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Sample records for capsaicin induced trigeminal

  1. Attenuation by butalbital of capsaicin-induced c-fos-like immunoreactivity in trigeminal nucleus caudalis.

    PubMed

    Cutrer, F M; Mitsikostas, D D; Ayata, G; Sanchez del Rio, M

    1999-01-01

    We examined the effects of butalbital (30, 100, and 1000 micrograms/kg) on the number of cells expressing c-fos-like immunoreactivity (c-fos-LI), a marker of neuronal activation, within lamina I, IIo of the trigeminal nucleus caudalis and the nucleus of the solitary tract 2 hours after the intracisternal injection of capsaicin (0.1 mL; 15.25 mg/mL) or vehicle in urethane-anesthetized guinea pigs (N = 45). Robust c-fos-LI was observed within nuclei of cells in the trigeminal nucleus caudalis after capsaicin (329 +/- 35). Butalbital dose-dependently reduced the number of labeled cells to a maximum of 66% (1000 micrograms/kg intraperitoneally [i.p.], P < .01) in lamina I, IIo but not within area postrema, medial reticular nucleus, or the nucleus of the solitary tract. Pretreatment with bicuculline (30 micrograms/kg i.p.) blocked the effect of butalbital, thereby suggesting the importance of the GABAA receptor to activation involved in the transmission of nociceptive information. Our studies suggest the possibility that GABAA receptors might provide an important therapeutic target in migraine and related headache disorders.

  2. Capsaicin, acid and heat-evoked currents in rat trigeminal ganglion neurons: relationship to functional VR1 receptors.

    PubMed

    Liu, L; Simon, S A

    2000-05-01

    Activation of primary trigeminal (TG) neurons by protons, capsaicin, or heat can evoke a variety of sensations, including tingling, stinging, warmth, and burning. Capsaicin and acid are trigeminal stimulants that are important in gustatory physiology. These stimuli can activate H(+)-gated ion channels and heterologously expressed VR1 receptors (vanilloid receptor 1). We have obtained evidence by using electrophysiological and pharmacological measurements on TG neurons that these three stimuli can activate many receptors, and we have determined the extent they behave similarly to VR1 receptors and H(+)-gated channels from the DEGenerin/ENaC superfamily. Whole-cell recordings from rat TG neurons revealed that protons evoked transient (Tp), sustained (Sp), and biphasic (TSp) currents. Tp currents had reversal potentials (Vr) of 24-45 mV, a pH(0.5) range from 5.5 to 6.5, and were inhibited by amiloride, suggesting the presence of functional H(+)-gated channels. Sp currents were inhibited by the VR1 antagonist capsazepine, had Vr's approximately 0 mV, and had pH(0.5) = 6.4. Capsaicin also activated transient (Tc), sustained (Sc), and biphasic (TSc) currents. At pH 5.9, the sensitivity of the Sc currents increased by about a factor of 10, which may partially account for the synergistic responses of acid in foods containing capsaicin. Heating TG neurons evoked a thermally active, capsazepine-inhibitable current with threshold temperature of 43 degrees C and Vr = 5 mV that is also present in neurons activated by and protons (Sp) and capsaicin (Sc). These data suggest that TG neurons have functional receptors that behave similarly to VR1. Activation of such receptors should result in a burning sensation, whereas activation of the transient and biphasic currents should result in other taste descriptors.

  3. Capsaicin induces immunogenic cell death in human osteosarcoma cells

    PubMed Central

    Jin, Tao; Wu, Hongyan; Wang, Yanlin; Peng, Hao

    2016-01-01

    Immunogenic cell death (ICD) is characterized by the early surface exposure of calreticulin (CRT). As a specific signaling molecule, CRT on the surface of apoptotic tumor cells mediates the recognition and phagocytosis of tumor cells by antigen presenting cells. To date, only a small quantity of anti-cancer chemicals have been found to induce ICD, therefore it is clinically important to identify novel chemicals that may induce ICD. The purpose of the present study is to explore the function of capsaicin in inducing ICD. In the current study, MTT assays were used to examine the growth inhibiting effects of MG-63 cells when they were treated with capsaicin or cisplatin. Mitochondrial membrane potential and western blot analysis were used to investigate capsaicin- and cisplatin-induced apoptosis. In addition, the effects of capsaicin and cisplatin were evaluated for their abilities in inducing calreticulin membrane translocation and mediating ICD in human osteosarcoma cells (MG-63). The results demonstrated that capsaicin and cisplatin can induce the apoptosis of MG-63 cells. However, only capsaicin induced a rapid translocation of CRT from the intracellular space to the cell surface. Treatment with capsaicin increased phagocytosis of MG-63 cells by dendritic cells (DCs), and these MG-63-loaded DCs could efficiently stimulate the secretion of IFN-γ by lymphocytes. These results identify capsaicin as an anti-cancer agent capable of inducing ICD in human osteosarcoma cells in vitro. PMID:27446273

  4. Olopatadine hydrochloride inhibits capsaicin-induced flare response in humans.

    PubMed

    Shindo, Masahisa; Yoshida, Yuichi; Yamamoto, Osamu

    2011-01-01

    Capsaicin, a vanilloid, has the potential for releasing substance P (SP) from sensory nerves. Topical application of capsaicin induces a flare response in the skin. However, it has not been clarified whether the release of SP is involved in the process of flare response or not. A potent antihistamine drug, olopatadine hydrochloride, is known to have inhibitory action against the release of SP. We examined the effects of olopatadine (at a dose of 5 mg) on skin reaction induced by topical application of capsaicin in 10 healthy subjects. The scores of capsaicin-induced flare responses after olopatadine administration were significantly lower at 30 min than at baseline. Our findings suggest that olopatadine hydrochloride could inhibit capsaicin-induced flare responses.

  5. Mitochondrial fission augments capsaicin-induced axonal degeneration.

    PubMed

    Chiang, Hao; Ohno, Nobuhiko; Hsieh, Yu-Lin; Mahad, Don J; Kikuchi, Shin; Komuro, Hitoshi; Hsieh, Sung-Tsang; Trapp, Bruce D

    2015-01-01

    Capsaicin, an agonist of transient receptor potential vanilloid receptor 1, induces axonal degeneration of peripheral sensory nerves and is commonly used to treat painful sensory neuropathies. In this study, we investigated the role of mitochondrial dynamics in capsaicin-induced axonal degeneration. In capsaicin-treated rodent sensory axons, axonal swellings, decreased mitochondrial stationary site length and reduced mitochondrial transport preceded axonal degeneration. Increased axoplasmic Ca(2+) mediated the alterations in mitochondrial length and transport. While sustaining mitochondrial transport did not reduce axonal swellings in capsaicin-treated axons, preventing mitochondrial fission by overexpression of mutant dynamin-related protein 1 increased mitochondrial length, retained mitochondrial membrane potentials and reduced axonal loss upon capsaicin treatment. These results establish that mitochondrial stationary site size significantly affects axonal integrity and suggest that inhibition of Ca(2+)-dependent mitochondrial fission facilitates mitochondrial function and axonal survival following activation of axonal cationic channels.

  6. Modulation of lipopolysaccharide-induced oxidative stress by capsaicin.

    PubMed

    Abdel-Salam, Omar M E; Abdel-Rahman, Rehab Fawzy; Sleem, Amany A; Farrag, Abdel Razik

    2012-08-01

    . Capsaicin exerted protective effects in the liver and lung against the LPS-induced tissue damage.

  7. Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system.

    PubMed

    Shatillo, A; Koroleva, K; Giniatullina, R; Naumenko, N; Slastnikova, A A; Aliev, R R; Bart, G; Atalay, M; Gu, C; Khazipov, R; Davletov, B; Grohn, O; Giniatullin, R

    2013-12-01

    Indirect evidence suggests the increased production of reactive oxygen species (ROS) in migraine pathophysiology. In the current study we measured lipid peroxidation product in the rat cortex, trigeminal ganglia and meninges after the induction of cortical spreading depression (CSD), a phenomenon known to be associated with migraine aura, and tested nociceptive firing triggered by ROS in trigeminal nerves ex vivo. Application of KCl to dura mater in anesthetized rats induced several waves of CSD recorded by an extracellular electrode in the cortex. Following CSD, samples of cortex (affected regions were identified with blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI)), meninges from left and right hemispheres and trigeminal ganglia were taken for biochemical analysis. We found that CSD increased the level of the lipid peroxidation product malondialdehyde (MDA) in the ipsilateral cerebral cortex and meninges, but also in both ipsi- and contralateral trigeminal ganglia. In order to test the pro-nociceptive action of ROS, we applied the mild oxidant hydrogen peroxide to isolated rat hemiskull preparations including preserved trigeminal innervations. Application of hydrogen peroxide to meninges transiently enhanced electrical spiking activity of trigeminal nerves showing a pro-nociceptive action of ROS. In the presence of hydrogen peroxide trigeminal nerves still responded to capsaicin by burst of spiking activity indicating integrity of neuronal structures. The action of hydrogen peroxide was mediated by TRPA1 receptors as it was abolished by the specific TRPA1 antagonist TCS-5861528. Using dorsal root ganglion sensory neurons as test system we found that hydrogen peroxide promoted the release of the migraine mediator calcitonin gene-related peptide (CGRP), which we previously identified as a trigger of delayed sensitization of trigeminal neurons. Our data suggest that, after CSD, oxidative stress spreads downstream within the

  8. Capsaicin prevents kainic acid-induced epileptogenesis in mice.

    PubMed

    Lee, Tae-Hee; Lee, Jong-Geol; Yon, Jung-Min; Oh, Ki-Wan; Baek, In-Jeoung; Nahm, Sang-Soep; Lee, Beom Jun; Yun, Young Won; Nam, Sang-Yoon

    2011-05-01

    Epilepsy is a neurodegenerative disease with periodic occurrences of spontaneous seizures as the main symptom. The aim of this study was to investigate the neuroprotective effects of capsaicin, the major ingredient of hot peppers, in a kainic acid (KA)-induced status epilepticus model. After intraperitoneal injections of KA (30mg/kg) in 8-week-old male ICR mice, the animals were treated subcutaneously with capsaicin (0.33mg/kg or 1mg/kg) and then examined for any anti-ictogenic, hypothermic, antioxidative, anti-inflammatory, and anti-apoptotic effects of the capsaicin treatment 3 days after KA treatment. KA injections significantly enhanced neurodegenerative conditions but co-injection with capsaicin reduced the detrimental effects of KA in a dose-dependent manner in mice. The co-administered group that received KA and 1mg/kg of capsaicin showed significantly decreased behavioral seizure activity and body temperature for 3h and also remarkably blocked intense and high-frequency seizure discharges in the parietal cortex for 3 days compared with those that received KA alone. Capsaicin treatment significantly diminished the levels of oxidant activity and malondialdehyde concentration and increased the antioxidant activity in the blood and brain of KA-treated mice. In addition, capsaicin significantly lowered the KA-induced increase in the concentration of the cytokines IL-1β and TNF-α in the brain. Furthermore, co-treatment of KA and capsaicin (1mg/kg) resulted in considerably decreased apoptotic cell death in the cornu ammonis sections of the hippocampus compared with that seen in the KA-alone group. These findings indicate that capsaicin is preventative for the epileptogenesis induced by KA in mice.

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

    PubMed Central

    Park, Chul-Kyu

    2015-01-01

    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. PMID:26617436

  10. Capsaicin induces apoptosis in PC12 cells through ER stress.

    PubMed

    Krizanova, Olga; Steliarova, Iveta; Csaderova, Lucia; Pastorek, Michal; Hudecova, Sona

    2014-02-01

    Capsaicin, the pungent agent in chili peppers, has been shown to act as a tumor-suppressor in cancer. In our previous study, capsaicin was shown to induce apoptosis in the rat pheochromocytoma cell line (PC12 cells). Thus, the aim of the present study was to determine the potential mechanism by which capsaicin induces apoptosis. We treated PC12 cells with 50, 100 and 500 µM capsaicin and measured the reticular calcium content and expression of the reticular calcium transport systems. These results were correlated with endoplasmic reticulum (ER) stress markers CHOP, ATF4 and X-box binding protein 1 (XBP1), as well as with apoptosis induction. We observed that capsaicin decreased reticular calcium in a concentration-dependent manner. Simultaneously, expression levels of the sarco/endoplasmic reticulum pump and ryanodin receptor of type 2 were modified. These changes were accompanied by increased ER stress, as documented by increased stress markers. Thus, from these results we propose that in PC12 cells capsaicin induces apoptosis through increased ER stress. PMID:24337105

  11. Endothelin-1-induced priming to capsaicin in young animals.

    PubMed

    Smith, Terika; Beasley, Sarah; Smith, Sherika; Mark, Isiasha; Sweitzer, Sarah M

    2014-05-01

    Endothelin-1 (ET-1) is a known algogen that causes acute pain and sensitization in humans and spontaneous nociceptive behaviors when injected into the periphery in rats. This study sought to examine the effect of ET-1 exposure in the neonatal period on subsequent contralateral capsaicin-induced secondary mechanical hyperalgesia. ET-1 or saline was injected into the left plantar hindpaw on postnatal day 7 (P7). On postnatal day 11 (P11), capsaicin cream or control lotion was applied to the right dorsum hind paw and mechanical paw withdrawal thresholds were measured in the plantar hind paw. In saline control males, P11 administration of capsaicin produced a secondary mechanical hyperalgesia that was still present at 2h. Neonatal priming with ET-1 did not alter the magnitude or the duration of secondary mechanical hyperalgesia in males. In contrast, in control females, P11 administration of capsaicin produced less than 40 min of mechanical hyperalgesia. Neonatal priming with ET-1 prolonged the duration of secondary mechanical hyperalgesia in females. Priming with ET-1 on P7 led to a significant increase in capsaicin-induced Fos expression in the dorsal horn of the spinal cord in both males and females compared to controls (p<0.001). These findings further suggest that pain in early life may alter future responses to painful stimuli at both the behavioral and neuronal level.

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

    PubMed

    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.

  13. TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats.

    PubMed

    Honda, Kuniya; Shinoda, Masamichi; Furukawa, Akihiko; Kita, Kozue; Noma, Noboru; Iwata, Koichi

    2014-12-01

    Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. The head-withdrawal reflex threshold (HWRT) to cold stimulation of the lateral facial skin was significantly decreased following facial capsaicin injection. This reduction of HWRT was significantly recovered following local injection of TRPV1 antagonist as well as TRPA1 antagonist. Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1-positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection.

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

    PubMed

    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) < 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.

  15. The pepper's natural ingredient capsaicin induces autophagy blockage in prostate cancer cells.

    PubMed

    Ramos-Torres, Ágata; Bort, Alicia; Morell, Cecilia; Rodríguez-Henche, Nieves; Díaz-Laviada, Inés

    2016-01-12

    Capsaicin, the pungent ingredient of red hot chili peepers, has been shown to have anti-cancer activities in several cancer cells, including prostate cancer. Several molecular mechanisms have been proposed on its chemopreventive action, including ceramide accumulation, endoplasmic reticulum stress induction and NFκB inhibition. However, the precise mechanisms by which capsaicin exerts its anti-proliferative effect in prostate cancer cells remain questionable. Herein, we have tested the involvement of autophagy on the capsaicin mechanism of action on prostate cancer LNCaP and PC-3 cells.The results showed that capsaicin induced prostate cancer cell death in a time- and concentration-dependent manner, increased the levels of microtubule-associated protein light chain 3-II (LC3-II, a marker of autophagy) and the accumulation of the cargo protein p62 suggesting an autophagy blockage. Moreover, confocal microscopy revealed that capsaicin treatment increased lysosomes which co-localized with LC3 positive vesicles in a similar extent to that produced by the lysosomal protease inhibitors E64 and pepstatin pointing to an autophagolysosomes breakdown inhibition. Furthermore, we found that capsaicin triggered ROS generation in cells, while the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Co-treatment of cells with NAC and capsaicin abrogated the effects of capsaicin on autophagy and cell death. Normal prostate PNT2 and RWPE-1 cells were more resistant to capsaicin-induced cytotoxicity and did not accumulate p62 protein.Taken together, these results suggest that ROS-mediated capsaicin-induced autophagy blockage contributes to antiproliferation in prostate cancer cells, which provides new insights into the anticancer molecular mechanism of capsaicin. PMID:26625315

  16. The pepper's natural ingredient capsaicin induces autophagy blockage in prostate cancer cells

    PubMed Central

    Ramos-Torres, Ágata; Bort, Alicia; Morell, Cecilia; Rodríguez-Henche, Nieves; Díaz-Laviada, Inés

    2016-01-01

    Capsaicin, the pungent ingredient of red hot chili peepers, has been shown to have anti-cancer activities in several cancer cells, including prostate cancer. Several molecular mechanisms have been proposed on its chemopreventive action, including ceramide accumulation, endoplasmic reticulum stress induction and NFκB inhibition. However, the precise mechanisms by which capsaicin exerts its anti-proliferative effect in prostate cancer cells remain questionable. Herein, we have tested the involvement of autophagy on the capsaicin mechanism of action on prostate cancer LNCaP and PC-3 cells. The results showed that capsaicin induced prostate cancer cell death in a time- and concentration-dependent manner, increased the levels of microtubule-associated protein light chain 3-II (LC3-II, a marker of autophagy) and the accumulation of the cargo protein p62 suggesting an autophagy blockage. Moreover, confocal microscopy revealed that capsaicin treatment increased lysosomes which co-localized with LC3 positive vesicles in a similar extent to that produced by the lysosomal protease inhibitors E64 and pepstatin pointing to an autophagolysosomes breakdown inhibition. Furthermore, we found that capsaicin triggered ROS generation in cells, while the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Co-treatment of cells with NAC and capsaicin abrogated the effects of capsaicin on autophagy and cell death. Normal prostate PNT2 and RWPE-1 cells were more resistant to capsaicin-induced cytotoxicity and did not accumulate p62 protein. Taken together, these results suggest that ROS-mediated capsaicin-induced autophagy blockage contributes to antiproliferation in prostate cancer cells, which provides new insights into the anticancer molecular mechanism of capsaicin. PMID:26625315

  17. The pepper's natural ingredient capsaicin induces autophagy blockage in prostate cancer cells.

    PubMed

    Ramos-Torres, Ágata; Bort, Alicia; Morell, Cecilia; Rodríguez-Henche, Nieves; Díaz-Laviada, Inés

    2016-01-12

    Capsaicin, the pungent ingredient of red hot chili peepers, has been shown to have anti-cancer activities in several cancer cells, including prostate cancer. Several molecular mechanisms have been proposed on its chemopreventive action, including ceramide accumulation, endoplasmic reticulum stress induction and NFκB inhibition. However, the precise mechanisms by which capsaicin exerts its anti-proliferative effect in prostate cancer cells remain questionable. Herein, we have tested the involvement of autophagy on the capsaicin mechanism of action on prostate cancer LNCaP and PC-3 cells.The results showed that capsaicin induced prostate cancer cell death in a time- and concentration-dependent manner, increased the levels of microtubule-associated protein light chain 3-II (LC3-II, a marker of autophagy) and the accumulation of the cargo protein p62 suggesting an autophagy blockage. Moreover, confocal microscopy revealed that capsaicin treatment increased lysosomes which co-localized with LC3 positive vesicles in a similar extent to that produced by the lysosomal protease inhibitors E64 and pepstatin pointing to an autophagolysosomes breakdown inhibition. Furthermore, we found that capsaicin triggered ROS generation in cells, while the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Co-treatment of cells with NAC and capsaicin abrogated the effects of capsaicin on autophagy and cell death. Normal prostate PNT2 and RWPE-1 cells were more resistant to capsaicin-induced cytotoxicity and did not accumulate p62 protein.Taken together, these results suggest that ROS-mediated capsaicin-induced autophagy blockage contributes to antiproliferation in prostate cancer cells, which provides new insights into the anticancer molecular mechanism of capsaicin.

  18. Involvement of endoplasmic reticulum stress in capsaicin-induced apoptosis of human pancreatic cancer cells.

    PubMed

    Lin, Shengzhang; Zhang, Jianhong; Chen, Hui; Chen, Kangjie; Lai, Fuji; Luo, Jiang; Wang, Zhaohong; Bu, Heqi; Zhang, Riyuan; Li, Honghai; Tong, Hongfei

    2013-01-01

    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-2 α (phospho-eIF2 α ), 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. Capsaicin triggers immunogenic PEL cell death, stimulates DCs and reverts PEL-induced immune suppression.

    PubMed

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

    2015-10-01

    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.

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

    PubMed

    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) < 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. PMID:25933112

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

    PubMed

    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.

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

    PubMed

    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. PMID:25813723

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

    PubMed

    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. Reflex hypertensive response induced by capsaicin involves endothelin-dependent mechanisms.

    PubMed

    Akella, Aparna; Deshpande, Shripad B

    2015-01-01

    Capsaicin, a nociceptive agent produces triphasic pressure response in rats. The mechanisms underlying capsaicin-induced pressure responses are not clear. Therefore, the present study was undertaken to determine the mechanisms involved in capsaicin - induced pressure responses. The trachea, jugular vein and femoral artery were cannulated in anaesthetized rats. Capsaicin (10 µg/kg; i.v) - induced reflex changes in the blood pressure, respiratory excursions and ECG were recorded before/after vagotomy in the absence/presence of antagonists. Capsaicin produced the triphasic pressure response characterized by immediate fall, recovery (intermediate phase) and delayed progressive fall. After vagotomy, the immediate hypotension was abolished and the intermediate pressure response was potentiated as a hypertensive response while the delayed hypotensive response persisted. The time-matched heart rate changes (bradycardia) and respiratory changes (tachypnea in delayed phase) were abolished after vagotomy. Pretreatment with endothelin receptor antagonist (bosentan; 10 mg/kg) blocked the capsiaicn-induced intermediate hypertensive response in vagotomised animals but not the delayed hypotension. Pretreatment with nitric oxide synthase (NOS) inhibitor (L-NAME; 30 pg/kg), prostaglandin synthase inhibitor (indomethacin; 10 mg/kg) and kinin synthase inhibitor (aprotinin; 6000 KIU) did not block the delayed hypotensive response. These results demonstrate that capsaicin-induced intermediate hypertensive response involves endothelin-dependent mechanisms and the delayed hypotensive response is independent of nitrergic, prostaglandinergic or kininergic mechanisms.

  5. Organization of pERK-immunoreactive cells in trigeminal spinal nucleus caudalis, upper cervical cord, NTS and Pa5 following capsaicin injection into masticatory and swallowing-related muscles in rats.

    PubMed

    Tsujimura, Takanori; Shinoda, Masamichi; Honda, Kuniya; Hitomi, Suzuro; Kiyomoto, Masaaki; Matsuura, Shingo; Katagiri, Ayano; Tsuji, Kojun; Inoue, Makoto; Shiga, Yoshi; Iwata, Koichi

    2011-10-12

    Many phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) cells are expressed in the trigeminal spinal subnucleus caudalis (Vc), upper cervical spinal cord (C1-C2), nucleus tractus solitarii (NTS) and paratrigeminal nucleus (Pa5) after capsaicin injection into the whisker pad (WP), masseter muscle (MM), digastric muscle (DM) or sternohyoideus muscle (SM). The pERK-IR cells also showed NeuN immunoreactivity, indicating that ERK phosphorylation occurs in neurons. The pERK-IR cells were significantly reduced after intrathecal injection of MEK 1/2 inhibitor PD98059. The pERK-IR cells expressed bilaterally in the Vc and C1-C2 after capsaicin injection into the unilateral DM or SM, whereas unilaterally in the Vc and C1-C2 after unilateral WP or MM injection. After capsaicin injection into the WP or MM, the pERK-IR cell expression in the Vc was restricted rostrocaudally within a narrow area. However, the distribution of pERK-IR cells was more wide spread without a clear peak in the Vc and C1-C2 after capsaicin injection into the DM or SM. In the NTS, the unimodal pERK-IR cell expression peaked at 0-720μm rostral from the obex following capsaicin injection into WP, MM, DM or SM. In the ipsilateral Pa5, many pERK-IR cells were observed following capsaicin injection into the SM. The number of swallows elicited by distilled water administration was significantly smaller after capsaicin injection into the WP, MM or DM but not SM compared to that of vehicle-injected rats. Various noxious inputs due to the masticatory or swallowing-related muscle inflammation may be differentially involved in muscle pain and swallowing reflex activity.

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

    PubMed

    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 < 0.05), while no mechanical hyperalgesia was observed in either animal group. The present model of topical 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.

  7. Capsaicin induces apoptosis in SCC-4 human tongue cancer cells through mitochondria-dependent and -independent pathways.

    PubMed

    Ip, Siu-Wan; Lan, Sheng-Hui; Huang, An-Cheng; Yang, Jai-Sing; Chen, Ya-Yin; Huang, Hui-Ying; Lin, Zen-Pin; Hsu, Yuan-Man; Yang, Mei-Due; Chiu, Chang-Fang; Chung, Jing-Gung

    2012-05-01

    Although there have been advances in the fields of surgery, radiotherapy, and chemotherapy of tongue cancer, the cure rates are still not substantially satisfactory. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the major pungent ingredient of hot chili pepper and has been reported to have an antitumor effect on many human cancer cell types. The molecular mechanisms of the antitumor effect of capsaicin are not yet completely understood. Herein, we investigated whether capsaicin induces apoptosis in human tongue cancer cells. Capsaicin decreased the percentage of viable cells in a dose-dependent manner in human tongue cancer SCC-4 cells. In addition, capsaicin produced DNA fragmentation, decreased the DNA contents (sub-G1 phase), and induced G0/G1 phase arrest in SCC-4 cells. We demonstrated that capsaicin-induced apoptosis is associated with an increase in reactive oxygen species and Ca²⁺ generations and a disruption of the mitochondrial transmenbrane potential (ΔΨ(m)). Treatment with capsaicin induced a dramatic increase in caspase-3 and -9 activities, as assessed by flow cytometric methods. A possible mechanism of capsaicin-induced apoptosis is involved in the activation of caspase-3 (one of the apoptosis-executing enzyme). Confocal laser microscope examination also showed that capsaicin induced the releases of AIF, ATF-4, and GADD153 from mitochondria of SCC-4 cells.

  8. Inhibiting ROS-STAT3-dependent autophagy enhanced capsaicin-induced apoptosis in human hepatocellular carcinoma cells.

    PubMed

    Chen, Xun; Tan, Miduo; Xie, Zhiqin; Feng, Bin; Zhao, Zhijian; Yang, Kaiqing; Hu, Chen; Liao, Ni; Wang, Taoli; Chen, Dongliang; Xie, Feng; Tang, Caixi

    2016-07-01

    Capsaicin, which is the pungent ingredient of red hot chili peppers, has been reported to possess anticancer activity, including that against hepatocellular carcinoma. However, the precise molecular mechanisms by which capsaicin exerts its anticancer effects remain poorly understood. Herein, we have tested the involvement of autophagy in the capsaicin mechanism of action in human hepatocellular carcinoma. HepG2 cancer cells were treated with different doses of capsaicin (50, 100 and 200μmol/L) for 6, 12, and 24 h. Flow cytometry and Caspase-3 activity assay were performed to determine cell apoptosis. Immunofluorescence was performed to visualize LC3-positive puncta. Western blotting was used to detect the expression of the hallmarks of apoptosis and autophagy. Capsaicin can induce apoptosis in HepG2 cells. The expression levels of CL-PARP and Bcl-2 were significantly increased. In line with the apoptosis, capsaicin can trigger autophagy in HepG2 cells. Capsaicin increased LC3-II and beclin-1 expression and GFP-LC3-positive autophagosomes. Pharmacological or genetic inhibition of autophagy further sensitized HepG2 cells to capsaicin-induced apoptosis. Mechanistically, capsaicin upregulated the Stat3 activity which contributed to autophagy. Importantly, we found that capsaicin triggered reactive oxygen species (ROS) generation in hepatoma cells and that the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Moreover, NAC abrogated the effects of capsaicin on Stat3-dependent autophagy. In this study, we demonstrated that capsaicin increased the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3)-dependent autophagy through the generation of ROS signaling pathways in human hepatoma. Inhibiting autophagy could enhance capsaicin-induced apoptosis in human hepatocellular carcinoma. PMID:27043357

  9. Inhibiting ROS-STAT3-dependent autophagy enhanced capsaicin-induced apoptosis in human hepatocellular carcinoma cells.

    PubMed

    Chen, Xun; Tan, Miduo; Xie, Zhiqin; Feng, Bin; Zhao, Zhijian; Yang, Kaiqing; Hu, Chen; Liao, Ni; Wang, Taoli; Chen, Dongliang; Xie, Feng; Tang, Caixi

    2016-07-01

    Capsaicin, which is the pungent ingredient of red hot chili peppers, has been reported to possess anticancer activity, including that against hepatocellular carcinoma. However, the precise molecular mechanisms by which capsaicin exerts its anticancer effects remain poorly understood. Herein, we have tested the involvement of autophagy in the capsaicin mechanism of action in human hepatocellular carcinoma. HepG2 cancer cells were treated with different doses of capsaicin (50, 100 and 200μmol/L) for 6, 12, and 24 h. Flow cytometry and Caspase-3 activity assay were performed to determine cell apoptosis. Immunofluorescence was performed to visualize LC3-positive puncta. Western blotting was used to detect the expression of the hallmarks of apoptosis and autophagy. Capsaicin can induce apoptosis in HepG2 cells. The expression levels of CL-PARP and Bcl-2 were significantly increased. In line with the apoptosis, capsaicin can trigger autophagy in HepG2 cells. Capsaicin increased LC3-II and beclin-1 expression and GFP-LC3-positive autophagosomes. Pharmacological or genetic inhibition of autophagy further sensitized HepG2 cells to capsaicin-induced apoptosis. Mechanistically, capsaicin upregulated the Stat3 activity which contributed to autophagy. Importantly, we found that capsaicin triggered reactive oxygen species (ROS) generation in hepatoma cells and that the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Moreover, NAC abrogated the effects of capsaicin on Stat3-dependent autophagy. In this study, we demonstrated that capsaicin increased the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3)-dependent autophagy through the generation of ROS signaling pathways in human hepatoma. Inhibiting autophagy could enhance capsaicin-induced apoptosis in human hepatocellular carcinoma.

  10. Capsaicin Induces “Brite” Phenotype in Differentiating 3T3-L1 Preadipocytes

    PubMed Central

    Baboota, Ritesh K.; Singh, Dhirendra P.; Sarma, Siddhartha M.; Kaur, Jaspreet; Sandhir, Rajat; Boparai, Ravneet K.; Kondepudi, Kanthi K.; Bishnoi, Mahendra

    2014-01-01

    Objective Targeting the energy storing white adipose tissue (WAT) by pharmacological and dietary means in order to promote its conversion to energy expending “brite” cell type holds promise as an anti-obesity approach. Present study was designed to investigate/revisit the effect of capsaicin on adipogenic differentiation with special reference to induction of “brite” phenotype during differentiation of 3T3-L1 preadipocytes. Methods Multiple techniques such as Ca2+ influx assay, Oil Red-O staining, nutrigenomic analysis in preadipocytes and matured adipocytes have been employed to understand the effect of capsaicin at different doses. In addition to in-vitro experiments, in-vivo studies were carried out in high-fat diet (HFD) fed rats treated with resiniferatoxin (RTX) (a TRPV1 agonist) and in mice administered capsaicin. Results TRPV1 channels are expressed in preadipocytes but not in adipocytes. In preadipocytes, both capsaicin and RTX stimulate Ca2+ influx in dose-dependent manner. This stimulation may be prevented by capsazepine, a TRPV1 antagonist. At lower doses, capsaicin inhibits lipid accumulation and stimulates TRPV1 gene expression, while at higher doses it enhances accumulation of lipids and suppresses expression of its receptor. In doses of 0.1–100 µM, capsaicin promotes expression of major pro-adipogenic factor PPARγ and some of its downstream targets. In concentrations of 1 µM, capsaicin up-regulates anti-adipogenic genes. Low-dose capsaicin treatment of 3T3-L1 preadipocytes differentiating into adipocytes results in increased expression of brown fat cell marker genes. In white adipose of mice, capsaicin administration leads to increase in browning-specific genes. Global TRPV1 ablation (i.p. by RTX administration) leads to increase in locomotor activity with no change in body weight. Conclusion Our findings suggest the dual modulatory role of capsaicin in adipogenesis. Capsaicin inhibits adipogenesis in 3T3-L1 via TRPV1 activation and

  11. Neonatal capsaicin treatment in rats induces chronic hyperthermia resulting in infectious disease

    PubMed Central

    JEONG, KEUN-YEONG; KIM, HWAN MOOK

    2015-01-01

    Treatment of neonatal animals with capsaicin has previously been associated with long-lasting hyperthermia and severe cutaneous lesions. The present study analyzed the effects of capsaicin-induced hyperthermia on the occurrence of infectious disease and pruritic dermatitis in a rat model. Pregnant Sprague-Dawley (SD) rats were obtained 1 week prior to parturition. Pups from each litter were randomly assigned to the following experimental groups: Capsaicin-treated (cap-treated; n=10) or vehicle-treated (n=5). Capsaicin (50 mg/kg) or vehicle were systemically administered to the SD rat pups (age, 48 h), after which body temperature was measured using a biotelemetry system, and the effects of hyperthermia on the ability of the rat pups to resist bacterial infection were analyzed. Furthermore, pruritus-induced scratching behavior and dermatitis were assessed, and changes in interleukin (IL)-4- and IL-13-induced immunoglobulin E expression were measured. Treatment of neonatal rats with capsaicin resulted in chronic hyperthermia, which had negative effects on the host immune defense response. The expression levels of T-helper type 2 cell-associated cytokines were significantly increased (P<0.01) in the cap-treated rats following bacterial infection with Staphylococcus aureus or Streptococcus agalactiae. Furthermore, cap-treated rats exhibited pruritus-induced scratching behavior and dermatitis. The results of the present study suggested that treatment of neonatal rats with capsaicin induces chronic hyperthermia and decreases the effectiveness of the host defense system. Therefore, a cap-treated neonatal rat model may be considered useful when investigating the association between hyperthermia and infectious disease. PMID:26668650

  12. Capsaicin induces apoptosis in human small cell lung cancer via the TRPV6 receptor and the calpain pathway.

    PubMed

    Lau, Jamie K; Brown, Kathleen C; Dom, Aaron M; Witte, Theodore R; Thornhill, Brent A; Crabtree, Clayton M; Perry, Haley E; Brown, J Michael; Ball, John G; Creel, Rebecca G; Damron, C Luke; Rollyson, William D; Stevenson, Cathryn D; Hardman, W Elaine; Valentovic, Monica A; Carpenter, A Betts; Dasgupta, Piyali

    2014-08-01

    Capsaicin, the pungent ingredient of chili peppers, displays potent anti-neoplastic activity in a wide array of human cancer cells. The present manuscript examines the signaling pathways underlying the apoptotic activity of capsaicin in human small cell lung cancer (SCLC) in vitro and in vivo. Studies in neuronal cells show that capsaicin exerts its biological activity via the transient receptor potential vanilloid (TRPV) superfamily of cation-channel receptors. The TRPV family is comprised of six members (TRPV1-6). Capsaicin is a known agonist of the TRPV1 receptor. We observed that capsaicin-induced apoptosis in human SCLC cells was mediated via the TRPV receptor family; however it was independent of TRPV1. Surprisingly, the apoptotic activity of capsaicin required the TRPV6 receptor. Depletion of TRPV6 receptor by siRNA methodology abolished the apoptotic activity of capsaicin in SCLC cells. Immunostaining and ELISA showed that TRPV6 receptor was robustly expressed on human SCLC tissues (from patients) and SCLC cell lines but almost absent in normal lung tissues. This correlates with our results that capsaicin induced very little apoptosis in normal lung epithelial cells. The pro-apoptotic activity of capsaicin was mediated by the intracellular calcium and calpain pathway. The treatment of human SCLC cells with capsaicin increased the activity of calpain 1 and 2 by threefold relative to untreated SCLC cells. Such calpain activation, in response to capsaicin, was downstream of the TRPV6 receptor. Taken together, our data provide insights into the mechanism underlying the apoptotic activity of capsaicin in human SCLCs. PMID:24878626

  13. Capsaicin induces apoptosis in human small cell lung cancer via the TRPV6 receptor and the calpain pathway.

    PubMed

    Lau, Jamie K; Brown, Kathleen C; Dom, Aaron M; Witte, Theodore R; Thornhill, Brent A; Crabtree, Clayton M; Perry, Haley E; Brown, J Michael; Ball, John G; Creel, Rebecca G; Damron, C Luke; Rollyson, William D; Stevenson, Cathryn D; Hardman, W Elaine; Valentovic, Monica A; Carpenter, A Betts; Dasgupta, Piyali

    2014-08-01

    Capsaicin, the pungent ingredient of chili peppers, displays potent anti-neoplastic activity in a wide array of human cancer cells. The present manuscript examines the signaling pathways underlying the apoptotic activity of capsaicin in human small cell lung cancer (SCLC) in vitro and in vivo. Studies in neuronal cells show that capsaicin exerts its biological activity via the transient receptor potential vanilloid (TRPV) superfamily of cation-channel receptors. The TRPV family is comprised of six members (TRPV1-6). Capsaicin is a known agonist of the TRPV1 receptor. We observed that capsaicin-induced apoptosis in human SCLC cells was mediated via the TRPV receptor family; however it was independent of TRPV1. Surprisingly, the apoptotic activity of capsaicin required the TRPV6 receptor. Depletion of TRPV6 receptor by siRNA methodology abolished the apoptotic activity of capsaicin in SCLC cells. Immunostaining and ELISA showed that TRPV6 receptor was robustly expressed on human SCLC tissues (from patients) and SCLC cell lines but almost absent in normal lung tissues. This correlates with our results that capsaicin induced very little apoptosis in normal lung epithelial cells. The pro-apoptotic activity of capsaicin was mediated by the intracellular calcium and calpain pathway. The treatment of human SCLC cells with capsaicin increased the activity of calpain 1 and 2 by threefold relative to untreated SCLC cells. Such calpain activation, in response to capsaicin, was downstream of the TRPV6 receptor. Taken together, our data provide insights into the mechanism underlying the apoptotic activity of capsaicin in human SCLCs.

  14. Influence of influenza A infection on capsaicin-induced responses in murine airways.

    PubMed

    Taylor, Samuel J; Mann, Tracy S; Henry, Peter J

    2012-02-01

    The principal aim of the study was to determine the influence of influenza A virus infection on capsaicin-induced relaxation responses in mouse isolated tracheal segments and clarify the underlying mechanisms. Anesthetized mice were intranasally inoculated with influenza A/PR-8/34 virus (VIRUS) or vehicle (SHAM), and 4 days later tracheal segments were harvested for isometric tension recording and biochemical and histologic analyses. Capsaicin induced dose-dependent relaxation responses in carbachol-contracted SHAM trachea (e.g., 10 μM capsaicin produced 66 ± 4% relaxation; n = 11), which were significantly inhibited by capsazepine [transient receptor potential vanilloid type 1 (TRPV1) antagonist], (2S,3S)-3-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-2-phenylpiperidine hydrochloride (L-733,060) [neurokinin 1 (NK₁) receptor antagonist], indomethacin [cyclooxygenase (COX) inhibitor], and the combination of 6-isopropoxy-9-oxoxanthene-2-carboxylic acid (AH6809) and 7-[5α-([1S,1α(Z)-biphenyl]-4-ylmethoxy)-2β-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid, calcium salt, hydrate (AH23848) [E-prostanoid (EP)₂ and EP₄ receptor antagonists, respectively], indicating that capsaicin-induced relaxation involved the TRPV1-mediated release of substance P (SP), activation of epithelial NK₁ receptors, and production of COX products capable of activating relaxant EP₂/EP₄ receptors. Consistent with this postulate, capsaicin-induced relaxation was associated with the significant release of SP and prostaglandin E₂ (PGE₂) from mouse tracheal segments. As expected, influenza A virus infection was associated with widespread disruption of the tracheal epithelium. Tracheal segments from VIRUS mice responded weakly to capsaicin (7 ± 3% relaxation) and were 25-fold less responsive to SP than tracheas from SHAM mice. In contrast, relaxation responses to exogenous PGE₂ and the β-adrenoceptor agonist isoprenaline were not inhibited in VIRUS trachea. Virus infection

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

    PubMed

    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.

  16. Role of Autophagy in Capsaicin-Induced Apoptosis in U251 Glioma Cells.

    PubMed

    Liu, Ya-Ping; Dong, Fu-Xing; Chai, Xiang; Zhu, Shuang; Zhang, Bao-Le; Gao, Dian-Shuai

    2016-07-01

    In recent years, the role of capsaicin in cancer prevention and treatment has gained people's attention. However, the mechanism of anti-glioma cells by capsaicin has not been elucidated. Here, we discuss the mechanism of capsaicin in U251 cells. Cell viability was detected by MTT and extracellular LDH measurements, while immunofluorescence was performed to measure changes of LC3 in U251 cells. The expressions of LC3II, Puma-α, Beclin1, P62, Procaspase-3, and P53 were observed by immunoblotting. The cell viability decreased and the punctate patterns of LC3 in U251 cells were observed after Capsaicin treatment. Meanwhile, the expressions of Beclin1, P62, and Puma-α increased. After using 3-MA, the expressions of Beclin1 and Procaspase-3 were reduced while those of P53 and Puma-α increased. The expression of LC3II was increased after Pifithrin-α treatment. Therefore, we believed that capsaicin could induce apoptosis in U251 cells, and the inhibition of autophagy could contribute to apoptosis. PMID:26351174

  17. Capsaicin Induces Apoptosis in Human Small Cell Lung Cancer via the TRPV6 Receptor and the Calpain Pathway

    PubMed Central

    Lau, Jamie K.; Brown, Kathleen C.; Dom, Aaron M.; Witte, Theodore R.; Thornhill, Brent A.; Crabtree, Clayton M.; Perry, Haley E.; Brown, J. Michael; Ball, John G.; Creel, Rebecca G.; Damron, C. Luke; Rollyson, William D.; Stevenson, Cathryn D.; Hardman, W. Elaine; Valentovic, Monica A.; Carpenter, A. Betts; Dasgupta, Piyali

    2014-01-01

    Capsaicin, the pungent ingredient of chili peppers, displays potent anti-neoplastic activity in a wide array of human cancer cells. The present manuscript examines the signaling pathways underlying the apoptotic activity of capsaicin in human small cell lung cancer (SCLC) in vitro and in vivo. Studies in neuronal cells show that capsaicin exerts its biological activity via the transient receptor potential vanilloid (TRPV) superfamily of cation-channel receptors. The TRPV family is comprised of six members (TRPV1-6). Capsaicin is an agonist of the TRPV1 receptor. We observed that capsaicin-induced apoptosis in human SCLC cells was mediated via the TRPV receptor family; however it was independent of TRPV1. Surprisingly, the apoptotic activity of capsaicin required the TRPV6 receptor. Depletion of TRPV6 receptor by siRNA methodology abolished the apoptotic activity of capsaicin in SCLC cells. Immunostaining and ELISA showed that TRPV6 receptor was robustly expressed on human SCLC tissues (from patients) and SCLC cell lines but almost absent in normal lung tissues. This correlates with our results that capsaicin induced very little apoptosis in normal lung epithelial cells. The proapoptotic activity of was mediated by the intracellular calcium and calpain pathway. The treatment of human SCLC cells with capsaicin induced increased the activity of calpain 1 and 2 by three-fold relative to untreated SCLC cells. Such calpain activation, in response to capsaicin, was downstream of the TRPV6 receptor. Taken together, our data provide insights into the mechanism underlying the apoptotic activity of capsaicin in human SCLCs. PMID:24878626

  18. Dose-dependent protective effect of BPC 157 on capsaicin-induced rhinitis in rats.

    PubMed

    Kalogjera, L; Ries, M; Baudoin, T; Ferencic, Z; Trotic, R; Pegan, B

    1997-01-01

    Protection of BPC 157 on capsaicin-induced rhinitis was studied in Wistar rats for its effect on mastocyte infiltration, degranulation and inflammatory cell infiltration. Animals were pretreated with 10 microg/kg, 10 ng/kg or 2 ml saline i.p. and capsaicin (0.05 ml/nostril of 1750 nmol/l sol.) was applied intranasally. They were then euthanized at 1, 3 and 12 h after capsaicin provocation. Nasal mucosa was analyzed and scored for mastocyte infiltration, degranulation and inflammatory cell infiltration. BPC 157 pretreatment significantly prevented mastocyte infiltration at 1 h. Polymorphonuclear leukocyte infiltration was significantly reduced in rats pretreated with 10 microg/kg BPC 157. A dose-dependent effect of BPC 157 pretreatment was demonstrated only for polymorphonuclear leukocyte infiltration at 12 h. PMID:9065615

  19. Capsaicin-Induced Changes in LTP in the Lateral Amygdala Are Mediated by TRPV1

    PubMed Central

    Zschenderlein, Carsten; Gebhardt, Christine; von Bohlen und Halbach, Oliver; Kulisch, Christoph; Albrecht, Doris

    2011-01-01

    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. PMID:21249195

  20. Recovery of viscerosensory innervation from the dorsal root ganglia of the adult rat following capsaicin-induced injury.

