark Obermann Department of Neurology, University of Duisburg-Essen, Essen, Germany Abstract: Despite the multitude of treatment options currently available for trigeminal neuralgia, its management remains challenging in a considerable number of patients. The response to any particular treatment can be quite variable interindividually, and personalized treatment options are both resource-consuming and time-consuming. Anticonvulsant drugs, muscle relaxants, and neuroleptic agents are the preferred medical treatment for trigeminal neuralgia. Large placebo-controlled clinical trials are scarce, and no specific established substance has been developed for the treatment of trigeminal neuralgia. Promising new treatment options currently in clinical evaluation are botulinum neurotoxin type A injections and CNV1014802, a novel sodium channel blocker that selectively blocks the Nav1.7 sodium channel. Patients who do not respond to medical therapy may be eligible for more invasive treatment options, such as percutaneous Gasserian ganglion techniques, gamma knife surgery, and microvascular decompression. Keywords: trigeminal neuralgia, treatment, current, future, options, orphan drugs 

  14. A Survey on Acupuncture Treatment of Trigeminal Neuralgia

    Institute of Scientific and Technical Information of China (English)

    TIAN Li-fang

    2010-01-01

    @@ In modern medicine, various measures such as medication, nerve block, radio frequency and surgeries can all be adopted for treating trigeminal neuralgia. However, acupuncture-moxibustion is still one of the important clinical measures for the treatment because of its less side effects, com-plications and relapse. A review on its clinical investigations is presented as follows.

  15. Repeat microvascular decompression for recurrent idiopathic trigeminal neuralgia

    NARCIS (Netherlands)

    Bakker, Nicolaas A.; van Dijk, J. Marc C.; Immenga, Steven; Wagemakers, Michiel; Metzemaekers, Jan D. M.

    2014-01-01

    Object. Microvascular decompression (MVD) is considered the method of choice to treat idiopathic trigeminal neuralgia (TN) refractory to medical treatment. However, repeat MVD for recurrent TN is not well established. In this paper, the authors describe a large case series in which patients underwen

  16. Comparison of different microsurgery methods for trigeminal neuralgia

    Institute of Scientific and Technical Information of China (English)

    Zihang Xie; Lin Chen; Yan Wang; Zhiqiang Cui; Shijie Wang; Qiang Ao; Yuqi Zhang; Huancong Zuo

    2016-01-01

    Objective: To study the influence of different microsurgical methods on surgical outcomes and complications, and to improve the surgical outcomes for trigeminal neuralgia. Methods: The clinical data of 109 patients with trigeminal neuralgia, who were treated with microsurgery, were analyzed retrospectively. All patients were divided into 3 groups according to surgical modality: the trigeminal neuralgia decompression group (TND group, 19 patients), the TND and rhizotomy group (rhizotomy group, 55 patients), and the TND and selective lesioning group (lesioning group, 35 patients). The mid-term and short-term effects of microsurgery, and the occurrences of com-plications, were compared between the 3 groups. Results: There were no statistical differences in the frequency of complications between the 3 groups (P > 0.05). Eighty-four patients were followed up for 6 to 33 months. The rate of pain disappearance was found to be 94.4% in the TND group, and 100% in both the rhizotomy and lesioning groups; thus, no significant differences were found between these 3 groups (P > 0.05). Additionally, 50% of the patients in the rhizotomy group and 3.6% of the patients in the lesioning group had facial numbness while no patients were affected with facial numbness in the TND group, and the differences between these 3 groups were significant (P < 0.05). Conclusions: Microsurgery is effective and safe for trigeminal neuralgia. The use of TND, in combination with selective lesioning, ensures therapeutic efficacy and improves the quality of life in postoperative patients.

  17. An additional trigeminal system in certain snakes possessing infrared receptors

    NARCIS (Netherlands)

    Molenaar, Gerard J.

    1974-01-01

    This communication describes a nucleus and tract of the trigeminal system whose existence is not mentioned in any account of brain stem architecture known to the present author. The structures were first recognised in the brain stem of a giant snake (Python reticulatus) and later were also found in

  18. Repeat microvascular decompression for recurrent idiopathic trigeminal neuralgia

    NARCIS (Netherlands)

    Bakker, Nicolaas A.; van Dijk, J. Marc C.; Immenga, Steven; Wagemakers, Michiel; Metzemaekers, Jan D. M.

    2014-01-01

    Object. Microvascular decompression (MVD) is considered the method of choice to treat idiopathic trigeminal neuralgia (TN) refractory to medical treatment. However, repeat MVD for recurrent TN is not well established. In this paper, the authors describe a large case series in which patients

  19. Pain. Part 2a: Trigeminal Anatomy Related to Pain.

    Science.gov (United States)

    Renton, Tara; Egbuniwe, Obi

    2015-04-01

    In order to understand the underlying principles of orofacial pain it is important to understand the corresponding anatomy and mechanisms. Paper 1 of this series explains the central nervous and peripheral nervous systems relating to pain. The trigeminal nerve is the 'great protector' of the most important region of our body. It is the largest sensory nerve of the body and over half of the sensory cortex is responsive to any stimulation within this system. This nerve is the main sensory system of the branchial arches and underpins the protection of the brain, sight, smell, airway, hearing and taste, underpinning our very existence. The brain reaction to pain within the trigeminal system has a significant and larger reaction to the threat of, and actual, pain compared with other sensory nerves. We are physiologically wired to run when threatened with pain in the trigeminal region and it is a 'miracle' that patients volunteer to sit in a dental chair and undergo dental treatment. Clinical Relevance: This paper aims to provide the dental and medical teams with a review of the trigeminal anatomy of pain and the principles of pain assessment.

  20. Cryotherapy in the management of paroxysmal trigeminal neuralgia.

    OpenAIRE

    Zakrzewska, J. M.

    1987-01-01

    Cryotherapy for the relief of pain is widely used in many conditions. The results of 83 cryotherapy sessions in 29 patients with paroxysmal trigeminal neuralgia are reviewed over a five year period. Sixty three per cent of treated nerves, 41% of patients were pain free over one year and there was no permanent sensory loss.

  1. An additional trigeminal system in certain snakes possessing infrared receptors

    NARCIS (Netherlands)

    Molenaar, Gerard J.

    1974-01-01

    This communication describes a nucleus and tract of the trigeminal system whose existence is not mentioned in any account of brain stem architecture known to the present author. The structures were first recognised in the brain stem of a giant snake (Python reticulatus) and later were also found in

  2. Study on vasoactive intestinal polypeptide receptor 1 gene translation in psoriatic epidermis with the topical treatment of capsaicin ointment

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To investigate the mechanism of capsaicin in treating active psoriasis vulgaris.Methods A total of 42 patients with active psoriasis vulgaris diagnosed by histology and clinical features were given either placebo or 0.025% capsaicin ointment four times daily for 30 days randomly by double-blind method.Vasoactive intestinal polypeptide receptor 1(VIPR1)gene translation in active psoriatic lesions before and after treatment with capsaicin ointment was detected by in situ hybridization.Results There ...

  3. Operant behavioral responses to orofacial cold stimuli in rats with chronic constrictive trigeminal nerve injury: effects of menthol and capsazepine

    Science.gov (United States)