    PubMed

    Gallaher, Zachary R; Larios, Rose Marie; Ryu, Vitaly; Sprunger, Leslie K; Czaja, Krzysztof

    2010-09-01

    Capsaicin is a neurotoxin selective for C- and Adelta-type neurons. Systemic treatment with capsaicin is known to reduce this subpopulation in the dorsal root ganglia (DRG) of neonatal rats. To better understand the effects of capsaicin on adult afferent fibers, we examined DRG neurons retrogradely labeled by an i.p. injection of Fast Blue (FB) administered 3, 30, or 60 days after systemic capsaicin treatment (125 mg/kg i.p.). FB labeling in the 12th and 13th thoracic DRG was dramatically reduced 3 and 30 days post capsaicin (50% and 35% of control, respectively). However, the number of retrogradely labeled neurons rose to 65% of control by 60 days post capsaicin. In addition to FB labeling, we quantified the immunoreactivity of NR1, the obligatory N-methyl-D-aspartate receptor subunit, and Na(v)1.8, a DRG-specific sodium channel, in FB-labeled neurons as well as mRNA levels for both proteins in the 5th and 6th lumbar DRG. NR1 immunoreactivity and mRNA expression followed a pattern of early reduction and subsequent partial restoration similar to FB labeling. Na(v)1.8 immunoreactivity and mRNA expression dropped to approximately 50% of control at 3 days post capsaicin but completely recovered by 60 days. These data strongly support the conclusion that restoration of spinal afferent projections and signaling occurs in adult rats following capsaicin-induced damage. PMID:20593356

  1. Capsaicin induces NKCC1 internalization and inhibits chloride secretion in colonic epithelial cells independently of TRPV1.

    PubMed

    Bouyer, Patrice G; Tang, Xu; Weber, Christopher R; Shen, Le; Turner, Jerrold R; Matthews, Jeffrey B

    2013-01-15

    Colonic chloride secretion is regulated via the neurohormonal and immune systems. Exogenous chemicals (e.g., butyrate, propionate) can affect chloride secretion. Capsaicin, the pungent ingredient of the chili peppers, exerts various effects on gastrointestinal function. Capsaicin is known to activate the transient receptor potential vanilloid type 1 (TRPV1), expressed in the mesenteric nervous system. Recent studies have also demonstrated its presence in epithelial cells but its role remains uncertain. Because capsaicin has been reported to inhibit colonic chloride secretion, we tested whether this effect of capsaicin could occur by direct action on epithelial cells. In mouse colon and model T84 human colonic epithelial cells, we found that capsaicin inhibited forskolin-dependent short-circuit current (FSK-I(sc)). Using PCR and Western blot, we demonstrated the presence of TRPV1 in colonic epithelial cells. In T84 cells, TRPV1 localized at the basolateral membrane and in vesicular compartments. In permeabilized monolayers, capsaicin activated apical chloride conductance, had no effect on basolateral potassium conductance, but induced NKCC1 internalization demonstrated by immunocytochemistry and basolateral surface biotinylation. AMG-9810, a potent inhibitor of TRPV1, did not prevent the inhibition of the FSK-I(sc) by capsaicin. Neither resiniferatoxin nor N-oleoyldopamine, two selective agonists of TRPV1, blocked the FSK-I(sc). Conversely capsaicin, resiniferatoxin, and N-oleoyldopamine raised intracellular calcium ([Ca(2+)](i)) in T84 cells and AMG-9810 blocked the rise in [Ca(2+)](i) induced by capsaicin and resiniferatoxin suggesting the presence of a functional TRPV1 channel. We conclude that capsaicin inhibits chloride secretion in part by causing NKCC1 internalization, but by a mechanism that appears to be independent of TRPV1. PMID:23139219

  2. Capsaicin avoidance as a measure of chemical hyperalgesia in orofacial nerve injury models.

    PubMed

    Boucher, Yves; Carstens, Mirela Iodi; Sawyer, Carolyn M; Zanotto, Karen L; Merrill, Austin W; Carstens, E

    2013-05-24

    Many patients suffer from trigeminal neuralgia and other types of orofacial pain that are poorly treated, necessitating preclininal animal models for development of mechanisms-based therapies. The present study assessed capsaicin avoidance and other nocifensive behavioral responses in three models of orofacial nerve injury in rats: chronic constriction injury (CCI) of the mental nerves, partial tight ligation of mental nerves, and CCI of lingual nerves. We additionally investigated if nerve injury resulted in enhanced capsaicin-evoked activation of neurons in trigeminal caudalis (Vc) or nucleus of the solitary tract (NTS) based on expression of Fos-like immunoreactivity (FLI). Mental nerve CCI resulted in an enhancement of capsaicin avoidance in a two-bottle preference paradigm, while neither mental nerve injury produced thermal hyperalgesia or mechanical allodynia. CCI of lingual nerves did not affect capsaicin avoidance. Counts of FLI in Vc were significantly higher in the lingual sham and mental nerve CCI groups compared to mental shams; FLI counts in NTS did not differ among groups. Mental nerve CCI may have induced central sensitization of chemical nociception since increased capsaicin avoidance was accompanied by greater activation of Vc neurons in response to oral capsaicin.

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

    PubMed

    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. PMID:25603234

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

    PubMed

    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.

  5. Increase in gastric secretion induced by 2-deoxy-D-glucose is impaired in capsaicin pretreated rats.

    PubMed Central

    Evangelista, S.; Santicioli, P.; Maggi, C. A.; Meli, A.

    1989-01-01

    Gastric acid secretion was determined following intravenous administration of 2-deoxy-D-glucose (2-DG; 60 mg kg-1) or electrical stimulation of the vagus nerve in urethane-anaesthetized rats pretreated when newborn with either capsaicin or the vehicle. The secretory response to 2-DG was substantially reduced in the capsaicin pretreated rats, while that induced by electrical vagal stimulation (1 mA, 1 ms. 3 Hz) was unaffected. These results suggest that capsaicin-sensitive fibres are involved in the afferent branch of the reflex response activated by 2-DG to stimulate gastric acid secretion. PMID:2804552

  6. Involvement of the phosphoinositide 3-kinase/Akt pathway in apoptosis induced by capsaicin in the human pancreatic cancer cell line PANC-1

    PubMed Central

    ZHANG, JIAN-HONG; LAI, FU-JI; CHEN, HUI; LUO, JIANG; ZHANG, RI-YUAN; BU, HE-QI; WANG, ZHAO-HONG; LIN, HONG-HAI; LIN, SHENG-ZHANG

    2013-01-01

    Capsaicin, one of the major pungent ingredients found in red peppers, has been recently demonstrated to induce apoptosis in various malignant cell lines through an unclear mechanism. In this study, the effect of capsaicin on proliferation and apoptosis in the human pancreatic cancer cell line PANC-1 and its possible mechanism(s) of action were investigated. The results of a Cell Counting Kit-8 (CCK-8) assay revealed that capsaicin significantly decreased the viability of PANC-1 cells in a dose-dependent manner. Capsaicin induced G0/G1 phase cell cycle arrest and apoptosis in PANC-1 cells as demonstrated by a flow cytometric assessment. Caspase-3 expression at both the protein and mRNA level was promoted following capsaicin treatment. Furthermore, we revealed that phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473) in PANC-1 cells were downregulated in response to capsaicin. Moreover, capsaicin gavage significantly inhibited the growth of pancreatic cancer PANC-1 cell xenografts in athymic nude mice. An increased number of TUNEL-positive cells and cleaved caspase-3 were observed in capsaicin-treated mice. In vivo, capsaicin downregulated the expression of phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473). In conclusion, we have demonstrated that capsaicin is an inhibitor of growth of PANC-1 cells, and downregulation of the phosphoinositide 3-kinase/Akt pathway may be involved in capsaicin-induced apoptosis in vitro and in vivo. PMID:23255891

  7. Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects

    PubMed Central

    Lee, Robert H; Korsapati, Hariprasad; Bhalla, Vikas; Varki, Nissi; Mittal, Ravinder K

    2016-01-01

    Background/Aims Transient receptor potential vanilloid-1 (TRPV1) is a candidate for mediating acid-induced symptoms in the esophagus. We conducted studies to determine if the presence of acid in the mucosa/submucosa and direct activation of TRPV1 by capsaicin elicited symptoms in normal healthy subjects. We also studied the presence of TRPV1 receptors in the esophagus. Methods Unsedated endoscopy was performed on healthy subjects with no symptoms. Using a sclerotherapy needle, normal saline (pH 2.0–7.5) was injected into the mucosa/submucosa, 5 cm above the Z line. In a separate group of healthy subjects, injection of capsaicin and vehicle was also studied. Quality of symptoms was reported using the McGill Pain Questionnaire, and symptom intensity using the visual analogue scale (VAS). Immunohistochemistry was performed on 8 surgical esophagus specimens using TRPV1 antibody. Results Acid injection either did not elicit or elicited mild symptoms in subjects at all pH solutions. Capsaicin but not the vehicle elicited severe heartburn/chest pain in all subjects. Mean VAS for capsaicin was 91 ± 3 and symptoms lasted for 25 ± 1 minutes. Immunohistochemistry revealed a linear TRPV1 staining pattern between the epithelial layer and the submucosa that extended into the papillae. Eighty-five percent of papillae stained positive for TRPV1 with a mean 1.1 positive papillae per high-powered field. Conclusions The mechanism of acid-induced heartburn and chest pain is not the simple interaction of hydrogen ions with afferents located in the esophageal mucosa and submucosa. TRPV1 receptors are present in the lamina propria and their activation induces heartburn and chest pain. PMID:26932896

  8. Dependence of Nociceptive Detection Thresholds on Physiological Parameters and Capsaicin-Induced Neuroplasticity: A Computational Study

    PubMed Central

    Yang, Huan; Meijer, Hil G. E.; Doll, Robert J.; Buitenweg, Jan R.; van Gils, Stephan A.

    2016-01-01

    Physiological properties of peripheral and central nociceptive subsystems can be altered over time due to medical interventions. The effective change for the whole nociceptive system can be reflected in changes of psychophysical characteristics, e.g., detection thresholds. However, it is challenging to separate contributions of distinct altered mechanisms with measurements of thresholds only. Here, we aim to understand how these alterations affect Aδ-fiber-mediated nociceptive detection of electrocutaneous stimuli. First, with a neurophysiology-based model, we study the effects of single-model parameters on detection thresholds. Second, we derive an expression of model parameters determining the functional relationship between detection thresholds and the interpulse interval for double-pulse stimuli. Third, in a case study with topical capsaicin treatment, we translate neuroplasticity into plausible changes of model parameters. Model simulations qualitatively agree with changes in experimental detection thresholds. The simulations with individual forms of neuroplasticity confirm that nerve degeneration is the dominant mechanism for capsaicin-induced increases in detection thresholds. In addition, our study suggests that capsaicin-induced central plasticity may last at least 1 month. PMID:27252644

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

    PubMed

    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.

  10. Behavioral and physiological effects of capsaicin in red-winged blackbirds.

    PubMed

    Mason, J R; Maruniak, J A

    1983-11-01

    We injected red-winged blackbirds (Agelaius phoeniceus) subcutaneously with capsaicin, and assessed (a) changes in basal body temperature, (b) ability to discriminate warm from cool drinking water, and (c) sensitivity to oral and topical applications of capsaicin, a trigeminal irritant. As predicted from studies of mammals, the injections seemed to disrupt thermoregulation when the ambient temperature increased, and eliminated discrimination between warm and cool drinking water (Figs. 1 and 2). In contrast to effects on mammals, injections failed to observably diminish oral or topical sensitivity to capsaicin and apparently induced a capsaicin preference in two-bottle drinking tests between capsaicin and its vehicle (Fig. 3). Such preferences were context-dependent, however, since water was reliably preferred to capsaicin or vehicle in three-bottle tests. To our knowledge, the present work is the first to report physiological and behavioral effects of capsaicin on birds, and the first to suggest that the substance may have different behavioral and physiological effects on different classes of animals.

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

    PubMed

    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.

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

    SciTech Connect

    Moon, Dong-Oh; Kang, Chang-Hee; Kang, Sang-Hyuck; Choi, Yung-Hyun; Hyun, Jin-Won; Chang, Weon-Young; Kang, Hee-Kyoung; Koh, Young-Sang; Maeng, Young-Hee; Kim, Young-Ree; Kim, Gi-Young

    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.

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

    PubMed

    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.

  14. Trigeminal Neuralgia

    MedlinePlus

    ... About NINDS NINDS Trigeminal Neuralgia Information Page Synonym(s): Tic Douloureux Condensed from Trigeminal Neuralgia Fact Sheet Table ... is Trigeminal Neuralgia? Trigeminal neuralgia (TN), also called tic douloureux , is a chronic pain condition that causes ...

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Reduced expression of SynGAP, a neuronal GTPase-activating protein, enhances capsaicin-induced peripheral sensitization

    PubMed Central

    Duarte, Djane Braz; Duan, Jian-Hong; Nicol, Grant D.; Vasko, Michael R.

    2011-01-01

    Synaptic GTPase-activating protein (SynGAP) is a neuronal-specific Ras/Rap-GAP that increases the hydrolysis rate of GTP to GDP, converting Ras/Rap from the active into the inactive form. The Ras protein family modulates a wide range of cellular pathways including those involved in sensitization of sensory neurons. Since GAPs regulate Ras activity, SynGAP might be an important regulator of peripheral sensitization and pain. Therefore, we evaluated excitability, stimulus-evoked release of the neuropeptide calcitonin gene-related peptide (CGRP), and nociception from wild-type (WT) mice and those with a heterozygous mutation of the SynGAP gene (SynGAP+/−). Our results demonstrate that SynGAP is expressed in primary afferent sensory neurons and that the capsaicin-stimulated CGRP release from spinal cord slices was two-fold higher from SynGAP+/− mice than that observed from WT mouse tissue, consistent with an increase in expression of the capsaicin receptor, transient receptor potential cation channel subfamily V member 1 (TRPV1), in SynGAP+/− dorsal root ganglia. However, there was no difference between the two genotypes in potassium-stimulated release of CGRP, the number of action potentials generated by a ramp of depolarizing current, or mechanical hypernociception elicited by intraplantar injection of capsaicin. In contrast, capsaicin-induced thermal hypernociception occurred at lower doses of capsaicin and had a longer duration in SynGAP+/− mice than WT mice. These results provide the first evidence that SynGAP is an important regulator of neuropeptide release from primary sensory neurons and can modulate capsaicin-induced hypernociception, demonstrating the importance of GAP regulation in signaling pathways that play a role in peripheral sensitization. PMID:21525372

  18. Octreotide inhibits capsaicin-induced activation of C and Aδ afferent fibres in rat hairy skin in vivo.

    PubMed

    Wang, Jun; Cao, Dong-Yuan; Guo, Yuan; Ma, Shao-Jie; Luo, Rong; Pickar, Joel G; Zhao, Yan

    2011-08-01

    1. The present study investigated whether the somatostatin receptor (SSTR) agonist, octreotide, could inhibit the activation of dorsal skin afferent fibres induced by local injection of capsaicin in the rat. 2. Single unit activity from Aδ mechano-heat sensitive (AMH; n = 41) and C mechano-heat sensitive (CMH; n = 30) afferents was recorded after their isolation in thin filaments from the dorsal cutaneous nerve branches. The effect of subcutaneous octreotide injection on the change in discharge rate and mechanical threshold induced by capsaicin was determined. 3. Capsaicin (0.05%) injection into the edge of the receptive field of both AMH and CMH units increased their discharge rate and decreased their mechanical threshold. Pre-injection of octreotide inhibited these responses, and co-application of SSTR antagonist, cyclosomatostatin, reversed the inhibitory effect of octreotide. 4. The present study provides electrophysiological evidence that the signal evoked by the somatostatin receptor inhibits the activation and mechanical sensitization evoked by capsaicin in the terminals in small-diameter sensory neurons.

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

    PubMed

    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.

  20. Selectively targeting pain in the trigeminal system

    PubMed Central

    Kim, Hyun Yeong; Kim, Kihwan; Li, Hai Ying; Chung, Gehoon; Park, Chul-Kyu; Kim, Joong Soo; Jung, Sung Jun; Lee, Min Kyung; Ahn, Dong Kuk; Hwang, Se Jin; Kang, Youngnam; Binshtok, Alexander M.; Bean, Bruce P.; Woolf, Clifford J.; Oh, Seog Bae

    2015-01-01

    We tested whether it is possible to selectively block pain signals in the orofacial area by delivering the permanently charged lidocaine derivative QX-314 into nociceptors via TPRV1 channels. We examined the effects of co-applied QX-314 and capsaicin on nociceptive, proprioceptive, and motor function in the rat trigeminal system. QX-314 alone failed to block voltage-gated sodium channel currents (INa) and action potentials (APs) in trigeminal ganglion (TG) neurons. However, co-application of QX-314 and capsaicin blocked INa and APs in TRPV1-positive TG and dental nociceptive neurons, but not in TRPV1-negative TG neurons or in small neurons from TRPV1 knock-out mice. Immunohistochemistry revealed that TRPV1 is not expressed by trigeminal motor and trigeminal mesencephalic neurons. Capsaicin had no effect on rat trigeminal motor and proprioceptive mesencephalic neurons and therefore should not allow QX-314 to enter these cells. Co-application of QX-314 and capsaicin inhibited the jaw-opening reflex evoked by noxious electrical stimulation of the tooth pulp when applied to a sensory but not a motor nerve, and produced long-lasting analgesia in the orofacial area. These data show that selective block of pain signals can be achieved by co-application of QX-314 with TRPV1 agonists. This approach has potential utility in the trigeminal system for treating dental and facial pain. PMID:20236764

  1. Selectively targeting pain in the trigeminal system.

    PubMed

    Kim, Hyun Yeong; Kim, Kihwan; Li, Hai Ying; Chung, Gehoon; Park, Chul-Kyu; Kim, Joong Soo; Jung, Sung Jun; Lee, Min Kyung; Ahn, Dong Kuk; Hwang, Se Jin; Kang, Youngnam; Binshtok, Alexander M; Bean, Bruce P; Woolf, Clifford J; Oh, Seog Bae

    2010-07-01

    We tested whether it is possible to selectively block pain signals in the orofacial area by delivering the permanently charged lidocaine derivative QX-314 into nociceptors via TPRV1 channels. We examined the effects of co-applied QX-314 and capsaicin on nociceptive, proprioceptive, and motor function in the rat trigeminal system. QX-314 alone failed to block voltage-gated sodium channel currents (I(Na)) and action potentials (APs) in trigeminal ganglion (TG) neurons. However, co-application of QX-314 and capsaicin blocked I(Na) and APs in TRPV1-positive TG and dental nociceptive neurons, but not in TRPV1-negative TG neurons or in small neurons from TRPV1 knock-out mice. Immunohistochemistry revealed that TRPV1 is not expressed by trigeminal motor and trigeminal mesencephalic neurons. Capsaicin had no effect on rat trigeminal motor and proprioceptive mesencephalic neurons and therefore should not allow QX-314 to enter these cells. Co-application of QX-314 and capsaicin inhibited the jaw-opening reflex evoked by noxious electrical stimulation of the tooth pulp when applied to a sensory but not a motor nerve, and produced long-lasting analgesia in the orofacial area. These data show that selective block of pain signals can be achieved by co-application of QX-314 with TRPV1 agonists. This approach has potential utility in the trigeminal system for treating dental and facial pain.

  2. Intrathecal dihydroergotamine inhibits capsaicin-induced vasodilatation in the canine external carotid circulation via GR127935- and rauwolscine-sensitive receptors.

    PubMed

    Marichal-Cancino, Bruno A; González-Hernández, Abimael; Manrique-Maldonado, Guadalupe; Ruiz-Salinas, Inna I; Altamirano-Espinoza, Alain H; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

    2012-10-01

    It has been suggested that during a migraine attack trigeminal nerves release calcitonin gene-related peptide (CGRP), producing central nociception and vasodilatation of cranial arteries, including the extracranial branches of the external carotid artery. Since trigeminal inhibition may prevent this vasodilatation, the present study has investigated the effects of intrathecal dihydroergotamine on the external carotid vasodilatation to capsaicin, α-CGRP and acetylcholine. Anaesthetized vagosympathectomized dogs were prepared to measure blood pressure, heart rate and external carotid conductance. A catheter was inserted into the right common carotid artery for the continuous infusion of phenylephrine (to restore the carotid vascular tone), whereas the corresponding thyroid artery was cannulated for one-min intracarotid infusions of capsaicin, α-CGRP and acetylcholine (which dose-dependently increased the external carotid conductance). Another cannula was inserted intrathecally (C(1)-C(3)) for the administration of dihydroergotamine, the α(2)-adrenoceptor antagonist rauwolscine or the serotonin 5-HT(1B/1D) receptor antagonist GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide hydrochloride monohydrate). Intrathecal dihydroergotamine (10, 31 and 100μg) inhibited the vasodilatation to capsaicin, but not that to α-CGRP or acetylcholine. This inhibition was: (i) unaffected by 10μg GR127935 or 100μg rauwolscine, but abolished by 31μg GR127935 or 310μg rauwolscine at 10μg dihydroergotamine; and (ii) abolished by the combination 10μg GR127935+100μg rauwolscine at 100μg dihydroergotamine. Thus, intrathecal (C(1)-C(3)) dihydroergotamine seems to inhibit the external carotid vasodilatation to capsaicin by spinal activation of serotonin 5-HT(1B/1D) (probably 5-HT(1B)) receptors and α(2) (probably α(2A/2C))-adrenoceptors.

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

    PubMed

    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. PMID:24075930

  4. Capsaicin for Rhinitis.

    PubMed

    Fokkens, Wytske; Hellings, Peter; Segboer, Christine

    2016-08-01

    Rhinitis is a multifactorial disease characterized by symptoms of sneezing, rhinorrhea, postnasal drip, and nasal congestion. Non-allergic rhinitis is characterized by rhinitis symptoms without systemic sensitization of infectious etiology. Based on endotypes, we can categorize non-allergic rhinitis into an inflammatory endotype with usually eosinophilic inflammation encompassing at least NARES and LAR and part of the drug induced rhinitis (e.g., aspirin intolerance) and a neurogenic endotype encompassing idiopathic rhinitis, gustatory rhinitis, and rhinitis of the elderly. Patients with idiopathic rhinitis have a higher baseline TRPV1 expression in the nasal mucosa than healthy controls. Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of chili peppers, plants of the genus Capsicum. 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. Patients with idiopathic rhinitis benefit from intranasal treatment with capsaicin. Expression of TRPV1 is reduced in patients with idiopathic rhinitis after capsaicin treatment. Recently, in a Cochrane review, the effectiveness of capsaicin in the management of idiopathic rhinitis was evaluated and the authors concluded that given that many other options do not work well in non-allergic rhinitis, capsaicin is a reasonable option to try under physician supervision. Capsaicin has not been shown to be effective in allergic rhinitis nor in other forms of non-allergic rhinitis like the inflammatory endotypes or other neurogenic endotypes like rhinitis of the elderly or smoking induced rhinitis. PMID:27485456

  5. Capsaicin for Rhinitis.

    PubMed

    Fokkens, Wytske; Hellings, Peter; Segboer, Christine

    2016-08-01

    Rhinitis is a multifactorial disease characterized by symptoms of sneezing, rhinorrhea, postnasal drip, and nasal congestion. Non-allergic rhinitis is characterized by rhinitis symptoms without systemic sensitization of infectious etiology. Based on endotypes, we can categorize non-allergic rhinitis into an inflammatory endotype with usually eosinophilic inflammation encompassing at least NARES and LAR and part of the drug induced rhinitis (e.g., aspirin intolerance) and a neurogenic endotype encompassing idiopathic rhinitis, gustatory rhinitis, and rhinitis of the elderly. Patients with idiopathic rhinitis have a higher baseline TRPV1 expression in the nasal mucosa than healthy controls. Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of chili peppers, plants of the genus Capsicum. 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. Patients with idiopathic rhinitis benefit from intranasal treatment with capsaicin. Expression of TRPV1 is reduced in patients with idiopathic rhinitis after capsaicin treatment. Recently, in a Cochrane review, the effectiveness of capsaicin in the management of idiopathic rhinitis was evaluated and the authors concluded that given that many other options do not work well in non-allergic rhinitis, capsaicin is a reasonable option to try under physician supervision. Capsaicin has not been shown to be effective in allergic rhinitis nor in other forms of non-allergic rhinitis like the inflammatory endotypes or other neurogenic endotypes like rhinitis of the elderly or smoking induced rhinitis.

  6. Trigeminal Neuralgia

    MedlinePlus

    ... Trigeminal neuralgia is more common in patients with multiple sclerosis. Cause The cause of trigeminal neuralgia is not ... five percent of patients with trigeminal neuralgia have multiple sclerosis. Patients with TN and multiple sclerosis are generally ...

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

    PubMed Central

    Tamaddonfard, Esmaeal; Tamaddonfard, Sina; Pourbaba, Salar

    2015-01-01

    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. PMID:26468465

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

    PubMed

    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.

  9. Latent Herpes Simplex Virus 1 Infection Does Not Induce Apoptosis in Human Trigeminal Ganglia

    PubMed Central

    Lindemann, Anja; Sinicina, Inga; Strupp, Michael; Brandt, Thomas; Hüfner, Katharina

    2015-01-01

    Herpes simplex virus 1 (HSV-1) can establish lifelong latency in human trigeminal ganglia. Latently infected ganglia contain CD8+ T cells, which secrete granzyme B and are thus capable of inducing neuronal apoptosis. Using immunohistochemistry and single-cell reverse transcription-quantitative PCR (RT-qPCR), higher frequency and transcript levels of caspase-3 were found in HSV-1-negative compared to HSV-1-positive ganglia and neurons, respectively. No terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-positive neurons were detected. The infiltrating T cells do not induce apoptosis in latently infected neurons. PMID:25762734

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

    PubMed

    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. PMID:26081756

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

    PubMed

    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.

  12. A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers

    PubMed Central

    Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

    2014-01-01

    Aims The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. Methods In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Results Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. Conclusions We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. PMID:24995954

  13. Identifying the integrated neural networks involved in capsaicin-induced pain using fMRI in awake TRPV1 knockout and wild-type rats.

    PubMed

    Yee, Jason R; Kenkel, William; Caccaviello, John C; Gamber, Kevin; Simmons, Phil; Nedelman, Mark; Kulkarni, Praveen; Ferris, Craig F

    2015-01-01

    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 vs. 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. PMID:25745388

  14. Identifying the integrated neural networks involved in capsaicin-induced pain using fMRI in awake TRPV1 knockout and wild-type rats

    PubMed Central

    Yee, Jason R.; Kenkel, William; Caccaviello, John C.; Gamber, Kevin; Simmons, Phil; Nedelman, Mark; Kulkarni, Praveen; Ferris, Craig F.

    2015-01-01

    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 vs. 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. PMID:25745388

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

    PubMed

    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.

  16. Carboxyl-terminal domain of transient receptor potential vanilloid 1 contains distinct segments differentially involved in capsaicin- and heat-induced desensitization.

    PubMed

    Joseph, John; Wang, Sen; Lee, Jongseok; Ro, Jin Y; Chung, Man-Kyo

    2013-12-13

    Multiple Ca(2+)-dependent processes are involved in capsaicin-induced desensitization of transient receptor potential vanilloid 1 (TRPV1), but desensitization of TRPV1 by heat occurs even in the absence of extracellular Ca(2+), although the mechanisms are unknown. In this study, we tested the hypothesis that capsaicin and heat desensitize TRPV1 through distinct mechanisms involving distinct structural segments of TRPV1. In HEK293 cells that heterologously express TRPV1, we found that heat-induced desensitization was not affected by the inclusion of intracellular ATP or alanine mutation of Lys(155), both of which attenuate capsaicin-induced desensitization, suggesting that heat-induced desensitization occurs through mechanisms distinct from capsaicin-induced desensitization. To determine protein domains involved in heat-induced desensitization, we generated chimeric proteins between TRPV1 and TRPV3, a heat-gated channel lacking heat-induced desensitization. We found that TRPV1 with the carboxyl-terminal domain (CTD) of TRPV3 retained heat activation but was impaired in heat-induced desensitization. Further experiments using chimeric or deletion mutants within TRPV1 CTD indicated that the distal half of CTD regulates the activation and desensitization of TRPV1 in modality-specific manners. Within the distal CTD, we identified two segments that distinctly regulated capsaicin- and heat-induced desensitization. The results suggest that the activation and desensitization of TRPV1 by capsaicin and heat can be modulated differentially and disproportionally through different regions of TRPV1 CTD. Identifying the domains involved in thermal regulation of TRPV1 may facilitate the development of novel anti-hyperalgesic approaches aimed at attenuating activation and enhancing desensitization of TRPV1 by thermal stimuli.

  17. Trigeminal Neuralgia

    MedlinePlus

    ... trigeminal neuralgia: Balloon compression works by injuring the insulation on nerves that are involved with the sensation ... glycerol injection bathes the ganglion and damages the insulation of trigeminal nerve fibers. This form of rhizotomy ...

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

    SciTech Connect

    Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang; Li, Junying

    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.

  19. Gingerol Reverses the Cancer-Promoting Effect of Capsaicin by Increased TRPV1 Level in a Urethane-Induced Lung Carcinogenic Model.

    PubMed

    Geng, Shengnan; Zheng, Yaqiu; Meng, Mingjing; Guo, Zhenzhen; Cao, Ning; Ma, Xiaofang; Du, Zhenhua; Li, Jiahuan; Duan, Yongjian; Du, Gangjun

    2016-08-10

    Both gingerol and capsaicin are agonists of TRPV1, which can negatively control tumor progression. This study observed the long-term effects of oral administration of 6-gingerol alone or in combination with capsaicin for 20 weeks in a urethane-induced lung carcinogenic model. We showed that lung carcinoma incidence and multiplicity were 70% and 21.2 ± 3.6, respectively, in the control versus 100% and 35.6 ± 5.2 in the capsaicin group (P < 0.01) and 50% and 10.8 ± 3.1 in the 6-gingerol group (P < 0.01). The combination of 6-gingerol and capsaicin reversed the cancer-promoting effect of capsaicin (carcinoma incidence of 100% versus 20% and multiplicity of 35.6 ± 5.2 versus 4.7 ± 2.3; P < 0.001). The cancer-promoting effect of capsaicin was due to increased epidermal growth-factor receptor (EGFR) level by decreased transient receptor potential vanilloid type-1 (TRPV1) level (P < 0.01) . The capsaicin-decreased EGFR level subsequently reduced levels of nuclear factor-κB (NF-κB) and cyclin D1 that favored enhanced lung epithelial proliferation and epithelial-mesenchymal transition (EMT) during lung carcinogenesis (P < 0.01). In contrast, 6-gingerol promoted TRPV1 level and drastically decreased the levels of EGFR, NF-κB, and cyclin D1 that favored reduced lung epithelial proliferation and EMT (P < 0.01). This study provides valuable information for the long-term consumption of chili-pepper-rich diets to decrease the risk of cancer development. PMID:27436516

  20. Characterizations of sphingosylphosphorylcholine-induced scratching responses in ICR mice using naltrexon, capsaicin, ketotifen and Y-27632.

    PubMed

    Kim, Hyoung June; Kim, Hyuk; Han, Eun-Sil; Park, Sun-Mi; Koh, Jae-Young; Kim, Kwang-Mi; Noh, Min-Soo; Kim, Jung-Ju; Lee, Chang-Hoon

    2008-03-31

    Sphingosylphosphorylcholine (SPC) is upregulated in the stratum corneum of atopic dermatitis patients by sphingomyelin deacylase. We conducted an investigation, both to confirm that intradermal injection of SPC elicits scratching in mice, and to elucidate the detailed mechanism of the SPC-induced itch-scratch response. Intradermal administration of SPC increased the incidence of scratching behavior in a dose-dependent manner. SPC-induced scratching could be suppressed, significantly, by the mu-opoid receptor antagonist, naltrexon, the vaniloid receptor agonist, capsaicin, and the histamine H1 receptor antagonist ketotifen. d-erythro SPC, one of the SPC stereotypes, could elicit the scratch response, but not l-threo SPC. Y-27632 (1 mg/kg, an inhibitor of Rho-associated protein kinase (ROCK)), was found to suppress SPC-induced scratching. Both the stereospecificity of SPC and the involvement of the Rho/ROCK pathway suggested that SPC-induced scratching is related to the receptor.

  1. The effect of topical capsaicin-induced sensitization on heat-evoked cutaneous vasomotor responses

    PubMed Central

    Nielsen, Thomas A; da Silva, Larissa Bittencourt; Arendt-Nielsen, Lars; Gazerani, Parisa

    2013-01-01

    Brief, localized, cutaneous, non-painful thermal stimuli can evoke a transient vasomotor response, causing increased cutaneous blood flow and elevated skin temperature. The aims of this study were to investigate 1) if cutaneous sensitization by topical application of capsaicin (TRPV1 receptor agonist) can facilitate the size, duration and spatial extent of this vasomotor response and 2) if males and females respond differently. Thermal pulses (43°C for 60 seconds) were applied on left/right volar forearms of 15 age-matched males and females. Skin temperature and cutaneous blood flow were measured 1, 5, 10, 15, and 30 minutes after heat application before and after topical capsaicin (1%, 30 min application) with contralateral arm serving as the control. Recordings were made from the region of interest at distances of 2, 4, 6, 8, and 10 cm from the capsaicin application site. Sensitization significantly enhanced skin temperature for up to 30 min and compared with non-sensitized skin at 10 min. Females showed the strongest response after sensitization, but the response lasted longer and spread more widely in males. The blood flow responses were significantly longer after capsaicin (from 5 to 30 minutes after thermal application). This increased blood flow extended outside the treated area up to 10 min after stimulation. After sensitization, the area under the blood flow response curves showed significantly stronger responses in females, spreading 4 cm outside the stimulation site. Cutaneous sensitizing caused prolonged and spatially expanded vasomotor responses to standardized thermal stimulation with sex specific differences. PMID:24044034

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

    PubMed

    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.

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

    PubMed Central

    Klein, Amanda H.; Joe, Christopher L.; Davoodi, Auva; Takechi, Kenichi; Carstens, Mirela Iodi; Carstens, E

    2014-01-01

    Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive TRPA1. 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. PMID:24759772

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

    PubMed

    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.

  5. Resveratrol attenuates inflammation-induced hyperexcitability of trigeminal spinal nucleus caudalis neurons associated with hyperalgesia in rats

    PubMed Central

    Sekiguchi, Kenta; Takehana, Shiori; Shibuya, Eri; Matsuzawa, Nichiwa; Hidaka, Shiori; Kanai, Yurie; Inoue, Maki; Kubota, Yoshiko; Shimazu, Yoshihito

    2016-01-01

    Background Resveratrol, a component of red wine, has been reported to decrease prostaglandin E2 production by inhibiting the cyclooxygenase-2 cascade and to modulate various voltage-dependent ion channels, suggesting that resveratrol could attenuate inflammatory hyperalgesia. However, the effects of resveratrol on inflammation-induced hyperexcitability of nociceptive neurons in vivo remain to be determined. Thus, the aim of the present study was to determine whether daily systemic administration of resveratrol to rats attenuates the inflammation-induced hyperexcitability of spinal trigeminal nucleus caudalis wide-dynamic range neurons associated with hyperalgesia. Results Inflammation was induced by injection of complete Freund’s adjuvant into the whisker pad. The threshold of escape from mechanical stimulation applied to whisker pad in inflamed rats was significantly lower than in control rats. The decreased mechanical threshold in inflamed rats was restored to control levels by daily systemic administration of resveratrol (2 mg/kg, i.p.). The mean discharge frequency of spinal trigeminal nucleus caudalis wide-dynamic range neurons to both nonnoxious and noxious mechanical stimuli in inflamed rats was significantly decreased after resveratrol administration. In addition, the increased mean spontaneous discharge of spinal trigeminal nucleus caudalis wide-dynamic range neurons in inflamed rats was significantly decreased after resveratrol administration. Similarly, resveratrol significantly diminished noxious pinch-evoked mean after discharge frequency and occurrence in inflamed rats. Finally, resveratrol restored the expanded mean size of the receptive field in inflamed rats to control levels. Conclusion These results suggest that chronic administration of resveratrol attenuates inflammation-induced mechanical inflammatory hyperalgesia and that this effect is due primarily to the suppression of spinal trigeminal nucleus caudalis wide dynamic range neuron

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

    PubMed Central

    Asad, Abu Bakar Ali; Seah, Stephanie; Baumgartner, Richard; Feng, Dai; Jensen, Andres; Manigbas, Elaine; Henry, Brian; Houghton, Andrea; Evelhoch, Jeffrey L.; Derbyshire, Stuart W. G.; Chin, Chih-Liang

    2016-01-01

    Background 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. Methodology 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). Principal Findings 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. Conclusions 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

  7. Translational Pharmacodynamics of Calcitonin Gene-Related Peptide Monoclonal Antibody LY2951742 in a Capsaicin-Induced Dermal Blood Flow Model.

    PubMed

    Vermeersch, Steve; Benschop, Robert J; Van Hecken, Anne; Monteith, David; Wroblewski, Victor J; Grayzel, David; de Hoon, Jan; Collins, Emily C

    2015-09-01

    LY2951742, a monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being developed for migraine prevention and osteoarthritis pain. To support the clinical development of LY2951742, capsaicin-induced dermal blood flow (DBF) was used as a target engagement biomarker to assess CGRP activity in nonhuman primates and healthy volunteers. Inhibition of capsaicin-induced DBF in nonhuman primates, measured with laser Doppler imaging, was dose dependent and sustained for at least 29 days after a single intravenous injection of the CGRP antibody. This information was used to generate a pharmacokinetic/pharmacodynamic model, which correctly predicted inhibition of capsaicin-induced DBF in humans starting at a single subcutaneous 5-mg dose. As expected, the degree of inhibition in capsaicin-induced DBF increased with higher LY2951742 plasma concentrations. Utilization of this pharmacodynamic biomarker with pharmacokinetic data collected in phase I studies provided the dose-response relationship that assisted in dose selection for the phase II clinical development of LY2951742.

  8. Flurbiprofen inhibits capsaicin induced calcitonin gene related peptide release from rat spinal cord via an endocannabinoid dependent mechanism.

    PubMed

    Seidel, Kay; Hamza, May; Ates, Mehmet; Gühring, Hans

    2003-02-27

    Calcitonin gene related peptide (CGRP) is involved in nociceptive transmission and modulation at the spinal level. In the spinal superperfusion model, Delta(9) tetrahydrocannabinol inhibited capsaicin induced CGRP release in a concentration dependent manner. Similarly, flurbiprofen (3 microM) inhibited spinal CGRP release. This inhibition was reversed by the CB(1) antagonist AM-251 (1 microM), but not by co-administration of prostaglandin E(2) (PGE(2); 285 nM). AM-251 had no modulatory effect on flurbiprofen-induced cyclooxygenase (COX) inhibiting capacity as shown by PGE(2) levels. Furthermore, the phospholipase A(2) inhibitor palmityl trifluromethyl ketone (15 microM) reversed flurbiprofen's inhibitory effect. In conclusion the present work provides evidence on the shift of arachidonic acid metabolism towards endocannabinoids formation in response to COX inhibition as a mechanism for flurbiprofen inhibitory effect on spinal CGRP release.

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

    PubMed

    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.

  10. Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia

    PubMed Central

    Dieb, Wisam; Ouachikh, Omar; Durif, Franck; Hafidi, Aziz

    2014-01-01

    Background Pain constitutes the major non motor syndrome in Parkinson's disease (PD) and includes neuropathic pain; however current drug therapies used to alleviate it have only limited efficacy. This is probably due to poor understanding of the mechanisms underlying it. Aims We investigated a major class of trigeminal neuropathic pain, dynamic mechanical allodynia (DMA), in a rat model of PD and in which a bilateral 6-hydroxy dopamine (6-OHDA) injection was administered to produce a lesion of the nigrostriatal dopaminergic pathway. Results and discussion Lesioned animals presented significant DMA in the orofacial area that occurred from 4 days to 5 weeks post-injury. To investigate a segmental implication in the neuropathic pain induced by dopamine depletion, the expression of the isoform gamma of the protein kinase C (PKCg) and phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2) was explored in the medullary dorsal horn (MDH). There was a high increase in PKCg expression in the III and IIi laminae of the MDH of lesioned-animals compared to shams. pERK1/2 expression was also significantly high in the ipsilateral MDH of lesioned rats in response to non-noxious tactile stimulus of the orofacial region. Since pERK1/2 is expressed only in response to nociceptive stimuli in the dorsal spinal horn, the current study demonstrates that non-noxious stimuli evoke allodynic response. Intraperitoneal and intracisternal administrations of bromocriptine, a dopamine 2 receptor (D2R) agonist, significantly decreased DMA compared to control rats injected with saline. These data demonstrate for the first time that nigrostriatal dopaminergic depletion produces trigeminal neuropathic pain that at least involves a segmental mechanism. In addition, bromocriptine was shown to have a remarkable analgesic effect on this neuropathic pain symptom. PMID:24944866

  11. Integrating TRPV1 Receptor Function with Capsaicin Psychophysics

    PubMed Central

    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. PMID:26884754

  12. Integrating TRPV1 Receptor Function with Capsaicin Psychophysics.

    PubMed

    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.

  13. Integrating TRPV1 Receptor Function with Capsaicin Psychophysics.

    PubMed

    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. PMID:26884754

  14. Capsaicin attenuates palmitate-induced expression of macrophage inflammatory protein 1 and interleukin 8 by increasing palmitate oxidation and reducing c-Jun activation in THP-1 (human acute monocytic leukemia cell) cells.

    PubMed

    Choi, Sung-E; Kim, Tae Ho; Yi, Sang-A; Hwang, Yun Cheong; Hwang, Won Sun; Choe, Sun Jung; Han, Seung Jin; Kim, Hae Jin; Kim, Dae Jung; Kang, Yup; Lee, Kwan-Woo

    2011-06-01

    Capsaicin, a spicy component of hot peppers, has been shown to improve inflammatory disease and obesity. In this study, we tested the hypothesis that the anti-inflammatory activity of capsaicin can be used to improve free fatty acid (FFA)-induced inflammation by reducing gene expression of macrophage inflammatory protein 1 (MIP-1) and interleukin 8 (IL-8) in THP-1 (human acute monocytic leukemia cell) macrophages. To investigate whether capsaicin ameliorates palmitate-induced MIP-1 and IL-8 gene expressions, we treated THP-1 cells with palmitate in the presence or absence of capsaicin and measured MIP-1 and IL-8 by real-time polymerase chain reaction. To elucidate the mechanism by which capsaicin effects on palmitate-induced MIP-1 and IL-8 gene expressions, we performed immunoblotting with stress kinase-related antibodies and measured palmitate oxidation and palmitate oxidation-related gene expression. Palmitate and stearate but not the unsaturated FFA oleate significantly increased MIP-1 and IL-8 expressions in THP-1 macrophages. Treatment with capsaicin or FFA oxidation stimulators inhibited palmitate-induced MIP-1 and IL-8 expressions in THP-1 macrophages. Capsaicin increased the gene expression of carnitine palmitoyltransferase 1 and the β-oxidation of palmitate. Furthermore, capsaicin significantly reduced palmitate-stimulated activation of c-Jun N-terminal kinase, c-Jun, and p38. Our data suggest that the attenuation of palmitate-induced MIP-1 and IL-8 gene expressions by capsaicin is associated with reduced activation of c-Jun N-terminal kinase, c-Jun, and p38 and preserved β-oxidation activity.

  15. Light-Induced Trigeminal Sensitization without Central Visual Pathways: Another Mechanism for Photophobia

    PubMed Central

    Dolgonos, Sarah; Ayyala, Haripriya

    2011-01-01

    Purpose. The authors investigated whether trigeminal sensitization occurs in response to bright light with the retina disconnected from the rest of the central nervous system by optic nerve section. Methods. In urethane-anesthetized rats, trigeminal reflex blinks were evoked with air puff stimuli directed at the cornea in darkness and at three different light intensities. After normative data were collected, the optic nerve was lesioned and the rats were retested. In an alert rat, reflex blinks were evoked by stimulation of the supraorbital branch of the trigeminal nerve in the dark and in the light. Results. A 9.1 × 103 μW/cm2 and a 15.1 × 103 μW/cm2 light significantly enhanced the magnitude of reflex blinks relative to blinks evoked by the same trigeminal stimulus when the rats were in the dark. In addition, rats exhibited a significant increase in spontaneous blinking in the light relative to the blink rate in darkness. After lesioning of the optic nerve, the 15.1 × 103 μW/cm2 light still significantly increased the magnitude of trigeminal reflex blinks. Conclusions. Bright lights increase trigeminal reflex blink amplitude and the rate of spontaneous blinking in rodents. Light can modify trigeminal activity without involving the central visual system. PMID:21896840

  16. LPS-induced dental pulp inflammation increases expression of ionotropic purinergic receptors in rat trigeminal ganglion.