    2013-01-01

    Both spinal and trigeminal somatosensory systems use the TRPM8 channel as a principal transducer for detecting cold stimuli. It is currently unclear whether this cold transducer may play a role in trigeminal neuropathic pain manifesting cold allodynia and hyperalgesia. In the present study, trigeminal neuropathy was induced by chronic constrictive nerve injury of the infraorbital nerve (ION-CCI). Behavioral responses to cold stimuli in orofacial regions were assessed by the newly developed orofacial operant test in the ION-CCI rats. We tested menthol and capsazepine, two compounds that can activate and inhibit TRPM8 respectively, on orofacial operant responses to cold stimuli in ION-CCI rats. Testing animals performed operant tasks by voluntarily contacting their orofacial regions to a cold stimulation module in order to access sweetened milk as a reward, and contact time and number of the operant behaviors were automatically recorded. Total contact time was significantly reduced at the cooling temperatures of 17°C and 12°C in ION-CCI group in comparison with sham group, indicating the presence of cold allodynia and hyperalgesia in ION-CCI rats. When menthol was administered to ION-CCI rats, total contact time was further reduced and total contact number increased at the cooling temperatures. In contrast, after administration of capsazepine to ION-CCI rats, total contact time was significantly increased at the cooling temperatures. The behavioral outcomes support the idea that TRPM8 plays a role in cold allodynia and hyperalgesia following chronic trigeminal nerve injury. PMID:23767981

  4. Trigeminal nerve injury ErbB3/ErbB2 promotes mechanical hypersensitivity.

    Science.gov (United States)

    Ma, Fei; Zhang, Liping; Westlund, Karin N

    2012-08-01

    Chronic constriction injury of the trigeminal infraorbital nerve results in transient analgesia followed by whisker pad mechanical allodynia in rats. Neuregulin 1 expressed on axonal membranes binds receptor tyrosine kinase ErbB, promoting Schwann cell development and remyelination. This study investigated whether orofacial mechanical allodynia is signaled by ErbB3-ErbB2 heterodimers in injured nerves. Whisker pad mechanical allodynia (von Frey stimuli) was quantified in wild type rats and in transgenic rats with Sleeping Beauty transposon mutation for neuregulin 1 transgene. Pain-related behavior was retested after intraperitoneal injection of the ErbB2 inhibitor Lapatinib, an agent shown by others to reduce breast cancer pain. Infraorbital nerve injury was evaluated histologically with myelin and neuronal biomarkers. ErbB3 changes over time were measured with western blots. Whisker pad mechanical hypersensitivity began in week 2 in wild type rats (3.11 ± 5.93 g vs. 18.72 ± 0.00 g after sham surgery, n = 9, P wild type rats was alleviated by Lapatinib (15 ± 3.89 g vs. 2.45 ± 1.13 g, n = 6, P wild type and transgenic rats (week 10) coincided with time points when mechanical hypersensitivity was present. The Neuregulin 1-ErbB3-ErbB2 complex is a causal mechanism in nerve injury-induced trigeminal neuropathic pain. Understanding peripheral glial mechanisms after nerve injury will improve neuropathic pain treatment.

  5. RNA Sequencing of Trigeminal Ganglia in Rattus Norvegicus after Glyceryl Trinitrate Infusion with Relevance to Migraine.

    Directory of Open Access Journals (Sweden)

    Sara Hougaard Pedersen

    Full Text Available Infusion of glyceryl trinitrate (GTN, a donor of nitric oxide, induces immediate headache in humans that in migraineurs is followed by a delayed migraine attack. In order to achieve increased knowledge of mechanisms activated during GTN-infusion this present study aims to investigate transcriptional responses to GTN-infusion in the rat trigeminal ganglia.Rats were infused with GTN or vehicle and trigeminal ganglia were isolated either 30 or 90 minutes post infusion. RNA sequencing was used to investigate transcriptomic changes in response to the treatment. Furthermore, we developed a novel method for Gene Set Analysis Of Variance (GSANOVA to identify gene sets associated with transcriptional changes across time.15 genes displayed significant changes in transcription levels in response to GTN-infusion. Ten of these genes showed either sustained up- or down-regulation in the 90-minute period after infusion. The GSANOVA analysis demonstrate enrichment of pathways pointing towards an increase in immune response, signal transduction, and neuroplasticity in response to GTN-infusion. Future functional in-depth studies of these mechanisms are expected to increase our understanding of migraine pathogenesis.

  6. RNA Sequencing of Trigeminal Ganglia in Rattus Norvegicus after Glyceryl Trinitrate Infusion with Relevance to Migraine

    Science.gov (United States)

    Hougaard Pedersen, Sara; Maretty, Lasse; Ramachandran, Roshni; Sibbesen, Jonas Andreas; Yakimov, Victor; Elgaard-Christensen, Rikke; Hansen, Thomas Folkmann; Krogh, Anders; Olesen, Jes; Jansen-Olesen, Inger

    2016-01-01

    Introduction Infusion of glyceryl trinitrate (GTN), a donor of nitric oxide, induces immediate headache in humans that in migraineurs is followed by a delayed migraine attack. In order to achieve increased knowledge of mechanisms activated during GTN-infusion this present study aims to investigate transcriptional responses to GTN-infusion in the rat trigeminal ganglia. Methods Rats were infused with GTN or vehicle and trigeminal ganglia were isolated either 30 or 90 minutes post infusion. RNA sequencing was used to investigate transcriptomic changes in response to the treatment. Furthermore, we developed a novel method for Gene Set Analysis Of Variance (GSANOVA) to identify gene sets associated with transcriptional changes across time. Results 15 genes displayed significant changes in transcription levels in response to GTN-infusion. Ten of these genes showed either sustained up- or down-regulation in the 90-minute period after infusion. The GSANOVA analysis demonstrate enrichment of pathways pointing towards an increase in immune response, signal transduction, and neuroplasticity in response to GTN-infusion. Future functional in-depth studies of these mechanisms are expected to increase our understanding of migraine pathogenesis. PMID:27213950

  7. Insular cortex representation of dynamic mechanical allodynia in trigeminal neuropathic rats.

    Science.gov (United States)

    Alvarez, Pedro; Dieb, Wisam; Hafidi, Aziz; Voisin, Daniel L; Dallel, Radhouane

    2009-01-01

    Dynamic mechanical allodynia is a widespread symptom of neuropathic pain for which mechanisms are still poorly understood. The present study investigated the organization of dynamic mechanical allodynia processing in the rat insular cortex after chronic constriction injury to the infraorbital nerve (IoN-CCI). Two weeks after unilateral IoN-CCI, rats showed a dramatic bilateral trigeminal dynamic mechanical allodynia. Light, moving stroking of the infraorbital skin resulted in strong, bilateral upregulation of extracellular-signal regulated kinase phosphorylation (pERK-1/2) in the insular cortex of IoN-CCI animals but not sham rats, in whose levels were similar to those of unstimulated IoN-CCI rats. pERK-1/2 was located in neuronal cells only. Stimulus-evoked pERK-1/2 immunopositive cell bodies displayed rostrocaudal gradient and layer selective distribution in the insula, being predominant in the rostral insula and in layers II-III of the dysgranular and to a lesser extent, of the agranular insular cortex. In layers II-III of the rostral dysgranular insular cortex, intense pERK also extended into distal dendrites, up to layer I. These results demonstrate that trigeminal nerve injury induces a significant alteration in the insular cortex processing of tactile stimuli and suggest that ERK phosphorylation contributes to the mechanisms underlying abnormal pain perception under this condition.

  8. Ultrasound-guided trigeminal nerve block via the pterygopalatine fossa: an effective treatment for trigeminal neuralgia and atypical facial pain.

    Science.gov (United States)

    Nader, Antoun; Kendall, Mark C; De Oliveria, Gildasio S; Chen, Jeffry Q; Vanderby, Brooke; Rosenow, Joshua M; Bendok, Bernard R