    PubMed

    Chen, Yangxi; Zhang, Li; Yang, Jingwen; Zhang, Lu; Chen, Zhi

    2014-09-10

    Severe toothache can be caused by dental pulp inflammation. The ionotropic purinergic receptor family (P2X) is reported to mediate nociception in primary afferent neurons. This study aims to investigate the involvement of P2X receptors in the sensitization of the trigeminal ganglion (TG) caused by dental pulp inflammation. Lipopolysaccharides were unilaterally applied to the pulp of the upper molar of the rat to induce dental pulp inflammation. Increased expression of c-fos, a marker of neuronal activity, was induced in V1-V2 division, indicating the activation of TG neurons. The expressions of P2X2, P2X3, and P2X5 were also increased in the V1-V2 division of TG, primarily in small-sized and medium-sized neurons. Markers of glutamatergic afferents, VGluT1, and GABAergic afferents, GAD67, were induced by lipopolysaccharides and coexpressed with P2X in small-sized TG neurons. The present findings suggest that the P2X2, P2X3, and P2X5 receptors are upregulated as part of the sensitization produced by dental pulp inflammation. PMID:25055139

  17. Effects of gustatory nerve transection and/or ovariectomy on oral capsaicin avoidance in rats.

    PubMed

    Boucher, Yves; Simons, Christopher T; Carstens, Mirela Iodi; Carstens, E

    2014-04-01

    The incidence of chronic oral pain such as burning mouth syndrome is greater in peri-menopausal females, and was postulated to be associated with gustatory nerve damage. We investigated whether bilateral transection of the chorda tympani, with or without accompanying ovariectomy, affected oral capsaicin avoidance in rats. Female rats had restricted access to 2 bottles, 1 bottle containing capsaicin (concentration range: 0.33-33 μM/L) and the other vehicle. Percent volume of capsaicin consumption and lick counts were measured. The concentration series was tested before and 0.5, 3, 6, 9, and 12 months after the following surgical procedures: (a) bilateral transection of the chorda tympani (CTx); (b) ovariectomy (OVx); (3) CTx plus OVx; or (4) sham CT surgery. Before surgery there was a concentration-dependent decrease in licks and volume of capsaicin consumed, with a threshold between 0.1 and 0.3 ppm. The majority of drink licks occurred during the first 9 minutes of access. Over the 12-month test period, the CTx group did not exhibit reduced capsaicin consumption, and consumed significantly more capsaicin at 6 and 9 months postsurgery. Rats in the OVx group consistently consumed significantly less capsaicin and exhibited significantly higher counts of capsaicin-evoked Fos-like immunoreactivity in the dorsomedial trigeminal subnucleus caudalis (Vc) compared to all other treatment groups. That CTx, with or without OVx, did not enhance capsaicin avoidance indicates that damage to the gustatory system does not disinhibit trigeminal nociceptive transmission.

  18. Corn gluten hydrolysate and capsaicin have complimentary actions on body weight reduction and lipid-related genes in diet-induced obese rats.

    PubMed

    Mun, Joo-Mi; Ok, Hyang Mok; Kwon, Oran

    2014-05-01

    The aim of this study was to test the hypothesis that a combination of corn gluten hydrolysate (CGH) and capsaicin may have an additive or synergistic effect on body weight reduction. For 13 weeks, male Sprague-Dawley rats were provided a diet to induce obesity. Afterward, the rats were randomly divided into 5 dietary groups: the normal control (n = 5), the high-fat control (n = 8), the high-fat diet (HFD) containing 35% CGH (n = 7), the HFD containing 0.02% capsaicin (HF-P) (n = 8), and the HFD containing both CGH and capsaicin (HF-CP) (n = 7) for an additional 4 weeks. Administration of CGH plus capsaicin, along with a HFD, led to significant decreases in body weight, fat mass, lipids in the liver, and plasma leptin as well as increases in plasma adiponectin. The pattern of gene expression was different in each target organ. In the liver, up-regulation of peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1α, and acyl-coenzyme A oxidase was found in the HF-CP group. In contrast, down-regulation of peroxisome proliferator-activated receptor γ was found in both the HFD containing 35% CGH and HF-CP groups. In skeletal muscle, up-regulation of insulin receptor and uncoupling protein 3 was found in the HF-P group only, whereas up-regulation of the glucose transporter 4 gene was observed in both the HF-CP and HF-P groups. In adipose tissue, up-regulation of peroxisome proliferator-activated receptor γ and hormone-sensitive lipase was only found in the HF-CP group. In summary, this study suggests that CGH and capsaicin perform complementary actions on food intake, lipid metabolism, and insulin sensitivity by a coordinated control of energy metabolism in the liver, adipose tissue, and skeletal muscle, thus exerting an additive effect on body weight reduction.

  19. Capsaicin induces metabolism of simvasatin in rat: involvement of upregulating expression of Ugt1a1.

    PubMed

    Zhu, Chaoran; Zhai, Xuejia; Chen, Fen; Wang, Nanxi; Zhang, Xinlin; Lu, Yongning

    2016-05-01

    Capsaicin (CAP, trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent substance in hot pepper. However, little is known about the interactions between CAP and clinically used drugs. This study investigated the effect of acute and chronic ingestion of CAP on pharmacokinetics of simvastatin (SV) and the mechanism of this CAP--drug intercation. CAP was orally administered at doses of 3 and 8 mg x kg(-1) for seven consecutive days once daily and on the 1st day and the 7th day, SV (8 mg x kg(-1)) was injected intravenously. Plasma concentrations of SV were determined using LC/MS/MS and expression of Ugt1a1 was analyzed by RT-qPCR and Western Blotting. We found that there were 78.0% (P < 0.05) and 81.2% (P < 0.05) reduction in the AUC(0-∞) of SV, respectively, following pretreatment with two doses of CAP. The AUC(0-∞) of SV in the two dose group pretreated with CAP for 7 days were decreased significantly, compared to the group for 1 day. Both the RT-qPCR and Western Blotting data indicated that 7 days pretreatment with CAP increased the expression level of Ugt1a1 in liver. In conclusion, chronic ingestion of CAP enhanced the expression level of Ugt1a1 in liver, causing the food -drug interaction and decrease in SV exposure in rats to a significant extent.

  20. Capsaicin induces metabolism of simvasatin in rat: involvement of upregulating expression of Ugt1a1.

    PubMed

    Zhu, Chaoran; Zhai, Xuejia; Chen, Fen; Wang, Nanxi; Zhang, Xinlin; Lu, Yongning

    2016-05-01

    Capsaicin (CAP, trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent substance in hot pepper. However, little is known about the interactions between CAP and clinically used drugs. This study investigated the effect of acute and chronic ingestion of CAP on pharmacokinetics of simvastatin (SV) and the mechanism of this CAP--drug intercation. CAP was orally administered at doses of 3 and 8 mg x kg(-1) for seven consecutive days once daily and on the 1st day and the 7th day, SV (8 mg x kg(-1)) was injected intravenously. Plasma concentrations of SV were determined using LC/MS/MS and expression of Ugt1a1 was analyzed by RT-qPCR and Western Blotting. We found that there were 78.0% (P < 0.05) and 81.2% (P < 0.05) reduction in the AUC(0-∞) of SV, respectively, following pretreatment with two doses of CAP. The AUC(0-∞) of SV in the two dose group pretreated with CAP for 7 days were decreased significantly, compared to the group for 1 day. Both the RT-qPCR and Western Blotting data indicated that 7 days pretreatment with CAP increased the expression level of Ugt1a1 in liver. In conclusion, chronic ingestion of CAP enhanced the expression level of Ugt1a1 in liver, causing the food -drug interaction and decrease in SV exposure in rats to a significant extent. PMID:27348971

  1. Beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress, ethanol, indomethacin, and capsaicin neurotoxicity.

    PubMed

    Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Gjurasin, M; Konjevoda, P; Separović, J; Ljubanović, D; Artuković, B; Bratulić, M; Tisljar, M; Jurina, L; Buljat, G; Miklić, P; Marović, A

    1996-08-01

    Very recently, the integrity of capsaicin somatosensory neurons and their protection were suggested to be related to the activity in nociception of a newly discovered 15-amino acid peptide, BPC 157, shown to have strong beneficial effect on intestinal and liver lesions. Therefore, from this viewpoint, we have studied the gastroprotective effect of the pentadecapeptide BPC 157, on gastric lesions produced in rats by 96% ethanol, restraint stress, and indomethacin. The possible involvement of sensory neurons in the salutary actions of BPC 157 (10 micrograms/kg, 10 ng/kg intraperitoneally) was studied with capsaicin, which has differential effects on sensory neurons: a high dose in adult (125 mg/kg subcutaneously, 3 months old) or administration (50 mg/kg subcutaneously) to neonatal animals (age of the 7 days) destroys sensory fibers, whereas a low dose (500 micrograms/kg intraperitoneally) activates neurotransmitter release and protective effects on the mucosa. In the absence of capsaicin, BPC 157 protected gastric mucosa against ethanol, restraint, and indomethacin application. In the presence of neurotoxic doses of capsaicin, the negative influence of capsaicin on restraint, ethanol, or indomethacin lesions consistently affected salutary activity of BPC 157. However, BPC 157 protection was still evident in the capsaicin-treated rats (either treated as adults or as newborns) in all of these assays. Interestingly, after neonatal capsaicin treatment, a complete abolition of BPC gastroprotection was noted if BPC 157 was applied as a single nanogram-regimen, but the mucosal protection was fully reversed when the same dose was used daily. In line with the excitatory dose of capsaicin the beneficial effectiveness of BPC 157 appears to be increased as well. Taken together, these data provide evidence for complex synergistic interaction between the beneficial effectiveness of BPC 157 and peptidergic sensory afferent neuron activity. PMID:8769287

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

    PubMed

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

    2015-06-01

    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. PMID:25818051

  3. Trigeminal Inflammatory Compression (TIC) Injury Induces Chronic Facial Pain and Susceptibility to Anxiety-Related Behaviors

    PubMed Central

    Lyons, Danielle N.; Kniffin, Tracey C.; Zhang, Liping; Danaher, Robert J.; Miller, Craig S.; Bocanegra, Jose L.; Carlson, Charles R.; Westlund, Karin N.

    2015-01-01

    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 8 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 which 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. PMID:25818051

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

    PubMed

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

    2015-06-01

    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.

  5. Molecular and cellular mechanisms of trigeminal chemosensation.

    PubMed

    Gerhold, Kristin A; Bautista, Diana M

    2009-07-01

    Three sensory systems, olfaction, taste, and somatosensation, are dedicated to the detection of chemicals in the environment. Trigeminal somatosensory neurons enable us to detect a wide range of environmental stimuli, including pressure, temperature, and chemical irritants, within the oral and nasal mucosa. Natural plant-derived irritants have served as powerful pharmacological tools for identifying receptors underlying somatosensation. This is illustrated by the use of capsaicin, menthol, and wasabi to identify the heat-sensitive ion channel TRPV1, the cold-sensitive ion channel TRPM8, and the irritant receptor TRPA1, respectively. In addition to TRP channels, members of the two-pore potassium channel family have also been implicated in trigeminal chemosensation. KCNK18 was recently identified as a target for hydroxy-alpha-sanshool, the tingling and numbing compound produced in Schezuan peppers and other members of the Xanthoxylum genus. The role of these channels in trigeminal thermosensation and pain will be discussed. PMID:19686135

  6. Capsaicin-Induced Activation of p53-SMAR1 Auto-Regulatory Loop Down-Regulates VEGF in Non-Small Cell Lung Cancer to Restrain Angiogenesis

    PubMed Central

    Chakraborty, Samik; Mukherjee, Shravanti; Bhattacharjee, Pushpak; Guha, Deblina; Choudhuri, Tathagata; Chattopadhyay, Samit; Sa, Gaurisankar; Sen, Aparna; Das, Tanya

    2014-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. Despite decades of research, the treatment options for lung cancer patients remain inadequate, either to offer a cure or even a substantial survival advantage owing to its intrinsic resistance to chemotherapy. Our results propose the effectiveness of capsaicin in down-regulating VEGF expression in non-small cell lung carcinoma (NSCLC) cells in hypoxic environment. Capsaicin-treatment re-activated p53-SMAR1 positive feed-back loop in these cells to persuade p53-mediated HIF-1α degradation and SMAR1-induced repression of Cox-2 expression that restrained HIF-1α nuclear localization. Such signal-modulations consequently down regulated VEGF expression to thwart endothelial cell migration and network formation, pre-requisites of angiogenesis in tumor micro-environment. The above results advocate the candidature of capsaicin in exclusively targeting angiogenesis by down-regulating VEGF in tumor cells to achieve more efficient and cogent therapy of resistant NSCLC. PMID:24926985

  7. Mastication induces long-term increases in blood perfusion of the trigeminal principal nucleus.

    PubMed

    Viggiano, A; Manara, R; Conforti, R; Paccone, A; Secondulfo, C; Lorusso, L; Sbordone, L; Di Salle, F; Monda, M; Tedeschi, G; Esposito, F

    2015-12-17

    Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing. PMID:26477983

  8. Hydrogen sulfide prevents ethanol-induced gastric damage in mice: role of ATP-sensitive potassium channels and capsaicin-sensitive primary afferent neurons.

    PubMed

    Medeiros, Jand Venes R; Bezerra, Víctor H; Gomes, Antoniella S; Barbosa, André Luiz R; Lima-Júnior, Roberto César P; Soares, Pedro Marcos G; Brito, Gerly Anne C; Ribeiro, Ronaldo A; Cunha, Fernando Q; Souza, Marcellus H L P

    2009-09-01

    The aim of this study was to evaluate the protective effect of hydrogen sulfide (H(2)S) on ethanol-induced gastric lesions in mice and the influence of ATP-sensitive potassium (K(ATP)) channels, capsaicin-sensitive sensory afferent neurons, and transient receptor potential vanilloid (TRPV) 1 receptors on such an effect. Saline and L-cysteine alone or with propargylglycine, sodium hydrogen sulfide (NaHS), or Lawesson's reagent were administrated for testing purposes. For other experiments, mice were pretreated with glibenclamide, neurotoxic doses of capsaicin, or capsazepine. Afterward, mice received L-cysteine, NaHS, or Lawesson's reagent. After 30 min, 50% ethanol was administrated by gavage. After 1 h, mice were sacrificed, and gastric damage was evaluated by macroscopic and microscopic analyses. L-cysteine, NaHS, and Lawesson's reagent treatment prevented ethanol-induced macroscopic and microscopic gastric damage in a dose-dependent manner. Administration of propargylglycine, an inhibitor of endogenous H(2)S synthesis, reversed gastric protection induced by L-cysteine. Glibenclamide reversed L-cysteine, NaHS, or Lawesson's reagent gastroprotective effects against ethanol-induced macroscopic damage in a dose-dependent manner. Chemical ablation of sensory afferent neurons by capsaicin reversed gastroprotective effects of L-cysteine or H(2)S donors (NaHS or Lawesson's reagent) in ethanol-induced macroscopic gastric damage. Likewise, in the presence of the TRPV1 antagonist capsazepine, the gastroprotective effects of L-cysteine, NaHS, or Lawesson's reagent were also abolished. Our results suggest that H(2)S prevents ethanol-induced gastric damage. Although there are many mechanisms through which this effect can occur, our data support the hypothesis that the activation of K(ATP) channels and afferent neurons/TRPV1 receptors is of primary importance. PMID:19491326

  9. Tunicamycin-induced cell death in the trigeminal ganglion is suppressed by nerve growth factor in the mouse embryo.

    PubMed

    Ichikawa, Hiroyuki; Zhao, Bing-Ran; Kano, Mitsuhiro; Shimizu, Yoshinaka; Suzuki, Toshihiko; Terayama, Ruji; Matsuo, Saburo; Sugimoto, Tomosada

    2010-04-01

    The effect of nerve growth factor (NGF) on tunicamycin (Tm)-treated neurons in the trigeminal ganglion was investigated by use of caspase-3 immunohistochemistry. In intact embryos at embryonic day 16.5, only a few caspase-3-immunoreactivity were detected in the ganglion neurons. Mean +/- SE of the density of the immunoreactivity was 0.22 +/- 0.03%. In contrast, the number of the immunoreactive neurons was increased at 24 h after injection of 0.5 microg Tm in 1 microl of 0.05 N NaOH solution into mouse embryos at embryonic day 15.5. The density of immunoreactivity was also increased (mean +/- SE = 1.44 +/- 0.11%) compared to intact and 0.05 N NaOH-treated embryos (mean +/- SE = 0.35 +/- 0.03%). The Tm treatment caused increase of the number of trigeminal neurons representing apoptotic profiles (intact, mean +/- SE = 79.3 +/- 8.5; 0.05 N NaOH, mean +/- SE = 132 +/- 11.5; 0.5 microg Tm, mean +/- SE = 370.2 +/- 64.8). In addition, NGF significantly prevented the increase of density of the immunoreactivity (mean +/- SE = 0.54 +/- 0.16%) and the number of apoptotic cells (mean +/- SE = 146.2 +/- 11.3). Saline application (without NGF) had no effect on Tm-induced increase of the immunoreactivity (mean +/- SE = 1.78 +/- 0.23%) or the apoptotic profiles (mean +/- SE = 431.9 +/- 80.5). These results indicate that Tm-induced cell death in the trigeminal ganglion is suppressed by NGF in the mouse embryo.

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

    PubMed

    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.

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

    PubMed

    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. PMID:24759772

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

    PubMed

    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.

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

    PubMed

    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.

  14. Trigeminal neuralgia

    PubMed Central

    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

  15. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin.

    PubMed

    Bley, Keith; Boorman, Gary; Mohammad, Bashir; McKenzie, Donald; Babbar, Sunita

    2012-08-01

    Human exposure to capsaicin, the most abundant pungent chili pepper component, is ubiquitous. Evaluation of capsaicin's carcinogenic potential has produced variable results in in vitro and in vivo genotoxicity and carcinogenicity assays. The capsaicin tested in older studies was often from pepper plant extracts and included other capsaicinoids and diverse impurities. Recent studies utilizing high-purity capsaicin and standardized protocols provide evidence that the genotoxic and carcinogenic potential of capsaicin is quite low and that the purity of capsaicin is important. Several small epidemiological studies suggest a link between capsaicin consumption and stomach or gall bladder cancer, but contamination of capsaicin-containing foods with known carcinogens renders their interpretation problematic. The postulated ability of capsaicin metabolites to damage DNA and promote carcinogenesis remains unsupported. Anticancer activities of capsaicin have been widely reported, as it inhibits the activity of carcinogens and induces apoptosis in numerous cancer cell lines in vitro and explanted into rodents. Diverse mechanisms have been postulated for capsaicin's anticancer properties. One hypothesis is that inhibition of cytochrome P450 enzymes-particularly CYP2E1-retards carcinogen activation but is contradicted by the low potency of capsaicin for CYP inhibition. The potential for dietary capsaicin to act as a chemopreventative is now widely postulated. PMID:22563012

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:24302912

  18. Inflammation enhanced brain-derived neurotrophic factor-induced suppression of the voltage-gated potassium currents in small-diameter trigeminal ganglion neurons projecting to the trigeminal nucleus interpolaris/caudalis transition zone.

    PubMed

    Takeda, M; Takahashi, M; Matsumoto, S

    2014-03-01

    We recently indicated that brain-derived neurotrophic factor (BDNF) enhances the excitability of small-diameter trigeminal ganglion (TRG) neurons projecting onto the trigeminal nucleus interpolaris/caudalis (Vi/Vc) transition zone via a paracrine mechanism following masetter muscle (MM) inflammation. The present study investigated whether modulation of voltage-gated potassium (K) channels by BDNF contributes to this hyperexcitability effect. To induce inflammation we injected complete Freund's adjuvant (CFA) into the MM. The escape threshold from mechanical stimulation applied to skin above the inflamed MM was significantly lower than in naïve rats. TRG neurons innervating the site of inflammation were subsequently identified by fluorogold (FG) labeling, and microbeads (MB) were used to label neurons projecting specifically to the Vi/Vc region. BDNF significantly decreased the total, transient (IA), and sustained (IK) currents in FG-/MB-labeled small-diameter TRG neurons under voltage-clamp conditions in naïve and inflamed rats. The magnitude of inhibition of IA and IK currents by BDNF in FG-/MB-labeled TRG neurons was significantly greater in inflamed rats than in naïve rats, and BDNF inhibited IA to a significantly greater extent than IK. Furthermore, co-administration of K252a, a tyrosine kinase inhibitor, abolished the suppression of IA and IK currents by BDNF. These results suggested that the inhibitory effects of BDNF on IA and IK currents in small-diameter TRG neurons projecting onto the Vi/Vc potentiate neuronal excitability, and in turn, contribute to MM inflammatory hyperalgesia. These findings support the development of voltage-gated K(+) channel openers and tyrosine kinase inhibitors as potential therapeutic agents for the treatment of trigeminal inflammatory hyperalgesia.

  19. Capsaicin binds to prohibitin 2 and displaces it from the mitochondria to the nucleus

    SciTech Connect

    Kuramori, Chikanori; Azuma, Motoki; Kume, Kanako; Kaneko, Yuki; Inoue, Atsushi; Yamaguchi, Yuki; Kabe, Yasuaki; Hosoya, Takamitsu; Kizaki, Masahiro; Suematsu, Makoto; Handa, Hiroshi

    2009-02-06

    Capsaicin is widely used as a food additive and as an analgesic agent. Besides its well-known role in nociception, which is mediated by vanilloid receptor 1 specifically expressed in dorsal root ganglion neurons, capsaicin has also been considered as a potential anticancer agent, as it inhibits cell proliferation and induces apoptosis in various types of cancer cells. Here we identified a new molecular target of capsaicin from human myeloid leukemia cells. We show that capsaicin binds to prohibitin (PHB) 2, which is normally localized to the inner mitochondrial membrane, and induces its translocation to the nucleus. PHB2 is implicated in the maintenance of mitochondrial morphology and the control of apoptosis. We also provide evidence suggesting that capsaicin causes apoptosis directly through the mitochondria and that PHB2 contributes to capsaicin-induced apoptosis at multiple levels. This work will serve as an important foundation for further understanding of anticancer activity of capsaicin.

  20. Trigeminal neuralgia

    PubMed Central

    2014-01-01

    Introduction Trigeminal neuralgia is a sudden, unilateral, brief, stabbing, recurrent pain in the distribution of one or more branches of the fifth cranial nerve. Pain occurs in paroxysms, which can last from a few seconds to several minutes. The frequency of the paroxysms ranges from a few to hundreds of attacks a day. Periods of remission can last for months to years, but tend to shorten over time. The condition can impair activities of daily living and lead to depression. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of ongoing treatments in people with trigeminal neuralgia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2013 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found seven studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: baclofen; carbamazepine; gabapentin; lamotrigine; oxcarbazepine; microvascular decompression; and destructive neurosurgical techniques (radiofrequency thermocoagulation, glycerol rhizolysis, balloon compression, and stereotactic radiosurgery). PMID:25299564

  1. Capsaicin and sensory neurones: a historical perspective.

    PubMed

    Szolcsányi, János

    2014-01-01

    Capsaicin, the pungent ingredient of red pepper has become not only a "hot" topic in neuroscience but its new target-related unique actions have opened the door for the drug industry to introduce a new chapter of analgesics. After several lines of translational efforts with over 1,000 patents and clinical trials, the 8% capsaicin dermal patch reached the market and its long-lasting local analgesic effect in some severe neuropathic pain states is now well established. This introductory chapter outlines on one hand the historical background based on the author's 50 years of experience in this field and on the other hand emphasizes new scopes, fascinating perspectives in pharmaco-physiology, and molecular pharmacology of nociceptive sensory neurons. Evidence for the effect of capsaicin on C-polymodal nociceptors (CMH), C-mechanoinsensitive (CHMi), and silent C-nociceptors are listed and the features of the capsaicin-induced blocking effects of nociceptors are demonstrated. Common and different characteristics of nociceptor-blocking actions after systemic, perineural, local, intrathecal, and in vitro treatments are summarized. Evidence for the misleading conclusions drawn from neonatal capsaicin pretreatment is presented. Perspectives opened from cloning the capsaicin receptor "Transient Receptor Potential Vanilloid 1" (TRPV1) are outlined and potential molecular mechanisms behind the long-lasting functional, ultrastructural, and nerve terminal-damaging effects of capsaicin and other TRPV1 agonists are summarized. Neurogenic inflammation and the long-list of "capsaicin-sensitive" tissue responses are mediated by an unorthodox dual sensory-efferent function of peptidergic TRPV1-expressing nerve terminals which differ from the classical efferent and sensory nerve endings that have a unidirectional role in neuroregulation. Thermoregulatory effects of capsaicin are discussed in detail. It is suggested that since hyperthermia and burn risk due to enhanced noxious heat

  2. Capsaicin and sensory neurones: a historical perspective.

    PubMed

    Szolcsányi, János

    2014-01-01

    Capsaicin, the pungent ingredient of red pepper has become not only a "hot" topic in neuroscience but its new target-related unique actions have opened the door for the drug industry to introduce a new chapter of analgesics. After several lines of translational efforts with over 1,000 patents and clinical trials, the 8% capsaicin dermal patch reached the market and its long-lasting local analgesic effect in some severe neuropathic pain states is now well established. This introductory chapter outlines on one hand the historical background based on the author's 50 years of experience in this field and on the other hand emphasizes new scopes, fascinating perspectives in pharmaco-physiology, and molecular pharmacology of nociceptive sensory neurons. Evidence for the effect of capsaicin on C-polymodal nociceptors (CMH), C-mechanoinsensitive (CHMi), and silent C-nociceptors are listed and the features of the capsaicin-induced blocking effects of nociceptors are demonstrated. Common and different characteristics of nociceptor-blocking actions after systemic, perineural, local, intrathecal, and in vitro treatments are summarized. Evidence for the misleading conclusions drawn from neonatal capsaicin pretreatment is presented. Perspectives opened from cloning the capsaicin receptor "Transient Receptor Potential Vanilloid 1" (TRPV1) are outlined and potential molecular mechanisms behind the long-lasting functional, ultrastructural, and nerve terminal-damaging effects of capsaicin and other TRPV1 agonists are summarized. Neurogenic inflammation and the long-list of "capsaicin-sensitive" tissue responses are mediated by an unorthodox dual sensory-efferent function of peptidergic TRPV1-expressing nerve terminals which differ from the classical efferent and sensory nerve endings that have a unidirectional role in neuroregulation. Thermoregulatory effects of capsaicin are discussed in detail. It is suggested that since hyperthermia and burn risk due to enhanced noxious heat

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

    PubMed

    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. PMID:26781688

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

    PubMed

    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.

  5. Capsaicin, Nociception and Pain.

    PubMed

    Frias, Bárbara; Merighi, Adalberto

    2016-01-01

    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. PMID:27322240

  6. Capsaicin, Nociception and Pain.

    PubMed

    Frias, Bárbara; Merighi, Adalberto

    2016-01-01

    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.

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

    PubMed

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

    2001-09-01

    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. PMID:11524152

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

    PubMed

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

    2001-09-01

    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.

  9. Characterizing the PK/PD relationship for inhibition of capsaicin-induced dermal vasodilatation by MK-3207, an oral calcitonin gene related peptide receptor antagonist

    PubMed Central

    Li, Chi-Chung; Vermeersch, Steve; Denney, William S; Kennedy, William P; Palcza, John; Gipson, Adrianna; Han, Tae H; Blanchard, Rebecca; De Lepeleire, Inge; Depré, Marleen; Murphy, M Gail; Van Dyck, Kristien; de Hoon, Jan N

    2015-01-01

    Aims Calcitonin gene related peptide (CGRP) receptor antagonists are effective acute migraine treatments. A capsaicin-induced dermal vasodilatation (CIDV) model has been developed to provide target-engagement information in healthy volunteers. In the model, CGRP release is provoked after dermal capsaicin application, by activating transient receptor potential vanilloid-type-1 (TRPV1) receptors at peripheral sensory nerves. Laser Doppler imaging is used to quantify CIDV and subsequent inhibition by CGRP receptor antagonists. We sought to evaluate a CGRP receptor antagonist, MK-3207, in the biomarker model and to assess the predictability of the CIDV response to migraine clinical efficacy. Methods An integrated population pharmacokinetic/pharmacodynamic (PK/PD) model was developed to describe the exposure−response relationship for CIDV inhibition by CGRP and TRPV1 receptor antagonists. MK-3207 dose−response predictions were made based on estimated potency from the PK/PD model and mean plasma concentrations observed at the doses investigated. Results The results suggested that a 20 mg dose of MK-3207 (EC50 of 1.59 nm) would be required to attain the peripheral CIDV response at a target level that was shown previously to correlate with 2 h clinical efficacy based on phase 3 telcagepant clinical data, and that a plateau of the dose−response would be reached around 40–100 mg. These predictions provided a quantitative rationale for dose selection in a phase 2 clinical trial of MK-3207 and helped with interpretation of the efficacy results from the trial. Conclusions The integrated CIDV PK/PD model provides a useful platform for characterization of PK/PD relationships and predictions of dose−response relationships to aid in future development of CGRP and TRPV1 receptor antagonists. PMID:25377933

  10. Painful Traumatic Trigeminal Neuropathy.

    PubMed

    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.

  11. [Trigeminal autonomic cephalgias].

    PubMed

    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.

  12. Toll-like receptor 4 signaling in neurons of trigeminal ganglion contributes to nociception induced by acute pulpitis in rats

    PubMed Central

    Lin, Jia-Ji; Du, Yi; Cai, Wen-Ke; Kuang, Rong; Chang, Ting; Zhang, Zhuo; Yang, Yong-Xiang; Sun, Chao; Li, Zhu-Yi; Kuang, Fang

    2015-01-01

    Pain caused by acute pulpitis (AP) is a common symptom in clinical settings. However, its underlying mechanisms have largely remained unknown. Using AP model, we demonstrated that dental injury caused severe pulp inflammation with up-regulated serum IL-1β. Assessment from head-withdrawal reflex thresholds (HWTs) and open-field test demonstrated nociceptive response at 1 day post injury. A consistent up-regulation of Toll-like receptor 4 (TLR4) in the trigeminal ganglion (TG) ipsilateral to the injured pulp was found; and downstream signaling components of TLR4, including MyD88, TRIF and NF-κB, and cytokines such as TNF-α and IL-1β, were also increased. Retrograde labeling indicated that most TLR4 positve neuron in the TG innnervated the pulp and TLR4 immunoreactivity was mainly in the medium and small neurons. Double labeling showed that the TLR4 expressing neurons in the ipsilateral TG were TRPV1 and CGRP positive, but IB4 negative. Furthermore, blocking TLR4 by eritoran (TLR4 antagonist) in TGs of the AP model significantly down-regulated MyD88, TRIF, NF-κB, TNF-α and IL-1β production and behavior of nociceptive response. Our findings suggest that TLR4 signaling in TG cells, particularly the peptidergic TRPV1 neurons, plays a key role in AP-induced nociception, and indicate that TLR4 signaling could be a potential therapeutic target for orofacial pain. PMID:26224622

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

    PubMed

    Fattori, Victor; Hohmann, Miriam S N; Rossaneis, Ana C; Pinho-Ribeiro, Felipe A; Verri, Waldiceu A

    2016-01-01

    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. PMID:27367653

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

    PubMed

    Fattori, Victor; Hohmann, Miriam S N; Rossaneis, Ana C; Pinho-Ribeiro, Felipe A; Verri, Waldiceu A

    2016-01-01

    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.

  15. Suppression of ATP-induced excitability in rat small-diameter trigeminal ganglion neurons by activation of GABAB receptor.

    PubMed

    Takeda, Mamoru; Ikeda, Mizuho; Takahashi, Masayuki; Kanazawa, Takuya; Nasu, Masanori; Matsumoto, Shigeji

    2013-09-01

    The aim of the present study was to investigate whether a GABAB receptor agonist could modulate ATP-activated neuronal excitability of nociceptive TRG neurons using perforated whole-cell patch-clamp and immunohistochemical techniques. Immunohistochemical analysis revealed that 86% of P2X3 receptor-immunoreactive, small-diameter TRG neurons co-expressed GABAB receptor. Under voltage-clamp conditions (Vh=-60mV), application of ATP activated the inward current in acutely isolated rat TRG neurons in a dose-dependent manner (10-50 μM) and this current could be blocked by pyridoxal-phosphate-6-azophenyl-27,47-disulfonic acid (PPADS) (10 μM), a selective P2 purinoreceptor antagonist. The peak amplitude of ATP-activated currents was significantly inhibited after application of GABAB receptor agonist, baclofen (10-50 μM), in a concentration-dependent and reversible manner. The baclofen-induced inhibition of ATP-activated current was abolished by co-application of 3-amino-2 (4-chlorophenyl)-2hydroxypropysufonic acid) saclofen, a GABAB receptor antagonist (50 μM). Under current-clamp conditions, application of 20 μM ATP significantly depolarized the membrane potential resulting in increased mean action potential frequencies, and these ATP-induced effects were significantly inhibited by baclofen and these effects were antagonized by co-application of saclofen. Together, the results suggested that GABAB receptor activation could inhibit the ATP-induced excitability of small-diameter TRG neurons activated through the P2X3 receptor. Thus, the interaction between P2X3 and GABAB receptors of small-diameter TRG neuronal cell bodies is a potential therapeutic target for the treatment of trigeminal nociception. PMID:24004472

  16. Attenuation of natural killer cell functions by capsaicin through a direct and TRPV1-independent mechanism.

    PubMed

    Kim, Hun Sik; Kwon, Hyung-Joon; Kim, Gye Eun; Cho, Mi-Hyang; Yoon, Seung-Yong; Davies, Alexander J; Oh, Seog Bae; Lee, Heuiran; Cho, Young Keol; Joo, Chul Hyun; Kwon, Seog Woon; Kim, Sun Chang; Kim, Yoo Kyum

    2014-07-01

    The assessment of the biological activity of capsaicin, the compound responsible for the spicy flavor of chili pepper, produced controversial results, showing either carcinogenicity or cancer prevention. The innate immune system plays a pivotal role in cancer pathology and prevention; yet, the effect of capsaicin on natural killer (NK) cells, which function in cancer surveillance, is unclear. This study found that capsaicin inhibited NK cell-mediated cytotoxicity and cytokine production (interferon-γ and tumor necrosis factor-α). Capsaicin impaired the cytotoxicity of NK cells, thereby inhibiting lysis of standard target cells and gastric cancer cells by modulating calcium mobilization in NK cells. Capsaicin also induced apoptosis in gastric cancer cells, but that effect required higher concentrations and longer exposure times than those required to trigger NK cell dysfunction. Furthermore, capsaicin inhibited the cytotoxicity of isolated NK cells and of an NK cell line, suggesting a direct effect on NK cells. Antagonists of transient receptor potential vanilloid subfamily member 1 (TRPV1), a cognate capsaicin receptor, or deficiency in TRPV1 expression failed to prevent the defects induced by capsaicin in NK cells expressing functional TRPV1. Thus, the mechanism of action of capsaicin on NK cells is largely independent of TRPV1. Taken together, capsaicin may have chemotherapeutic potential but may impair NK cell function, which plays a central role in tumor surveillance. PMID:24743513

  17. 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

    SciTech Connect

    Sá-Júnior, Paulo Luiz de; Pasqualoto, Kerly Fernanda Mesquita; Ferreira, Adilson Kleber; Tavares, Maurício Temotheo; Damião, Mariana Celestina Frojuello Costa Bernstorff; Azevedo, Ricardo Alexandre de; Câmara, Diana Aparecida Dias; Pereira, Alexandre; Madeiro de Souza, Dener; Parise Filho, Roberto

    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.

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

    PubMed

    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.

  19. Capsaicin Blocks the Hyperpolarization-Activated Inward Currents via TRPV1 in the Rat Dorsal Root Ganglion Neurons.

    PubMed

    Kwak, Jiyeon

    2012-06-01

    Capsaicin, the pungent ingredient in hot pepper, activates nociceptors to produce pain and inflammation. However, prolonged exposures of capsaicin will cause desensitization to nociceptive stimuli. Hyperpolarization-activated cation currents (I(h)) contribute to the maintenance of the resting membrane potential and excitability of neurons. In the cultured dorsal root ganglion (DRG) neurons, we investigated mechanisms underlying capsaicin-mediated modulation of I(h) using patch clamp recordings. Capsaicin (1 µM) inhibited I(h) only in the capsaicin-sensitive neurons. The capsaicin-induced inhibition of I(h) was prevented by preexposing the TRPV1 antagonist, capsazepine (CPZ). Capsaicin-induced inhibition of I(h) was dose dependent (IC(50)= 0.68 µM) and partially abolished by intracellular BAPTA and cyclosporin A, specific calcineurin inhibitor. In summary, the inhibitory effects of capsaicin on I(h) are mediated by activation of TRPV1 and Ca(2+)-triggered cellular responses. Analgesic effects of capsaicin have been thought to be related to desensitization of nociceptive neurons due to depletion of pain-related substances. In addition, capsaicin-induced inhibition of I(h) is likely to be important in understanding the analgesic mechanism of capsaicin.

  20. Perception of trigeminal mixtures.

    PubMed

    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. PMID:25500807

  1. Perception of trigeminal mixtures.

    PubMed

    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.

  2. Blockade of calcium channels can prevent the onset of secondary hyperalgesia and allodynia induced by intradermal injection of capsaicin in rats.

    PubMed

    Sluka, K A

    1997-06-01

    Intradermal capsaicin injection in humans results in primary hyperalgesia to heat and mechanical stimuli applied near the injection site, as well as secondary mechanical hyperalgesia (increased pain from noxious stimuli) and mechanical allodynia (pain from innocuous stimuli) in an area surrounding the site of primary hyperalgesia. This study in rats tested the hypothesis that the secondary hyperalgesia and allodynia observed following intradermal injection of capsaicin was dependent upon activation of voltage sensitive calcium channels in the spinal cord. Responses to application of von Frey filaments of 10 mN and 90 mN bending forces were tested in all rats before and after injection of capsaicin into the plantar surface of a hindpaw. Animals were pretreated with L-type (nifedipine), N-type (omega-conotoxin GVIA) or P-type (omega-agatoxin IVA) calcium channels blockers through a microdialysis fiber implanted in the spinal dorsal horn prior to the injection of capsaicin. None of the calcium channel blockers had any affect on normal sensory or motor responses. However, all three blockers dose dependently prevented the development of secondary mechanical hyperalgesia and allodynia. The threshold to mechanical stimulation with von Frey filaments was also increased significantly in animals treated with these calcium channel blockers when compared to articial cerebrospinal fluid control animals. These data suggest that calcium channels are important for the development of mechanical hyperalgesia and allodynia that occurs following capsaicin injection. PMID:9211477

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

    PubMed

    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 < 0.001). L-menthol evoked secondary hyperalgesia to pinprick (P < 0.001) particularly in females (P < 0.05) and also induced secondary allodynia to von Frey and brush (P < 0.001). Application of cold stimuli kept these areas enlarged with a higher response in females to brush after the third cold cycle (P < 0.05). Skin blood flow increased after L-menthol (P < 0.001) and stayed stable after cold cycles. Repeated application of cold on skin treated by L-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. PMID:25719613

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

    PubMed

    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 < 0.001). L-menthol evoked secondary hyperalgesia to pinprick (P < 0.001) particularly in females (P < 0.05) and also induced secondary allodynia to von Frey and brush (P < 0.001). Application of cold stimuli kept these areas enlarged with a higher response in females to brush after the third cold cycle (P < 0.05). Skin blood flow increased after L-menthol (P < 0.001) and stayed stable after cold cycles. Repeated application of cold on skin treated by L-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.

  5. Strychnine blockade of the non-reciprocal inhibition of trigeminal motoneurons induced by stimulation of the parvocellular reticular formation.

    PubMed

    Castillo, P; Pedroarena, C; Chase, M H; Morales, F R

    1991-12-20

    Stimulation of a region within the parvocellular medullary reticular formation (PcRF) that contains somas of premotor interneurons produces short latency inhibitory synaptic potentials (IPSPs) in cat trigeminal motoneurons. The present study was undertaken to determine whether glycinergic synapses are responsible for these IPSPs. The intravenous administration of strychnine, an established glycine antagonist, abolished these PcRF-IPSPs. This effect appears to be specific for glycinergic inhibitory synapses because the short lasting component of the IPSP produced by inferior alveolar nerve (IAN) stimulation was also abolished, whereas, in contrast, the long lasting non-glycinergic component of this IPSP was not suppressed. These results indicate that a glycinergic system in the reticular formation is responsible for the non-reciprocal postsynaptic inhibition of trigeminal motoneurons. PMID:1817740

  6. P2X3 and TRPV1 functionally interact and mediate sensitization of trigeminal sensory neurons

    PubMed Central

    Saloman, Jami L.; Chung, Man-Kyo; Ro, Jin Y.

    2012-01-01

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) affect a large percentage of the population. Identifying mechanisms underlying hyperalgesia could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. In this study, we provide evidence of functional interactions between two ligand-gated channels, P2X3 and TRPV1, in trigeminal sensory neurons, and propose that the interactions serve as an underlying mechanism for the development of mechanical hyperalgesia. Mechanical sensitivity of the masseter muscle was assessed in lightly anesthetized rats via an electronic anesthesiometer (Ro et al., 2009). Direct intramuscular injection of a selective P2X3 agonist, αβmeATP, induced a dose- and time-dependent hyperalgesia. Mechanical sensitivity in the contralateral muscle was unaffected suggesting local P2X3 mediate the hyperalgesia. Anesthetizing the overlying skin had no effect on αβmeATP-induced hyperalgesia confirming the contribution of P2X3 from muscle. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810. P2X3 was co-expressed with TRPV1 in masseter muscle afferents confirming the possibility for intracellular interactions. Additionally, in a subpopulation of P2X3/TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly amplified following P2X3 activation. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal ganglia cultures. Significant phosphorylation was observed at 15 min, the time point at which behavioral hyperalgesia was prominent. Previously, activation of either P2X3 or TRPV1 had been independently implicated in the development of mechanical hyperalgesia. Our data propose P2X3 and TRPV1 interact in a facilitatory manner, which could contribute to the peripheral sensitization

  7. P2X₃ and TRPV1 functionally interact and mediate sensitization of trigeminal sensory neurons.

    PubMed

    Saloman, J L; Chung, M-K; Ro, J Y

    2013-03-01

    Musculoskeletal pain conditions, particularly those associated with temporomandibular disorders (TMD) affect a large percentage of the population. Identifying mechanisms underlying hyperalgesia could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. In this study, we provide evidence of functional interactions between two ligand-gated channels, P2X₃ and transient receptor potential V1 (TRPV1), in trigeminal sensory neurons, and propose that the interactions serve as an underlying mechanism for the development of mechanical hyperalgesia. Mechanical sensitivity of the masseter muscle was assessed in lightly anesthetized rats via an electronic anesthesiometer (Ro et al., 2009). Direct intramuscular injection of a selective P2X₃ agonist, alpha,beta-methylene adenosine triphosphate (αβmeATP), induced a dose- and time-dependent hyperalgesia. Mechanical sensitivity in the contralateral muscle was unaffected suggesting local P2X₃ mediate hyperalgesia. Anesthetizing the overlying skin had no effect on αβmeATP-induced hyperalgesia confirming the contribution of P2X₃ from the muscle. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810. P2X₃ was co-expressed with TRPV1 in the masseter muscle afferents confirming the possibility for intracellular interactions. Additionally, in a subpopulation of P2Xv/TRPV1 positive neurons, capsaicin-induced Ca(2+) transients were significantly amplified following P2X₃ activation. Finally, activation of P2X₃ induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal ganglia cultures. Significant phosphorylation was observed at 15 min, the time point at which behavioral hyperalgesia was prominent. Previously, activation of either P2X₃ or TRPV1 had been independently implicated in the development of mechanical hyperalgesia. Our data propose P2X₃ and TRPV1

  8. The two faces of capsaicin.

    PubMed

    Bode, Ann M; Dong, Zigang

    2011-04-15

    Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the principal pungent component in hot peppers, including red chili peppers, jalapeños, and habaneros. Consumed worldwide, capsaicin has a long and convoluted history of controversy about whether its consumption or topical application is entirely safe. Conflicting epidemiologic data and basic research study results suggest that capsaicin can act as a carcinogen or as a cancer preventive agent. Capsaicin is unique among naturally occurring irritant compounds because the initial neuronal excitation evoked 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 is referred to as desensitization and has been exploited for its therapeutic potential. Capsaicin-containing creams have been in clinical use for many years to relieve a variety of painful conditions. However, their effectiveness in pain relief is also highly debated and some adverse side effects have been reported. We have found that chronic, long-term topical application of capsaicin increased skin carcinogenesis in mice treated with a tumor promoter. These results might imply that caution should be exercised when using capsaicin-containing topical applications in the presence of a tumor promoter, such as, for example, sunlight.

  9. Capsaicin represses transcriptional activity of β-catenin in human colorectal cancer cells.

    PubMed

    Lee, Seong-Ho; Richardson, Raphael L; Dashwood, Roderick H; Baek, Seung Joon

    2012-06-01

    Capsaicin is a pungent ingredient in chili red peppers and has been linked to suppression of growth in various cancer cells. However, the underlying mechanism(s) by which capsaicin induces growth arrest and apoptosis of cancer cells is not completely understood. In the present study, we investigated whether capsaicin alters β-catenin-dependent signaling in human colorectal cancer cells in vitro. Exposure of SW480, LoVo and HCT-116 cells to capsaicin suppressed cell proliferation. Transient transfection with a β-catenin/T-cell factor (TCF)-responsive reporter indicated that capsaicin suppressed the transcriptional activity of β-catenin/TCF. Capsaicin treatment resulted in a decrease of intracellular β-catenin levels and a reduction of transcripts from the β-catenin gene (CTNNB1). These results were confirmed by a reduced luciferase reporter activity driven by promoter-reporter construct containing the promoter region of the Catnb gene. In addition, capsaicin destabilized β-catenin through enhancement of proteosomal-dependent degradation. Western blot and immunoprecipitation studies indicated that capsaicin treatment suppressed TCF-4 expression and disrupted the interaction of TCF-4 and β-catenin. This study identifies a role for the β-catenin/TCF-dependent pathway that potentially contributes to the anticancer activity of capsaicin in human colorectal cancer cells. PMID:21764279

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

    PubMed

    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.

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

    PubMed

    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.

  12. Capsaicin mediates cell cycle arrest and apoptosis in human colon cancer cells via stabilizing and activating p53.

    PubMed

    Jin, Junzhe; Lin, Guofu; Huang, Hong; Xu, Dong; Yu, Hao; Ma, Xu; Zhu, Lisi; Ma, Dongyan; Jiang, Honglei

    2014-01-01

    Capsaicin is the major pungent ingredient in red peppers which is world widely consumed. Except its potent pain relieving efficacy as reported, capsaicin also exerted its antitumor activity in several tumor models. Here, we reported that capsaicin had a profound anti-proliferative effect on human colon cancer cells via inducing cell cycle G0/G1 phase arrest and apoptosis, which was associated with an increase of p21, Bax and cleaved PARP. The underlying mechanism of capsaicin's antitumor potency was mainly attributed to the stabilization and activation of p53. Capsaicin substantially prolonged the half-life of p53 and significantly elevated the transcriptional activity of p53. Through suppressing the interaction between p53 and MDM2, MDM2-mediated p53 ubiquitination was remarkably decreased after capsaicin treatment, which resulted in the stabilization and accumulation of p53. The results of p53-shRNA experiment further demonstrated that p53 knockdown severely impaired the sensitivity of tested cells to capsaicin, G0/G1 phase arrest and the apoptosis induced by capsaicin in p53-knockdown cells was also dramatically decreased, implicating the important role of p53 played in capsaicin's antitumor activity. In summary, our data suggested that capsaicin, or a related analogue, may have a role in the management of human colon cancer.

  13. Effect of protons on the inward current evoked by capsaicin in isolated dorsal root ganglion cells.

    PubMed

    Petersen, M; LaMotte, R H

    1993-07-01

    Capsaicin excites a subset of dorsal root ganglion (DRG) neurons by inducing an inward current. We have examined this inward current in response to high concentrations of protons in the external medium. The experiments were done in freshly dissociated DRG cells under whole-cell voltage-clamp conditions. The amplitude of the current evoked by capsaicin (200-300 nM) was increased with increasing concentrations of protons (pH 6.9-6.3). Increasing the acidification of the external medium from a physiological pH of 7.3 to 6.3 enhanced 7-fold the current induced by capsaicin (300 nM). Cells unresponsive to capsaicin in a physiological pH were also unresponsive to capsaicin in an acidic solution. There was a progressive decrease in the amplitude of the capsaicin-evoked current when the drug was repeatedly applied either at a physiological pH or an acidic pH of 6.3. Exposure of the cell to acidic solutions of capsaicin did not subsequently increase an evoked inward current when capsaicin was applied at a physiological pH nor did it lead to an inward current evoked by proton ions where there had been none. Our results suggest that increased proton concentrations in the extracellular medium could play an important modulatory role in the function of chemosensitive sensory neurons.

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

    PubMed Central

    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

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

    PubMed

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

    PubMed

    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

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

    PubMed

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

    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 percent 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. PMID:23938388

  18. Biotechnological enhancement of capsaicin biosynthesis in cell suspension cultures of Naga King Chili (Capsicum chinense Jacq.).

    PubMed

    Kehie, Mechuselie; Kumaria, Suman; Tandon, Pramod

    2016-01-01

    Cell suspension cultures were initiated from hypocotyl derived callus to induce capsaicin biosynthesis in suspension cultures of Naga King Chili (Capsicum chinense Jacq.). Efficient capsaicin production with high growth index (GI) was obtained by exposing cells to salicylic acid (SA) and calcium channel modulators in suspension cultures. The time course of capsaicin formation is related to the cell growth profile in a batch culture. Cells cultivated in the standard medium (SM) initially showed low level of capsaicin yield during active growth. When the cells approached stationary phase, cell growth and cell viability decreased whereas capsaicin production increased continuously. In the fed-batch cultures, the highest capsaicin yield (567.4 ± 8.1 μgg(1) fresh weight) (f.wt) was obtained by feeding the cells with 1 mM SA. However, SA feeding during cultivation repressed the cell growth. Enhanced cell growth (3.1 ± 0.1 GI/culture) and capsaicin yield (534 ± 7.8 μgg(-1)f.wt) were obtained when the cells were fed with calcium ionophore A23187 (0.5 mM) on day 25 as compared to the control. Addition of the calcium channel blocker verapamil hydrochloride (100 mM) inhibited cell growth and capsaicin production in Naga King Chili suspension cell cultures. PMID:26578343

  19. Biotechnological enhancement of capsaicin biosynthesis in cell suspension cultures of Naga King Chili (Capsicum chinense Jacq.).

    PubMed

    Kehie, Mechuselie; Kumaria, Suman; Tandon, Pramod

    2016-01-01

    Cell suspension cultures were initiated from hypocotyl derived callus to induce capsaicin biosynthesis in suspension cultures of Naga King Chili (Capsicum chinense Jacq.). Efficient capsaicin production with high growth index (GI) was obtained by exposing cells to salicylic acid (SA) and calcium channel modulators in suspension cultures. The time course of capsaicin formation is related to the cell growth profile in a batch culture. Cells cultivated in the standard medium (SM) initially showed low level of capsaicin yield during active growth. When the cells approached stationary phase, cell growth and cell viability decreased whereas capsaicin production increased continuously. In the fed-batch cultures, the highest capsaicin yield (567.4 ± 8.1 μgg(1) fresh weight) (f.wt) was obtained by feeding the cells with 1 mM SA. However, SA feeding during cultivation repressed the cell growth. Enhanced cell growth (3.1 ± 0.1 GI/culture) and capsaicin yield (534 ± 7.8 μgg(-1)f.wt) were obtained when the cells were fed with calcium ionophore A23187 (0.5 mM) on day 25 as compared to the control. Addition of the calcium channel blocker verapamil hydrochloride (100 mM) inhibited cell growth and capsaicin production in Naga King Chili suspension cell cultures.

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

    PubMed

    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.

  1. Trigeminal neuralgia as the first clinical manifestation of anti-hu paraneoplastic syndrome induced by a borderline ovarian mucinous tumor.

    PubMed

    Kalanie, Hossein; Harandi, Ali Amini; Mardani, Masoud; Shahverdi, Zohre; Morakabati, Arman; Alidaei, Shapoor; Heydari, Daryoosh; Soroush, Ziaeddin; Pakdaman, Hossein; Hosseinzadeh, Zahra

    2014-01-01

    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. PMID:24575026

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

    PubMed Central

    Kalanie, Hossein; Harandi, Ali Amini; Mardani, Masoud; Shahverdi, Zohre; Morakabati, Arman; Alidaei, Shapoor; Heydari, Daryoosh; Soroush, Ziaeddin; Pakdaman, Hossein; Hosseinzadeh, Zahra

    2014-01-01

    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. PMID:24575026

  3. Facial pain: trigeminal neuralgia.

    PubMed

    Lee, K H

    1993-03-01

    Atypical facial pain is a loose term used to encompass a wide range of facial pain syndromes including those of dental and ear, nose and throat (ENT) aetiology. Often, it is associated with psychiatric conditions like depression and psychosomatic illnesses. This facial pain typically does not follow anatomical boundaries or its explainable by present day neurophysiological understanding. The pain is often constant with no remission and is aggravated by stress. Treatment is difficult and often directed to the psychiatric cause. Surgical treatment is contraindicated. Trigeminal neuralgia on the other hand, can be effectively treated. Pain in the trigeminal distribution is paroxysmal, precipitated by trigger factors and there is no pain in between attacks. The aetiology of trigeminal neuralgia is still unknown though current thinking is that there is a peripheral disturbance or damage with cerebral brainstem disinhibition of the trigeminal apparatus. This results in a paroxysmal discharge and reverberation of pain impulses when a trigger point is elicited. Therefore, anti-epileptic drugs like tegretol can be effective in controlling trigeminal neuralgia in the majority of patients, at least in the initial stages. For unknown reasons however, medical treatment either is not effective at all from the very beginning or fails after a few years. Surgery then becomes the only available therapeutic option. If the peripheral disturbance is due to an organic cause like a tumour, surgical approaches should be directed towards its removal. Often the pain will also resolve. If the trigeminal neuralgia is of the idiopathic variety, then the surgeon has a choice of either peripheral percutaneous retrogasserian ganglionectomies or central approaches like microvascular decompression and trigeminal tractotomy. PMID:8363331

  4. Anticancer Properties of Capsaicin Against Human Cancer.

    PubMed

    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. PMID:26976969

  5. Anticancer Properties of Capsaicin Against Human Cancer.

    PubMed

    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.

  6. Trigeminal trophic syndrome.

    PubMed

    Kumar, Parimalam; Thomas, Jayakar

    2014-01-01

    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. PMID:24470665

  7. Chemosensory information processing between keratinocytes and trigeminal neurons.

    PubMed

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

    2014-06-20

    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

  8. Chemosensory Information Processing between Keratinocytes and Trigeminal Neurons

    PubMed Central

    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

  9. Intractable trigeminal neuralgia.

    PubMed Central

    Watts, P G

    1987-01-01

    In 49 cases of trigeminal neuralgia seen at the Abingdon Pain Relief Unit, Oxfordshire, the average time between initial onset of pain and first referral to the unit was 9.8 years. The pattern of presentation and distribution was no different from previously published studies, indicating that the more intractable cases cannot be predicted at first presentation. PMID:3681871

  10. Capsaicin-Sensitive Sensory Nerves Mediate the Cellular and Microvascular Effects of H2S via TRPA1 Receptor Activation and Neuropeptide Release.

    PubMed

    Hajna, Zsófia; Sághy, Éva; Payrits, Maja; Aubdool, Aisah A; Szőke, Éva; Pozsgai, Gábor; Bátai, István Z; Nagy, Lívia; Filotás, Dániel; Helyes, Zsuzsanna; Brain, Susan D; Pintér, Erika

    2016-10-01

    It is supposed that TRPA1 receptor can be activated by hydrogen sulphide (H2S). Here, we have investigated the role of TRPA1 receptor in H2S-induced [Ca(2+)]i increase in trigeminal ganglia (TRG) neurons, and the involvement of capsaicin-sensitive sensory nerves in H2S-evoked cutaneous vasodilatation. [Ca(2+)]i was measured with ratiometric technique on TRG neurons of TRPA1(+/+) and TRPA1(-/-) mice after NaHS, Na2S, allylisothiocyanate (AITC) or KCl treatment. Microcirculatory changes in the ear were detected by laser Doppler imaging in response to topical NaHS, AITC, NaOH, NaSO3 or NaCl. Mice were either treated with resiniferatoxin (RTX), or CGRP antagonist BIBN4096, or NK1 receptor antagonist CP99994, or K(+) ATP channel blocker glibenclamide. Alpha-CGRP(-/-) and NK1 (-/-) mice were also investigated. NaHS and Na2S increased [Ca(2+)]i in TRG neurons derived from TRPA(+/+) but not from TRPA1(-/-) mice. NaHS increased cutaneous blood flow, while NaOH, NaSO3 and NaCl did not cause significant changes. NaHS-induced vasodilatation was reduced in RTX-treated animals, as well as by pre-treatment with BIBN4096 or CP99994 alone or in combination. NaHS-induced vasodilatation was significantly smaller in alpha-CGRP(-/-) or NK1 (-/-) mice compared to wild-types. H2S activates capsaicin-sensitive sensory nerves through TRPA1 receptors and the resultant vasodilatation is mediated by the release of vasoactive sensory neuropeptides CGRP and substance P. PMID:27525636

  11. Identification of compounds that contribute to trigeminal burn in aqueous ethanol solutions.

    PubMed

    Kokkinidou, Smaro; Peterson, Devin G

    2016-11-15

    The influence of carbonyl species on the trigeminal burn of distilled spirit model systems was investigated. Quantities of the intrinsic carbonyl compounds were significantly altered in 40% ethanol solutions using two methods; (1) increasing or decreasing the product pH, to induce hemiacetal formation and acetal stabilization or induce and stabilize carbonyl species such as aldehydes, respectively and (2) utilizing a sulfonyl hydrazine polymer treatment. Samples with reduced carbonyl concentrations had significantly lower perceived trigeminal burn intensity. Sensory recombination experiments revealed that addition of carbonyl compounds increased trigeminal burn perception in model systems; confirming the direct relationship between the concentration of carbonyl compounds and trigeminal burn. The strongest potentiators of the trigeminal response were carbonyl compounds octanal, nonanal, benzaldehyde and 2-heptanone suggesting the probability that carbonyl species such as saturated aldehydes and ketones act as agonists to activate nociceptors such as TRPV1 and TRPA1 and elicit trigeminal burn. PMID:27283693

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

    PubMed Central

    Malmierca, Eduardo; Chaves-Coira, Irene; Rodrigo-Angulo, Margarita; Nuñez, Angel

    2014-01-01

    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 min) 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. PMID:24904321

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

    PubMed

    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. PMID:25959004

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

    PubMed

    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.

  15. Pharmacological evidence for CGRP uptake into perivascular capsaicin sensitive nerve terminals

    PubMed Central

    Sams-Nielsen, Anette; Orskov, Cathrine; Jansen-Olesen, Inger

    2001-01-01

    Specific mechanisms, providing reuptake of cathecholamine and amino acid neurotransmitters (e.g. serotonin and glutamate) into cells of the central nervous system are well known, whereas neuronal uptake of neuropeptide transmitters have not previously been reported. In the present study we present evidence for uptake of the 37 amino acid neuropeptide, calcitonin gene-related peptide (CGRP) into perivascular terminals of capsaicin sensitive nerve fibres, innervating the guinea-pig basilar artery. Release of CGRP from perivascular nerve terminals was obtained by capsaicin-induced vanilloid receptor-stimulation and detected as CGRP receptor-mediated dilation of isolated segments of the guinea-pig basilar artery. Following three repeated capsaicin challenges, CGRP-depleted segments were incubated with CGRP. This caused significant reappearance of capsaicin-induced vasodilatory responses. These responses were dependent on duration and concentration of the preceding CGRP incubation and were inhibited by the CGRP receptor antagonist, CGRP8–37. The CGRP-re-depletion was significantly reduced when CGRP8–37 was present during the preceding CGRP incubation. Thus, presynaptic CGRP receptors are likely to be involved in neuronal CGRP uptake. Incubating the artery segments with 125I-CGRP allowed subsequent detection of capsaicin-induced 125I-release. Immunohistochemical experiments showed that only terminal CGRP is subject to capsaicin-induced depletion in vitro, whereas CGRP-immunoreactivity endures in the nerve fibres. PMID:11226146

  16. Capsaicin suppresses the migration of cholangiocarcinoma cells by down-regulating matrix metalloproteinase-9 expression via the AMPK-NF-κB signaling pathway.

    PubMed

    Lee, Gong-Rak; Jang, Soo Hwa; Kim, Chang Jae; Kim, Ah-Ram; Yoon, Dong-Joon; Park, Neung-Hwa; Han, In-Seob

    2014-12-01

    Cholangiocarcinoma is one of the most difficult malignancies to cure. An important prognostic factor is metastasis, which precludes curative surgical resection. Recent evidence shows that capsaicin has an inhibitory effect on cancer cell migration and invasion. Here, we investigated the molecular mechanism of the capsaicin-induced anti-migration and anti-invasion effects on HuCCT1 cholangiocarcinoma cells. Migration and invasion were significantly reduced in response to capsaicin. Capsaicin also inhibited the expression of matrix metalloproteinase-9 (MMP-9). In capsaicin-treated cells, levels of phosphorylated AMPK increased, and this effect was abolished by treatment with the AMPK inhibitor, Compound C. Capsaicin enhanced the expression of SIRT1, which can activate the transcription factor NF-κB by deacetylation. This suggests that NF-κB is activated by capsaicin via the SIRT1 pathway. In addition, capsaicin-activated AMPK induced the phosphorylation of IκBα and nuclear localization of NF-κB p65. Chromatin immunoprecipitation assays demonstrated that capsaicin reduced MMP-9 transcription by inhibiting NF-κB p65 translocation and deacetylation via SIRT1. These findings provide evidence that capsaicin suppresses the migration and invasion of cholangiocarcinoma cells by inhibiting NF-κB p65 via the AMPK-SIRT1 and the AMPK-IκBα signaling pathways, leading to subsequent suppression of MMP-9 expression.

  17. Trigeminal neuralgia in wind musicians.

    PubMed

    Cheshire, William P

    2006-10-01

    The author reports 3 patients with trigeminal neuralgia whose pain was triggered by musical performance. Use of the muscles of embouchure activated the trigger zone when playing the clarinet, saxophone, flute, piccolo, trombone, or whistling. In each case, the location of the trigger zone was perioral, regardless of which division of the trigeminal nerve emanated pain. Trigeminal neuralgia is a particularly disabling affliction when it occurs in wind musicians.

  18. Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress.

    PubMed

    Ip, S-W; Lan, S-H; Lu, H-F; Huang, A-C; Yang, J-S; Lin, J-P; Huang, H-Y; Lien, J-C; Ho, C-C; Chiu, C-F; Wood, Wg; Chung, J-G

    2012-06-01

    Capsaicin, a pungent compound found in hot chili peppers, has been reported to have antitumor activities in many human cancer cell lines, but the induction of precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent manner. Capsaicin treatment triggered ER stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Other effects included an increase in cytosolic Ca(2+), loss of the mitochondrial transmembrane potential (ΔΨ(m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and abundance of apoptosis-related protein levels. These results suggest that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells. PMID:21859781

  19. Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress.

    PubMed

    Ip, S-W; Lan, S-H; Lu, H-F; Huang, A-C; Yang, J-S; Lin, J-P; Huang, H-Y; Lien, J-C; Ho, C-C; Chiu, C-F; Wood, Wg; Chung, J-G

    2012-06-01

    Capsaicin, a pungent compound found in hot chili peppers, has been reported to have antitumor activities in many human cancer cell lines, but the induction of precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent manner. Capsaicin treatment triggered ER stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Other effects included an increase in cytosolic Ca(2+), loss of the mitochondrial transmembrane potential (ΔΨ(m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and abundance of apoptosis-related protein levels. These results suggest that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells.

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

    PubMed

    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.

  1. The Brain Mechanisms Underlying the Perception of Pungent Taste of Capsaicin and the Subsequent Autonomic Responses.

    PubMed

    Kawakami, Shinpei; Sato, Hajime; Sasaki, Akihiro T; Tanabe, Hiroki C; Yoshida, Yumiko; Saito, Mitsuru; Toyoda, Hiroki; Sadato, Norihiro; Kang, Youngnam

    2015-01-01

    In a human fMRI study, it has been demonstrated that tasting and ingesting capsaicin activate the ventral part of the middle and posterior short gyri (M/PSG) of the insula which is known as the primary gustatory area, suggesting that capsaicin is recognized as a taste. Tasting and digesting spicy foods containing capsaicin induce various physiological responses such as perspiration from face, salivation, and facilitation of cardiovascular activity, which are thought to be caused through viscero-visceral autonomic reflexes. However, this does not necessarily exclude the possibility of the involvement of higher-order sensory-motor integration between the M/PSG and anterior short gyrus (ASG) known as the autonomic region of the insula. To reveal a possible functional coordination between the M/PSG and ASG, we here addressed whether capsaicin increases neural activity in the ASG as well as the M/PSG using fMRI and a custom-made taste delivery system. Twenty subjects participated in this study, and three tastant solutions: capsaicin, NaCl, and artificial saliva (AS) were used. Group analyses with the regions activated by capsaicin revealed significant activations in the bilateral ASG and M/PSG. The fMRI blood oxygenation level-dependent (BOLD) signals in response to capsaicin stimulation were significantly higher in ASG than in M/PSG regardless of the side. Concomitantly, capsaicin increased the fingertip temperature significantly. Although there was no significant correlation between the fingertip temperatures and BOLD signals in the ASG or M/PSG when the contrast [Capsaicin-AS] or [Capsaicin-NaCl] was computed, a significant correlation was found in the bilateral ASG when the contrast [2 × Capsaicin-NaCl-AS] was computed. In contrast, there was a significant correlation in the hypothalamus regardless of the contrasts. Furthermore, there was a significant correlation between M/PSG and ASG. These results indicate that capsaicin increases neural activity in the ASG as

  2. Trigeminal autonomic cephalgias

    PubMed Central

    2012-01-01

    Summary points 1. Trigeminal autonomic cephalgias (TACs) are headaches/facial pains classified together based on:a suspected common pathophysiology involving the trigeminovascular system, the trigeminoparasympathetic reflex and centres controlling circadian rhythms;a similar clinical presentation of trigeminal pain, and autonomic activation. 2. There is much overlap in the diagnostic features of individual TACs. 3. In contrast, treatment response is relatively specific and aids in establishing a definitive diagnosis. 4. TACs are often presentations of underlying pathology; all patients should be imaged. 5. The aim of the article is to provide the reader with a broad introduction to, and an overview of, TACs. The reading list is extensive for the interested reader. PMID:26516482

  3. Review: Effect of drugs on human cough reflex sensitivity to inhaled capsaicin

    PubMed Central

    2012-01-01

    Capsaicin, the pungent extract of red peppers, has been used in clinical research for almost three decades. Capsaicin has gained favor as the provocative agent of choice to measure cough reflex sensitivity, as it induces cough in a safe, reproducible, and dose-dependent manner. One of the major uses of capsaicin cough challenge testing has been to evaluate the effect of a pharmacological intervention on the human cough reflex. The current review summarizes the published experience with capsaicin inhalation challenge in the evaluation of drug effects on cough reflex sensitivity. A notable contrast evident between studies demonstrating a drug effect (inhibition of cough reflex sensitivity) and those that do not, is the predominance of healthy volunteers as subjects in the latter. This observation suggests that subjects with pathological cough, rather than normal volunteers, comprise the optimal group in which to evaluate the effect of potential antitussive agents on human cough reflex sensitivity. PMID:23146824

  4. Capsaicin-evoked brain activation and central sensitization in anaesthetised rats: a functional magnetic resonance imaging study.

    PubMed

    Moylan Governo, Ricardo Jose; Morris, Peter Gordon; Prior, Malcolm John William; Marsden, Charles Alexander; Chapman, Victoria

    2006-12-15

    Functional magnetic resonance imaging (fMRI) of blood oxygen level dependent (BOLD) haemodynamic responses was used to study the effects of the noxious substance capsaicin on whole brain activation in isofluorane anaesthetised rats. Rats (n=8) received intradermal injection of capsaicin (30 microg/5 microl), or topical cream (0.1%) capsaicin and BOLD responses were acquired for up to 120 min. Effects of capsaicin versus placebo cream treatment on the BOLD response to a 15 g mechanical stimulus applied adjacent to the site of cream application were also studied. Both injection and cream application of capsaicin activated brain areas involved in pain processing, including the thalamus and periaqueductal grey (PAG) (p<0.05, corrected for multiple comparisons). Capsaicin also produced increases in BOLD signal intensity in other regions that contribute to pain processing, such as the parabrachial nucleus and superior colliculus. Mechanical stimulation in capsaicin-treated rats, but not placebo-treated rats, induced a significant decrease in BOLD signal intensity in the PAG (p<0.001). These data demonstrate that the noxious substance capsaicin produces brain activation in the midbrain regions and reveals the importance of the PAG in central sensitization. PMID:16843597

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

    PubMed

    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.

  6. Could calcitonin be a useful therapeutic agent for trigeminal neuralgia?

    PubMed

    Qin, Han; Cai, Jun; Yang, Fu Sheng

    2008-01-01

    Trigeminal neuralgia (TN) has been recognized as one of the most common neurovascular syndromes caused by the vascular contact of the trigeminal nerve in its root entry zone (REZ) with a branch of the superior or anterior inferior cerebellar arteries, leading to a demyelinization of trigeminal sensory fibers within either the nerve root or, less commonly, the brainstem. There is a lack of certainty regarding the aetiology and pathophysiology of TN, therefore the treatment of trigeminal neuropathic pain disorders continues to be a major therapeutic challenge. The identification of novel therapeutic agents for the treatment of these disorders is important. Calcitonin (especially intranasal) provides an interesting analgesic effect in a series of painful conditions including reflex sympathetic dystrophy syndrome, adhesive capsulitis, ankylosing spondylitis, rheumatoid arthritis, vertebral crush fractures and metastasis, phantom limb pain, etc. Exogenous calcitonin is thought to cross the blood-brain barrier and to accumulate slowly in the brain, inducing analgesia once sufficient receptors are occupied. We hypothesize that calcitonin may has anti - trigeminal neuralgia properties. From the clinical point of use, the analgesic effect of calcitonin will be beneficial throughout the whole period of medical treatment of trigeminal neuralgia patients. PMID:18343043

  7. Could calcitonin be a useful therapeutic agent for trigeminal neuralgia?

    PubMed

    Qin, Han; Cai, Jun; Yang, Fu Sheng

    2008-01-01

    Trigeminal neuralgia (TN) has been recognized as one of the most common neurovascular syndromes caused by the vascular contact of the trigeminal nerve in its root entry zone (REZ) with a branch of the superior or anterior inferior cerebellar arteries, leading to a demyelinization of trigeminal sensory fibers within either the nerve root or, less commonly, the brainstem. There is a lack of certainty regarding the aetiology and pathophysiology of TN, therefore the treatment of trigeminal neuropathic pain disorders continues to be a major therapeutic challenge. The identification of novel therapeutic agents for the treatment of these disorders is important. Calcitonin (especially intranasal) provides an interesting analgesic effect in a series of painful conditions including reflex sympathetic dystrophy syndrome, adhesive capsulitis, ankylosing spondylitis, rheumatoid arthritis, vertebral crush fractures and metastasis, phantom limb pain, etc. Exogenous calcitonin is thought to cross the blood-brain barrier and to accumulate slowly in the brain, inducing analgesia once sufficient receptors are occupied. We hypothesize that calcitonin may has anti - trigeminal neuralgia properties. From the clinical point of use, the analgesic effect of calcitonin will be beneficial throughout the whole period of medical treatment of trigeminal neuralgia patients.

  8. Mechanisms and clinical uses of capsaicin.

    PubMed

    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. PMID:24211679

  9. Bioconversion of Capsaicin by Aspergillus oryzae.

    PubMed

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

    2015-07-01

    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.

  10. Vitamin B complex attenuated heat hyperalgesia following infraorbital nerve constriction in rats and reduced capsaicin in vivo and in vitro effects.

    PubMed

    Kopruszinski, Caroline M; Reis, Renata C; Bressan, Elisangela; Reeh, Peter W; Chichorro, Juliana G

    2015-09-01

    Vitamins of the B complex attenuate some neuropathic pain sensory aspects in various animal models and in patients, but the mechanisms underlying their effects remain to be elucidated. Herein it was investigated if the treatment with a vitamin B complex (VBC) reduces heat hyperalgesia in rats submitted to infraorbital nerve constriction and the possibility that TRPV1 receptors represent a target for B vitamins. In the present study, the VBC refers to a combination of vitamins B1, B6 and B12 at low- (18, 18 and 1.8mg/kg, respectively) or high- (180, 180 and 18mg/kg, respectively) doses. Acute treatment of rats with either the low- or the high-doses combination reduced heat hyperalgesia after nerve injury, but the high-doses combination resulted in a long-lasting effect. Repeated treatment with the low-dose combination reduced heat hyperalgesia on day four after nerve injury and showed a synergist effect with a single injection of carbamazepine (3 or 10mg/kg), which per se failed to modify the heat threshold. In naïve rats, acute treatment with the high-dose of VBC or B1 and B12 vitamins independently reduced heat hyperalgesia evoked by capsaicin (3µg into the upper lip). Moreover, the VBC, as well as, each one of the B vitamins independently reduced the capsaicin-induced calcium responses in HEK 293 cells transiently transfected with the human TRPV1 channels. Altogether, these results indicate that B vitamins can be useful to control heat hyperalgesia associated with trigeminal neuropathic pain and that modulation of TRPV1 receptors may contribute to their anti-hyperalgesic effects.

  11. 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.

    PubMed

    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

  12. Sirtuin 1 (SIRT1) Deacetylase Activity and NAD⁺/NADH Ratio Are Imperative for Capsaicin-Mediated Programmed Cell Death.

    PubMed

    Lee, Yi-Hui; Chen, Huei-Yu; Su, Lilly J; Chueh, Pin Ju

    2015-08-26

    Capsaicin is considered a chemopreventive agent by virtue of its selective antigrowth activity, commonly associated with apoptosis, against cancer cells. However, noncancerous cells possess relatively higher tolerance to capsaicin, although the underlying mechanism for this difference remains unclear. Hence, this study aimed to elucidate the differential effects of capsaicin on cell lines from lung tissues by addressing the signal pathway leading to two types of cell death. In MRC-5 human fetal lung cells, capsaicin augmented silent mating type information regulation 1 (SIRT1) deacetylase activity and the intracellular NAD(+)/NADH ratio, decreasing acetylation of p53 and inducing autophagy. In contrast, capsaicin decreased the intracellular NAD(+)/NADH ratio, possibly through inhibition of tumor-associated NADH oxidase (tNOX), and diminished SIRT1 expression leading to enhanced p53 acetylation and apoptosis. Moreover, SIRT1 depletion by RNA interference attenuated capsaicin-induced apoptosis in A549 cancer cells and autophagy in MRC-5 cells, suggesting a vital role for SIRT1 in capsaicin-mediated cell death. Collectively, these data not only explain the differential cytotoxicity of capsaicin but shed light on the distinct cellular responses to capsaicin in cancerous and noncancerous cell lines.

  13. Sphingosine 1-phosphate to p38 signaling via S1P1 receptor and Gαi/o evokes augmentation of capsaicin-induced ionic currents in mouse sensory neurons.

    PubMed

    Langeslag, Michiel; Quarta, Serena; Leitner, Michael G; Kress, Michaela; Mair, Norbert

    2014-01-01

    The perception of painful thermal stimuli by sensory neurons is largely mediated by TRPV1. Upon tissue injury or inflammation, S1P is secreted by thrombocytes as part of an inflammatory cocktail, which sensitizes nociceptive neurons towards thermal stimuli. S1P acts on G-protein coupled receptors that are expressed in sensory neurons and sensitize TRPV1 channels towards thermal stimuli. In this study, the S1P mediated signaling pathway required for sensitization of TRPV1 channels was explored.The capsaicin induced peak inward current (ICAPS) of sensory neurons was significantly increased after S1P stimulation within minutes after application. The potentiation of ICAPS resulted from activation of Gαi through G-protein coupled receptors for S1P. Consequently, Gαi led to a signaling cascade, involving phosphoinositide-3-kinase (PI3K) and protein kinase C, which augmented ICAPS in nociceptive neurons. The S1P1 receptor agonist SEW2871 resulted in activation of the same signaling pathway and potentiation of ICAPS. Furthermore, the mitogen-activated protein kinase p38 was phosphorylated after S1P stimulation and inhibition of p38 signaling by SB203580 prevented the S1P-induced ICAPS potentiation. The current data suggest that S1P sensitized ICAPS through G-protein coupled S1P1 receptor activation of Gαi-PI3K-PKC-p38 signaling pathway in sensory neurons. PMID:25431213

  14. No relevant modulation of TRPV1-mediated trigeminal pain by intranasal carbon dioxide in healthy humans

    PubMed Central

    2013-01-01

    Background Nasal insufflation of CO2 has been shown to exert antinociceptive respectively antihyperalgesic effects in animal pain models using topical capsaicin with activation of TRPV1-receptor positive nociceptive neurons. Clinical benefit from CO2 inhalation in patients with craniofacial pain caused by a putative activation of TRPV1 receptor positive trigeminal neurons has also been reported. These effects are probably mediated via an activation of TRPV1 receptor - positive neurons in the nasal mucosa with subsequent central inhibitory effects (such as conditioned pain modulation). In this study, we aimed to examine the effects of intranasal CO2 on a human model of craniofacial pain elicited by nasal application of capsaicin. Methods In a first experiment, 48 healthy volunteers without previous craniofacial pain received intranasal capsaicin to provoke trigeminal pain elicited by activation of TRVP1 positive nociceptive neurons. Then, CO2 or air was insufflated alternatingly into the nasal cavity at a flow rate of 1 l/min for 60 sec each. In the subsequent experiment, all participants were randomized into 2 groups of 24 each and received either continuous nasal insufflation of CO2 or placebo for 18:40 min after nociceptive stimulation with intranasal capsaicin. In both experiments, pain was rated on a numerical rating scale every 60 sec. Results Contrary to previous animal studies, the effects of CO2 on experimental trigeminal pain were only marginal. In the first experiment, CO2 reduced pain ratings only minimally by 5.3% compared to air if given alternatingly with significant results for the main factor GROUP (F1,47 = 4.438; p = 0.041) and the interaction term TIME*GROUP (F2.6,121.2 = 3.3; p = 0.029) in the repeated-measures ANOVA. However, these effects were abrogated after continuous insufflation of CO2 or placebo with no significant changes for the main factors or the interaction term. Conclusions Although mild modulatory effects of low

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

    PubMed

    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. Trigeminal autonomic cephalalgias.

    PubMed

    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.

  17. Capsaicin may have important potential for promoting vascular and metabolic health

    PubMed Central

    McCarty, Mark F; DiNicolantonio, James J; O'Keefe, James H

    2015-01-01

    Capsaicin, the phytochemical responsible for the spiciness of peppers, has the potential to modulate metabolism via activation of transient receptor potential vanilloid 1 (TRPV1) receptors, which are found not only on nociceptive sensory neurons, but also in a range of other tissues. TRPV1 activation induces calcium influx, and in certain tissues this is associated with increased activation or expression of key proteins such as endothelial nitric oxide synthase (eNOS), uncoupling protein 2 (UCP2), KLF2, PPARdelta, PPARgamma, and LXRα. The calcium influx triggered by TRPV1 activation in endothelial cells mimics the impact of shear stress in this regard, activating and increasing the expression of eNOS—but also increasing expression of cox-2, thrombomodulin, and nrf2-responsive antioxidant enzymes, while decreasing expression of proinflammatory proteins. Hence, dietary capsaicin has favourably impacted endothelium-dependent vasodilation in rodents. TRPV1-mediated induction of LXRα in foam cells promotes cholesterol export, antagonising plaque formation. Capsaicin-mediated activation of TRPV1-expressing neurons in the gastrointestinal tract promotes sympathetically mediated stimulation of brown fat, raising metabolic rate. The increased expression of UCP2 induced by TRPV1 activation exerts a protective antioxidant effect on the liver in non-alcoholic fatty liver disease, and on vascular endothelium in the context of hyperglycaemia. In rodent studies, capsaicin-rich diets have shown favourable effects on atherosclerosis, metabolic syndrome, diabetes, obesity, non-alcoholic fatty liver, cardiac hypertrophy, hypertension and stroke risk. Clinically, ingestion of capsaicin—or its less stable non-pungent analogue capsiate—has been shown to boost metabolic rate modestly. Topical application of capsaicin via patch was found to increase exercise time to ischaemic threshold in patients with angina. Further clinical studies with capsaicin administered in food, capsules

  18. Neutralization of nerve growth factor induces plasticity of ATP-sensitive P2X3 receptors of nociceptive trigeminal ganglion neurons.

    PubMed

    D'Arco, Marianna; Giniatullin, Rashid; Simonetti, Manuela; Fabbro, Alessandra; Nair, Asha; Nistri, Andrea; Fabbretti, Elsa

    2007-08-01

    The molecular mechanisms of migraine pain are incompletely understood, although migraine mediators such as NGF and calcitonin gene-related peptide (CGRP) are believed to play an algogenic role. Although NGF block is proposed as a novel analgesic approach, its consequences on nociceptive purinergic P2X receptors of trigeminal ganglion neurons remain unknown. We investigated whether neutralizing NGF might change the function of P2X3 receptors natively coexpressed with NGF receptors on cultured mouse trigeminal neurons. Treatment with an NGF antibody (24 h) decreased P2X3 receptor-mediated currents and Ca2+ transients, an effect opposite to exogenously applied NGF. Recovery from receptor desensitization was delayed by anti-NGF treatment without changing desensitization onset. NGF neutralization was associated with decreased threonine phosphorylation of P2X3 subunits, presumably accounting for their reduced responses and slower recovery. Anti-NGF treatment could also increase the residual current typical of heteromeric P2X2/3 receptors, consistent with enhanced membrane location of P2X2 subunits. This possibility was confirmed with cross-linking and immunoprecipitation studies. NGF neutralization also led to increased P2X2e splicing variant at mRNA and membrane protein levels. These data suggest that NGF controlled plasticity of P2X3 subunits and their membrane assembly with P2X2 subunits. Despite anti-NGF treatment, CGRP could still enhance P2X3 receptor activity, indicating separate NGF- or CGRP-mediated mechanisms to upregulate P2X3 receptors. In an in vivo model of mouse trigeminal pain, anti-NGF pretreatment suppressed responses evoked by P2X3 receptor activation. Our findings outline the important contribution by NGF signaling to nociception of trigeminal sensory neurons, which could be counteracted by anti-NGF pretreatment.

  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.

    PubMed

    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. The role of capsaicin in dermatology.

    PubMed

    Boyd, Katherine; Shea, Sofia M; Patterson, James W

    2014-01-01

    Neurogenic pain and pruritus are the common chief complaints at dermatology office visits. Unfortunately, they are also notoriously difficult conditions to treat. Topical capsaicin used as a single therapy or as an adjuvant offers a low-risk option for patients who do not achieve control on other therapies. This chapter presents the evidence behind topical capsaicin use in dermatologic conditions characterized by neurogenic pain or pruritus, including postherpetic neuralgia, notalgia paresthetica, brachioradial pruritus, lichen simplex chronicus, prurigo nodularis, pruritus ani, pruritus of hemodialysis, aquagenic pruritus, apocrine chromhidrosis, lipodermatosclerosis, alopecia areata, and psoriasis. It presents the most common capsaicin formulations, dosages, and durations of treatment for each condition. Additionally, the chapter addresses various adverse effects and limitations in the use of topical capsaicin in dermatology. PMID:24941674

  1. Somatosensory profiling of intra-oral capsaicin and menthol in healthy subjects.

    PubMed

    Lu, Shengyi; Baad-Hansen, Lene; List, Thomas; Zhang, Zhenting; Svensson, Peter

    2013-02-01

    This study was designed to investigate the effect of surrogate orofacial pain models on the quantitative sensory testing (QST) profile in healthy participants. Capsaicin, menthol, or saline (control) were applied topically onto the gingiva of 15 healthy subjects for 15 min. During application, the subjects rated pain intensity on a score of 0-10, on an electronic visual analog scale (VAS). A standardized intra-oral QST protocol was performed before and immediately after application. Data obtained before and after application were compared using rank-sum tests, and QST profiles were made after Z-transformation. Application of capsaicin caused moderate levels of pain (VAS(peak)  = 6.0 ± 0.7), and application of menthol produced mild levels of pain (VAS(peak)  = 1.8 ± 0.6). Capsaicin induced hypersensitivity to warmth, heat pain and cold pain and hyposensitivity to mechanical stimuli. Menthol induced hypersensitivity to cold and warmth. Saline caused hypersensitivity to heat pain and hyposensitivity to mechanical stimuli. However, somatosensory profiles from Z-scores demonstrated sensory gains regarding warmth detection and heat pain only after application of capsaicin. In conclusion, a standardized battery of QST showed somatosensory changes after application of capsaicin, menthol and saline to the gingiva. However, the Z-score-based profiles may only reflect the most prominent somatosensory changes and thus represent a conservative approach for evaluation of data. PMID:23331421

  2. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction.

    PubMed

    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.

  3. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction

    PubMed Central

    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. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction.

    PubMed

    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

  5. Inhibitory control of nociceptive responses of trigeminal spinal nucleus cells by somatosensory corticofugal projection in rat.

    PubMed

    Malmierca, E; Martin, Y B; Nuñez, A

    2012-09-27

    The caudal division of the trigeminal spinal nucleus (Sp5C) is an important brainstem relay station of orofacial pain transmission. The aim of the present study was to examine the effect of cortical electrical stimulation on nociceptive responses in Sp5C neurons. Extracellular recordings were performed in the Sp5C nucleus by tungsten microelectrodes in urethane-anesthetized Sprague-Dawley rats. Nociceptive stimulation was produced by application of capsaicin cream on the whisker pad or by constriction of the infraorbital nerve. Capsaicin application evoked a long-lasting increase in the spontaneous firing rate from 1.4±0.2 to 3.4±0.6 spikes/s. Non-noxious tactile responses from stimuli delivered to the receptive field (RF) center decreased 5 min. after capsaicin application (from 2.3±0.1 to 1.6±0.1 spikes/stimulus) while responses from the whisker located at the RF periphery increased (from 1.3±0.2 to 2.0±0.1 spikes/stimulus under capsaicin). Electrical train stimulation of the primary (S1) or secondary (S2) somatosensory cortical areas reduced the increase in the firing rate evoked by capsaicin. Also, S1, but not S2, cortical stimulation reduced the increase in non-noxious tactile responses from the RF periphery. Inhibitory cortical effects were mediated by the activation of GABAergic and glycinergic neurons because they were blocked by bicuculline or strychnine. The S1 and S2 cortical stimulation also inhibited Sp5C neurons in animals with constriction of the infraorbital nerve. Consequently, the corticofugal projection from S1 and S2 cortical areas modulates nociceptive responses of Sp5C neurons and may control the transmission of nociceptive sensory stimulus.

  6. Comparison of in vitro metabolism and cytotoxicity of capsaicin and dihydrocapsaicin.

    PubMed

    Halme, Mia; Pesonen, Maija; Salo, Heta; Söderström, Martin; Pasanen, Markku; Vähäkangas, Kirsi; Vanninen, Paula

    2016-01-15

    Capsaicin and dihydrocapsaicin are the major active components in pepper spray products, which are widely used for law enforcement and self-protection. The use of pepper sprays, due to their irreversible and other health effects has been under a strong debate. In this study, we compared metabolism and cytotoxicity of capsaicin and dihydrocapsaicin using human and pig liver cell fractions and human lung carcinoma cell line (A549) in vitro. Metabolites were screened and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Using liver cell fractions, a novel aliphatic hydroxylated metabolite (m/z 322) was detected to dihydrocapsaicin but no structure was found corresponding to capsaicin. Instead, a novel phase I metabolite of capsaicin, corresponding to the structure of aliphatic demethylation and dehydrogenation (m/z 294) was identified. In addition, two novel conjugates, glycine conjugates (m/z 363 and m/z 365) and bi-glutathione (GSH) conjugates (m/z 902 and m/z 904), were identified for both capsaicin and dihydrocapsaicin. The medium of the exposed A549 cells contained ω-hydroxylated (m/z 322) and alkyl dehydrogenated (m/z 304) forms, as well as a glycine conjugate of capsaicin. As to dihydrocapsaicin, an alkyl dehydrogenated (m/z 306) form, a novel alkyl hydroxylated form, and a novel glycine conjugate were found. In A549 cells, dihydrocapsaicin evoked vacuolization and decreased cell viability more efficiently than capsaicin. Furthermore, both compounds induced p53 protein and G1 phase cell cycle arrest. Usefulness of the found metabolites as biomarkers for capsaicinoid exposures will need further investigations with additional toxicity endpoints. PMID:26688344

  7. Comparison of in vitro metabolism and cytotoxicity of capsaicin and dihydrocapsaicin.

    PubMed

    Halme, Mia; Pesonen, Maija; Salo, Heta; Söderström, Martin; Pasanen, Markku; Vähäkangas, Kirsi; Vanninen, Paula

    2016-01-15

    Capsaicin and dihydrocapsaicin are the major active components in pepper spray products, which are widely used for law enforcement and self-protection. The use of pepper sprays, due to their irreversible and other health effects has been under a strong debate. In this study, we compared metabolism and cytotoxicity of capsaicin and dihydrocapsaicin using human and pig liver cell fractions and human lung carcinoma cell line (A549) in vitro. Metabolites were screened and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Using liver cell fractions, a novel aliphatic hydroxylated metabolite (m/z 322) was detected to dihydrocapsaicin but no structure was found corresponding to capsaicin. Instead, a novel phase I metabolite of capsaicin, corresponding to the structure of aliphatic demethylation and dehydrogenation (m/z 294) was identified. In addition, two novel conjugates, glycine conjugates (m/z 363 and m/z 365) and bi-glutathione (GSH) conjugates (m/z 902 and m/z 904), were identified for both capsaicin and dihydrocapsaicin. The medium of the exposed A549 cells contained ω-hydroxylated (m/z 322) and alkyl dehydrogenated (m/z 304) forms, as well as a glycine conjugate of capsaicin. As to dihydrocapsaicin, an alkyl dehydrogenated (m/z 306) form, a novel alkyl hydroxylated form, and a novel glycine conjugate were found. In A549 cells, dihydrocapsaicin evoked vacuolization and decreased cell viability more efficiently than capsaicin. Furthermore, both compounds induced p53 protein and G1 phase cell cycle arrest. Usefulness of the found metabolites as biomarkers for capsaicinoid exposures will need further investigations with additional toxicity endpoints.

  8. Changes in levels of nerve growth factor in nasal secretions after capsaicin inhalation in patients with airway symptoms from scents and chemicals.