    2013-01-01

    Patients presenting with facial pain often have ineffective pain relief with medical therapy. Cases refractory to medical management are frequently treated with surgical or minimally invasive procedures with variable success rates. We report on the use of ultrasound-guided trigeminal nerve block via the pterygopalatine fossa in patients following refractory medical and surgical treatment. To present the immediate and long-term efficacy of ultrasound-guided injections of local anesthetic and steroids in the pterygopalatine fossa in patients with unilateral facial pain that failed pharmacological and surgical interventions. Academic pain management center. Prospective case series. Fifteen patients were treated with ultrasound-guided trigeminal nerve block with local anesthetic and steroids placed into the pterygopalatine fossa. All patients achieved complete sensory analgesia to pin prick in the distribution of the V2 branch of the trigeminal nerve and 80% (12 out of 15) achieved complete sensory analgesia in V1, V2, V3 distribution within 15 minutes of the injection. All patients reported pain relief within 5 minutes of the injection. The majority of patients maintained pain relief throughout the 15 month study period. No patients experienced symptoms of local anesthetic toxicity or onset of new neurological sequelae. Prospective case series. We conclude that the use of ultrasound guidance for injectate delivery in the pterygopalatine fossa is a simple, free of radiation or magnetization, safe, and effective percutaneous procedure that provides sustained pain relief in trigeminal neuralgia or atypical facial pain patients who have failed previous medical interventions.

  9. 治伤巴布剂的镇痛作用及对大鼠背根神经节辣椒受体表达的影响%Impact of Injury Papua Agent on Analgesia and the Expression of Capsaicin Receptor in Model Rats with Formaldehyde-Induced Inflammatory Pain

    Institute of Scientific and Technical Information of China (English)

    贺渊哲; 邵先舫; 熊辉; 刘志军; 李前; 严望; 汤思敏

    2014-01-01

    目的:探讨治伤巴布剂对福尔马林足底炎性疼痛大鼠模型背根神经节中辣椒素受体水平的影响,研究治伤巴布剂对大鼠炎性疼痛是否有镇痛作用。方法:SD大鼠36只,随机分为空白对照组(n=12)、模型组(n=12)及治疗组(n=12);空白对照组大鼠不予任何处理,模型组左后足底注射0.1 mL5%福尔马林,治疗组大鼠造模前1 d于左后足外敷治伤巴布剂,然后左后足底注射0.1 mL5%福尔马林,再一直外敷治伤巴布剂,观察造模后大鼠疼痛行为学反应,并以Dubuisson评分方法进行记录比较。各组大鼠在指定时间点取出L3-6节段背根神经节,运用实时荧光定量(RT-PCR)、蛋白质印迹(Western blot)检测辣椒素受体在大鼠背根神经节中的表达水平。结果:模型组及治疗组呈典型的双相伤害性行为反应,但治疗组大鼠疼痛反应积分低于模型组,差异有统计学意义(P<0.05﹚;实时荧光定量检查结果显示模型组辣椒素受体mRNA相对表达量大于治疗组,治疗组辣椒素受体mRNA相对表达量大于空白对照组,3组比较,差异有统计学意义(P<0.05﹚,3组组内3个时相点的相对表达量差异均无统计学意义(P>0.05);蛋白质印迹法灰度扫描显示模型组辣椒素受体相对表达量大于治疗组,治疗组辣椒素受体相对表达量大于空白对照组,3组比较,差异有统计学意义(P<0.05﹚,3组组内3个时相点的相对表达量差异均无统计学意义(P>0.05)。结论:治伤巴布剂能缓解大鼠炎性疼痛反应,对大鼠炎性疼痛具有一定的镇痛作用,可降低福尔马林足底炎性疼痛大鼠模型背根神经节中辣椒素受体的表达水平。%Objective: To investigate the effects of Zhishang cataplasm on the levels of capsaicin receptor in dorsal root ganglion in formalin injected rats, and explore the analgesic effects of

  10. Characterization of cubosomes as a targeted and sustained transdermal delivery system for capsaicin

    Directory of Open Access Journals (Sweden)