    PubMed

    Millqvist, Eva; Ternesten-Hasséus, Ewa; Ståhl, Arne; Bende, Mats

    2005-07-01

    Patients complaining of upper and lower airway symptoms caused by scents and chemicals have previously been shown to have increased cough sensitivity to inhaled capsaicin, but the precise mechanisms behind this reaction are unknown. Hypothesizing that a neurochemical alteration related to sensory hyperreactivity (SHR) of the airway mucosa occurs, we measured levels of nerve growth factor (NGF) in nasal lavage fluid (NAL) before and after capsaicin inhalation provocations and related the capsaicin cough sensitivity to the NGF levels. Thirteen patients with SHR and 14 control subjects were provoked with capsaicin inhalation at three different doses. We measured NGF in NAL before and after provocation and recorded cough and capsaicin-induced symptoms. All subjects demonstrated a dose-dependent cough response to capsaicin inhalation, with a more pronounced effect in patients than in controls. Basal levels of NGF were significantly lower in the patient group than in the control subjects (p < 0.01). After capsaicin provocation, the patients showed a significant increase in NGF (p < 0.01), which was related to capsaicin cough sensitivity. The findings demonstrate that, in patients with airway symptoms induced by scents and chemicals, SHR is real and measurable, demonstrating a pathophysiology in the airways of these patients compared to healthy subjects.

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

    PubMed

    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.

  10. 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.

    PubMed

    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

  11. Inhaled ethanol potentiates the cough response to capsaicin in patients with airway sensory hyperreactivity.

    PubMed

    Millqvist, Eva; Ternesten-Hasséus, Ewa; Bende, Mats

    2008-10-01

    A suggested explanation for airway symptoms induced by chemicals and scents is sensory hyperreactivity (SHR) of airway mucosal nerves. Patients with SHR have increased cough sensitivity to inhaled capsaicin, mediated by transient receptor potential (TRP) ion channels. In animal experiments, some TRP receptors are potentiated by ethanol, which is why in this study, the aim was to evaluate whether a pre-inhalation of ethanol could influence the capsaicin cough response in patients with SHR. Fifteen patients with SHR and 15 healthy controls were provoked on three occasions with two concentrations of inhaled capsaicin. Before each capsaicin provocation, a pre-inhalation of saline or one of two concentrations of ethanol was given in a double-blind, randomized fashion. The participants reacted in a dose-dependent way with cough on the capsaicin inhalations. Among the patients, but not in the control group, pre-inhalation of ethanol increased the cough response dose-dependently. The results suggest that the pathophysiology of SHR is related to airway mucosal TRP receptors in the sensory nerves. In scented products, the combination of ethanol as a solvent and perfume may augment an airway reaction in sensitive individuals.

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

    SciTech Connect

    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.

  13. Historical characterization of trigeminal neuralgia.

    PubMed

    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.

  14. The Brain Mechanisms Underlying the Perception of Pungent Taste of Capsaicin and the Subsequent Autonomic Responses

    PubMed Central

    Kawakami, Shinpei; Sato, Hajime; Sasaki, Akihiro T.; Tanabe, Hiroki C.; Yoshida, Yumiko; Saito, Mitsuru; Toyoda, Hiroki; Sadato, Norihiro; Kang, Youngnam

    2016-01-01

    In a human fMRI study, it has been demonstrated that tasting and ingesting capsaicin activate the ventral part of the middle and posterior short gyri (M/PSG) of the insula which is known as the primary gustatory area, suggesting that capsaicin is recognized as a taste. Tasting and digesting spicy foods containing capsaicin induce various physiological responses such as perspiration from face, salivation, and facilitation of cardiovascular activity, which are thought to be caused through viscero-visceral autonomic reflexes. However, this does not necessarily exclude the possibility of the involvement of higher-order sensory-motor integration between the M/PSG and anterior short gyrus (ASG) known as the autonomic region of the insula. To reveal a possible functional coordination between the M/PSG and ASG, we here addressed whether capsaicin increases neural activity in the ASG as well as the M/PSG using fMRI and a custom-made taste delivery system. Twenty subjects participated in this study, and three tastant solutions: capsaicin, NaCl, and artificial saliva (AS) were used. Group analyses with the regions activated by capsaicin revealed significant activations in the bilateral ASG and M/PSG. The fMRI blood oxygenation level-dependent (BOLD) signals in response to capsaicin stimulation were significantly higher in ASG than in M/PSG regardless of the side. Concomitantly, capsaicin increased the fingertip temperature significantly. Although there was no significant correlation between the fingertip temperatures and BOLD signals in the ASG or M/PSG when the contrast [Capsaicin–AS] or [Capsaicin–NaCl] was computed, a significant correlation was found in the bilateral ASG when the contrast [2 × Capsaicin–NaCl–AS] was computed. In contrast, there was a significant correlation in the hypothalamus regardless of the contrasts. Furthermore, there was a significant correlation between M/PSG and ASG. These results indicate that capsaicin increases neural activity in the

  15. Double peak sensory responses: effects of capsaicin.

    PubMed

    Aprile, I; Tonali, P; Stalberg, E; Di Stasio, E; Caliandro, P; Foschini, M; Vergili, G; Padua, L

    2007-10-01

    The aim of this study is to verify whether degeneration of skin receptors or intradermal nerve endings by topical application of capsaicin modifies the double peak response obtained by submaximal anodal stimulation. Five healthy volunteers topically applied capsaicin to the finger-tip of digit III (on the distal phalanx) four times daily for 4-5 weeks. Before and after local capsaicin applications, we studied the following electrophysiological findings: compound sensory action potential (CSAP), double peak response, sensory threshold and double peak stimulus intensity. Local capsaicin application causes disappearance or decrease of the second component of the double peak, which gradually increases after the suspension of capsaicin. Conversely, no significant differences were observed for CSAP, sensory threshold and double peak stimulus intensity. This study suggests that the second component of the double peak may be a diagnostic tool suitable to show an impairment of the extreme segments of sensory nerve fibres in distal sensory axonopathy in the early stages of damage, when receptors or skin nerve endings are impaired but undetectable by standard nerve conduction studies.

  16. Roles of JNK-1 and p38 in selective induction of apoptosis by capsaicin in ras-transformed human breast epithelial cells.

    PubMed

    Kang, Hye-Jung; Soh, Yunjo; Kim, Mi-Sung; Lee, Eun-Jung; Surh, Young-Joon; Kim, Hyeong-Reh Choi; Kim, Seung Hee; Moon, Aree

    2003-02-10

    Efforts have been made to develop a chemoprevention strategy that selectively triggers apoptosis in malignant cancer cells. Previous studies showed that capsaicin, the major pungent ingredient of red pepper, had differential effect between normal and transformed cells. As an approach to unveil the molecular mechanism by which capsaicin selectively induces apoptosis in transformed cells, we investigated the effect of capsaicin in nontransformed and ras-transformed cells of a common origin: parental (MCF10A) and H-ras-transformed (H-ras MCF10A) human breast epithelial cells. Here, we show that capsaicin selectively induces apoptosis in H-ras-transformed cells but not in their normal cell counterparts. The capsaicin-induced apoptosis, which is dependent on ras transformation, involves the activity of DEVDase (caspase-3 like). In H-ras MCF10A cells, capsaicin treatment markedly activated c-Jun N-terminal protein kinase (JNK)-1 and p38 matigen-activated protein kinase (MAPK) while it deactivated extracellular signal-regulated protein kinases (ERKs). The use of kinase inhibitors and overexpression of dominant-negative forms of MAPKs demonstrated a role of JNK-1 and p38, but not that of ERKs, in apoptosis induced by capsaicin in H-ras-transformed MCF10A cells. Based on the present study, we propose that capsaicin selectively induces apoptosis through modulation of ras-downstream signaling molecules in ras-activated MCF10A cells. Taken in conjunction with the fact that uncontrolled ras activation is probably the most common genetic defect in human cancer cells, our finding may be critical to the chemopreventive potential of capsaicin and for developing a strategy to induce tumor cell-specific apoptosis.

  17. Trigeminal neuralgia: a new therapy?

    PubMed

    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).

  18. Evaluation of surgical procedures for trigeminal neuralgia.

    PubMed Central

    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 surgical procedures. Arguments for and against the use of surgery for trigeminal neuralgia are presented. In addition, the surgical procedures were compared with other treatments for trigeminal neuralgia. PMID:14959906

  19. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    SciTech Connect

    Aubuchon, Adam C.; Chan, Michael D.; Lovato, James F.; Balamucki, Christopher J.; Ellis, Thomas L.; Tatter, Stephen B.; McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G.

    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.

  20. Adaptation to capsaicin within and across days.

    PubMed

    McBurney, D H; Balaban, C D; Christopher, D E; Harvey, C

    1997-02-01

    Subjects judged the time-course of the burn caused by 100 ppm capsaicin applied to the tongue on Day 1 and Day 5. On Days 2-4, they tasted hard candy containing capsaicin. Most subjects did not show adaptation within Day 1, but either plateaued after about 16 min or rose monotonically for the entire 34 min. Intensity was less on Day 5 and levelled off or declined for most subjects. Data were fit to a mathematical model of adaptation. Adaptation across days was accounted for by changes in the gains of the three processes.

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

    PubMed

    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. PMID:26135547

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

    PubMed

    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.

  3. Capsaicin Inhibits Preferentially the NADH Oxidase and Growth of Transformed Cells in Culture

    NASA Astrophysics Data System (ADS)

    Morre, D. James; Chueh, Pin-Ju; Morre, Dorothy M.

    1995-03-01

    A hormone- and growth factor-stimulated NADH oxidase of the mammalian plasma membrane, constitutively activated in transformed cells, was inhibited preferentially in HeLa, ovarian carcinoma, mammary adenocarcinoma, and HL-60 cells, all of human origin, by the naturally occurring quinone analog capsaicin (8-methyl-N-vanillyl-6-noneamide), compared with plasma membranes from human mammary epithelial, rat liver, normal rat kidney cells, or HL-60 cells induced to differentiate with dimethyl sulfoxide. With cells in culture, capsaicin preferentially inhibited growth of HeLa, ovarian carcinoma, mammary adenocarcinoma, and HL-60 cells but was largely without effect on the mammary epithelial cells, rat kidney cells, or HL-60 cells induced to differentiate with dimethyl sulfoxide. Inhibited cells became smaller and cell death was accompanied by a condensed and fragmented appearance of the nuclear DNA, as revealed by fluorescence microscopy with 4',6-diamidino-2-phenylindole, suggestive of apoptosis. The findings correlate capsaicin inhibition of cell surface NADH oxidase activity and inhibition of growth that correlate with capsaicin-induced apoptosis.

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

    PubMed

    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.

  5. The Effect of Capsaicin on Salivary Gland Dysfunction.

    PubMed

    Shin, Yong-Hwan; Kim, Jin Man; Park, Kyungpyo

    2016-01-01

    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. PMID:27347918

  6. The Effect of Capsaicin on Salivary Gland Dysfunction.

    PubMed

    Shin, Yong-Hwan; Kim, Jin Man; Park, Kyungpyo

    2016-01-01

    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.

  7. Incorporation of capsaicin in silicone coatings for enhanced antifouling performance

    NASA Astrophysics Data System (ADS)

    Reddy Jaggari, Karunakar; Zhang Newby, Bi-Min

    2002-03-01

    Successful use of capsaicin as insect and animal repellant propelled us to use it as a possible antifouling agent. Its non-toxic, non-biocidal, non-leaching properties make it a viable alternative to organotin compounds. In order to optimize the anti-fouling performance of the coating, silicone, the most effective foul-release marine coating, was chosen as the carrier. We have incorporated capsaicin into silicone coating, by both bulk entrapment and surface immobilization. Contact angle measurements on capsaicin-incorporated silicone exhibited an increase in wettability, owing to the presence of capsaicin. FTIR study further confirmed the incorporation of capsaicin in silicone. Bacterial attachment studies were conducted using lake Erie water. While bacteria liberally inhabited the control coating, their presence on the capsaicin-incorporated coating was found to be minimal. These preliminary studies indicate that capsaicin incorporated silicone could be a viable environment friendly alternative to currently used antifouling coatings.

  8. Acetylsalicylic acid enhances tachyphylaxis of repetitive capsaicin responses in TRPV1-GFP expressing HEK293 cells.

    PubMed

    Maurer, Kristina; Binzen, Uta; Mörz, Handan; Bugert, Peter; Schedel, Angelika; Treede, Rolf-Detlef; Greffrath, Wolfgang

    2014-03-20

    Since many years acetylsalicylic acid (ASA) is known for its antithrombotic, antiphlogistic and analgesic effects caused by irreversible acetylation of cyclooxygenase. ASA also inhibits capsaicin- and heat-induced responses in cultured dorsal root ganglia (DRG) neurons, suggesting TRPV1 (transient receptor potential channel of the vanilloid receptor family, subtype 1) to be an additional target of ASA. We now studied the effect of ASA on heterologously expressed rat TRPV1 using calcium microfluorimetry. Capsaicin dose-dependently increased intracellular calcium with an EC50 of 0.29 μM in rTRPV1 expressing HEK293 cells. During repetitive stimulation the second response to capsaicin was reduced (53.4 ± 8.3% compared to vehicle control; p<0.005; Student's unpaired t-test) by 1μM ASA, a concentration much below the one needed to inhibit cyclooxygenase (IC50 of 35 μM in thromboxane B2 production assay). In contrast, calcium transients induced by a single stimulus of 0.3 or 1 μM capsaicin were not significantly reduced by 0.3 or 1 μM ASA. These data suggest that ASA increases the tachyphylaxis of rTRPV1 channel activation. Mechanisms are unknown and may be direct by e.g. stabilization of the desensitized state or indirect via inhibition of intracellular signaling pathways e.g. of the mitogen-activated protein kinase family (MAPK/ERK).

  9. Gender differences in itch and pain-related sensations provoked by histamine, cowhage and capsaicin.

    PubMed

    Hartmann, Elisabeth M; Handwerker, Hermann O; Forster, Clemens

    2015-01-01

    Cowhage, capsaicin and histamine, all applied via spicules, were used to induce itch and pain-related sensations in 15 male and 15 female subjects. Sensory qualities were assessed by questionnaire; intensities and time courses of the "itching" and "burning" sensation were measured alternately, but continuously on a VAS. In addition, axon reflexes were assessed. Only histamine and capsaicin produced a clear axon reflex flare (histamine > capsaicin, male = female). The 3 types of spicules caused mixed burning and itching sensations with different time courses. In the beginning burning prevailed, in the following minutes histamine induced mostly itching, capsaicin predominantly burning, cowhage both sensory components equally. Female subjects experienced more pain-related sensations (questionnaire), and their ratings leaned more toward burning than those of males. These findings indicate that the mixed itching and burning sensations are differentially processed by both genders. No indications were found for gender specific differential processing in the primary afferents as reflected by nearly identical flare responses. PMID:24819823

  10. Trigeminal trophic syndrome with histopathologic correlation.

    PubMed

    Dolohanty, Lindsey B; Richardson, Steven J; Herrmann, David N; Markman, John; Mercurio, Mary Gail

    2015-03-01

    We present the case of a 49-year-old woman with trigeminal trophic syndrome (TTS), also known as trophic trigeminal neuralgia, trigeminal neurotrophic ulceration, and/or trigeminal neuropathy with nasal ulceration. Our case represents an uncommon report of intractable itching and chronic pain associated with TTS. Emphasis was placed on skin biopsy histology, which revealed no neuronal innervation of the affected scalp despite reports of intractable itching and chronic pain. Trigeminal trophic syndrome of the V1 branch of the trigeminal nerve secondary to herpes zoster (HZ) with correlated histology is described. This article provides a discussion of TTS and correlated histology as well as a brief discussion of intractable itching and postherpetic neuralgia.

  11. Topographical differences in the trigeminal sensitivity of the human nasal mucosa.

    PubMed

    Scheibe, Mandy; Zahnert, Thomas; Hummel, Thomas

    2006-09-18

    The aim of the study was to investigate differences in the distribution of intranasal trigeminal receptors in humans using an electrophysiological measure of trigeminally induced activation, the negative mucosa potential. A total of 29 young, healthy volunteers participated, results were on the basis of data from 18 participants. The trigeminal irritant CO2 was presented using a computer-controlled olfactometer. Negative mucosa potential recording sites included the anterior olfactory cleft, the anterior septum, and the lower turbinate. Lowest amplitudes of the negative mucosa potential were found in the olfactory cleft, maximum amplitudes at the septum. Intranasal measurements of CO2 concentrations suggested that these differences were not due to the intranasal distribution of CO2. These results are compatible with the idea that the trigeminal system acts as a sentinel of the human airways.

  12. Transoval trigeminal cisternography and glycerol injection in trigeminal neuralgia.

    PubMed

    Van de Velde, C; Smeets, P; Caemaert, J; Van de Velde, E

    1989-04-01

    In a series of 25 consecutive patients suffering from essential trigeminal neuralgia, transoval glycerol injection following Håkanson was performed in order to alleviate the pain attacks. This treatment proved to be successful in 76% of the patients. No major side-effects were reported. Authors stress the importance of a precise cisternography of Meckel's cave to ascertain the correct position of the needle, before injecting the glycerol. They discuss their mode of conducting the examination in using a conventional radiologic set-up. Transoval glycerol injection is a valuable interventional radiologic procedure and has to be taken into account as an alternative treatment of essential trigeminal neuralgia, especially when current therapeutic measures have failed. PMID:2788644

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

    PubMed

    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.

  14. Morphine Increases Acetylcholine Release in the Trigeminal Nuclear Complex

    PubMed Central

    Zhu, Zhenghong; Bowman, Heather R.; Baghdoyan, Helen A.; Lydic, Ralph

    2008-01-01

    Study Objectives: The trigeminal nuclear complex (V) contains cholinergic neurons and includes the principal sensory trigeminal nucleus (PSTN) which receives sensory input from the face and jaw, and the trigeminal motor nucleus (MoV) which innervates the muscles of mastication. Pain associated with pathologies of V is often managed with opioids but no studies have characterized the effect of opioids on acetylcholine (ACh) release in PSTN and MoV. Opioids can increase or decrease ACh release in brainstem nuclei. Therefore, the present experiments tested the 2-tailed hypothesis that microdialysis delivery of opioids to the PSTN and MoV significantly alters ACh release. Design: Using a within-subjects design and isoflurane-anesthetized Wistar rats (n = 53), ACh release in PSTN during microdialysis with Ringer's solution (control) was compared to ACh release during dialysis delivery of the sodium channel blocker tetrodotoxin, muscarinic agonist bethanechol, opioid agonist morphine, mu opioid agonist DAMGO, antagonists for mu (naloxone) and kappa (nor-binaltorphimine; nor-BNI) opioid receptors, and GABAA antagonist bicuculline. Measurements and Results: Tetrodotoxin decreased ACh, confirming action potential-dependent ACh release. Bethanechol and morphine caused a concentration-dependent increase in PSTN ACh release. The morphine-induced increase in ACh release was blocked by nor-BNI but not by naloxone. Bicuculline delivered to the PSTN also increased ACh release. ACh release in the MoV was increased by morphine, and this increase was not blocked by naloxone or nor-BNI. Conclusions: These data comprise the first direct measures of ACh release in PSTN and MoV and suggest synaptic disinhibition as one possible mechanism by which morphine increases ACh release in the trigeminal nuclei. Citation: Zhu Z; Bowman HR; Baghdoyan HA; Lydic R. Morphine increases acetylcholine release in the trigeminal nuclear complex. SLEEP 2008;31(12):1629–1637. PMID:19090318

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

    PubMed

    Holst, H; Arendt-Nielsen, L; Mosbech, H; Vesterhauge, S; Elberling, J

    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 between groups in age, body mass index or pulmonary function. The median C5 were 129 micromol/L (control group), 48 micromol/L (multiple chemical sensitivity patients), 32 micromol/L (eczema patients). The reporting of lower airway symptoms from odorous chemicals was significantly (p<0.05) correlated to increased cough reflex sensitivity to capsaicin, independent of patient group or co-existence of asthma. The results suggest that the C5 is not reliable for diagnosing MCS but C5 can be used to verify presence of lower airway symptoms related to odorous chemicals.

  16. Mechanisms of trigeminal nerve injuries.

    PubMed

    Ziccardi, V B; Assael, L A

    2001-09-01

    Injuries to the trigeminal nerve branches are a known and accepted risk in oral and maxillofacial surgery. It is prudent for the practitioner to explain the risks to patients as part of the informed consent process and to recognize and document the presence of nerve injury postoperatively. Patients should be referred to a surgeon experienced in microsurgical techniques in a timely fashion for evaluation and possible surgical intervention if an injury is not resolving.

  17. Multimodality Management of Trigeminal Schwannomas.

    PubMed

    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. PMID:27441164

  18. Rehabilitation of the trigeminal nerve

    PubMed Central

    Iro, Heinrich; Bumm, Klaus; Waldfahrer, Frank

    2005-01-01

    When it comes to restoring impaired neural function by means of surgical reconstruction, sensory nerves have always been in the role of the neglected child when compared with motor nerves. Especially in the head and neck area, with its either sensory, motor or mixed cranial nerves, an impaired sensory function can cause severe medical conditions. When performing surgery in the head and neck area, sustaining neural function must not only be highest priority for motor but also for sensory nerves. In cases with obvious neural damage to sensory nerves, an immediate neural repair, if necessary with neural interposition grafts, is desirable. Also in cases with traumatic trigeminal damage, an immediate neural repair ought to be considered, especially since reconstructive measures at a later time mostly require for interposition grafts. In terms of the trigeminal neuralgia, commonly thought to arise from neurovascular brainstem compression, a pharmaceutical treatment is considered as the state of the art in terms of conservative therapy. A neurovascular decompression of the trigeminal root can be an alternative in some cases when surgical treatment is sought after. Besides the above mentioned therapeutic options, alternative treatments are available. PMID:22073060

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

    PubMed

    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. PMID:25307998

  20. Bioavailability of capsaicin and its implications for drug delivery

    PubMed Central

    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

    2014-01-01

    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. PMID:25307998

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

    PubMed

    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. Capsaicin and its analogues: structure-activity relationship study.

    PubMed

    Huang, X-F; Xue, J-Y; Jiang, A-Q; Zhu, H-L

    2013-01-01

    Capsaicin, the main ingredient responsible for the hot pungent taste of chilli peppers, is an alkaloid found in the Capsicum family. Capsaicin was traditionally used for muscular pain, headaches, to improve circulation and for its gastrointestinal protective effects. It was also commonly added to herbal formulations because it acts as a catalyst for other herbs and aids in their absorption. In addition, capsaicin and other capsaicinoid compounds showed strong evidence of having promising potential in the fight against many types of cancer. The mechanism of action of capsaicin has been extensively studied over the past decade. It has been established that capsaicin binds to the transient receptor potential vanilloid 1 receptor which was expressed predominantly by sensory neurons. And many analogues of capsaicin have been synthesized and evaluated for diverse bioactivities. In this review, we will attempt to summarize the biology and structure-activity relationship of capsaicinoids.

  3. Depletion of substance P, neurokinin A and calcitonin gene-related peptide from the contralateral and ipsilateral caudal trigeminal nucleus following unilateral electrical stimulation of the trigeminal ganglion; a possible neurophysiological and neuroanatomical link to generalized head pain.

    PubMed

    Samsam, M; Coveñas, R; Csillik, B; Ahangari, R; Yajeya, J; Riquelme, R; Narváez, J A; Tramu, G

    2001-03-01

    Primary trigeminal neurons of the trigeminal ganglion (TG) innervate major parts of the face and head, including the dura. Electrical stimulation of the TG at specific parameters, can activate its nociceptive neurons and may serve as an experimental pain model. Markowitz [J. Neurosci. 7 (1987) 4129] reported that electrical stimulation of the trigeminal ganglion (TG) causes extravasation of plasma proteins from venules of the trigeminally innervated domain possibly due to the release of vasoactive substances. Neurogenic inflammation (vasodilatation, plasma protein extravasation, release of vasoactive peptides) in dura may serve as one of the possible pathomechanisms underlying vascular head pain [Moskowitz, Ann. Neurol. 16 (1984) 157]. We performed a unilateral electrical stimulation (7.5 Hz, 5 ms, 0.8-1.4 mA for 5 min) of the TG in rat, to induce a neurogenic inflammation in the peripheral trigeminal domain including the dura, looking for calcitonin gene related peptide (CGRP), substance P (SP) and neurokinin A (NKA) immunoreactivity (IR) in the caudal trigeminal nucleus (CTN) into which massive central trigeminal processes terminate. Here, we show patchy depletion(s) of CGRP-, SP- and NKA-IRs in the contralateral CTN of the rat in addition to their ipsilateral depletion. Such depletion is due to the release of these neuropeptides in the CTN leading to the activation of bilateral trigeminal nociceptive pathway. These data afford the possibility that under specific frequencies (which may roughly correlate to the intensity of the painful stimulus) and/or specific intensities (may correlate to specific areas of the peripheral trigeminal domain) of stimulation, activation of one side of the TG may activate bilateral trigeminal nociceptive pathway leading to the perception of an ill localized/generalized pain or headache rather than a unilateral one.

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

    PubMed

    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

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

    PubMed

    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

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

    PubMed

    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.

  7. Neuronal NTPDase3 Mediates Extracellular ATP Degradation in Trigeminal Nociceptive Pathway

    PubMed Central

    Ma, Lihua; Trinh, Thu; Ren, Yanfang; Dirksen, Robert T.; Liu, Xiuxin

    2016-01-01

    ATP induces pain via activation of purinergic receptors in nociceptive sensory nerves. ATP signaling is terminated by ATP hydrolysis mediated by cell surface-localized ecto-nucleotidases. Using enzymatic histochemical staining, we show that ecto-ATPase activity is present in mouse trigeminal nerves. Using immunofluorescence staining, we found that ecto-NTPDase3 is expressed in trigeminal nociceptive neurons and their projections to the brainstem. In addition, ecto-ATPase activity and ecto-NTPDase3 are also detected in the nociceptive outermost layer of the trigeminal subnucleus caudalis. Furthermore, we demonstrate that incubation with anti-NTPDase3 serum reduces extracellular ATP degradation in the nociceptive lamina of both the trigeminal subnucleus caudalis and the spinal cord dorsal horn. These results are consistent with neuronal NTPDase3 activity modulating pain signal transduction and transmission by affecting extracellular ATP hydrolysis within the trigeminal nociceptive pathway. Thus, disruption of trigeminal neuronal NTPDase3 expression and localization to presynaptic terminals during chronic inflammation, local constriction and injury may contribute to the pathogenesis of orofacial neuropathic pain. PMID:27706204

  8. [Capsaicin in treatment of neuropathic pain].

    PubMed

    Kamchatnov, P R; Evzelman, M A; Abusueva, B A; Volkov, A I

    2014-01-01

    Treatment of neuropathic pain (NP) is a serious medical problem. Antiepileptic drugs and antidepressants, used to relief pain, act on the central pain mechanisms and cause several side-effects, thus substantially restricting possibilities of their clinical application.At the same time, NP often has a peripheral component. Ligand-associated channels, including vanilloid receptors TRPV1, play a key role in the development of regional NP syndromes. Capsaicin, a component of chili pepper and several other plants, is a highly selective ligand of TRPV1 receptors and has long been used in treatment of pain syndromes. However, its using is limited by short-term action and relatively low efficacy. Recently it has been shown that the local use of single high doses of capsaicin during 30-60 min causes a marked stable(> 12 weeks) effect. The decrease in NP (>50%) is seen in about half of patients. Current studies will allow to single out groups of patients with the maximal treatment effect of capsaicin. PMID:25629137

  9. Simulated microgravity [bed rest] has little influence on taste, odor or trigeminal sensitivity

    NASA Technical Reports Server (NTRS)

    Vickers, Z. M.; Rice, B. L.; Rose, M. S.; Lane, H. W.

    2001-01-01

    Anecdotal evidence suggests that astronauts' perceptions of foods in space flight may differ from their perceptions of the same foods on Earth. Fluid shifts toward the head experienced in space may alter the astronauts' sensitivity to odors and tastes, producing altered perceptions. Our objective was to determine whether head-down bed rest, which produces similar fluid shifts, would produce changes in sensitivity to taste, odor or trigeminal sensations. Six subjects were rested three times prior to bed rest, three times during bed rest and two times after bed rest to determine their threshold sensitivity to the odors isoamylbutyrate and menthone, the tastants sucrose, sodium chloride, citric acid, quinine and monosodium glutamate, and to capsaicin. Thresholds were measured using a modified staircase procedure. Self-reported congestion was also recorded at each test time. Thresholds for monosodium glutamate where slightly higher during bed rest. None of the other thresholds were altered by bed rest.

  10. Altered thermal grill response and paradoxical heat sensations after topical capsaicin application.

    PubMed

    Schaldemose, Ellen L; Horjales-Araujo, Emilia; Svensson, Peter; Finnerup, Nanna B

    2015-06-01

    The thermal grill illusion, where interlaced warm and cold bars cause an unusual burning sensation, and paradoxical heat sensations (PHS), where cold is perceived as warm when alternating warm and cold, are examples of a complex integration of thermal sensations. Here, we investigated the effect of sensitization of heat-sensitive neurons on cold and warm integration. We examined thermal thresholds, PHS, and warm, cold, and pain sensations to alternating cold (10°C) and warm (40°C) bars (the thermal grill [TG]) in the primary area (application site) after topical application with capsaicin and vehicle control (ethanol) on the volar forearms in randomized order in 80 healthy participants. As expected, capsaicin induced heat allodynia and hyperalgesia and decreased cold and cold pain sensation. In addition, we found that after capsaicin application, the TG caused less pain and burning than the 40°C bars alone in contrast to the control side where the TG caused more pain and burning, consistent with the thermal grill illusion. In both situations, the pain intensity during the TG correlated inversely with both cold and warm pain thresholds but not with detection thresholds. Paradoxical heat sensation was only seen in 3 participants after control application but in 19 participants after capsaicin. Those with PHS after capsaicin application had higher detection thresholds to both cold and warm than those without PHS, but there was no difference in thermal pain threshold. These results suggest that a complex cross talk among several cold and warm sensitive pathways shapes thermal perception. PMID:25782365

  11. Altered thermal grill response and paradoxical heat sensations after topical capsaicin application.

    PubMed

    Schaldemose, Ellen L; Horjales-Araujo, Emilia; Svensson, Peter; Finnerup, Nanna B

    2015-06-01

    The thermal grill illusion, where interlaced warm and cold bars cause an unusual burning sensation, and paradoxical heat sensations (PHS), where cold is perceived as warm when alternating warm and cold, are examples of a complex integration of thermal sensations. Here, we investigated the effect of sensitization of heat-sensitive neurons on cold and warm integration. We examined thermal thresholds, PHS, and warm, cold, and pain sensations to alternating cold (10°C) and warm (40°C) bars (the thermal grill [TG]) in the primary area (application site) after topical application with capsaicin and vehicle control (ethanol) on the volar forearms in randomized order in 80 healthy participants. As expected, capsaicin induced heat allodynia and hyperalgesia and decreased cold and cold pain sensation. In addition, we found that after capsaicin application, the TG caused less pain and burning than the 40°C bars alone in contrast to the control side where the TG caused more pain and burning, consistent with the thermal grill illusion. In both situations, the pain intensity during the TG correlated inversely with both cold and warm pain thresholds but not with detection thresholds. Paradoxical heat sensation was only seen in 3 participants after control application but in 19 participants after capsaicin. Those with PHS after capsaicin application had higher detection thresholds to both cold and warm than those without PHS, but there was no difference in thermal pain threshold. These results suggest that a complex cross talk among several cold and warm sensitive pathways shapes thermal perception.

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

    PubMed Central

    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

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

    PubMed

    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. PMID:15927376

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

    PubMed

    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.

  15. Antimicrobial and Anti-Virulence Activity of Capsaicin Against Erythromycin-Resistant, Cell-Invasive Group A Streptococci.

    PubMed

    Marini, Emanuela; Magi, Gloria; Mingoia, Marina; Pugnaloni, Armanda; Facinelli, Bruna

    2015-01-01

    Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of Capsicum plants (chili 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

  16. Antimicrobial and Anti-Virulence Activity of Capsaicin Against Erythromycin-Resistant, Cell-Invasive Group A Streptococci

    PubMed Central

    Marini, Emanuela; Magi, Gloria; Mingoia, Marina; Pugnaloni, Armanda; Facinelli, Bruna

    2015-01-01

    Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of Capsicum plants (chili 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

  17. Antimicrobial and Anti-Virulence Activity of Capsaicin Against Erythromycin-Resistant, Cell-Invasive Group A Streptococci.

    PubMed

    Marini, Emanuela; Magi, Gloria; Mingoia, Marina; Pugnaloni, Armanda; Facinelli, Bruna

    2015-01-01

    Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of Capsicum plants (chili 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

    PubMed Central

    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. PMID:26492045

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

    PubMed

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

    PubMed

    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

  1. Capsaicin: From Plants to a Cancer-Suppressing Agent.

    PubMed

    Chapa-Oliver, Angela M; Mejía-Teniente, Laura

    2016-01-01

    Capsaicinoids are plant secondary metabolites, capsaicin being the principal responsible for the pungency of chili peppers. It is biosynthesized through two pathways involved in phenylpropanoid and fatty acid metabolism. Plant capsaicin concentration is mainly affected by genetic, environmental and crop management factors. However, its synthesis can be enhanced by the use of elicitors. Capsaicin is employed as food additive and in pharmaceutical applications. Additionally, it has been found that capsaicin can act as a cancer preventive agent and shows wide applications against various types of cancer. This review is an approach in contextualizing the use of controlled stress on the plant to increase the content of capsaicin, highlighting its synthesis and its potential use as anticancer agent. PMID:27472308

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

    PubMed

    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. PMID:26456215

  3. Capsaicin: From Plants to a Cancer-Suppressing Agent.

    PubMed

    Chapa-Oliver, Angela M; Mejía-Teniente, Laura

    2016-07-27

    Capsaicinoids are plant secondary metabolites, capsaicin being the principal responsible for the pungency of chili peppers. It is biosynthesized through two pathways involved in phenylpropanoid and fatty acid metabolism. Plant capsaicin concentration is mainly affected by genetic, environmental and crop management factors. However, its synthesis can be enhanced by the use of elicitors. Capsaicin is employed as food additive and in pharmaceutical applications. Additionally, it has been found that capsaicin can act as a cancer preventive agent and shows wide applications against various types of cancer. This review is an approach in contextualizing the use of controlled stress on the plant to increase the content of capsaicin, highlighting its synthesis and its potential use as anticancer agent.

  4. Capsaicin modulates proliferation, migration, and activation of hepatic stellate cells.

    PubMed

    Bitencourt, Shanna; Mesquita, Fernanda; Basso, Bruno; Schmid, Júlia; Ferreira, Gabriela; Rizzo, Lucas; Bauer, Moises; Bartrons, Ramon; Ventura, Francesc; Rosa, Jose Luis; Mannaerts, Inge; van Grunsven, Leo Adrianus; Oliveira, Jarbas

    2014-03-01

    Capsaicin, the active component of chili pepper, has been reported to have antiproliferative and anti-inflammatory effects on a variety of cell lines. In the current study, we aimed to investigate the effects of capsaicin during HSC activation and maintenance. Activated and freshly isolated HSCs were treated with capsaicin. Proliferation was measured by incorporation of EdU. Cell cycle arrest and apoptosis were investigated using flow cytometry. The migratory response to chemotactic stimuli was evaluated by a modified Boyden chamber assay. Activation markers and inflammatory cytokines were determined by qPCR, immunocytochemistry, and flow cytometry. Our results show that capsaicin reduces HSC proliferation, migration, and expression of profibrogenic markers of activated and primary mouse HSCs. In conclusion, the present study shows that capsaicin modulates proliferation, migration, and activation of HSC in vitro. PMID:23955514

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

    SciTech Connect

    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.

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

    PubMed

    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.

  7. Overview and History of Trigeminal Neuralgia.

    PubMed

    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. PMID:27324994

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

    PubMed

    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. PMID:26643391

  9. [Sensitivity of cough with capsaicin in smokers].

    PubMed

    Yildirim, Cetin Aydin; Celik, Pinar; Havlucu, Yavuz; Coşkun, Evşen; Yorgancioğlu, Arzu; Sakar, Ayşin; Dinç, Gönül

    2008-01-01

    In this study, effect of long term smoking on sensitivity of cough reflex was investigated. Healthy, current smoker male and female was evaluated by capsaicin cough challenge test and they were compared with healthy, non-smoker persons with similar age and gender, prospectively. In current smokers, there were 50 male and 39 female, in non-smoker control group, there were 20 male and 21 female. Mean and log C5 dosage in current smoker and non-smoker groups and mean and log C5 dosage in current smoker according to gender were calculated by using Mann-Whitney U-test. Results of capsaicin cough challenge test in current and non-smoker groups were evaluated by using Pearson Chi-Square test and Fisher's Exact test. In current smokers comparison of results of capsaicin cough challenge test with smoking history (age with first smoking, duration, pocket year and smoking per day) was evaluated by using Mann-Whitney U-test. Mean C5 and mean log C5 dosage were found decreased in current smokers when they were compared to control group (p< 0.00). In current smoker group mean C5 and mean log C5 dosage were found decreased in male (p< 0.002). When the results of capsaicin cough challenge test were compared between current smoker and control groups, sensitivity of cough reflex in concentration with 0.49, 0.98, 1.95, 3.9, 7.8, 15.6 microM was significantly decreased in current smoker group. Also there was a significant correlation between concentration with 0.98, 1.95, 3.9, 7.8, 15.6, 31.2 microM, and duration of smoking and pocket year of smoking. Also there was a correlation between concentration with 15.6, 31.2, 62.5, 125 microM and smoking per day. This results were correlated with hypothesis about inhibition of C-fibers with nicotin or decrease of C-fibers' sensitivity due to induction of neuropeptide wasting. PMID:18330750

  10. Treatment of notalgia paresthetica with capsaicin.

    PubMed

    Leibsohn, E

    1992-05-01

    Twenty-four patients with notalgia paresthetica were treated with topical capsaicin (Zostrix) in a concentration of 0.025 percent for four months. In approximately 70 percent of the patients who remained in the study, relief of pruritus was achieved up to the 90 percent level. In the majority of these patients pruritus returned when use of the medication was stopped. The history, causes, and prevalence of the condition are reviewed. This treatment is the first described that is relatively effective. PMID:1521492

  11. Capsaicin-mediated tNOX (ENOX2) up-regulation enhances cell proliferation and migration in vitro and in vivo.

    PubMed

    Liu, Nei-Chi; Hsieh, Pei-Fang; Hsieh, Ming-Kun; Zeng, Zih-Ming; Cheng, Hsiao-Ling; Liao, Jiunn-Wang; Chueh, Pin Ju

    2012-03-14

    Cancer chemoprevention is employed to block or reverse the progression of malignancies. To date, several thousands of agents have been found to possess chemopreventative activity, one of which is capsaicin, a component of chili peppers that exhibits antigrowth activity against various cancer cell lines. However, the role of capsaicin in tumorigenesis remains controversial because both cancer prevention and promotion have been proposed. Here, we made the unexpected discovery that treatment with low concentrations of capsaicin up-regulates tNOX (tumor-associated NADH oxidase) expression in HCT116 human colon carcinoma cells in association with enhanced cell proliferation and migration, as evidenced by down-regulation of epithelial markers and up-regulation of mesenchymal markers. Importantly, tNOX-knockdown in HCT116 cells by RNA interference reversed capsaicin-induced cell proliferation and migration in vitro and decreased tumor growth in vivo. Collectively, these findings provide a basis for explaining the tumor-promoting effect of capsaicin and might imply that caution should be taken when using capsaicin as a chemopreventive agent. PMID:22353011

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

    PubMed

    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.

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

    PubMed

    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.

  14. A randomized, double-blind, placebo-controlled trial of injected capsaicin for pain in Morton's neuroma.

    PubMed

    Campbell, Claudia M; Diamond, Eric; Schmidt, William K; Kelly, Margaret; Allen, Robert; Houghton, William; Brady, Kerrie L; Campbell, James N

    2016-06-01

    Intermetatarsal neuroma or Morton's neuroma is a painful condition of the foot resulting from an entrapment of the common digital nerve typically in the third intermetatarsal space. The pain can be severe and especially problematic with walking. Treatment options are limited and surgery may lead to permanent numbness in the toes. Capsaicin, the pungent ingredient of hot peppers, produces analgesia by inducing retraction of nociceptive afferents from the area of innervation and is effective in treating certain neuropathic pain disorders. A randomized double-blind placebo-controlled study was conducted to test the efficacy, tolerability, and safety of a single 0.1 mg dose of capsaicin vs placebo injected into the region of the neuroma. A total of 58 subjects diagnosed with Morton's neuroma with foot pain ≥4 (0-10 numerical pain rating scale) were injected with 2 mL of lidocaine into the intermetatarsal space proximal to the neuroma to provide local anesthesia. After 5 minutes, 0.1 mg capsaicin or placebo was injected into the intermetatarsal space containing the painful neuroma. Average foot pain was rated for 2 weeks before through 4 weeks after injection. At weeks 1 and 4, the decrease in pain was significantly greater in the subjects treated with capsaicin (P = 0.021 and P = 0.019, respectively). A trend toward significance was noted at weeks 2 and 3. Improvements in functional interference scores and reductions in oral analgesic use were also seen in the capsaicin-treated group. These findings suggest that injection of capsaicin is an efficacious treatment option for patients with painful intermetatarsal neuroma.

  15. Tumor cell growth inhibition is correlated with levels of capsaicin present in hot peppers.

    PubMed

    Dou, Dan; Ahmad, Aamir; Yang, Huanjie; Sarkar, Fazlul H

    2011-01-01

    There are conflicting reports with regard to the value of hot peppers and their primary active component compound, capsaicin, as an anticancer agent. We tested extracts from a number of peppers and found them to induce significant growth arrest and apoptosis in human breast and leukemia cancer cell lines in vitro with no significant effect on normal breast epithelial cells. Further, cell growth inhibition and cell death induction were positively correlated with the capsaicin content (based on the Scoville scale) of the peppers, and the hydroxyl radical scavenger thiourea significantly inhibited the activity of pepper extracts, suggesting the involvement of free radicals in mediating the biological activity of the pepper extracts. These results suggest a potential use of pepper extracts as anticancer agents.

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

    PubMed Central

    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

  17. Aspergillus granuloma of the trigeminal ganglion

    PubMed Central

    Wiles, C M; Kocen, R S; Symon, L; Scaravilli, F

    1981-01-01

    A patient is described with aspergillus flavus granuloma of the trigeminal ganglion. The patient was effectively treated by surgical excision of most of the infected tissue followed by intensive chemotherapy with amphotericin B and flucytosine. Images PMID:6973615

  18. Effective Management of Trigeminal Neuralgia by Neurostimulation

    PubMed Central

    Abd-Elsayed, Alaa A.; Grandhi, Ravi; Sachdeva, Harsh

    2015-01-01

    Background Treatment of trigeminal neuralgia can be challenging for many physicians; patients who do not respond to conventional treatments and traditional surgical approaches often continue to suffer with pain. The peripheral nerve stimulator (PNS) has been used to treat many chronic pain conditions, but few reports exist about its use to treat trigeminal neuralgia. Case Report We present the case of a patient with trigeminal neuralgia resistant to conventional techniques of pain management. Conservative pain management was attempted but was ineffective. As a result, a PNS was placed with minimally invasive surgery. Pain scores were recorded before and after the procedure, and the patient reported complete resolution of her pain. Conclusion PNS implantation can be a safe and effective method to treat trigeminal neuralgia. More research is needed to define its mechanism of action. PMID:26130986

  19. Atypical Trigeminal Neuralgia Secondary to Meningioma

    PubMed Central

    Niwant, Premeshwar; Motwani, Mukta; Naik, Sushil

    2015-01-01

    Trigeminal neuralgia is a disorder of the fifth cranial nerve that causes episodes of intense, stabbing, electric shock-like pain that lasts from few seconds to few minutes in the areas of the face where the branches of the nerve are distributed. More than one nerve branch can be affected by the disorder. We report an unusual case of trigeminal neuralgia affecting right side of face presenting atypical features of neuralgia and not responding to the usual course of treatment. The magnetic resonance imaging study of brain revealed a large extra-axial mass involving right cerebellopontine angle region causing moderate pressure effect on trigeminal nerve and brain stem. The aim of this case report is to show a tumor of cerebellopontine angle, presenting clinically as atypical trigeminal neuralgia. PMID:26664753

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

    PubMed

    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.

  1. Perception of specific trigeminal chemosensory agonists

    PubMed Central

    Frasnelli, J; Albrecht, J; Bryant, B; Lundström, JN

    2011-01-01

    The intranasal trigeminal system is a third chemical sense in addition to olfaction and gustation. As opposed to smell and taste, we still lack knowledge on the relationship between receptor binding and perception for the trigeminal system. We therefore investigated the sensitivity of the intranasal trigeminal system towards agonists of the trigeminal receptors TRPM8 and TRPA1 by assessing subjects’ ability to identify which nostril has been stimulated in a monorhinal stimulation design. We summed the number of correct identifications resulting in a lateralization score. Stimuli were menthol (activating TRPM8 receptors), eucalyptol (TRPM8), mustard oil (TRPA1) and two mixtures thereof (menthol/eucalyptol and menthol/mustard oil). In addition, we examined the relationship between intensity and lateralization scores and investigated whether intensity evaluation and lateralization scores of the mixtures show additive effects. All stimuli were correctly lateralized significantly above chance. Across subjects the lateralization scores for single compounds activating the same receptor showed a stronger correlation than stimuli activating different receptors. Although single compounds were isointense, the mixture of menthol and eucalyptol (activating only TRPM8) was perceived as weaker and was lateralized less accurately than the mixture of menthol and mustard oil (activating both TRPM8 and TRPA1) suggesting suppression effects in the former mixture. In conclusion, sensitivity of different subpopulations of trigeminal sensory neurons seems to be related, but only to a certain degree. The large coherence in sensitivity between various intranasal trigeminal stimuli suggests that measuring sensitivity to one single trigeminal chemical stimulus may be sufficient to generally assess the trigeminal system’s chemosensitivity. Further, for stimuli activating the same receptor a mixture suppression effect appears to occur similar to that observed in the other chemosensory

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

    PubMed

    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.

  3. Trigeminal neuralgia--an update.

    PubMed

    Türp, J C; Gobetti, J P

    2000-04-01

    The purpose of this article is to give a concise review of the diagnosis and management of trigeminal neuralgia (TN), with particular emphasis on idiopathic TN and symptomatic TN. The clinical characteristics of both conditions are presented, and the suspected underlying etiologies are discussed. Because it is crucial for clinicians to be able to rule out pain unrelated to TN, a list of differential diagnoses is presented. The authors stress that the diagnosis of TN is made clinically; however, diagnostic imaging may be indicated in selected cases. Current pharmacological and neurosurgical options for the management of TN are discussed in detail. In light of the popularity of unconventional treatments in the United States, the value of acupuncture and homeopathy, both of which have been suggested by some authors for the treatment of TN, is critically assessed. PMID:11199681

  4. Capsaicin stimulates the non-store-operated Ca{sup 2+} entry but inhibits the store-operated Ca{sup 2+} entry in neutrophils

    SciTech Connect

    Wang, J.-P. . E-mail: w1994@vghtc.gov.tw; Tseng, C.-S.; Sun, S.-P.; Chen, Y.-S.; Tsai, C.-R.; Hsu, M.-F.

    2005-12-01

    Rat neutrophils express the mRNA encoding for transient receptor potential (TRP) V1. However, capsaicin-stimulated [Ca{sup 2+}]{sub i} elevation occurred only at high concentrations ({>=}100 {mu}M). This response was substantially decreased in a Ca{sup 2+}-free medium. Vanilloids displayed similar patterns of Ca{sup 2+} response with the rank order of potency as follows: scutigeral>resiniferatoxin>capsazepine>capsaicin=olvanil>isovelleral. Arachidonyl dopamine (AAD), an endogenous ligand for TRPV1, failed to desensitize the subsequent capsaicin challenge. Capsaicin-induced Ca{sup 2+} response was not affected by 8-bromo-cyclic ADP-ribose (8-Br-cADPR), the ryanodine receptor blocker, but was slightly attenuated by 1-[6-[17{beta}-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,= 5-dione (U-73122), the inhibitor of phospholipase C-coupled processes, 1-[{beta}-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365), the blocker of receptor-gated and store-operated Ca{sup 2+} (SOC) channels, 2-aminoethyldiphenyl borate (2-APB), the blocker of D-myo-inositol 1,4,5-trisphospahte (IP{sub 3}) receptor and Ca{sup 2+} influx, and by ruthenium red, a blocker of TRPV channels, and enhanced by the Ca{sup 2+} channels blocker, cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL-12330A) and Na{sup +}-deprivation. In addition, capsaicin had no effect on the plasma membrane Ca{sup 2+}-ATPase activity or the production of nitric oxide (NO) and reactive oxygen intermediates (ROI) or on the total thiols content. Capsaicin ({>=}100 {mu}M) inhibited the cyclopiazonic acid (CPA)-induced store-operated Ca{sup 2+} entry (SOCE). In the absence of external Ca{sup 2+}, the robust Ca{sup 2+} entry after subsequent addition of Ca{sup 2+} was decreased by capsaicin in CPA-activated cells. Capsaicin alone increased the actin cytoskeleton, and also increased the actin filament content in cell activation with CPA. These results indicate that capsaicin

  5. Inhibition of chronic pancreatitis and pancreatic intraepithelial neoplasia (PanIN) by capsaicin in LSL-KrasG12D/Pdx1-Cre mice.

    PubMed

    Bai, Han; Li, Haonan; Zhang, Wanying; Matkowskyj, Kristina A; Liao, Jie; Srivastava, Sanjay K; Yang, Guang-Yu

    2011-11-01

    Capsaicin is a major biologically active ingredient of chili peppers. Extensive studies indicate that capsaicin is a cancer-suppressing agent via blocking the activities of several signal transduction pathways including nuclear factor-kappaB, activator protein-1 and signal transducer and activator of transcription 3. However, there is little study on the effect of capsaicin on pancreatic carcinogenesis. In the present study, the effect of capsaicin on pancreatitis and pancreatic intraepithelial neoplasia (PanIN) was determined in a mutant Kras-driven and caerulein-induced pancreatitis-associated carcinogenesis in LSL-Kras(G12D)/Pdx1-Cre mice. Forty-five LSL-Kras(G12D)/Pdx1-Cre mice and 10 wild-type mice were subjected to one dose of caerulein (250 μg/kg body wt, intraperitoneally) at age 4 weeks to induce and synchronize the development of chronic pancreatitis and PanIN lesions. One week after caerulein induction, animals were randomly distributed into three groups and fed with either AIN-76A diet, AIN-76A diet containing 10 p.p.m. capsaicin or 20 p.p.m. capsaicin for a total of 8 weeks. The results showed that capsaicin significantly reduced the severity of chronic pancreatitis, as determined by evaluating the loss of acini, inflammatory cell infiltration and stromal fibrosis. PanIN formation was frequently observed in the LSL-Kras(G12D)/Pdx1-Cre mice. The progression of PanIN-1 to high-grade PanIN-2 and -3 were significantly inhibited by capsaicin. Further immunochemical studies revealed that treatment with 10 and 20 p.p.m. capsaicin significantly reduced proliferating cell nuclear antigen-labeled cell proliferation and suppressed phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun as well blocked Hedgehog/GLI pathway activation. These results indicate that capsaicin could be a promising agent for the chemoprevention of pancreatic carcinogenesis, possibly via inhibiting pancreatitis and mutant Kras-led ERK activation. PMID:21859833

  6. Gamma knife radiosurgery to the trigeminal ganglion for treatment of trigeminal neuralgia secondary to vertebrobasilar ectasia

    PubMed Central

    Somaza, Salvador; Hurtado, Wendy; Montilla, Eglee; Ghaleb, Jose

    2014-01-01

    Background: We report the result obtained using Gamma knife stereotactic radiosurgery on the trigeminal ganglion (TG) in a patient with trigeminal neuralgia (TN) secondary to vertebrobasilar ectasia (VBE). Case Description: Retrospective review of medical records corresponding to one patient with VBE-related trigeminal pain treated with radiosurgery. Because of the impossibility of visualization of the entry zone or the path of trigeminal nerve through the pontine cistern, we proceeded with stereotactic radiosurgery directed to the TG. The maximum radiation dose was 86 Gy with a 8-mm and a 4-mm collimator. The follow-up period was 24 months. The pain disappeared in 15 days, passing from Barrow Neurological Institute (BNI) grade V to BNI grade IIIa in 4 months and then to grade I. The patient did not experience noticeable subjective facial numbness. Conclusions: This experience showed that Gamma knife radiosurgery was effective in the management of VBE-related trigeminal pain, using the TG as radiosurgical target. PMID:25593782

  7. Synergistic anticancer activity of capsaicin and 3,3'-diindolylmethane in human colorectal cancer.

    PubMed

    Clark, Ruth; Lee, Jihye; Lee, Seong-Ho

    2015-05-01

    Cancer is a leading cause of morbidity and mortality worldwide. A promising area of cancer research is focused on chemoprevention by nutritional compounds. Epidemiological studies have shown a strong negative correlation between fruit, vegetable, and spice intake and rates of cancer. Although individual active compounds have demonstrated significant anticancer activity, an emerging area of research is focusing on the combination of multiple dietary compounds that act synergistically on cancer to exert greater effects. The current study evaluated the potential synergistic effects of capsaicin, an active compound from red chili peppers, in combination with 3,3'-diindolylmethane (DIM), from cruciferous vegetables. A synergistic induction of apoptosis and inhibition of cell proliferation was observed in human colorectal cancer cells treated with the combination of capsaicin and DIM. It was also observed that these two compounds activated transcriptional activity of NF-κB and p53 synergistically. Combination treatment stabilized nuclear p53 and up- or down-regulated expression of several target genes that are downstream of NF-κB and p53. The present study suggests capsaicin and DIM work synergistically to inhibit cell proliferation and induce apoptosis in colorectal cancer through modulating transcriptional activity of NF-κB, p53, and target genes associated with apoptosis. PMID:25876645

  8. Synergistic anticancer activity of capsaicin and 3,3'-diindolylmethane in human colorectal cancer.

    PubMed

    Clark, Ruth; Lee, Jihye; Lee, Seong-Ho

    2015-05-01

    Cancer is a leading cause of morbidity and mortality worldwide. A promising area of cancer research is focused on chemoprevention by nutritional compounds. Epidemiological studies have shown a strong negative correlation between fruit, vegetable, and spice intake and rates of cancer. Although individual active compounds have demonstrated significant anticancer activity, an emerging area of research is focusing on the combination of multiple dietary compounds that act synergistically on cancer to exert greater effects. The current study evaluated the potential synergistic effects of capsaicin, an active compound from red chili peppers, in combination with 3,3'-diindolylmethane (DIM), from cruciferous vegetables. A synergistic induction of apoptosis and inhibition of cell proliferation was observed in human colorectal cancer cells treated with the combination of capsaicin and DIM. It was also observed that these two compounds activated transcriptional activity of NF-κB and p53 synergistically. Combination treatment stabilized nuclear p53 and up- or down-regulated expression of several target genes that are downstream of NF-κB and p53. The present study suggests capsaicin and DIM work synergistically to inhibit cell proliferation and induce apoptosis in colorectal cancer through modulating transcriptional activity of NF-κB, p53, and target genes associated with apoptosis.

  9. Role of COX-2 in cough reflex sensitivity to inhaled capsaicin in patients with sinobronchial syndrome

    PubMed Central

    2010-01-01

    Background Sinobronchial syndrome is a cause of chronic productive cough. Inflammatory mediators are involved in the pathophysiology of chronic productive cough. Accumulating evidences indicate that cyclooxygenase (COX)-2, one of the inducible isoforms of COX, is a key element in the pathophysiological process of a number of inflammatory disorders. However, little is known about the role of COX-2 in chronic productive cough in patients with sinobronchial syndrome known as neutrophilic bronchial inflammation. Methods The effect of etodolac, a potent COX-2 inhibitor, on cough response to inhaled capsaicin was examined in 15 patients with sinobronchial syndrome in a randomized, placebo-controlled cross-over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. Results The cough threshold was significantly (p < 0.03) increased after two-week treatment with etodolac (200 mg twice a day orally) compared with placebo [37.5 (GSEM 1.3) vs. 27.2 (GSEM 1.3) μM]. Conclusions These findings indicate that COX-2 may be a possible modulator augmenting airway cough reflex sensitivity in patients with sinobronchial syndrome. PMID:20696045

  10. Inhibition of capsaicin-driven nasal hyper-reactivity by SB-705498, a TRPV1 antagonist

    PubMed Central

    Holland, Carlijn; Drunen, Cornelis Van; Denyer, Jane; Smart, Kevin; Segboer, Christine; Terreehorst, Ingrid; Newlands, Amy; Beerahee, Misba; Fokkens, Wytske; Tsitoura, Daphne C

    2014-01-01

    AIMS To assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of intranasal SB-705498, a selective TRPV1 antagonist. METHODS Two randomized, double-blind, placebo-controlled, clinical studies were performed: (i) an intranasal SB-705498 first time in human study to examine the safety and PK of five single escalating doses from 0.5 to 12 mg and of repeat dosing with 6 mg and 12 mg twice daily for 14 days and (ii) a PD efficacy study in subjects with non-allergic rhinitis (NAR) to evaluate the effect of 12 mg intranasal SB-705498 against nasal capsaicin challenge. RESULTS Single and repeat dosing with intranasal SB-705498 was safe and well tolerated. The overall frequency of adverse events was similar for SB-705498 and placebo and no dose-dependent increase was observed. Administration of SB-705498 resulted in less than dose proportional AUC(0,12 h) and Cmax, while repeat dosing from day 1 to day 14 led to its accumulation. SB-705498 receptor occupancy in nasal tissue was estimated to be high (>80%). Administration of 12 mg SB-705498 to patients with NAR induced a marked reduction in total symptom scores triggered by nasal capsaicin challenge. Inhibition of rhinorrhoea, nasal congestion and burning sensation was associated with 2-to 4-fold shift in capsaicin potency. CONCLUSIONS Intranasal SB-705498 has an appropriate safety and PK profile for development in humans and achieves clinically relevant attenuation of capsaicin-provoked rhinitis symptoms in patients with NAR. The potential impact intranasal SB-705498 may have in rhinitis treatment deserves further evaluation. PMID:23909699

  11. [Trigeminal neuralgia associated with primitive trigeminal artery: report of two cases].

    PubMed

    Tokimura, H; Atsuchi, M; Kawasaki, T; Sato, E; Todoroki, K; Asakura, T; Fukushima, T

    1990-02-01

    Two cases of trigeminal neuralgia associated with the primitive trigeminal artery are reported. From 1981, the authors have treated 131 trigeminal neuralgia patients with microvascular decompression. Among them, we encountered two rare cases of trigeminal neuralgia associated with the primitive trigeminal artery (PTA) and its variant (PTAV). Case 1 is a 74-year-old woman who was admitted to our hospital due to pain of maxilla and mandible. We diagnosed her pain as trigeminal neuralgia. Preoperative angiogram showed the primitive trigeminal artery arising from the cavernous portion of the right internal carotid artery (ICA). She underwent a microvascular decompression operation. We found that her right trigeminal nerve was compressed by the right superior cerebellar artery (SCA) and the right anterior inferior cerebellar artery (AICA). We transferred the offending arteries, and her pain disappeared. Case 2 is a 48-year-old man who was admitted to our hospital due to severe mandibular pain. We diagnosed his pain as trigeminal neuralgia, and he underwent a microvascular decompression operation. His left trigeminal nerve was found compressed by the left SCA and the AICA, and the AICA was arising from the direction of Meckel's cave. His severe pain disappeared completely after operation. Postoperative angiogram of his left ICA showed an aberrant artery arising from the cavernous portion of the ICA, to the region of the left AICA. This aberrant artery is a variant of PTA (PTAV). PTA and PTAV, the so called persistent congenital arteries, are said to accompany aneurysms and other vascular lesions, and affect hemodynamic stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2336149

  12. A Rare Association of Trigeminal Autonomic Cephalgia: Pontine Capillary Telangiectasia

    PubMed Central

    Kurt, Erdal; Arslan, Sabina; Unal-Cevik, Isin; Karli Oguz, Kader; Tezer, F Irsel

    2015-01-01

    This report describes a case of pontine capillary telangiectasia in a 43-year-old woman with a clinical diagnosis of trigeminal autonomic cephalgia. The possible association with pontine capillary telangiectasia and trigeminal autonomic cephalgia is discussed. PMID:25963152

  13. Trigeminal Cardiac Reflex and Cerebral Blood Flow Regulation

    PubMed Central

    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

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

    PubMed

    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.

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

    SciTech Connect

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

    PubMed Central

    Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I.; Cruzblanca, Humberto; Mancilla, Evelyn

    2016-01-01

    Objective 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. Materials and Methods 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. Results 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

  17. Direct reticular projections of trigeminal sensory fibers immunoreactive to CGRP: potential monosynaptic somatoautonomic projections

    PubMed Central

    Panneton, W. Michael; Gan, Qi

    2014-01-01

    Few trigeminal sensory fibers project centrally beyond the trigeminal sensory complex, with only projections of fibers carried in its sensory anterior ethmoidal (AEN) and intraoral nerves described. Fibers of the AEN project into the brainstem reticular formation where immunoreactivity against substance P and CGRP are found. We investigated whether the source of these peptides could be from trigeminal ganglion neurons by performing unilateral rhizotomies of the trigeminal root and looking for absence of label. After an 8–14 days survival, substance P immunoreactivity in the trigeminal sensory complex was diminished, but we could not conclude that the sole source of this peptide in the lateral parabrachial area and lateral reticular formation arises from primary afferent fibers. Immunoreactivity to CGRP after rhizotomy however was greatly diminished in the trigeminal sensory complex, confirming the observations of others. Moreover, CGRP immunoreactivity was nearly eliminated in fibers in the lateral parabrachial area, the caudal ventrolateral medulla, both the peri-ambiguus and ventral parts of the rostral ventrolateral medulla, in the external formation of the nucleus ambiguus, and diminished in the caudal pressor area. The nearly complete elimination of CGRP in the lateral reticular formation after rhizotomy suggests this peptide is carried in primary afferent fibers. Moreover, the arborization of CGRP immunoreactive fibers in these areas mimics that of direct projections from the AEN. Since electrical stimulation of the AEN induces cardiorespiratory adjustments including an apnea, peripheral vasoconstriction, and bradycardia similar to those seen in the mammalian diving response, we suggest these perturbations of autonomic behavior are enhanced by direct somatic primary afferent projections to these reticular neurons. We believe this to be first description of potential direct somatoautonomic projections to brainstem neurons regulating autonomic activity. PMID

  18. Trigeminal neuralgia treatment dosimetry of the Cyberknife

    SciTech Connect

    Ho, Anthony; Lo, Anthony T.; Dieterich, Sonja; Soltys, Scott G.; Gibbs, Iris C.; Chang, Steve G.; Adler, John R.

    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.

  19. Pharmaceutical Management of Trigeminal Neuralgia in the Elderly.

    PubMed

    Oomens, M A E-M; Forouzanfar, T

    2015-09-01

    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 give an overview of the current literature on pharmaceutical treatment options for CTN in the elderly. The first-line treatment for the management of CTN in adults is an antiepileptic-carbamazepine or oxcarbazepine. There is a lack of research on the use of antiepileptics in the elderly. This is a deficiency, as the use of antiepileptics raises a number of problems due to the polypharmacotherapy common in older patients. This can induce drug interactions due to co-morbidities and changes in pharmacokinetics and pharmacodynamics. Furthermore, the side effects of carbamazepine include central nervous system disturbances, such as a lack of balance, dizziness, somnolence, renal dysfunction and cardiac arrhythmias, which are poorly tolerated by the elderly. Unfortunately, the efficacy and safety of alternative treatment options have not been systematically evaluated. On the basis of the current literature, it is not possible to give an evidence-based recommendation for first-line pharmaceutical management of CTN specifically for the elderly.

  20. Effects of aural stimulation with capsaicin ointment on swallowing function in elderly patients with non-obstructive dysphagia

    PubMed Central

    Kondo, Eiji; Jinnouchi, Osamu; Ohnishi, Hiroki; Kawata, Ikuji; Nakano, Seiichi; Goda, Masakazu; Kitamura, Yoshiaki; Abe, Koji; Hoshikawa, Hiroshi; Okamoto, Hidehiko; Takeda, Noriaki

    2014-01-01

    Objective In the present study, an attempt was made to examine the effects of aural stimulation with ointment containing capsaicin on swallowing function in order to develop a novel and safe treatment for non-obstructive dysphagia in elderly patients. Design A prospective pilot, non-blinded, non-controlled study with case series evaluating a new treatment. Setting Secondary hospitals. Patients and methods The present study included 26 elderly patients with non-obstructive dysphagia. Ointment containing 0.025% capsaicin (0.5 g) was applied to the external auditory canal with a cotton swab under otoscope only once or once a day for 7 days before swallowing of a bolus of colored water (3 mL), which was recorded by transnasal videoendoscopy and evaluated according to the endoscopic swallowing score. Results After a single application of 0.025% capsaicin ointment to the right external auditory canal, the endoscopic swallowing score was significantly decreased, and this effect lasted for 60 minutes. After repeated applications of the ointment to each external auditory canal alternatively once a day for 7 days, the endoscopic swallowing score decreased significantly in patients with more severe non-obstructive dysphagia. Of the eight tube-fed patients of this group, three began direct swallowing exercises using jelly, which subsequently restored their oral food intake. Conclusion These findings suggest that stimulation of the external auditory canal with ointment containing capsaicin improves swallowing function in elderly patients with non-obstructive dysphagia. By the same mechanism used by angiotensin-converting enzyme inhibitors to induce cough reflex, which has been shown to prevent aspiration pneumonia, aural stimulation with capsaicin may reduce the incidence of aspiration pneumonia in dysphagia patients via Arnold’s ear-cough reflex stimulation. PMID:25328387

  1. Endothelin and neonatal capsaicin regulate gastric resistance to injury in BDL rats

    PubMed Central

    Câmara, Paula RS; Ferraz, Gerson JN; Velloso, Licio A; Zeitune, José Murilo R; Suassuna, Fernando AB; Ferraz, Jose Geraldo P

    2012-01-01

    AIM: To investigate the relationship between primary afferent neurons, endothelin (ET) and the role of its receptors on ethanol-induced gastric damage in cirrhotic rats. METHODS: Cirrhosis and portal hypertension were induced in rats by bile duct ligation (BDL) while controls had a sham operation. The association between ET and afferent neurons on the gastric mucosa was evaluated by capsaicin treatment in newborn rats, the use of ET agonists or antagonists, gastric ET-1 and -3 mRNA and synthetic capacity. Ethanol-induced damage was assessed using ex vivo gastric chamber experiments. Gastric blood flow was measured by laser-Doppler flowmetry. RESULTS: ET-3 and an ETB receptor antagonist significantly reduced the extent of ethanol-induced gastric damage in BDL rats. Gastric ET-1 and -3 levels were 30% higher in BDL rats compared to control rats. Capsaicin treatment restored the gastric resistance and blood flow responses to topical application of ethanol in BDL rats and ET-1 and -3 production to levels observed in controls. CONCLUSION: Our results suggest that the reduced resistance of the gastric mucosa of cirrhotic rats to ethanol-induced injury is a phenomenon modulated by ET through the ETB receptor and by sensory afferent neurons. PMID:23293745

  2. [Diagnostics and treatment of trigeminal neuralgia].

    PubMed

    Maarbjerg, Stine; Heinskou, Tone Bruvik; Wolfram, Frauke; Rochat, Per; Brennum, Jannick; Bendtsen, Lars

    2016-07-18

    Trigeminal neuralgia (TN) is characterized by unilateral evoked short-lasting intense pain paroxysms in the face. A concomitant persistent background pain is frequently present. Neurovascular contact causing displacement or atrophy of the trigeminal nerve is important to TN aetiology. TN can also be secondary to a space-occupying lesion or multiple sclerosis. Early high-quality magnetic resonance imaging is mandatory as a part of the work-up. First-choice treatment is medical. Medically refractory patients are referred to neurosurgery. Nationwide in Denmark, there is a need for structured and uniform treatment of TN. PMID:27460468

  3. Reduced GABAA receptor α6 expression in the trigeminal ganglion alters inflammatory TMJ hypersensitivity

    PubMed Central

    Puri, Jyoti; Vinothini, Priya; Reuben, Jayne; Bellinger, Larry L.; Ailing, Li; Peng, Yuan B.; Kramer, Phillip R.

    2012-01-01

    Trigeminal ganglia neurons express the GABAA receptor subunit alpha 6 (Gabrα6) but the role of this particular subunit in orofacial hypersensitivity is unknown. In this report the function of Gabrα6 was tested by reducing its expression in the trigeminal ganglia and measuring the effect of this reduction on inflammatory temporomandibular joint (TMJ) hypersensitivity. Gabrα6 expression was reduced by infusing the trigeminal ganglia of male Sprague Dawley rats with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabrα6 siRNA) or no known gene (control siRNA). Sixty hours after siRNA infusion the rats received a bilateral TMJ injection of complete Freund’s adjuvant to induce an inflammatory response. Hypersensitivity was then quantitated by measuring meal duration, which lengthens when hypersensitivity increases. Neuronal activity in the trigeminal ganglia was also measured by quantitating the amount of phosphorylated ERK. Rats in a different group that did not have TMJ inflammation had an electrode placed in the spinal cord at the level of C1 sixty hours after siRNA infusion to record extracellular electrical activity of neurons that responded to TMJ stimulation. Our results show that Gabrα6 was expressed in both neurons and satellite glia of the trigeminal ganglia and that Gabrα6 positive neurons within the trigeminal ganglia have afferents in the TMJ. Gabrα6 siRNA infusion reduced Gabrα6 gene expression by 30% and significantly lengthened meal duration in rats with TMJ inflammation. Gabrα6 siRNA infusion also significantly increased p-ERK expression in the trigeminal ganglia of rats with TMJ inflammation and increased electrical activity in the spinal cord of rats without TMJ inflammation. These results suggest that maintaining Gabrα6 expression was necessary to inhibit primary sensory afferents in the trigeminal pathway and reduce inflammatory orofacial nociception. PMID:22521829

  4. Non-Invasive Mapping of Human Trigeminal Brainstem Pathways

    PubMed Central

    Upadhyay, Jaymin; Knudsen, Jamie; Anderson, Julie; Becerra, Lino; Borsook, David

    2008-01-01

    The human trigeminal system mediates facial pain and somatosensory processing. The anatomic location of neuronal substrates and axonal pathways of the trigeminal system have previously been characterized with conventional in vitro methods. The present investigation implemented diffusion tensor imaging (DTI) and probabilistic tractography to first segment the peripheral trigeminal circuitry; trigeminal nerve branches (ophthalmic, maxillary and mandibular nerves), ganglion and nerve root. Subsequent segmentations involved the spinal trigeminal and trigeminal thalamic tracts, which respectively convey information to spinal trigeminal nuclei and ventral thalamic regions. This latter procedure also identified (1) spinal thalamic (anterolateral) system pathways (propagating pain and temperature information from the body); (2) trigeminal lemniscus (touch and face position) and 3) medial lemniscus (touch and limb position). The anatomic location of the identified pain and somatosensory pathways compared well with previous functional findings in human trigeminal system as well as the tract position in human histological cross-sections. Probabilistic tractography may be a useful method to further comprehend the functional and structural properties of trigeminal and other related systems. Application of DTI to map pain and somatosensory pathways in conjunction with a characterization of function properties of pain and somatosensory processing would further define the systematic changes that occur in trigeminal pathology. PMID:18956455

  5. Cannabinoid receptor-independent actions of the aminoalkylindole WIN 55,212-2 on trigeminal sensory neurons

    PubMed Central

    Price, Theodore J; Patwardhan, Amol; Akopian, Armen N; Hargreaves, Kenneth M; Flores, Christopher M

    2004-01-01

    The prototypical aminoalkylindole cannabinoid WIN 55,212-2 (WIN-2) has been shown to produce antihyperalgesia through a peripheral mechanism of action. However, it is not known whether WIN-2 exerts this action directly via cannabinoid receptors located on primary afferents or if other, perhaps indirect or noncannabinoid, mechanisms are involved. To address this question, we have examined the specific actions of WIN-2 on trigeminal ganglion (TG) neurons in vitro by quantifying its ability to modulate the evoked secretion of the proinflammatory neuropeptide CGRP as well as the inflammatory mediator-induced generation of cAMP. WIN-2 evoked CGRP release from TG neurons in vitro (EC50=26 μM) in a concentration- and calcium-dependent manner, which was mimicked by the cannabinoid receptor-inactive enantiomer WIN 55,212-3 (WIN-3). Moreover, WIN-2-evoked CGRP release was attenuated by the nonselective cation channel blocker ruthenium red but not by the vanilloid receptor type 1 (TRPV1) antagonist capsazepine, suggesting that, unlike certain endogenous and synthetic cannabinoids, WIN-2 is not a TRPV1 agonist but rather acts at an as yet unidentified cation channel. The inhibitory effects of WIN-2 on TG neurons were also examined. WIN-2 neither inhibited capsaicin-evoked CGRP release nor did it inhibit forskolin-, isoproteranol- or prostaglandin E2-stimulated cAMP accumulation. On the other hand, WIN-2 significantly inhibited (EC50=1.7 μM) 50 mM K+-evoked CGRP release by approximately 70%. WIN-2 inhibition of 50 mM K+-evoked CGRP release was not reversed by antagonists of cannabinoid type 1 (CB1) receptor, but was mimicked in magnitude and potency (EC50=2.7 μM) by its cannabinoid-inactive enantiomer WIN-3. These findings indicate that WIN-2 exerts both excitatory and inhibitory effects on TG neurons, neither of which appear to be mediated by CB1, CB2 or TRPV1 receptors, but by a novel calcium-dependent mechanism. The ramifications of these results are discussed in relation

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

    PubMed

    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. Capsaicin inhibits collagen fibril formation and increases the stability of collagen fibers.

    PubMed

    Perumal, Sathiamurthi; Dubey, Kriti; Badhwar, Rahul; George, Kodimattan Joseph; Sharma, Rakesh Kumar; Bagler, Ganesh; Madhan, Balaraman; Kar, Karunakar

    2015-02-01

    Capsaicin is a versatile plant product which has been ascribed several health benefits and anti-inflammatory and analgesic properties. We have investigated the effect of capsaicin on the molecular stability, self-assembly, and fibril stability of type-I collagen. It was found that capsaicin suppresses collagen fibril formation, increases the stability of collagen fibers in tendons, and has no effect on the molecular stability of collagen. Turbidity assay data show that capsaicin does not promote disassembly of collagen fibrils. However, capsaicin moderately protects collagen fibrils from enzymatic degradation. Computational studies revealed the functions of the aromatic group and amide region of capsaicin in the collagen-capsaicin interaction. The results may have significant implications for capsaicin-based therapeutics that target excess collagen accumulation-linked pathology, for example thrombosis, fibrosis, and sclerosis.

  8. The Anticancer Role of Capsaicin in Experimentallyinduced Lung Carcinogenesis

    PubMed Central

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

    2015-01-01

    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(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. 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. PMID:26120484

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

    PubMed

    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.

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

    PubMed Central

    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

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

    PubMed

    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.

  12. Microstructural abnormalities of the trigeminal nerve by diffusion-tensor imaging in trigeminal neuralgia without neurovascular compression.

    PubMed

    Neetu, Soni; Sunil, Kumar; Ashish, Awasthi; Jayantee, Kalita; Usha Kant, Misra

    2016-02-01

    Microstructural changes of the trigeminal nerve in trigeminal neuralgia due to neurovascular compression have been reported by using diffusion tensor imaging. Other aetiologies such as primary demyelinating lesions, brain stem infarction and nerve root infiltration by tumour affecting the trigeminal pathway may also present as trigeminal neuralgia. The aim of this study was to evaluate the microstructural tissue abnormalities in the trigeminal nerve in symptomatic trigeminal neuralgia not related to neurovascular compression using diffusion tensor imaging. Mean values of the quantitative diffusion parameters of trigeminal nerve, fractional anisotropy and apparent diffusion coefficient, were measured in a group of four symptomatic trigeminal neuralgia patients without neurovascular compression who showed focal non-enhancing T2-hyperintense lesions in the pontine trigeminal pathway. These diffusion parameters were compared between the affected and unaffected sides in the same patient and with four age-matched healthy controls. Cranial magnetic resonance imaging revealed hyperintense lesions in the dorsolateral part of the pons along the central trigeminal pathway on T2-fluid-attenuated inversion recovery sequences. The mean fractional anisotropy value on the affected side was significantly decreased (P = 0.001) compared to the unaffected side and healthy controls. Similarly, the mean apparent diffusion coefficient value was significantly higher (P = 0.001) on the affected side compared to the unaffected side and healthy controls. The cause of trigeminal neuralgia in our patients was abnormal pontine lesions affecting the central trigeminal pathway. The diffusion tensor imaging results suggest that microstructural tissue abnormalities of the trigeminal nerve also exist even in non-neurovascular compression-related trigeminal neuralgia.

  13. 40 CFR 180.1165 - Capsaicin; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    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...

  14. 40 CFR 180.1165 - Capsaicin; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 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...

  15. 40 CFR 180.1165 - Capsaicin; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 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...

  16. 40 CFR 180.1165 - Capsaicin; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 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...

  17. 40 CFR 180.1165 - Capsaicin; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 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...

  18. Chemosensory properties of the trigeminal system.

    PubMed

    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. PMID:22778855

  19. Trigeminal Neuralgia due to Vertebrobasilar Dolichoectasia

    PubMed Central

    Campos, Wuilker Knoner; Guasti, André Accioly; da Silva, Benjamin Franklin; Guasti, José Antonio

    2012-01-01

    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. PMID:22937350

  20. Bright light activates a trigeminal nociceptive pathway

    PubMed Central

    Okamoto, Keiichiro; Tashiro, Akimasa; Chang, Zheng; Bereiter, David A.

    2010-01-01

    Bright light can cause ocular discomfort and/or pain; however, the mechanism linking luminance to trigeminal nerve activity is not known. In this study we identify a novel reflex circuit necessary for bright light to excite nociceptive neurons in superficial laminae of trigeminal subnucleus caudalis (Vc/C1). Vc/C1 neurons encoded light intensity and displayed a long delay (>10 s) for activation. Microinjection of lidocaine into the eye or trigeminal root ganglion (TRG) inhibited light responses completely, whereas topical application onto the ocular surface had no effect. These findings indicated that light-evoked Vc/C1 activity was mediated by an intraocular mechanism and transmission through the TRG. Disrupting local vasomotor activity by intraocular microinjection of the vasoconstrictive agents, norepinephrine or phenylephrine, blocked light-evoked neural activity, whereas ocular surface or intra-TRG microinjection of norepinephrine had no effect. Pupillary muscle activity did not contribute since light-evoked responses were not altered by atropine. Microinjection of lidocaine into the superior salivatory nucleus diminished light-evoked Vc/C1 activity and lacrimation suggesting that increased parasympathetic outflow was critical for light-evoked responses. The reflex circuit also required input through accessory visual pathways since both Vc/C1 activity and lacrimation were prevented by local blockade of the olivary pretectal nucleus. These findings support the hypothesis that bright light activates trigeminal nerve activity through an intraocular mechanism driven by a luminance-responsive circuit and increased parasympathetic outflow to the eye. PMID:20206444

  1. Trigeminal nerve: Anatomic correlation with MR imaging

    SciTech Connect

    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.

  2. Chemosensory Properties of the Trigeminal System

    PubMed Central

    2010-01-01

    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. PMID:22778855

  3. Trigeminal schwannoma extending into the parapharyngeal space.

    PubMed

    Yumuşakhuylu, Ali Cemal; Sari, Murat; Topuz, Muhammet Fatih; Bağlam, Tekin; Binnetoğlu, Adem

    2014-07-01

    Parapharyngeal space tumors are very rarely seen, and surgical approach to these tumors has not been well established. Most of these tumors are benign and originated from salivary glands and neurogenic in nature. In this case, we report a patient who has a trigeminal schwannoma extending into the deep parapharyngeal space and explain our surgical approach.

  4. A medullary inhibitory region for trigeminal motoneurons in the cat.

    PubMed

    Castillo, P; Pedroarena, C; Chase, M H; Morales, F R

    1991-05-24

    The present report describes the effects on trigeminal motoneurons of stimulation of a circumscribed site within the parvocellular region of the medullary reticular formation. This medullary site was selected because anatomical studies have shown that premotor interneurons project from this site to the trigeminal motorpool. Electrical stimulation of this site induced IPSPs (PcRF-IPSPs) in jaw-closer motoneurons. A population of these IPSPs, recorded contralateral to the site of stimulation, exhibited latencies shorter than 1.5 ms (mean 1.16 +/- 0.08 SD). Their mean amplitude was 1.72 mV +/- 1.13 SD and their mean duration was 3.52 ms +/- 2.15 SD. We believe that these PcRF-IPSPs arose as the result of activation of a monosynaptic pathway. A comparable inhibitory input from this site to ipsilateral jaw-closer motoneurons and to both contra and ipsilateral digastric motoneurons was also observed. We therefore conclude that this medullary PcRF site contains premotor interneurons that are capable of postsynaptically inhibiting motoneurons that innervate antagonistic jaw muscles. PMID:1884229

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

    NASA Astrophysics Data System (ADS)

    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".

  6. Involvement of a CCK-dependent capsaicin-sensitive afferent pathway in the inhibitory effect of pinaverium bromide on the colonic motor response to eating in rats.

    PubMed

    Fioramonti, J; Christen, M O; Dupre, I; Bueno, L

    1997-01-01

    The effects of pinaverium bromide on the stimulation of colonic motility induced by meal and cholecystokinin (CCK) were investigated in rats chronically fitted with intraparietal electrodes on the proximal colon and previously treated or not by capsaicin. Pinaverium bromide inhibited in a dose-related manner (2-50 mg/kg, per os) the increase in colonic spike burst frequency induced by a 3 g meal or CCK-8 (2 micrograms/kg, i.v.). The CCK-A and CCK-B antagonists, devazepide and L 365260 (100 micrograms/kg, i.p.), respectively, inhibited the postprandial colonic motor response while only L 365260 reduced the CCK-induced stimulation. The effects of pinaverium bromide and CCK antagonists were not observed in capsaicin-treated animals. Moreover, CCK-8 (2 micrograms/kg, i.v.) did not stimulate colonic motility after capsaicin treatment. The inhibition of postprandial colonic motility by pinaverium bromide, given orally at therapeutic doses, involves a CCK-dependent pathway which requires the integrity of capsaicin-sensitive afferents. PMID:9243254

  7. Reproducibility of the heat/capsaicin skin sensitization model in healthy volunteers

    PubMed Central

    Cavallone, Laura F; Frey, Karen; Montana, Michael C; Joyal, Jeremy; Regina, Karen J; Petersen, Karin L; Gereau, Robert W

    2013-01-01

    Introduction 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 experimental pain models is critical to the advancement of translational pain research. PMID:24232380

  8. Effects of capsaicin on adipogenic differentiation in bovine bone marrow mesenchymal stem cell.

    PubMed

    Jeong, Jin Young; Suresh, Sekar; Park, Mi Na; Jang, Mi; Park, Sungkwon; Gobianand, Kuppannan; You, Seungkwon; Yeon, Sung-Heom; Lee, Hyun-Jeong

    2014-12-01

    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. PMID:25358373

  9. Effects of capsaicin on adipogenic differentiation in bovine bone marrow mesenchymal stem cell.

    PubMed

    Jeong, Jin Young; Suresh, Sekar; Park, Mi Na; Jang, Mi; Park, Sungkwon; Gobianand, Kuppannan; You, Seungkwon; Yeon, Sung-Heom; Lee, Hyun-Jeong

    2014-12-01

    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.

  10. Transcriptome analysis of trigeminal ganglia following masseter muscle inflammation in rats

    PubMed Central

    Park, Jennifer; Asgar, Jamila; Ro, Jin Y.

    2016-01-01

    Background Chronic pain in masticatory muscles is a major medical problem. Although mechanisms underlying persistent pain in masticatory muscles are not fully understood, sensitization of nociceptive primary afferents following muscle inflammation or injury contributes to muscle hyperalgesia. It is well known that craniofacial muscle injury or inflammation induces regulation of multiple genes in trigeminal ganglia, which is associated with muscle hyperalgesia. However, overall transcriptional profiles within trigeminal ganglia following masseter inflammation have not yet been determined. In the present study, we performed RNA sequencing assay in rat trigeminal ganglia to identify transcriptome profiles of genes relevant to hyperalgesia following inflammation of the rat masseter muscle. Results Masseter inflammation differentially regulated >3500 genes in trigeminal ganglia. Predominant biological pathways were predicted to be related with activation of resident non-neuronal cells within trigeminal ganglia or recruitment of immune cells. To focus our analysis on the genes more relevant to nociceptors, we selected genes implicated in pain mechanisms, genes enriched in small- to medium-sized sensory neurons, and genes enriched in TRPV1-lineage nociceptors. Among the 2320 candidate genes, 622 genes showed differential expression following masseter inflammation. When the analysis was limited to these candidate genes, pathways related with G protein-coupled signaling and synaptic plasticity were predicted to be enriched. Inspection of individual gene expression changes confirmed the transcriptional changes of multiple nociceptor genes associated with masseter hyperalgesia (e.g., Trpv1, Trpa1, P2rx3, Tac1, and Bdnf) and also suggested a number of novel probable contributors (e.g., Piezo2, Tmem100, and Hdac9). Conclusion These findings should further advance our understanding of peripheral mechanisms involved in persistent craniofacial muscle pain conditions and provide a

  11. Capsaicin interaction with TRPV1 channels in a lipid bilayer: molecular dynamics simulation.

    PubMed

    Hanson, Sonya M; Newstead, Simon; Swartz, Kenton J; Sansom, Mark S P

    2015-03-24

    Transient receptor potential vanilloid subtype 1 (TRPV1) is a heat-sensitive ion channel also involved in pain sensation, and is the receptor for capsaicin, the active ingredient of hot chili peppers. The recent structures of TRPV1 revealed putative ligand density within the S1 to S4 voltage-sensor-like domain of the protein. However, questions remain regarding the dynamic role of the lipid bilayer in ligand binding to TRPV1. Molecular dynamics simulations were used to explore behavior of capsaicin in a 1-palmitoyl-2-oleoyl phosphatidylcholine bilayer and with the target S1-S4 transmembrane helices of TRPV1. Equilibrium simulations reveal a preferred interfacial localization for capsaicin. We also observed a capsaicin molecule flipping from the extracellular to the intracellular leaflet, and subsequently able to access the intracellular TRPV1 binding site. Calculation of the potential of mean force (i.e., free energy profile) of capsaicin along the bilayer normal confirms that it prefers an interfacial localization. The free energy profile indicates that there is a nontrivial but surmountable barrier to the flipping of capsaicin between opposing leaflets of the bilayer. Molecular dynamics of the S1-S4 transmembrane helices of the TRPV1 in a lipid bilayer confirm that Y511, known to be crucial to capsaicin binding, has a distribution along the bilayer normal similar to that of the aromatic group of capsaicin. Simulations were conducted of the TRPV1 S1-S4 transmembrane helices in the presence of capsaicin placed in the aqueous phase, in the lipid, or docked to the protein. No stable interaction between ligand and protein was seen for simulations initiated with capsaicin in the bilayer. However, interactions were seen between TRPV1 and capsaicin starting from the cytosolic aqueous phase, and capsaicin remained stable in the majority of simulations from the docked pose. We discuss the significance of capsaicin flipping from the extracellular to the intracellular

  12. Involvement of trigeminal transition zone and laminated subnucleus caudalis in masseter muscle hypersensitivity associated with tooth inflammation.

    PubMed

    Shimizu, Kohei; Matsumoto, Kunihito; Noma, Noboru; Matsuura, Shingo; Ohara, Kinuyo; Komiya, Hiroki; Watase, Tetsuro; Ogiso, Bunnai; Tsuboi, Yoshiyuki; Shinoda, Masamichi; Hatori, Keisuke; Nakaya, Yuka; Iwata, Koichi

    2014-01-01

    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 periapical

  13. Binding of Capsaicin to the TRPV1 Ion Channel.

    PubMed

    Darré, Leonardo; Domene, Carmen

    2015-12-01

    Transient receptor potential (TRP) ion channels constitute a notable family of cation channels involved in the ability of an organisms to detect noxious mechanical, thermal, and chemical stimuli that give rise to the perception of pain, taste, and changes in temperature. One of the most experimentally studied agonist of TRP channels is capsaicin, which is responsible for the burning sensation produced when chili pepper is in contact with organic tissues. Thus, understanding how this molecule interacts and regulates TRP channels is essential to high impact pharmacological applications, particularly those related to pain treatment. The recent publication of a three-dimensional structure of the vanilloid receptor 1 (TRPV1) in the absence and presence of capsaicin from single particle electron cryomicroscopy experiments provides the opportunity to explore these questions at the atomic level. In the present work, molecular docking and unbiased and biased molecular dynamics simulations were employed to generate a structural model of the capsaicin-channel complex. In addition, the standard free energy of binding was estimated using alchemical transformations coupled with conformational, translational, and orientational restraints on the ligand. Key binding modes consistent with previous experimental data are identified, and subtle but essential dynamical features of the binding site are characterized. These observations shed some light into how TRPV1 interacts with capsaicin, and may help to refine design parameters for new TRPV1 antagonists, and potentially guide further developments of TRP channel modulators. PMID:26502196

  14. Natural Capsaicin in Capsicum chinense: Concentration vs. Origin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  15. Binding of Capsaicin to the TRPV1 Ion Channel.

    PubMed

    Darré, Leonardo; Domene, Carmen

    2015-12-01

    Transient receptor potential (TRP) ion channels constitute a notable family of cation channels involved in the ability of an organisms to detect noxious mechanical, thermal, and chemical stimuli that give rise to the perception of pain, taste, and changes in temperature. One of the most experimentally studied agonist of TRP channels is capsaicin, which is responsible for the burning sensation produced when chili pepper is in contact with organic tissues. Thus, understanding how this molecule interacts and regulates TRP channels is essential to high impact pharmacological applications, particularly those related to pain treatment. The recent publication of a three-dimensional structure of the vanilloid receptor 1 (TRPV1) in the absence and presence of capsaicin from single particle electron cryomicroscopy experiments provides the opportunity to explore these questions at the atomic level. In the present work, molecular docking and unbiased and biased molecular dynamics simulations were employed to generate a structural model of the capsaicin-channel complex. In addition, the standard free energy of binding was estimated using alchemical transformations coupled with conformational, translational, and orientational restraints on the ligand. Key binding modes consistent with previous experimental data are identified, and subtle but essential dynamical features of the binding site are characterized. These observations shed some light into how TRPV1 interacts with capsaicin, and may help to refine design parameters for new TRPV1 antagonists, and potentially guide further developments of TRP channel modulators.

  16. Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review.

    PubMed

    Srinivasan, Krishnapura

    2016-07-01

    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.