    Peng X

    2015-08-01

    Full Text Available Xinsheng Peng,1* Yanfang Zhou,1* Ke Han,2,3 Lingzhen Qin,3 Linghui Dian,1 Ge Li,4 Xin Pan,3 Chuanbin Wu3 1Guangdong Medical University, Dongguan, 2The Second Affiliated Hospital of Guangzhou Medical University, 3School of Pharmaceutical Sciences, Sun Yat-Sen University, 4Guangzhou Neworld Pharmaceuticals Co. Ltd., Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this work Abstract: Phytantriol- and glycerol monooleate-based cubosomes were produced and characterized as a targeted and sustained transdermal delivery system for capsaicin. The cubosomes were prepared by emulsification and homogenization of phytantriol (F1, glycerol monooleate (F2, and poloxamer dispersions, characterized for morphology and particle size distribution by transmission electron microscope and photon correlation spectroscopy. Their Im3m crystallographic space group was confirmed by small-angle X-ray scattering. An in vitro release study showed that the cubosomes provided a sustained release system for capsaicin. An in vitro diffusion study conducted using Franz diffusion cells indicated that the skin retention of capsaicin from cubosomes in the stratum corneum was much higher (2.75±0.22 µg versus 4.32±0.13 µg, respectively than that of capsaicin cream (0.72±0.13 µg. The stress testing showed that the cubosome formulations were stable under strong light and high temperature for up to 10 days. After multiapplications on mouse skin, the irritation of capsaicin cubosomes and cream was light with the least amount of side effects. Overall, the present study demonstrated that cubosomes may be a suitable skin-targeted and sustained delivery system for the transdermal administration of capsaicin. Keywords: cubosomes, skin-targeted delivery, capsaicin

  11. Vascular and Psychophysical Effects of Topical Capsaicin Application to Orofacial Tissues

    Science.gov (United States)

    Boudreau, Shellie A.; Wang, Kelun; Svensson, Peter; Sessle, Barry J.; Arendt-Nielsen, Lars

    2011-01-01

    Aims To characterize and contrast human sensory and vascular changes produced by topical application of the algesic chemical capsaicin to the glabrous lips and tongue. Methods Applications of 1% capsaicin or vehicle cream to the glabrous lips and tongue were randomized between two two-trial sessions. The capsaicin trial followed the vehicle trial for each session. Before and 5, 15, and 30 minutes after capsaicin or vehicle cream application, six parameters were recorded from the glabrous lips or the tongue dorsum: (1) burning pain intensity, as measured on a visual analog scale; (2) burning pain area, as indicated by subjects on an orofacial drawing; (3) mechanical sensitivity, as measured by a von Frey filament; (4) visual flare; (5) blood flow and temperature, as measured by laser-Doppler imaging and thermography, respectively; and (6) areas of increased temperature (hot spots), as calculated by a digital tracer from the thermographs. Data were analyzed by ANOVAs and Pearson’s correlations. Results Compared to vehicle application, capsaicin elicited burning pain, increases in blood flow and temperature, but no change in mechanical sensitivity in the glabrous lips or tongue. Greater increases in blood flow and temperature paralleled more intense burning pain and larger areas of perceived pain for the lips compared to the tongue. The location of distinct areas of increased temperature within the orofacial area differed between the capsaicin-lip and capsaicin-tongue trials. Conclusion The several differences between these responses to noxious stimulation of the glabrous lips and tongue may have implications for examinations of orofacial somatosensory functions. PMID:19639105

  12. Enzymatic changes in phenylalanine ammonia-lyase, cinnamic-4-hydroxylase, capsaicin synthase, and peroxidase activities in capsicum under drought stress.

    Science.gov (United States)

    Phimchan, Paongpetch; Chanthai, Saksit; Bosland, Paul W; Techawongstien, Suchila

    2014-07-23

    Penylalanine ammonia-lyase (PAL), cinnamic-4-hydroxylase (C4H), capsaicin synthase (CS), and peroxidase (POD) are involved in the capsaicinoid biosynthesis pathway and may be altered in cultivars with different pungency levels. This study clarified the action of these enzymes under drought stress for hot Capsicum cultivars with low, medium,and high pungency levels. At the flowering stage, control plants were watered at field capacity, whereas drought-induced plants were subjected to gradual drought stress. Under drought stress, PAL, C4H, CS, and POD enzyme activities inc