  17. Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review.

    PubMed

    Srinivasan, Krishnapura

    2016-07-01

    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. PMID:25675368

  18. Capsaicin inhibits cell proliferation by cytochrome c release in gastric cancer cells.

    PubMed

    Meral, Ogunc; Alpay, Merve; Kismali, Gorkem; Kosova, Funda; Cakir, Dilek Ulker; Pekcan, Mert; Yigit, Serbulent; Sel, Tevhide

    2014-07-01

    Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the principal pungent component in hot peppers. The role of capsaicin in carcinogenesis is quite controversial. Although some investigators suspect that capsaicin is a carcinogen, co-carcinogen, or tumor promoter, others have reported that it has chemopreventive and chemotherapeutic effects. The present study aimed to evaluate the cytotoxicity and chemosensitizing activities of capsaicin alone and on 5-flourouracil (5-FU)-treated gastric cancer cells. In this study, the gastric cancer cell line HGC-27 was used and capsaicin used as a chemosensitizer and 5-flourouracil (5-FU) was used as chemotherapeutic. Cytotoxicity and chemosensitizing activities were analyzed with MTT assay; supernatant levels of LDH and glucose were detected as biochemical markers of cell viability; cytochrome c and AIF were evaluated with western blot; and additionally, wound-healing assays were employed. Results suggested that capsaicin had significant anticancer abilities; such capsaicin were capable of causing multifold decreases in the half maximal inhibitory concentration IC50 value of 5-FU. The continuing controversy surrounding consumption or topical application of capsaicin clearly suggests that more well-controlled epidemiologic studies are needed to evaluate the safety and efficacy of capsaicin use. In summary, the present study demonstrated that capsaicin has the potential to be used for treating gastric carcinoma with 5-FU in vitro.

  19. P2X purinoceptor-mediated excitation of trigeminal lingual nerve terminals in an in vitro intra-arterially perfused rat tongue preparation.

    PubMed

    Rong, W; Burnstock, G; Spyer, K M

    2000-05-01

    A novel in vitro intra-arterially perfused adult rat tongue-nerve preparation was used to explore the possible actions of P2X purinoceptor agonists (ATP and alpha,beta-methylene ATP (alpha, beta-meATP)) on sensory nerve terminals innervating the rat tongue. We made whole-nerve recordings of the trigeminal branch of the lingual nerve (LN), which conducts general sensory information (pain, temperature, touch, etc.), and the chorda tympani (CT), which conducts taste information. Changes in LN and CT activity following intra-arterial application of P2X agonists were compared. In seven preparations, bolus close-arterial injection of ATP (30-3000 microM, 0.1 ml) or alpha,beta-meATP (10-300 microM, 0.1 ml) induced a rapid (< 1 s after injection), dose-related increase in LN activity that decayed within a few seconds. The minimal concentration of ATP (100 microM) required to elicit a response was about 10-fold higher than that of alpha,beta-meATP (10 microM). Bolus injection of ATP or alpha,beta-meATP induced a moderate decrease in firing frequency in three of seven CT preparations. LN responses to P2X agonists showed signs of rapid desensitisation with the peak frequency of discharge being smaller when the agonists were applied at short intervals. Suramin (200 microM) or PPADS (200 microM) applied by intra-arterial perfusion each antagonised the rapid increase in LN activity following application of alpha,beta-meATP (100 microM). Capsaicin (10 microM, 0.1 ml, n = 5 preparations) was injected intra-arterially to desensitise nociceptive fibres. This was found to block (n = 2) or greatly reduce (n = 3) the excitatory effects of alpha,beta-meATP (100 microM, 0.1 ml) on LN activity, implying that only capsaicin-sensitive nociceptive fibres in LN were responsive to P2X agonists. In contrast to the consistent excitatory responses in LN activity following fast application of P2X agonists as bolus, a variable and moderate change in discharge rate of LN and no change in CT activity

  20. Trigeminal neuralgia and pain related to multiple sclerosis.

    PubMed

    Cruccu, G; Biasiotta, A; Di Rezze, S; Fiorelli, M; Galeotti, F; Innocenti, P; Mameli, S; Millefiorini, E; Truini, A

    2009-06-01

    Although many patients with multiple sclerosis (MS) complain of trigeminal neuralgia (TN), its cause and mechanisms are still debatable. In a multicentre controlled study, we collected 130 patients with MS: 50 patients with TN, 30 patients with trigeminal sensory disturbances other than TN (ongoing pain, dysaesthesia, or hypoesthesia), and 50 control patients. All patients underwent pain assessment, trigeminal reflex testing, and dedicated MRI scans. The MRI scans were imported and normalised into a voxel-based, 3D brainstem model that allows spatial statistical analysis. The onset ages of MS and trigeminal symptoms were significantly older in the TN group. The frequency histogram of onset age for the TN group showed that many patients fell in the age range of classic TN. Most patients in TN and non-TN groups had abnormal trigeminal reflexes. In the TN group, 3D brainstem analysis showed an area of strong probability of lesion (P<0.0001) centred on the intrapontine trigeminal primary afferents. In the non-TN group, brainstem lesions were more scattered, with the highest probability for lesions (P<0.001) in a region involving the subnucleus oralis of the spinal trigeminal complex. We conclude that the most likely cause of MS-related TN is a pontine plaque damaging the primary afferents. Nevertheless, in some patients a neurovascular contact may act as a concurring mechanism. The other sensory disturbances, including ongoing pain and dysaesthesia, may arise from damage to the second-order neurons in the spinal trigeminal complex.

  1. The capsaicin receptor TRPV1 as a novel modulator of neural precursor cell proliferation.

    PubMed

    Stock, Kristin; Garthe, Alexander; de Almeida Sassi, Felipe; Glass, Rainer; Wolf, Susanne A; Kettenmann, Helmut

    2014-12-01

    The capsaicin receptor (TRPV1, transient receptor potential vanilloid type 1) was first discovered in the peripheral nervous system as a detector of noxious chemical and thermal stimuli including the irritant chili pepper. Recently, there has been increasing evidence of TRPV1 expression in the central nervous system. Here, we show that TRPV1 is expressed in neural precursor cells (NPCs) during postnatal development, but not in the adult. However, expression of TRPV1 is induced in the adult in paradigms linked to an increase in neurogenesis, such as spatial learning in the Morris water maze or voluntary exercise. Loss of TRPV1 expression in knockout mice leads to an increase in NPC proliferation. Functional TRPV1 expression has been confirmed in cultured NPCs. Our results indicate that TRPV1 expression influences both postnatal and activity-induced neurogenesis in adulthood. PMID:25092424

  2. Recent advances in basic research on the trigeminal ganglion.

    PubMed

    Goto, Tetsuya; Oh, Seog Bae; Takeda, Mamoru; Shinoda, Masamichi; Sato, Tadasu; Gunjikake, Kaori K; Iwata, Koichi

    2016-09-01

    Peripheral tissue inflammation can alter the properties of somatic sensory pathways, causing behavioral hypersensitivity and resulting in increased responses to pain caused by noxious stimulation (hyperalgesia) and normally innocuous stimulation (allodynia). These hypersensitivities for nociception are caused by changes in the excitability of trigeminal ganglion (TG) neurons. These changes alter sensory information processing in the neurons in the medullary trigeminal nucleus of caudalis. Increasing information is becoming available regarding trigeminal neuron-neuron/neuron-satellite glial cells (SGCs) communication. The activation of intraganglionic communication plays an important role in the creation and maintenance of trigeminal pathological pain. Therefore, in this review, we focus on the recent findings for sensory functions and pharmacological modulation of TG neurons and SGCs under normal and pathological conditions, and we discuss potential therapeutic targets in glia-neuronal interactions for the prevention of trigeminal neuropathic and inflammatory pain. PMID:27023716

  3. Effect of capsaicin on potassium conductance and electromotility of guinea pig outer hair cell

    PubMed Central

    Wu, T; Song, L; Shi, X; Jiang, Z; Santos-Sacchi, J; Nuttall, A.L

    2012-01-01

    Capsaicin, the classic activator of TRPV-1 channels in primary sensory neurons, evokes nociception. Interestingly, auditory reception is also modulated by this chemical, possibly by direct actions on outer hair cells (OHCs). Surprisingly, we find two novel actions of capsaicin unrelated to TRPV-1 channels, which likely contribute to its auditory effects in vivo. First, capsaicin is a potent blocker of OHC K conductances (IK and IK,n). Second, capsaicin substantially alters OHC nonlinear capacitance, the signature of electromotility – a basis of cochlear amplification. These new findings of capsaicin have ramifications for our understanding of the pharmacological properties of OHC IK, IK,n and electromotility and for interpretation of capsaicin pharmacological actions. PMID:21044673

  4. Trigeminal neuralgia caused by an anomalous posterior inferior cerebellar artery from the primitive trigeminal artery: case report.

    PubMed

    Lee, Seung Hwan; Koh, Jun Seok; Lee, Cheol Young

    2011-06-01

    A 61-year-old woman presented with typical trigeminal neuralgia (TN), caused by an aberrant posterior inferior cerebellar artery (PICA) associated with the primitive trigeminal artery (PTA). Magnetic resonance angiography and digital subtraction angiography clearly showed an anomalous artery directly originating from the PTA and coursing into the PICA territory at the cerebellum. During microvascular decompression (MVD), we confirmed and decompressed vascular compression of the trigeminal nerve by this anomalous, PICA-variant type of PTA. The PTA did not conflict with the trigeminal nerve, and the anomalous PICA only compressed the caudolateral part of the trigeminal nerve, without the more common compression at its root entry zone. This case is informative due not only to its very unusual angioanatomical variation but also to its helpfulness for surgeons preparing a MVD for a TN associated with such a rare vascular anomaly. PMID:21279490

  5. Topical capsaicin formulations in the management of neuropathic pain.

    PubMed

    Schumacher, Mark; Pasvankas, George

    2014-01-01

    This chapter reviews the scientific and clinical evidence supporting the use of topical formulations containing the pungent principle of chili peppers--capsaicin, for the treatment of peripheral neuropathic pain. Given the limitations of current oral and parenteral therapies for the management of pain arising from various forms of nerve injury, alternate therapeutic approaches that are not associated with systemic adverse events that limit quality of life, impair function, or threaten respiratory depression are critically needed. Moreover, neuropathic conditions can be complicated by progressive changes in the central and peripheral nervous system, leading to persistent reorganization of pain pathways and chronic neuropathic pain. Recent advances in the use of high-dose topical capsaicin preparations hold promise in managing a wide range of painful conditions associated with peripheral neuropathies and may in fact help reduce suffering by reversing progressive changes in the nervous system associated with chronic neuropathic pain conditions. PMID:24941666

  6. Trigeminal nerve section for chronic migrainous neuralgia.

    PubMed

    Kirkpatrick, P J; O'Brien, M D; MacCabe, J J

    1993-01-01

    We report a series of 14 patients who underwent partial or complete trigeminal nerve root section for chronic unremitting migrainous neuralgia. They had all suffered attacks with severe pain for over 18 months without remission (mean duration 5.5 years). Symptoms were refractory to extended medical intervention and had caused prolonged disruption of lifestyle. The sensory root was completely divided in two cases with complete relief of pain (mean follow-up period 5.6 years). In the other 12 patients, 50-90% of the superomedial portion of the sensory root was divided. Of these, five received no further surgery, and experienced complete (n = 2), near complete (n = 2), or incomplete (n = 1) relief of neuralgia (mean follow-up 5.5 years). The remaining seven patients in the partially divided group were not relieved of pain after operation (n = 5) or suffered early recurrence of pain (n = 2). They showed incomplete sensory loss in the first trigeminal division (V1) and had a second operation to extend the nerve division. V1 anaesthesia was established in all cases after the second procedure, and as a result, four are currently completely free of pain and one has near complete relief of pain. The remaining two patients are still experiencing severe neuralgia (mean follow up 4.1 years). Twelve out of 14 patients (85.7%) receiving surgery for chronic migrainous neuralgia experienced adequate pain relief and are able to follow a normal life (mean follow up 5.6 years). Corneal abrasion was the commonest long-term complication, occurring in three cases (28.5%) and progressing to chronic keratitis in one. We conclude that total trigeminal nerve root section is an effective treatment for patients suffering from chronic migrainous neuralgia and can be safely offered as a primary surgical treatment.

  7. Some like it hot: The emerging role of spicy food (capsaicin) in autoimmune diseases.

    PubMed

    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. PMID:26812350

  8. Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases.

    PubMed

    Basith, Shaherin; Cui, Minghua; Hong, Sunhye; Choi, Sun

    2016-01-01

    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. PMID:27455231

  9. Environmental risk assessment on capsaicin used as active substance for antifouling system on ships.

    PubMed

    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.

  10. Some like it hot: The emerging role of spicy food (capsaicin) in autoimmune diseases.

    PubMed

    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.

  11. Capsaicin: a potent inhibitor of carbonic anhydrase isoenzymes.

    PubMed

    Arabaci, Betul; Gulcin, Ilhami; Alwasel, Saleh

    2014-01-01

    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. PMID:25014536

  12. Capsaicin: a potent inhibitor of carbonic anhydrase isoenzymes.

    PubMed

    Arabaci, Betul; Gulcin, Ilhami; Alwasel, Saleh

    2014-01-01

    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.

  13. RPF151, a novel capsaicin-like analogue: in vitro studies and in vivo preclinical antitumor evaluation in a breast cancer model.

    PubMed

    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. PMID:25894379

  14. RPF151, a novel capsaicin-like analogue: in vitro studies and in vivo preclinical antitumor evaluation in a breast cancer model.

    PubMed

    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.

  15. Functional roles of capsaicin-sensitive intrinsic neural circuit in the regulation of esophageal peristalsis in rats: in vivo studies using a novel method.

    PubMed

    Shima, Takeshi; Shiina, Takahiko; Naitou, Kiyotada; Nakamori, Hiroyuki; Shimizu, Yasutake

    2014-05-01

    A well-developed myenteric plexus exists in the esophagus composed of striated muscle layers, but its functional role in controlling peristaltic movements remains to be clarified. The purpose of this study was to clarify the role of a local neural reflex consisting of capsaicin-sensitive primary afferent neurons and intrinsic neurons in esophageal peristalsis. We firstly devised a method to measure peristaltic movement of esophagus in vivo in rats. Rats were anesthetized with urethane, and esophageal intraluminal pressure and propelled intraluminal liquid volume were recorded. In the experimental system, an intraluminal pressure stimulus evoked periodic changes in intraluminal pressure of the esophagus, which were consistently accompanied by intraluminal liquid propulsion. Bilateral vagotomy abolished changes in intraluminal pressure as well as liquid propulsion. These results indicate that the novel method is appropriate for inducing peristalsis in the esophagus composed of striated muscles. Then, by using the method, we examined functional roles of the local reflex in esophageal peristalsis. For that purpose, we used rats in which capsaicin-sensitive neurons had been destroyed. The esophagus of capsaicin-treated rats showed a multiphasic rise in intraluminal pressure, which may due to noncoordinated contractions of esophageal muscles, whereas a monophasic response was observed in the intact rat esophagus. In addition, destruction of capsaicin-sensitive neurons increased the propelled liquid volume and lowered the pressure threshold for initiating peristalsis. These results suggest that the local neural reflex consisting of capsaicin-sensitive neurons and intrinsic neurons contributes to coordination of peristalsis and suppresses mechanosensory function of vagal afferents in the esophagus.

  16. Histopathological effects of radiosurgery on a human trigeminal nerve

    PubMed Central

    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

  17. Thermal nociceptive properties of trigeminal afferent neurons in rats

    PubMed Central

    2010-01-01

    Background Although nociceptive afferents innervating the body have been heavily studied form many years, much less attention has been paid to trigeminal afferent biology. In particular, very little is known concerning trigeminal nociceptor responses to heat, and almost nothing in the rat. This study uses a highly controlled and reproducible diode laser stimulator to investigate the activation of trigeminal afferents to noxious skin heating. Results The results of this experiment demonstrate that trigeminal thermonociceptors are distinct from themonociceptors innervating the limbs. Trigeminal nociceptors have considerably slower action potential conduction velocities and lower temperature thresholds than somatic afferent neurons. On the other hand, nociceptors innervating both tissue areas separate into those that respond to short pulse, high rate skin heating and those that respond to long pulse, low rate skin heating. Conclusions This paper provides the first description in the literature of the in vivo properties of thermonociceptors in rats. These finding of two separate populations aligns with the separation between C and A-delta thermonociceptors innervating the paw, but have significant differences in terms of temperature threshold and average conduction velocities. An understanding of the temperature response properties of afferent neurons innervating the paw skin have been critical in many mechanistic discoveries, some leading to new pain therapies. A clear understanding of trigeminal nociceptors may be similarly useful in the investigation of trigeminal pain mechanisms and potential therapies. PMID:20609212

  18. The influence of repetitive painful stimulation on peripheral and trigeminal pain thresholds.

    PubMed

    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.

  19. Strain differences in the toxicity of cadmium to trigeminal ganglia in mice.

    PubMed

    Habeebu, S S; Liu, Y; Park, J D; Klaassen, C D

    2001-12-15

    Cadmium (Cd) is toxic to sensory ganglia in many animal species. Cadmium uptake is low in the central nervous system, but it distributes preferentially to peripheral sensory and autonomic ganglia. Strain differences have been demonstrated in the sensitivity of mice to Cd-induced hepatotoxicity, testicular toxicity, and teratogenicity. To study the sensitivity of different mouse strains to Cd toxicity in sensory ganglia, eight strains of mice (four sensitive to testicular toxicity: 129/SVIM, AKR/J, DBA/1J, and C57BR/J; and four resistant: Balb/C, C3H/HeJ, A/J, and C57BL/6J) were given 15 micromol CdCl(2)/kg iv. Trigeminal ganglia (TG) were harvested 24 h later and examined by light microscopy for pathologic lesions. Cadmium induced degeneration of ganglion cells in five strains, namely 129/SVIM, AKR/J, DBA/1J, C57BR/J, and C3H/HeJ mice. These are the same strains that show sensitivity to testicular toxicity, except for C3H/HeJ, which is resistant to testicular toxicity. Cd also induced focal hemorrhages around the ganglion cells and nerve fibers in two of these strains (129/SVIM and AKR/J) and scattered foci of necrosis in C3H/HeJ and 129/SVIM strains. There was no morphologic abnormality in three strains, namely Balb/C, A/J, and C57BL/6J. To examine the mechanism of these strain differences in toxicity, all eight strains of mice were given a nontoxic dose of Cd (0.4 micromol CdCl(2)/kg, 20 microCi (109)Cd/kg iv). Cadmium distribution to the brain and trigeminal ganglia was determined 30 min later by gamma scintillation spectrometry. Cadmium content in the brain was very low and did not differ among the eight strains. In contrast, Cd content was higher in trigeminal ganglia of four of the five strains showing trigeminal ganglia sensitivity than in the three strains showing resistance. In conclusion, the toxicity of Cd to trigeminal ganglia is different among various strains of mice. This strain difference in toxicity appears to be due, at least in part, to

  20. [Functional anatomy of the trigeminal nerve].

    PubMed

    Leston, J M

    2009-04-01

    The cranial nerve (CN) V is a mixed nerve that consists primarily of sensory neurons. It exits the brain on the lateral surface of the pons, entering the trigeminal ganglion within a few millimeters. Three major branches emerge from the trigeminal ganglion. The first division (V1, the ophthalmic nerve) exits the cranium through the superior orbital fissure, entering the orbit to innervate the globe and skin in the area above the eye and forehead. The second division (V2, the maxillary nerve) exits through a round hole, the foramen rotundum, into a space posterior to the orbit, the pterygopalatine fossa. It then re-enters a canal running inferior to the orbit, the infraorbital canal, and exits through a small hole, the infraorbital foramen, to innervate the skin below the eye and above the mouth. The third division (V3, the mandibular nerve) exits the cranium through an oval hole, the foramen ovale. The third division also has an additional motor component, which may run in a separate fascial compartment. Most fibers travel directly to their target tissues. Sensory axons innervate skin on the lateral side of the head, the tongue, and the mucosal wall of the oral cavity. Motor fibers innervate the muscles that are attached to the mandible. Some sensory axons enter in the mandible to innervate the teeth and emerge from the mental foramen to innervate the skin of the lower jaw.

  1. Hemicrania continua. Unquestionably a trigeminal autonomic cephalalgia.

    PubMed

    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.

  2. Capsaicin and dihydrocapsaicin determination in chili pepper genotypes using ultra-fast liquid chromatography.

    PubMed

    Usman, Magaji G; Rafii, Mohd Y; Ismail, Mohd R; Malek, Md Abdul; Latif, Mohammad Abdul

    2014-01-01

    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. PMID:24853712

  3. Capsaicin and dihydrocapsaicin determination in chili pepper genotypes using ultra-fast liquid chromatography.

    PubMed

    Usman, Magaji G; Rafii, Mohd Y; Ismail, Mohd R; Malek, Md Abdul; Latif, Mohammad Abdul

    2014-01-01

    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.

  4. Local administration of resveratrol inhibits excitability of nociceptive wide-dynamic range neurons in rat trigeminal spinal nucleus caudalis.

    PubMed

    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. PMID:27288246

  5. Local administration of resveratrol inhibits excitability of nociceptive wide-dynamic range neurons in rat trigeminal spinal nucleus caudalis.

    PubMed

    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.

  6. Diabetes mellitus affects activity of calcium/calmodulin-dependent protein kinase II alpha in rat trigeminal ganglia.

    PubMed

    Jerić, Milka; Vuica, Ana; Borić, Matija; Puljak, Livia; Jeličić Kadić, Antonia; Grković, Ivica; Filipović, Natalija

    2015-01-01

    The activity of calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) may play a critical role in the modulation of nociceptor activity and plasticity of primary sensory trigeminal neurons. The aim of this study was to investigate the immunoreactivity of phosphorylated CaMKIIα (pCaMKIIα) in subpopulations of trigeminal ganglion (TG) neurons in rat models of early diabetes type 1 (dm1) and 2 (dm2). DM1 model was induced with intraperitoneally (i.p.) injected streptozotocin (STZ) (55mg/kg). DM2 rats were fed with the high fat diet (HFD) for 2 weeks and then received 35mg/kg of STZ i.p. Two weeks and 2 months after the STZ-diabetes induction, rats were sacrificed and immunohistochemical analysis for detection of pCaMKIIα immunoreactivity and double immunofluorescence labelling with isolectin (IB4) was performed. Increased intensity of pCaMKIIα immunofluorescence, restricted to IB4-negative small-diameter neurons, was seen in TG neurons two months after STZ-DM1 induction. DM1 model, as well as the obesity (control dm2 groups) resulted in neuronal impaired growth while dm2 model led to neuron hypertrophy in TG. Observed changes may play a critical role in the modulation of nociceptor activity and plasticity of primary sensory trigeminal neurons. In future, innovative strategies for modulation of CaMKIIα activity in specific subpopulations of neurons could be a novel approach in therapy of diabetic trigeminal neuropathy.

  7. Eugenol inhibits the GABAA current in trigeminal ganglion neurons.

    PubMed

    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 < 0.05) in TG neurons, which recovered after a 3-min washout. In HEK 293 cells expressing the α1β2γ2 subtype, 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.

  8. Capsicum and capsaicin--a review: case report of the use of hot peppers in child abuse.

    PubMed

    Tominack, R L; Spyker, D A

    1987-01-01

    Capsaicin, the active principle of hot peppers of the genus Capsicum, exhibits broad bioactivity. It targets neuronal structures which contain substance P, clinically seen as gastrointestinal and dermatologic irritation, bronchospasm and fibrinolysis. As a research tool, capsaicin profoundly alters neurologic anatomy and function. We review the toxicity of capsaicin and comment briefly on the use of hot peppers in child abuse. PMID:3328791

  9. Influence of Dietary Capsaicin on Redox Status in Red Blood Cells During Human Aging

    PubMed Central

    Kumar, Prabhanshu; Chand, Subhash; Chandra, Pranjal; Maurya, Pawan Kumar

    2015-01-01

    Purpose: Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a major pungent compound found in hot peppers of the plant genus Capsicum. In vitro effects of dietary capsaicin on redox status in red blood cells during human aging have been explored. Methods: Total antioxidant potential of capsaicin was evaluated using Ferric reducing ability of plasma (FRAP) assay. GSH was measured as per standard protocol. The in vitro effect of capsaicin was evaluated by incubation of the cells in the assay medium with 10-5M capsaicin (final concentration) for 60 min at 37°C. Results: Treatment with capsaicin (10-5M) caused a significant (p < 0.01) increase in GSH level in all age groups. Reduced glutathione (GSH) / Oxidized glutathione (GSSG) ratio measures the redox status of the red blood cell. Significant increase in GSH level due to capsaicin, shift the GSH/GSSG ratio, thus alters the redox status of the cell. Conclusion: The results conclusively prove the efficacy of the antioxidant property of capsaicin and its role in modulating the redox status of red blood cells. This evidence suggests that dietary factors that act as antioxidants to increase GSH level may contribute to a protective effect against age related diseases. This antioxidant effect may, in part, explain the high consumption of capsicum in certain regions of the world. PMID:26819932

  10. Location, Partitioning Behavior, and Interaction of Capsaicin with Lipid Bilayer Membrane: Study Using Its Intrinsic Fluorescence.

    PubMed

    Swain, Jitendriya; Kumar Mishra, Ashok

    2015-09-10

    Capsaicin is an ingredient of a wide variety of red peppers, and it has various pharmacological and biological applications. The present study explores the interaction of capsaicin with dimyristoylphosphatidylcholine (DMPC) lipid bilayer membrane by monitoring various photophysical parameters using its intrinsic fluorescence. In order to have a clearer understanding of the photophysical responses of capsaicin, studies involving (i) its solvation behavior in different solvents, (ii) the partition coefficient of capsaicin in different thermotropic phase states of lipid bilayer membrane, and (iii) its location inside lipid bilayer membrane have been carried out. Capsaicin has a reasonably high partition coefficient for DMPC liposome membrane, in both solid gel (2.8 ± 0.1 × 10(5)) and liquid crystalline (2.6 ± 0.1 × 10(5)) phases. Fluorescence quenching study using cetylpyridinium chloride (CPC) as quencher suggests that the phenolic group of capsaicin molecule is generally present near the headgroup region and hydrophobic tail present inside hydrophobic core region of the lipid bilayer membrane. The intrinsic fluorescence intensity and lifetime of capsaicin sensitively respond to the temperature dependent phase changes of liposome membrane. Above 15 mol %, capsaicin in the aqueous liposome suspension medium lowers the thermotropic phase transition temperature by about 3 °C, and above 30 mol %, the integrity of the membrane is significantly lost.

  11. Characterization of cardiovascular reflexes evoked by airway stimulation with allylisothiocyanate, capsaicin, and ATP in Sprague-Dawley rats.

    PubMed

    Hooper, J S; Hadley, S H; Morris, K F; Breslin, J W; Dean, J B; Taylor-Clark, T E

    2016-03-15

    Acute inhalation of airborne pollutants alters cardiovascular function and evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the effect of capsaicin [transient receptor potential (TRP) vanilloid 1 (TRPV1) agonist], AITC [TRP ankyrin 1 (TRPA1) agonist], and ATP (P2X2/3 agonist) on bronchopulmonary sensory activity and cardiovascular responses of conscious Sprague-Dawley (SD) rats. Single fiber recordings show that allyl isothiocyanate (AITC) and capsaicin selectively activate C fibers, whereas subpopulations of both A and C fibers are activated by stimulation of P2X2/3 receptors. Inhalation of the agonists by conscious rats caused significant bradycardia, atrioventricular (AV) block, and prolonged PR intervals, although ATP-induced responses were lesser than those evoked by AITC or capsaicin. Responses to AITC were inhibited by the TRP channel blocker ruthenium red and the muscarinic antagonist atropine. AITC inhalation also caused a biphasic blood pressure response: a brief hypertensive phase followed by a hypotensive phase. Atropine accentuated the hypertensive phase, while preventing the hypotension. AITC-evoked bradycardia was not abolished by terazosin, the α1-adrenoceptor inhibitor, which prevented the hypertensive response. Anesthetics had profound effects on AITC-evoked bradycardia and AV block, which was abolished by urethane, ketamine, and isoflurane. Nevertheless, AITC inhalation caused bradycardia and AV block in paralyzed and ventilated rats following precollicular decerebration. In conclusion, we provide evidence that activation of ion channels expressed on nociceptive airway sensory nerves causes significant cardiovascular effects in conscious SD rats via reflex modulation of the autonomic nervous system. PMID:26718787

  12. Capsaicin Interaction with TRPV1 Channels in a Lipid Bilayer: Molecular Dynamics Simulation

    PubMed Central

    Hanson, Sonya M.; Newstead, Simon; Swartz, Kenton J.; Sansom, Mark S.P.

    2015-01-01

    Transient receptor potential vanilloid subtype 1 (TRPV1) is a heat-sensitive ion channel also involved in pain sensation, and is the receptor for capsaicin, the active ingredient of hot chili peppers. The recent structures of TRPV1 revealed putative ligand density within the S1 to S4 voltage-sensor-like domain of the protein. However, questions remain regarding the dynamic role of the lipid bilayer in ligand binding to TRPV1. Molecular dynamics simulations were used to explore behavior of capsaicin in a 1-palmitoyl-2-oleoyl phosphatidylcholine bilayer and with the target S1–S4 transmembrane helices of TRPV1. Equilibrium simulations reveal a preferred interfacial localization for capsaicin. We also observed a capsaicin molecule flipping from the extracellular to the intracellular leaflet, and subsequently able to access the intracellular TRPV1 binding site. Calculation of the potential of mean force (i.e., free energy profile) of capsaicin along the bilayer normal confirms that it prefers an interfacial localization. The free energy profile indicates that there is a nontrivial but surmountable barrier to the flipping of capsaicin between opposing leaflets of the bilayer. Molecular dynamics of the S1–S4 transmembrane helices of the TRPV1 in a lipid bilayer confirm that Y511, known to be crucial to capsaicin binding, has a distribution along the bilayer normal similar to that of the aromatic group of capsaicin. Simulations were conducted of the TRPV1 S1–S4 transmembrane helices in the presence of capsaicin placed in the aqueous phase, in the lipid, or docked to the protein. No stable interaction between ligand and protein was seen for simulations initiated with capsaicin in the bilayer. However, interactions were seen between TRPV1 and capsaicin starting from the cytosolic aqueous phase, and capsaicin remained stable in the majority of simulations from the docked pose. We discuss the significance of capsaicin flipping from the extracellular to the intracellular

  13. Capsaicin interaction with TRPV1 channels in a lipid bilayer: molecular dynamics simulation.

    PubMed

    Hanson, Sonya M; Newstead, Simon; Swartz, Kenton J; Sansom, Mark S P

    2015-03-24

    Transient receptor potential vanilloid subtype 1 (TRPV1) is a heat-sensitive ion channel also involved in pain sensation, and is the receptor for capsaicin, the active ingredient of hot chili peppers. The recent structures of TRPV1 revealed putative ligand density within the S1 to S4 voltage-sensor-like domain of the protein. However, questions remain regarding the dynamic role of the lipid bilayer in ligand binding to TRPV1. Molecular dynamics simulations were used to explore behavior of capsaicin in a 1-palmitoyl-2-oleoyl phosphatidylcholine bilayer and with the target S1-S4 transmembrane helices of TRPV1. Equilibrium simulations reveal a preferred interfacial localization for capsaicin. We also observed a capsaicin molecule flipping from the extracellular to the intracellular leaflet, and subsequently able to access the intracellular TRPV1 binding site. Calculation of the potential of mean force (i.e., free energy profile) of capsaicin along the bilayer normal confirms that it prefers an interfacial localization. The free energy profile indicates that there is a nontrivial but surmountable barrier to the flipping of capsaicin between opposing leaflets of the bilayer. Molecular dynamics of the S1-S4 transmembrane helices of the TRPV1 in a lipid bilayer confirm that Y511, known to be crucial to capsaicin binding, has a distribution along the bilayer normal similar to that of the aromatic group of capsaicin. Simulations were conducted of the TRPV1 S1-S4 transmembrane helices in the presence of capsaicin placed in the aqueous phase, in the lipid, or docked to the protein. No stable interaction between ligand and protein was seen for simulations initiated with capsaicin in the bilayer. However, interactions were seen between TRPV1 and capsaicin starting from the cytosolic aqueous phase, and capsaicin remained stable in the majority of simulations from the docked pose. We discuss the significance of capsaicin flipping from the extracellular to the intracellular

  14. Exposure to Allergen Causes Changes in NTS Neural Activities after Intratracheal Capsaicin Application, in Endocannabinoid Levels and in the Glia Morphology of NTS.

    PubMed

    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.

  15. Exposure to Allergen Causes Changes in NTS Neural Activities after Intratracheal Capsaicin Application, in Endocannabinoid Levels and in the Glia Morphology of NTS

    PubMed Central

    Spaziano, Giuseppe; Petrosino, Stefania; Matteis, Maria; Palazzo, Enza; Sullo, Nikol; de Novellis, Vito; 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. PMID:25866824

  16. Identification of a Potential Target of Capsaicin by Computational Target Fishing.

    PubMed

    Ye, Xuan-Yi; Ling, Qing-Zhi; Chen, Shao-Jun

    2015-01-01

    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. PMID:26770256

  17. Identification of a Potential Target of Capsaicin by Computational Target Fishing

    PubMed Central

    Ye, Xuan-yi; Ling, Qing-zhi; Chen, Shao-jun

    2015-01-01

    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. PMID:26770256

  18. Identification of a Potential Target of Capsaicin by Computational Target Fishing.

    PubMed

    Ye, Xuan-Yi; Ling, Qing-Zhi; Chen, Shao-Jun

    2015-01-01

    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.

  19. The effects of a series of capsaicin analogues on nociception and body temperature in the rat.

    PubMed

    Hayes, A G; Oxford, A; Reynolds, M; Shingler, A H; Skingle, M; Smith, C; Tyers, M B

    1984-03-26

    A series of capsaicin analogues have been synthesized in an attempt to try to separate the antinociceptive properties of capsaicin from its hypothermic effects. In capsaicin analogues with an unbranched alkyl side-chain of varying length, maximum antinociceptive and hypothermic activity was achieved with a chain length of 8-9 C atoms. Decreasing the chain length decreased both parameters equally. Substitution in the aromatic ring abolished activity. Several compounds related to homovanilloyl dodecylamide, an analogue of capsaicin in which the acylamide linkage is reversed, produced some antinociceptive activity without concomitant hypothermia, but the maximum antinociceptive effect achieved was very small. In the present series of capsaicin analogues good antinociception without hypothermia was not found.

  20. Decreased inflammatory response in rat bladder after intravesical administration of capsaicin-loaded liposomes.

    PubMed

    Cirino, Lorena M D; Vergne, Daviane M C; Santana, Patrícia F; Almeida, Enrik DE; Costa, Luiz P DA; Albuquerque-Júnior, Ricardo L C DE; Lima-Verde, Isabel B; Padilha, Francine F; Cardoso, Juliana C

    2016-09-01

    The objective of this work was to study the reduction in the capsaicin toxicity by encapsulation in liposomes. Capsaicin was extracted from peppers and characterized with high performance liquid chromatography (HPLC). We determined the zeta potential, polydispersivity index (PdI) and vesicle size of liposomes. Wistar rats were submitted to intravesical instillation of liposomes (LIP), capsaicin (CAP) or liposomes with capsaicin (CAPLIP). After 24 hours, bladders were removed for histological analysis. Vesicle size ranged from 68 to 105 nm with PdI smaller than 0.2 and zeta potential around -30 mV. The vesicles maintained stability over the 14-day study. The histological analysis of the CAP group showed intense inflammation in almost all bladder layers, as well as ulcer formation. Conversely, the CAPLIP group showed a smooth inflammatory reaction and hyperemia. In conclusion, the liposomes effectively protected the bladder against the irritative action of capsaicin. PMID:27598840

  1. Hemimasticatory spasm treated with microvascular decompression of the trigeminal nerve.

    PubMed

    Chon, Kyu-Hyon; Lee, Jong-Myong; Koh, Eun-Jeong; Choi, Ha-Young

    2012-09-01

    Hemimasticatory spasm is a very rare disorder of the trigeminal nerve characterized by paroxysmal involuntary contraction of the jaw-closing muscles. The mechanisms leading to hemimasticatory spasm are still unclear. Recently, injection of botulinum toxin has become the treatment of choice due to its excellent results. We report a case of a successful treatment of hemimasticatory spasm via microvascular decompression of the motor branch of the trigeminal nerve.

  2. Physiological temperatures drive glutamate release onto trigeminal superficial dorsal horn neurons

    PubMed Central

    Hegarty, Deborah M.; Aicher, Sue A.; Andresen, Michael C.

    2014-01-01

    Trigeminal sensory afferent fibers terminating in nucleus caudalis (Vc) relay sensory information from craniofacial regions to the brain and are known to express transient receptor potential (TRP) ion channels. TRP channels are activated by H+, thermal, and chemical stimuli. The present study investigated the relationships among the spontaneous release of glutamate, temperature, and TRPV1 localization at synapses in the Vc. Spontaneous excitatory postsynaptic currents (sEPSCs) were recorded from Vc neurons (n = 151) in horizontal brain-stem slices obtained from Sprague-Dawley rats. Neurons had basal sEPSC rates that fell into two distinct frequency categories: High (≥10 Hz) or Low (<10 Hz) at 35°C. Of all recorded neurons, those with High basal release rates (67%) at near-physiological temperatures greatly reduced their sEPSC rate when cooled to 30°C without amplitude changes. Such responses persisted during blockade of action potentials indicating that the High rate of glutamate release arises from presynaptic thermal mechanisms. Neurons with Low basal frequencies (33%) showed minor thermal changes in sEPSC rate that were abolished after addition of TTX, suggesting these responses were indirect and required local circuits. Activation of TRPV1 with capsaicin (100 nM) increased miniature EPSC (mEPSC) frequency in 70% of neurons, but half of these neurons had Low basal mEPSC rates and no temperature sensitivity. Our evidence indicates that normal temperatures (35–37°C) drive spontaneous excitatory synaptic activity within superficial Vc by a mechanism independent of presynaptic action potentials. Thus thermally sensitive inputs on superficial Vc neurons may tonically activate these neurons without afferent stimulation. PMID:24598529

  3. Early dexamethasone relieves trigeminal neuropathic pain.

    PubMed

    Han, S R; Yeo, S P; Lee, M K; Bae, Y C; Ahn, D K

    2010-09-01

    The analgesic effects of dexamethasone on neuropathic pain have been controversial. The present study investigated the effects of dexamethasone on mechanical allodynia in rats with mal-positioned dental implants. Under anesthesia, the left mandibular second molar was extracted and replaced by a miniature dental implant to injure the inferior alveolar nerve. Nociceptive behavior was examined on each designated day after surgery. Mal-positioned dental implants significantly decreased air-puff thresholds both ipsilateral and contralateral to the injury site. Distinct mechanical hyperalgesia and cold and thermal hypersensitivity were also observed bilaterally. Daily administration of dexamethasone produced prolonged anti-allodynic effects (25 or 50 mg/kg, i.p.), but failed to reduce mechanical allodynia when it had already been established. Therefore, our findings provide that early treatment with dexamethasone is important in the treatment of nociceptive behavior suggestive of trigeminal neuropathic pain. PMID:20581355

  4. Trigeminal neuralgia caused by the vertebral artery associated with primitive trigeminal artery and agenesis of the internal carotid artery.

    PubMed

    Fukuda, M; Kameyama, S; Takahashi, H; Tanaka, R

    1998-06-01

    A 69-year-old female presented with trigeminal neuralgia caused by tortuous vertebrobasilar artery associated with primitive trigeminal artery (PTA) and agenesis of the ipsilateral internal carotid artery (ICA). Left vertebral angiography showed marked elongation of the left vertebral artery and filling of the left ICA via the PTA. Bone window computed tomography suggested agenesis of the left ICA. Intraoperative findings showed that the vertebrobasilar junction had compressed the root entry zone of the trigeminal nerve. The neuralgia improved immediately after microvascular decompression. There has been no recurrence for 20 months. Trigeminal neuralgia may be caused by a tortuous vertebrobasilar system due to hemodynamic stress associated with PTA and agenesis of the ICA. PMID:9689822

  5. Cocoa Enriched Diets Enhance Expression of Phosphatases and Decrease Expression of Inflammatory Molecules in Trigeminal Ganglion Neurons

    PubMed Central

    Cady, Ryan J.; Durham, Paul L.

    2010-01-01

    Activation of trigeminal nerves and release of neuropeptides that promote inflammation are implicated in the underlying pathology of migraine and temporomandibular joint (TMJ) disorders. The overall response of trigeminal nerves to peripheral inflammatory stimuli involves a balance between enzymes that promote inflammation, kinases, and those that restore homeostasis, phosphatases. The goal of this study was to determine the effects of a cocoa-enriched diet on the expression of key inflammatory proteins in trigeminal ganglion neurons under basal and inflammatory conditions. Rats were fed a control diet or an isocaloric diet enriched in cocoa for 14 days prior to an injection of noxious stimuli to cause acute or chronic excitation of trigeminal neurons. In animals fed a cocoa-enriched diet, basal levels of the mitogen-activated kinase (MAP) phosphatases MKP-1 and MKP-3 were elevated in neurons. Importantly, the stimulatory effects of acute or chronic peripheral inflammation on neuronal expression of the MAPK p38 and extracellular signal-regulated kinases (ERK) were significantly repressed in response to cocoa. Similarly, dietary cocoa significantly suppressed basal neuronal expression of calcitonin gene-related peptide (CGRP) as well as stimulated levels of the inducible form of nitric oxide synthase (iNOS), proteins implicated in the underlying pathology of migraine and TMJ disorders. To our knowledge, this is first evidence that a dietary supplement can cause upregulation of MKP, and that cocoa can prevent inflammatory responses in trigeminal ganglion neurons. Furthermore, our data provide evidence that cocoa contains biologically active compounds that would be beneficial in the treatment of migraine and TMJ disorders. PMID:20138852

  6. Aqueous two-phase extraction combined with chromatography: new strategies for preparative separation and purification of capsaicin from capsicum oleoresin.

    PubMed

    Zhao, Pei-Pei; Lu, Yan-Min; Tan, Cong-Ping; Liang, Yan; Cui, Bo

    2015-01-01

    Capsaicin was preparatively separated and purified from capsicum oleoresin with a new method combined with aqueous two-phase extraction (ATPE) and chromatography. Screening experiments of ATPE systems containing salts and hydrophilic alcohols showed that potassium carbonate/ethanol system was the most suitable system for capsaicin recovery among the systems considered. Response surface methodology was used to determine an optimized aqueous two-phase system for the extraction of capsaicin from capsaicin oleoresin. In a 20 % (w/w) ethanol/22.3 % (w/w) potassium carbonate system, 85.4 % of the capsaicin was recovered in the top ethanol-rich phase while most oil and capsanthin ester were removed in the interphase. The capsaicinoid extract was then subjected to two chromatographic steps using D101 macroporous resin and inexpensive SKP-10-4300 reverse-phase resin first applied for the purification of capsaicin. After simple optimization of loading/elution conditions for D101 macroporous resin chromatography and SKP-10-4300 reverse-phase resin chromatography, the purities of capsaicin were improved from 7 to 85 %. In the two chromatography processes, the recoveries of capsaicin were 93 and 80 % respectively; the productivities of capsaicin were 1.86 and 4.2 (g capsaicin/L resin) per day respectively. It is worth mentioning that a by-product of capsaicin production was also obtained with a high purity (90 %). PMID:25355002

  7. Electrochemical impedance spectroscopy versus cyclic voltammetry for the electroanalytical sensing of capsaicin utilising screen printed carbon nanotube electrodes.

    PubMed

    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.

  8. Aqueous two-phase extraction combined with chromatography: new strategies for preparative separation and purification of capsaicin from capsicum oleoresin.

    PubMed

    Zhao, Pei-Pei; Lu, Yan-Min; Tan, Cong-Ping; Liang, Yan; Cui, Bo

    2015-01-01

    Capsaicin was preparatively separated and purified from capsicum oleoresin with a new method combined with aqueous two-phase extraction (ATPE) and chromatography. Screening experiments of ATPE systems containing salts and hydrophilic alcohols showed that potassium carbonate/ethanol system was the most suitable system for capsaicin recovery among the systems considered. Response surface methodology was used to determine an optimized aqueous two-phase system for the extraction of capsaicin from capsaicin oleoresin. In a 20 % (w/w) ethanol/22.3 % (w/w) potassium carbonate system, 85.4 % of the capsaicin was recovered in the top ethanol-rich phase while most oil and capsanthin ester were removed in the interphase. The capsaicinoid extract was then subjected to two chromatographic steps using D101 macroporous resin and inexpensive SKP-10-4300 reverse-phase resin first applied for the purification of capsaicin. After simple optimization of loading/elution conditions for D101 macroporous resin chromatography and SKP-10-4300 reverse-phase resin chromatography, the purities of capsaicin were improved from 7 to 85 %. In the two chromatography processes, the recoveries of capsaicin were 93 and 80 % respectively; the productivities of capsaicin were 1.86 and 4.2 (g capsaicin/L resin) per day respectively. It is worth mentioning that a by-product of capsaicin production was also obtained with a high purity (90 %).

  9. Cuneus and fusiform cortices thickness is reduced in trigeminal neuralgia

    PubMed Central

    2014-01-01

    Background Chronic pain disorders are presumed to induce changes in brain grey and white matters. Few studies have focused CNS alterations in trigeminal neuralgia (TN). Methods The aim of this study was to explore changes in white matter microstructure in TN subjects using diffusion tensor images (DTI) with tract-based spatial statistics (TBSS); and cortical thickness changes with surface based morphometry. Twenty-four patients with classical TN (37-67 y-o) and 24 healthy controls, matched for age and sex, were included in the study. Results Comparing patients with controls, no diffusivity abnormalities of brain white matter were detected. However, a significant reduction in cortical thickness was observed at the left cuneus and left fusiform cortex in the patients group. The thickness of the fusiform cortex correlated negatively with the carbamazepine dose (p = 0.023). Conclusions Since the cuneus and the fusiform gyrus have been related to the multisensory integration area and cognitive processing, as well as the retrieval of shock perception conveyed by Aδ fibers, our results support the role of these areas in TN pathogenesis. Whether such changes occurs as an epiphenomenon secondary to daily stimulation or represent a structural predisposition to TN in the light of peripheral vascular compression is a matter of future studies. PMID:24661349

  10. Advanced technologies and novel neurostimulation targets in trigeminal autonomic cephalalgias.

    PubMed

    Lambru, Giorgio; Giakoumakis, Emmanouil; Al-Kaisy, Adnan

    2015-05-01

    The trigeminal autonomic cephalalgias (TACs) are a group of rare but disabling primary headache disorders. Their management is challenging, since only few effective treatments are available and high doses may be required to control the headache, compromising patients' adherence to treatments. A significant minority of patients, who fail to respond to or tolerate established treatments, are left with enormous level of disability and disruption to their quality of life. A growing body of evidence demonstrates the efficacy of central and peripheral neuromodulation approaches for management of patients with refractory TACs. In view of the potential risks related to deep brain stimulation of the posterior hypothalamic region, occipital nerve stimulation is currently considered the first treatment option for refractory chronic TACs. However, in view of the presence of paraesthesia induced by the stimulator, no robust controlled trials have been possible so far. Additionally, the equipment used for occipital nerve stimulation is not designed specifically for peripheral nerve stimulation, thus a significant proportion of patients experience device-related complications that often require surgical revisions. To overcome these issues, new neurostimulation technologies using less invasive or non-invasive approaches and modulating different neuroanatomical targets have been recently studied. PMID:26017527

  11. Antioxidant and iron-binding properties of curcumin, capsaicin, and S-allylcysteine reduce oxidative stress in rat brain homogenate.

    PubMed

    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. Enhanced itch elicited by capsaicin in a chronic itch model

    PubMed Central

    Yu, Guang; Yang, Niuniu; Li, Fengxian; Chen, Meijuan; Guo, Changxiong J; Wang, Changming; Hu, Danyou; Yang, Yan; Zhu, Chan; Wang, Zhongli; Shi, Hao; Gegen, Tana; Tang, Ming; He, Qian

    2016-01-01

    Chronic itch (pruritus) is an important clinical problem. However, the underlying molecular basis has yet to be understood. The Transient Receptor Potential Vanilloid 1 channel is a heat-sensitive cation channel expressed in primary sensory neurons and involved in both thermosensation and pain, but its role in chronic itch remains elusive. Here, we for the first time revealed an increased innervation density of Transient Receptor Potential Vanilloid 1-expressing sensory fibers in the skin afflicted with chronic itch. Further analysis indicated that this phenomenon is due to an expansion of Transient Receptor Potential Vanilloid 1-expressing sensory neurons under chronic itch conditions. As a functional correlates of this neuronal expansion, we observed an enhanced neuronal responsiveness to capsaicin under the dry skin conditions. Importantly, the neuronal hypersensitivity to capsaicin results in itch, rather than pain sensation, suggesting that the up-regulated Transient Receptor Potential Vanilloid 1 underlies the pain-to-itch switch under chronic itchy conditions. The study shows that there are different mechanisms of chronic pain and itching, and Transient Receptor Potential Vanilloid 1 plays an important role in chronic itch. PMID:27118771

  13. Chitosan encapsulation modulates the effect of capsaicin on the tight junctions of MDCK cells

    PubMed Central

    Kaiser, M.; Pereira, S.; Pohl, L.; Ketelhut, S.; Kemper, B.; Gorzelanny, C.; Galla, H. -J.; Moerschbacher, B. M.; Goycoolea, F. M.

    2015-01-01

    Capsaicin has known pharmacological effects including the ability to reversibly open cellular tight junctions, among others. The aim of this study was to develop a strategy to enhance the paracellular transport of a substance with low permeability (FITC-dextran) across an epithelial cell monolayer via reversible opening of cellular tight junctions using a nanosystem comprised by capsaicin and of chitosan. We compared the biophysical properties of free capsaicin and capsaicin-loaded chitosan nanocapsules, including their cytotoxicity towards epithelial MDCK-C7 cells and their effect on the integrity of tight junctions, membrane permeability and cellular uptake. The cytotoxic response of MDCK-C7 cells to capsaicin at a concentration of 500 μM, which was evident for the free compound, is not observable following its encapsulation. The interaction between nanocapsules and the tight junctions of MDCK-C7 cells was investigated by impedance spectroscopy, digital holographic microscopy and structured illumination fluorescence microscopy. The nanocapsules modulated the interaction between capsaicin and tight junctions as shown by the different time profile of trans-epithelial electrical resistance and the enhanced permeability of monolayers incubated with FITC-dextran. Structured illumination fluorescence microscopy showed that the nanocapsules were internalized by MDCK-C7 cells. The capsaicin-loaded nanocapsules could be further developed as drug nanocarriers with enhanced epithelial permeability. PMID:25970096

  14. Voltage-activated sodium current is inhibited by capsaicin in rat atrial myocytes.

    PubMed

    Milesi, V; Rebolledo, A; Alvis, A G; Raingo, J; Grassi de Gende, A O

    2001-04-13

    The effects of capsaicin, the active principle of hot pepper genus Capsicum, were studied on voltage-activated, tetrodotoxin-sensitive Na+ currents in isolated rat atrial cells using the patch clamp technique in the whole-cell configuration. 0.4 and 4 microM of capsaicin produced a significant tonic block on voltage-activated Na+ current (I(Na)) evoked by a depolarizing step to -40 mV from a holding potential of -100 mV (49 +/- 7% n = 11, P < 0.05 and 72 +/- 13% n = 4, P < 0.05 respectively). We didn't observe any use-dependent block of capsaicin in our experimental conditions. Capsaicin slowed the time decay of inactivation of I(Na), and increased the time constant of the recovery of inactivation. Capsaicin and tetrodotoxin (TTX) depressed contractility of isolated electrically driven left rat atria, being the depression of maximal velocity of force development (dF/dt(max)) with respect to control values of 19 +/- 3% at 1 microM of capsaicin and 22 +/- 2% at 1 microM of TTX. These results show an inhibitory effect of capsaicin on I(Na) in isolated atrial cells that may modify the electrical and contractile function of the rat heart. PMID:11352646

  15. Chitosan encapsulation modulates the effect of capsaicin on the tight junctions of MDCK cells.

    PubMed

    Kaiser, M; Pereira, S; Pohl, L; Ketelhut, S; Kemper, B; Gorzelanny, C; Galla, H-J; Moerschbacher, B M; Goycoolea, F M

    2015-05-13

    Capsaicin has known pharmacological effects including the ability to reversibly open cellular tight junctions, among others. The aim of this study was to develop a strategy to enhance the paracellular transport of a substance with low permeability (FITC-dextran) across an epithelial cell monolayer via reversible opening of cellular tight junctions using a nanosystem comprised by capsaicin and of chitosan. We compared the biophysical properties of free capsaicin and capsaicin-loaded chitosan nanocapsules, including their cytotoxicity towards epithelial MDCK-C7 cells and their effect on the integrity of tight junctions, membrane permeability and cellular uptake. The cytotoxic response of MDCK-C7 cells to capsaicin at a concentration of 500 μM, which was evident for the free compound, is not observable following its encapsulation. The interaction between nanocapsules and the tight junctions of MDCK-C7 cells was investigated by impedance spectroscopy, digital holographic microscopy and structured illumination fluorescence microscopy. The nanocapsules modulated the interaction between capsaicin and tight junctions as shown by the different time profile of trans-epithelial electrical resistance and the enhanced permeability of monolayers incubated with FITC-dextran. Structured illumination fluorescence microscopy showed that the nanocapsules were internalized by MDCK-C7 cells. The capsaicin-loaded nanocapsules could be further developed as drug nanocarriers with enhanced epithelial permeability.

  16. The effects of chronic low-dose capsaicin treatment on substance P levels.

    PubMed

    Erin, Nuray; Zik, Berrin; Sarigül, Münevver; Tütüncü, Serife

    2009-02-25

    Capsaicin, the pungent ingredient of red pepper, is consumed in varying amounts by many ethnic groups. It serves both therapeutically and as a specific tool to investigate sensory neurons. Although effects of high capsaicin doses are well-established, systemic effects of chronic low-dose capsaicin exposure are unknown. Sprague-Dawley rats (21-day old) were injected with capsaicin (0.5 mg/kg, ip) for 6 and 19 days. Changes in Substance P (SP) levels of lung and skin were measured. Two-step sequential acetic acid extraction was used to estimate neuronal and non-neuronal SP. Six-day, but not 19-day capsaicin treatment decreased SP levels in first as well as second extractions of both tissues. Because the cumulative dose used here was much lower than the neurotoxic doses of capsaicin, initial decrease of SP levels must be due to continuous release of SP from nerve endings as well as non-neuronal tissues. The fact that SP levels returned to control values at the end of 19-day treatment demonstrates that reactive increases in SP synthesis occurred. These findings suggest that systemic exposure to low-dose capsaicin enhances sensory nerve function and also increases SP in non-neuronal tissues. In addition, significantly decreased SP levels of both tissues were observed in 40-day, compared to 27-day old rats.

  17. Capsaicin inhibits the Wnt/β-catenin signaling pathway by down-regulating PP2A.

    PubMed

    Park, Dong-Seok; Yoon, Gang-Ho; Lee, Hyun-Shik; Choi, Sun-Cheol

    2016-09-01

    Xenopus embryo serves as an ideal model for teratogenesis assays to examine the effects of any substances on the cellular processes critical for early development and adult tissue homeostasis. In our chemical library screening with frog embryo, capsaicin was found to repress the Wnt/β-catenin signaling. Depending on the stages at which embryos became exposed to capsaicin, it could disrupt formation of dorsal or posterior body axis of embryo, which is associated with inhibition of maternal or zygotic Wnt signal in early development. In agreement with these phenotypes, capsaicin suppressed the expression of Wnt target genes such as Siamois and Chordin in the organizer region of embryo and in Wnt signals-stimulated tissue explants. In addition, the cellular level of β-catenin, a key component of Wnt pathway, was down-regulated in capsaicin-treated embryonic cells. Unlike wild-type β-catenin, its non-phosphorylatable mutant in which serine and threonine residues phosphorylated by GSK3 are substituted with alanine was not destabilized by capsaicin, indicative of the effect of this chemical on the phosphorylation status of β-catenin. In support of this, capsaicin up-regulated the level of GSK3- or CK1-phosphorylated β-catenin, concomitantly lowering that of its de-phosphorylated version. Notably, capsaicin augmented the phosphorylation of a phosphatase, PP2A at tyrosine 307, suggesting its repression of the enzymatic activity of the phosphatase. Furthermore, capsaicin still enhanced β-catenin phosphorylation in cells treated with a GSK3 inhibitor, LiCl but not in those treated with a phosphatase inhibitor, okadaic acid. Together, these results indicate that capsaicin inhibits the patterning of the dorso-ventral and anterior-posterior body axes of embryo by repressing PP2A and thereby down-regulating the Wnt/β-catenin signaling. PMID:27318088

  18. Standardized method for solubility and storage of capsaicin-based solutions for cough induction

    PubMed Central

    2014-01-01

    Background Preparation of inhaled capsaicin solutions for cough induction varies greatly from one lab to another, which creates inconsistencies between tussigenic challenge results. The addition of Tween to these capsaicin solutions provides increased solubility and stability; however, the foul taste of Tween makes inhaling the solution for any prolonged period of time unpleasant. We sought to create a standard method for preparing soluble and stable capsaicin-based solutions (in 10% ethanol/water), without the addition of Tween. Methods Capsaicin solutions were created at concentrations ranging from 0 to 500 μM in a variety of solvent systems, with and without Tween. Samples were stored in four different environments (-20°C, 3°C, and room temperature, protected from light; and room temperature, exposed to light) to test stability. Detection of capsaicin was carried out by UV absorption. A Grubb’s test was performed on all data to remove statistical outliers. Results Similar capsaicin concentrations were seen for solutions prepared with or without Tween (Tween provided a slight increase in solubility), with neither solvent system providing complete solubility. Of the four environments tested, storing capsaicin solutions at 3°C while protected from light afforded the greatest stability, for a minimum of 30 weeks. Conclusion We recommend the use of a 10% ethanol/water solvent system without Tween in the preparation of capsaicin solutions for tussigenic challenges. While this solvent system does not provide complete solubility, we have detailed a method for capsaicin solution preparation that will account for this loss of solubility, while maintaining a solution that is Tween-free and safe for human inhalation. PMID:25342957

  19. The effects of sensorial denervation on the ovarian function, by the local administration of capsaicin, depend on the day of the oestrous cycle when the treatment was performed.

    PubMed

    Trujillo, Angélica; Morales, Leticia; Domínguez, Roberto

    2015-02-01

    There is evidence that sensory innervation plays a role in the regulation of puberty. The present study investigates the effects of functional sensorial desensitisation induced by capsaicin administration to adult female rats in the days of diestrus 1, diestrus 2, pro-oestrus or oestrus on ovulation and serum oestradiol and progesterone concentration. The animals were allotted at random to one of the following groups: (1) animals with capsaicin administration into the bursa ovarica (local administration) (2) animals with vehicle administration into the bursa ovarica and (3) untreated animals group. The animals treated were killed on the day of oestrus after three consecutive 4-day oestrous cycles. No differences were observed in oestrous cyclicity or the average number of ova shed between the sensorial desensitisation animals and the vehicle-treated groups. Capsaicin administration resulted in a significant increase in the intra-ovarian noradrenaline levels in the day of diestrus 2 and pro-oestrus. Serum oestradiol and progesterone concentrations were different, depending on the day of the oestrous cycle in which the treatment was performed. These results suggest that in adult normal female rats, ovarian sensorial innervations participate together with the sympathetic innervation in the ovarian function regulating the hormone secretion and this participation varies along the oestrous cycle.

  20. TRPV1 Activation in Primary Cortical Neurons Induces Calcium-Dependent Programmed Cell Death.

    PubMed

    Song, Juhyun; Lee, Jun Hong; Lee, Sung Ho; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

    2013-03-01

    Transient receptor potential cation channel, subfamily V, member 1 (TRPV1, also known as vanilloid receptor 1) is a receptor that detects capsaicin, a pungent component of chili peppers, and noxious heat. Although its function in the primary nociceptor as a pain receptor is well established, whether TRPV1 is expressed in the brain is still under debate. In this study, the responses of primary cortical neurons were investigated. Here, we report that 1) capsaicin induces caspase-3-dependent programmed cell death, which coincides with increased production of nitric oxide and peroxynitrite ; that 2) the prolonged capsaicin treatment induces a steady increase in the degree of capase-3 activation, which is prevented by the removal of capsaicin; 3) and that blocking calcium entry and calcium-mediated signaling prevents capsaicin-induced cell death. These results indicate that cortical neurons express TRPV1 whose prolonged activation causes cell death. PMID:23585723

  1. Calcium Channel α2δ1 Proteins Mediate Trigeminal Neuropathic Pain States Associated with Aberrant Excitatory Synaptogenesis*

    PubMed Central

    Li, Kang-Wu; Yu, Yanhui Peter; Zhou, Chunyi; Kim, Doo-Sik; Lin, Bin; Sharp, Kelli; Steward, Oswald; Luo, Z. David

    2014-01-01

    To investigate a potential mechanism underlying trigeminal nerve injury-induced orofacial hypersensitivity, we used a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION) to study whether CCI-ION caused calcium channel α2δ1 (Cavα2δ1) protein dysregulation in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 cervical dorsal spinal cord (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to spinal neuron sensitization and neuropathic pain states. CCI-ION caused orofacial hypersensitivity that correlated with Cavα2δ1 up-regulation in trigeminal ganglion neurons and Vc/C2. Blocking Cavα2δ1 with gabapentin, a ligand for the Cavα2δ1 proteins, or Cavα2δ1 antisense oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting an important role of Cavα2δ1 in orofacial pain processing. Importantly, increased Cavα2δ1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogenesis and increased frequency, but not the amplitude, of miniature excitatory postsynaptic currents in dorsal horn neurons that could be blocked by gabapentin. Thus, CCI-ION-induced Cavα2δ1 up-regulation may contribute to orofacial neuropathic pain states through abnormal excitatory synapse formation and enhanced presynaptic excitatory neurotransmitter release in Vc/C2. PMID:24459143

  2. Activation of TRPV1 mediates calcitonin gene-related peptide release, which excites trigeminal sensory neurons and is attenuated by a retargeted botulinum toxin with anti-nociceptive potential.

    PubMed

    Meng, Jianghui; Ovsepian, Saak V; Wang, Jiafu; Pickering, Mark; Sasse, Astrid; Aoki, K Roger; Lawrence, Gary W; Dolly, J Oliver

    2009-04-15

    Excessive release of inflammatory/pain mediators from peripheral sensory afferents renders nerve endings hyper-responsive, causing central sensitization and chronic pain. Herein, the basal release of proinflammatory calcitonin gene-related peptide (CGRP) was shown to increase the excitability of trigeminal sensory neurons in brainstem slices via CGRP1 receptors because the effect was negated by an antagonist, CGRP8-37. This excitatory action could be prevented by cleaving synaptosomal-associated protein of M(r) 25,000 (SNAP-25) with botulinum neurotoxin (BoNT) type A, a potent inhibitor of exocytosis. Strikingly, BoNT/A proved unable to abolish the CGRP1 receptor-mediated effect of capsaicin, a nociceptive TRPV1 stimulant, or its elevation of CGRP release from trigeminal ganglionic neurons (TGNs) in culture. Although the latter was also not susceptible to BoNT/E, apparently attributable to a paucity of its acceptors (glycosylated synaptic vesicle protein 2 A/B), this was overcome by using a recombinant chimera (EA) of BoNT/A and BoNT/E. It bound effectively to the C isoform of SV2 abundantly expressed in TGNs and cleaved SNAP-25, indicating that its /A binding domain (H(C)) mediated uptake of the active /E protease. The efficacy of /EA is attributable to removal of 26 C-terminal residues from SNAP-25, precluding formation of SDS-resistant SNARE complexes. In contrast, exocytosis could be evoked after deleting nine of the SNAP-25 residues with /A but only on prolonged elevation of [Ca(2+)](i) with capsaicin. This successful targeting of /EA to nociceptive neurons and inhibition of CGRP release in vitro and in situ highlight its potential as a new therapy for sensory dysmodulation and chronic pain.

  3. Capsaicin-like activity of some natural pungent substances on peripheral endings of visceral primary afferents.

    PubMed

    Patacchini, R; Maggi, C A; Meli, A

    1990-07-01

    1. The effects of some naturally occurring pungent substances, piperine, mustard oil, eugenol and curcumin, were compared to those of capsaicin in the rat isolated urinary bladder. 2. All test compounds dose-dependently contracted the rat bladder and produced desensitization toward capsaicin (1 mumol/l). Development of cross-tachyphylaxis among the natural pungent substances on one hand and capsaicin on the other, suggested a common site of action on visceral primary afferents. 3. Contractile responses to piperine, mustard oil and eugenol were partially tetrodotoxin and ruthenium red-sensitive, suggesting that activation of sensory terminals by these agents takes place indirectly, as well as by a direct action on sensory receptors. 4. The presence of the secondary acrylamide linkage (present in the backbone of capsaicin, but not in that of test compounds) does not appear to be essential to produce desensitization of sensory nerve terminals.

  4. Oral capsaicin provides temporary relief for oral mucositis pain secondary to chemotherapy/radiation therapy.

    PubMed

    Berger, A; Henderson, M; Nadoolman, W; Duffy, V; Cooper, D; Saberski, L; Bartoshuk, L

    1995-04-01

    Pain from oral mucositis afflicts from 40% to 70% of patients receiving chemotherapy or radiation therapy. Current methods of clinical pain management (for example, topical anesthetics, systemic analgesics) have limited success. In a pilot study, we examined the ability of oral capsaicin to provide temporary relief of oral mucositis pain. Capsaicin, the active ingredient in chili peppers, desensitizes some neurons and has provided moderate pain relief when applied to the skin surface. Oral capsaicin in a candy (taffy) vehicle produced substantial pain reduction in 11 patients with oral mucositis pain from cancer therapy. However, this pain relief was not complete for most patients and was only temporary. Additional research is needed to fully utilize the properties of capsaicin desensitization and thus optimize analgesia. PMID:7629418

  5. Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study

    PubMed Central

    McCleane, Gary

    2000-01-01

    Aims To assess the analgesic efficacy of topical administration of 3.3% doxepin hydrochloride, 0.025% capsaicin and a combination of 3.3% doxepin and 0.025% capsaicin in human chronic neuropathic pain. Methods A randomized, double-blind, placebo-controlled study of 200 consenting adult patients. Patients applied placebo, doxepin, capsaicin or doxepin/capsaicin cream daily for 4 weeks. Patients recorded on a daily basis overall pain, shooting, burning, paraesthesia and numbness using a 0–10 visual analogue scale during the week prior to cream application (baseline levels) and for the 4 week study period. Side-effects and desire to continue treatment were also recorded. Results Overall pain was significantly reduced by doxepin, capsaicin and doxepin/capsaicin to a similar extent. The analgesia with doxepin/capsaicin was of more rapid onset. Capsaicin significantly reduced sensitivity and shooting pain. Burning pain was increased by doxepin and by capsaicin and to a lesser extent by doxepin/capsaicin. Side-effects were minor. One patient requested to continue placebo cream, 17 doxepin cream, 13 capsaicin and 9 the combination of doxepin and capsaicin. Conclusions Topical application of 3.3% doxepin, 0.025% capsaicin and 3.3% doxepin/0.025% capsaicin produces analgesia of similar magnitude. The combination produces more rapid analgesia. PMID:10848721

  6. Antinociceptive Effects of Botulinum Toxin Type A on Trigeminal Neuropathic Pain.

    PubMed

    Yang, K Y; Kim, M J; Ju, J S; Park, S K; Lee, C G; Kim, S T; Bae, Y C; Ahn, D K

    2016-09-01

    Previous studies have demonstrated that botulinum toxin type A (BoNT-A) attenuates orofacial nociception. However, there has been no evidence of the participation of the voltage-gated sodium channels (Navs) in the antinociceptive mechanisms of BoNT-A. This study investigated the cellular mechanisms underlying the antinociceptive effects of BoNT-A in a male Sprague-Dawley rat model of trigeminal neuropathic pain produced by malpositioned dental implants. The left mandibular second molar was extracted under anesthesia, followed by a miniature dental implant placement to induce injury to the inferior alveolar nerve. Mechanical allodynia was monitored after subcutaneous injection of BoNT-A at 3, 7, or 12 d after malpositioned dental implant surgery. Subcutaneous injections of 1 or 3 U/kg of BoNT-A on postoperative day 3 significantly attenuated mechanical allodynia, although 0.3 U/kg of BoNT-A did not affect the air-puff threshold. A single injection of 3 U/kg of BoNT-A produced prolonged antiallodynic effects over the entire experimental period. Treatment with BoNT-A on postoperative days 7 and 12, when pain had already been established, also produced prolonged antiallodynic effects. Double treatments with 1 U/kg of BoNT-A produced prolonged, more antiallodynic effects as compared with single treatments. Subcutaneous administration of 3 U/kg of BoNT-A significantly inhibited the upregulation of Nav isoform 1.7 (Nav1.7) expression in the trigeminal ganglion in the nerve-injured animals. These results suggest that antinociceptive effects of BoNT-A are mediated by an inhibition of upregulated Nav1.7 expression in the trigeminal ganglion. BoNT-A is therefore a potential new therapeutic agent for chronic pain control, including neuropathic pain. PMID:27418174

  7. Reduced GABAA Receptor α6 Expression in The Trigeminal Ganglion Enhanced Myofascial Nociceptive Response

    PubMed Central

    Kramer, P. R.; Bellinger, L. L.

    2013-01-01

    Activation of the GABAA receptor results in inhibition of neuronal activity. One subunit of this multi-subunit receptor termed alpha 6 (Gabrα6) contributed to inflammatory temporomandibular joint (TMJ) nociception but TMJ disorders often include myofascial pain. To address Gabrα6 role in myofascial pain we hypothesized that Gabrα6 has an inhibitory role in myofascial nociceptive responses similar to inflammatory TMJ arthritis. To test this hypothesis a, myofascial nociceptive response was induced by placing a ligature bilaterally on the tendon attachment of the anterior superficial part of a male rat's masseter muscle. Four days after ligature placement Gabrα6 expression was reduced by infusing the trigeminal ganglia (TG) with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabra6 siRNA) or no known gene (control siRNA). After siRNA infusion nociceptive behavioral responses were measured, i.e., feeding behavior and head withdrawal after pressing upon the region above the ligature with von Frey filaments. Neuronal activity in the TG and trigeminal nucleus caudalis and upper cervical region (Vc–C1) was measured by quantitating the amount of phosphorylated extracellular signalregulated kinase (p-ERK). Total Gabrα6 and GABAA receptor contents in the TG and Vc–C1 were determined. Gabrα6 siRNA infusion reduced Gabrα6 and GABAA receptor expression and significantly increased the nociceptive response in both nociceptive assays. Gabra6 siRNA infusion also significantly increased TG p-ERK expression of the ligated rats. From these results we conclude GABAA receptors consisting of the Gabrα6 subunit inhibit TG nociceptive sensory afferents in the trigeminal pathway and have an important role in the regulation of myofascial nociception. PMID:23602886

  8. Oxaliplatin enhances gap junction-mediated coupling in cell cultures of mouse trigeminal ganglia.

    PubMed

    Poulsen, Jeppe Nørgaard; Warwick, Rebekah; Duroux, Meg; Hanani, Menachem; Gazerani, Parisa

    2015-08-01

    Communications between satellite glial cells and neighboring neurons within sensory ganglia may contribute to neuropathic and inflammatory pain. To elucidate the role of satellite glial cells in chemotherapy-induced pain, we examined the effects of oxaliplatin on the gap junction-mediated coupling between these cells. We also examined whether the gap junction blocker, carbenoxolone, can reverse the coupling. Primary cultures of mice trigeminal ganglia, 24-48h after cell isolation, were used. Satellite glial cells were injected with Lucifer yellow in the presence or absence of oxaliplatin (60 μM). In addition, the effect of carbenoxolone (100 μM) on coupling, and the expression of connexin 43 proteins were evaluated. Dye coupling between adjacent satellite glial cells was significantly increased (2.3-fold, P<0.05) following a 2h incubation with oxaliplatin. Adding carbenoxolone to the oxaliplatin-treated cultures reversed oxaliplatin-evoked coupling to baseline (P<0.05). Immunostaining showed no difference between expression of connexin 43 in control and oxaliplatin-treated cultures. Our findings indicated that oxaliplatin-increased gap junction-mediated coupling between satellite glial cells in primary cultures of mouse trigeminal ganglia, and carbenoxolone reversed this effect. Hence, it is proposed that increased gap junction-mediated coupling was seen between satellite glial cells in TG. This observation together with our previous data obtained from a behavioral study suggests that this phenomenon might contribute to chemotherapy-induced nociception following oxaliplatin treatment. PMID:25999145

  9. Oxaliplatin enhances gap junction-mediated coupling in cell cultures of mouse trigeminal ganglia.

    PubMed

    Poulsen, Jeppe Nørgaard; Warwick, Rebekah; Duroux, Meg; Hanani, Menachem; Gazerani, Parisa

    2015-08-01

    Communications between satellite glial cells and neighboring neurons within sensory ganglia may contribute to neuropathic and inflammatory pain. To elucidate the role of satellite glial cells in chemotherapy-induced pain, we examined the effects of oxaliplatin on the gap junction-mediated coupling between these cells. We also examined whether the gap junction blocker, carbenoxolone, can reverse the coupling. Primary cultures of mice trigeminal ganglia, 24-48h after cell isolation, were used. Satellite glial cells were injected with Lucifer yellow in the presence or absence of oxaliplatin (60 μM). In addition, the effect of carbenoxolone (100 μM) on coupling, and the expression of connexin 43 proteins were evaluated. Dye coupling between adjacent satellite glial cells was significantly increased (2.3-fold, P<0.05) following a 2h incubation with oxaliplatin. Adding carbenoxolone to the oxaliplatin-treated cultures reversed oxaliplatin-evoked coupling to baseline (P<0.05). Immunostaining showed no difference between expression of connexin 43 in control and oxaliplatin-treated cultures. Our findings indicated that oxaliplatin-increased gap junction-mediated coupling between satellite glial cells in primary cultures of mouse trigeminal ganglia, and carbenoxolone reversed this effect. Hence, it is proposed that increased gap junction-mediated coupling was seen between satellite glial cells in TG. This observation together with our previous data obtained from a behavioral study suggests that this phenomenon might contribute to chemotherapy-induced nociception following oxaliplatin treatment.

  10. Trigeminal neuralgia caused by brain arteriovenous malformations: A case report and literature review

    PubMed Central

    YUAN, YONGJIE; ZHANG, YANDONG; LUO, QI; YU, JINLU

    2016-01-01

    Few cases of trigeminal neuralgia (TGN) induced by brain arteriovenous malformations (bAVMs) have previously been reported. The present case report described one case of TGN caused by bAVMs in a 32-year-old male patient who suffered from recurrent pain in his right cheek for a period of two years, for whom the seizure frequency and duration of pain increased for 6 months. Magnetic resonance imaging was performed, which demonstrated flow-void signals in the abnormal vessels in the right cerebellopontine angle. Subsequent digital subtraction angiography confirmed the diagnosis of bAVMs, and showed the nidus was fed by the right superior cerebellar and the right anterior inferior cerebellar, and drained into the adjacent venous sinuses on the same side. The patient underwent an interventional embolization treatment. TGN was completely relieved following embolization of the majority of the bAVMs. Pain relief may be associated with blocking of the pulsatile compression of the feeding arteries of the bAVMs, the arterialized draining veins or the malformed niduses following embolization, which is similar to the effects induced by microvascular decompression surgery of the trigeminal nerve. In the present case study and review, the underlying mechanism and treatment strategy of TGN caused by bAVMs were discussed in the context of present case, and a literature review was carried out. PMID:27347019

  11. Trigeminal projections to thalamus and subthalamus in the hedgehog tenrec.

    PubMed

    Künzle, H

    1998-09-01

    The objective of the present study was the identification and characterization of the trigemino-diencephalic target areas in the Madagascan lesser hedgehog tenrec in order to get a more comprehensive view on the mammalian somatosensory thalamus, its evolution and representation in different species. Such an analysis has been considered important because in lower mammals the head and face are relatively well represented, but their ascending trigeminal projections have scarcely been analysed. Following injections of different tracer substances into the rostral and caudal portions of the trigeminal nuclear complex the most prominent area of termination was found in the medial ventroposterior nucleus. These projections were patchy and scarcely overlapped the region previously shown to receive spinal and dorsal column nuclear afferents. On the basis of the laterality and the intensity of the projections, two subdivisions were distinguished, the principal portion and the accessory portion receiving a dense contralateral and a weak bilateral input, respectively. They were considered equivalents to the magnocellular and parvocellular subdivisions of the medial ventroposterior nucleus in more differentiated mammals. In the latter species, however, the overlap between trigeminal and parabrachial fibres appears less extensive than in the tenrec. In addition, a weak bilateral projection was shown from the caudal trigeminal nucleus to the caudal and dorsal subdivision of the nucleus submedius. There was little, if any evidence for a trigeminal projection to the intralaminar nuclei and we failed to identify a correlate to the posterior nuclear complex of higher mammals. On the other hand, there was a distinct contralateral projection to the ventral portion of the zona incerta. This projection was of similar strength as the projection to the medial ventroposterior nucleus; it supports the notion that the zona incerta may play a crucial role in relaying trigeminal information.

  12. Trigeminal nociceptive transmission in migraineurs predicts migraine attacks.

    PubMed

    Stankewitz, Anne; Aderjan, David; Eippert, Falk; May, Arne

    2011-02-01

    Several lines of evidence suggest a major role of the trigeminovascular system in the pathogenesis of migraine. Using functional magnetic resonance imaging (fMRI), we compared brain responses during trigeminal pain processing in migraine patients with those of healthy control subjects. The main finding is that the activity of the spinal trigeminal nuclei in response to nociceptive stimulation showed a cycling behavior over the migraine interval. Although interictal (i.e., outside of attack) migraine patients revealed lower activations in the spinal trigeminal nuclei compared with controls, preictal (i.e., shortly before attack) patients showed activity similar to controls, which demonstrates that the trigeminal activation level increases over the pain-free migraine interval. Remarkably, the distance to the next headache attack was predictable by the height of the signal intensities in the spinal nuclei. Migraine patients scanned during the acute spontaneous migraine attack showed significantly lower signal intensities in the trigeminal nuclei compared with controls, demonstrating activity levels similar to interictal patients. Additionally we found-for the first time using fMRI-that migraineurs showed a significant increase in activation of dorsal parts of the pons, previously coined "migraine generator." Unlike the dorsal pons activation usually linked to migraine attacks, the gradient-like activity following nociceptive stimulation in the spinal trigeminal neurons likely reflects a raise in susceptibility of the brain to generate the next attack, as these areas increase their activity long before headache starts. This oscillating behavior may be a key player in the generation of migraine headache, whereas attack-specific pons activations are most likely a secondary event.

  13. Capsaicin Protects Mice from Community-Associated Methicillin-Resistant Staphylococcus aureus Pneumonia

    PubMed Central

    Xing, Yan; Leng, Bingfeng; Dong, Jing; Li, Hongen; Luo, Mingjing; Zhang, Yu; Dai, Xiaohan; Luo, Yonghuang; Deng, Xuming

    2012-01-01

    Background α-toxin is one of the major virulence factors secreted by most Staphylococcus aureus strains, which played a central role in the pathogenesis of S. aureus pneumonia. The aim of this study was to investigate the impact of capsaicin on the production of α-toxin by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA 300 and to further assess its performance in the treatment of CA-MRSA pneumonia in a mouse model. Methodology/Principal Findings The in vitro effects of capsaicin on α-toxin production by S. aureus USA 300 were determined using hemolysis, western blot, and real-time RT-PCR assays. The influence of capsaicin on the α-toxin-mediated injury of human alveolar epithelial cells was determined using viability and cytotoxicity assays. Mice were infected intranasally with S. aureus USA300; the in vivo protective effects of capsaicin against S. aureus pneumonia were assessed by monitoring the mortality, histopathological changes and cytokine levels. Low concentrations of capsaicin substantially decreased the production of α-toxin by S. aureus USA 300 without affecting the bacterial viability. The addition of capsaicin prevented α-toxin-mediated human alveolar cell (A549) injury in co-culture with S. aureus. Furthermore, the in vivo experiments indicated that capsaicin protected mice from CA-MRSA pneumonia caused by strain USA 300. Conclusions/Significance Capsaicin inhibits the production of α-toxin by CA-MRSA strain USA 300 in vitro and protects mice from CA-MRSA pneumonia in vivo. However, the results need further confirmation with other CA-MRSA lineages. This study supports the views of anti-virulence as a new antibacterial approach for chemotherapy. PMID:22427935

  14. Percutaneous Procedures for the Treatment of Trigeminal Neuralgia.

    PubMed

    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.

  15. Percutaneous Procedures for the Treatment of Trigeminal Neuralgia.

    PubMed

    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. PMID:27324995

  16. Characterization of cubosomes as a targeted and sustained transdermal delivery system for capsaicin

    PubMed Central

    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. PMID:26345516

  17. Differences in the chemesthetic subqualities of capsaicin, ibuprofen, and olive oil.

    PubMed

    Bennett, Samantha M; Hayes, John E

    2012-06-01

    Chemesthetic sensations elicited by ibuprofen, extra-virgin olive oil, and capsaicin were compared to quantify perceptual differences between known agonists of TRPA1 and TRPV1. Extra virgin olive oil contains a phenolic compound, oleocanthal, which is thought to share unique chemesthetic qualities with the nonsteroidal anti-inflammatory drug, ibuprofen. Pilot work suggested participants had difficulty distinguishing between multiple chemesthetic subqualities (e.g., burn, sting, itch, tickle, etc.) in a multiattribute rating task. Here, we assessed overall irritation via direct scaling, and a check all that apply task was used to collect information about chemesthetic subqualities over time. Replicated ratings were collected at discrete intervals using the generalized labeled magnitude scale to generate time-intensity curves; maximum intensity (Imax) and area under the curve were extracted for each participant. Intensity responses varied substantially across participants, and within a participant, the relationship was strongest between ibuprofen and olive oil. However, there were also positive, albeit weaker, correlations between capsaicin and ibuprofen and capsaicin and olive oil. The correlation found between olive oil and capsaicin may suggest the presence of unknown TRPV1 agonists in olive oil. This view was also supported by the qualitative data: capsaicin was described most often as burning and warm/hot, whereas ibuprofen was numbing and tickling. Olive oil shared characteristics with both capsaicin (warm/hot) and ibuprofen (tickle). PMID:22281531

  18. Differences in the Chemesthetic Subqualities of Capsaicin, Ibuprofen, and Olive Oil

    PubMed Central

    Bennett, Samantha M.

    2012-01-01

    Chemesthetic sensations elicited by ibuprofen, extra-virgin olive oil, and capsaicin were compared to quantify perceptual differences between known agonists of TRPA1 and TRPV1. Extra virgin olive oil contains a phenolic compound, oleocanthal, which is thought to share unique chemesthetic qualities with the nonsteroidal anti-inflammatory drug, ibuprofen. Pilot work suggested participants had difficulty distinguishing between multiple chemesthetic subqualities (e.g., burn, sting, itch, tickle, etc.) in a multiattribute rating task. Here, we assessed overall irritation via direct scaling, and a check all that apply task was used to collect information about chemesthetic subqualities over time. Replicated ratings were collected at discrete intervals using the generalized labeled magnitude scale to generate time-intensity curves; maximum intensity (Imax) and area under the curve were extracted for each participant. Intensity responses varied substantially across participants, and within a participant, the relationship was strongest between ibuprofen and olive oil. However, there were also positive, albeit weaker, correlations between capsaicin and ibuprofen and capsaicin and olive oil. The correlation found between olive oil and capsaicin may suggest the presence of unknown TRPV1 agonists in olive oil. This view was also supported by the qualitative data: Capsaicin was described most often as burning and warm/hot, whereas ibuprofen was numbing and tickling. Olive oil shared characteristics with both capsaicin (warm/hot) and ibuprofen (tickle). PMID:22281531

  19. The capsaicin cough reflex in eczema patients with respiratory symptoms elicited by perfume.

    PubMed

    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.

  20. Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour.

    PubMed

    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.

  1. Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel.

    PubMed

    Yang, Fan; Xiao, Xian; Cheng, Wei; Yang, Wei; Yu, Peilin; Song, Zhenzhen; Yarov-Yarovoy, Vladimir; Zheng, Jie

    2015-07-01

    Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Although a capsaicin-bound channel structure was previously resolved by cryo-EM at 4.2- to 4.5-Å resolution, capsaicin was registered as a small electron density, reflecting neither its chemical structure nor specific ligand-channel interactions--important details required for mechanistic understanding. We obtained the missing atomic-level details by iterative computation and confirmed them by systematic site-specific functional tests. We observed that the bound capsaicin takes a 'tail-up, head-down' configuration. The vanillyl and amide groups form specific interactions to anchor its bound position, while the aliphatic tail may sample a range of conformations, making it invisible in cryo-EM images. Capsaicin stabilizes TRPV1's open state by 'pull-and-contact' interactions between the vanillyl group and the S4-S5 linker. Our study provides a structural mechanism for the agonistic function of capsaicin and its analogs, and demonstrates an effective approach to obtain atomic-level information from cryo-EM structures.

  2. Characterization of cubosomes as a targeted and sustained transdermal delivery system for capsaicin.

    PubMed

    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.

  3. Differences in the chemesthetic subqualities of capsaicin, ibuprofen, and olive oil.

    PubMed

    Bennett, Samantha M; Hayes, John E

    2012-06-01

    Chemesthetic sensations elicited by ibuprofen, extra-virgin olive oil, and capsaicin were compared to quantify perceptual differences between known agonists of TRPA1 and TRPV1. Extra virgin olive oil contains a phenolic compound, oleocanthal, which is thought to share unique chemesthetic qualities with the nonsteroidal anti-inflammatory drug, ibuprofen. Pilot work suggested participants had difficulty distinguishing between multiple chemesthetic subqualities (e.g., burn, sting, itch, tickle, etc.) in a multiattribute rating task. Here, we assessed overall irritation via direct scaling, and a check all that apply task was used to collect information about chemesthetic subqualities over time. Replicated ratings were collected at discrete intervals using the generalized labeled magnitude scale to generate time-intensity curves; maximum intensity (Imax) and area under the curve were extracted for each participant. Intensity responses varied substantially across participants, and within a participant, the relationship was strongest between ibuprofen and olive oil. However, there were also positive, albeit weaker, correlations between capsaicin and ibuprofen and capsaicin and olive oil. The correlation found between olive oil and capsaicin may suggest the presence of unknown TRPV1 agonists in olive oil. This view was also supported by the qualitative data: capsaicin was described most often as burning and warm/hot, whereas ibuprofen was numbing and tickling. Olive oil shared characteristics with both capsaicin (warm/hot) and ibuprofen (tickle).

  4. Determination of capsaicin and dihydrocapsaicin in Capsicum fruit samples using high performance liquid chromatography.

    PubMed

    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.

  5. Palvanil, a non-pungent capsaicin analogue, inhibits inflammatory and neuropathic pain with little effects on bronchopulmonary function and body temperature.

    PubMed

    Luongo, Livio; Costa, Barbara; D'Agostino, Bruno; Guida, Francesca; Comelli, Francesca; Gatta, Luisa; Matteis, Maria; Sullo, Nikol; De Petrocellis, Luciano; de Novellis, Vito; Maione, Sabatino; Di Marzo, Vincenzo

    2012-09-01

    N-Palmitoyl-vanillamide (palvanil) is a non-pungent capsaicinoid, found in low amounts in Capsicum and shown to rapidly desensitize transient receptor potential vanilloid type-1 (TRPV1) channels to the action of capsaicin and to exert analgesic effects after local administration. We have investigated here if systemic administration of palvanil to mice causes two typical adverse events of TRPV1 agonists, i.e. profound changes in body temperature and bronchoconstriction, and if it can still produce effective inhibition of inflammatory and chronic pain in different experimental models. Varying doses of palvanil were tested subcutaneously and acutely on body temperature in vivo or, or as a bolus, on bronchopulmunary function ex vivo, in comparison with capsaicin. Intraperitoneal palvanil was also tested against formalin-induced nocifensive behavior and carrageenan-induced oedema and thermal hyperalgesia, acutely, and against mechanical allodynia and thermal hyperalgesia in mice with spared nerve injury (SNI) of the sciatic nerve, after repeated administration over 7 days from SNI. Palvanil, at therapeutically relevant doses, produced significantly less hypothermia and bronchoconstriction than capsaicin. Palvanil (0.5-2.5 mg/kg) abolished formalin-induced nocifensive behavior and strongly attenuated SNI-induced mechanical allodynia and thermal hyperalgesia and carrageenan-induced oedema and thermal hyperalgesia. Systemic administration of the non-pungent capsaicinoid, palvanil, produces, at least in mice, much less of those side effects typical of TRPV1 agonists (hypothermia and bronchoconstriction), whilst being very effective at reducing pain and oedema. Thus, palvanil might be developed further as a novel pharmacological treatment for chronic abnormal pain.

  6. Attenuation of pain-related behavior in a rat model of trigeminal neuropathic pain by viral-driven enkephalin overproduction in trigeminal ganglion neurons.

    PubMed

    Meunier, Alice; Latrémolière, Alban; Mauborgne, Annie; Bourgoin, Sylvie; Kayser, Valérie; Cesselin, François; Hamon, Michel; Pohl, Michel

    2005-04-01

    Trigeminal neuropathic pain represents a real challenge to therapy because commonly used drugs are devoid of real beneficial effect or patients frequently become intolerant or refractory to some of these compounds. In a rat model of trigeminal neuropathic pain, which shares numerous similarities with human trigeminal neuralgia and trigeminal neuropathic pain, we used a genomic herpes simplex virus-derived vector (HSVLatEnk) to examine the possible effect of a local overproduction of proenkephalin A (PA) targeted to the trigeminal primary sensory neurons. Unilateral peripheral inoculation of recombinant vectors on the vibrissal pad territory resulted in an about ninefold increase in proenkephalin A mRNA levels in trigeminal ganglion ipsilateral to the infected side. Transgene-derived met-enkephalin accumulated in numerous nerve cell bodies of trigeminal ganglion and was transported through the sensory nerve fibers located in the infraorbital nerve. Bilateral mechanical hyperresponsiveness, which developed 2 weeks after chronic constrictive injury of the left infraorbital nerve, was significantly attenuated in animals overproducing PA in the trigeminal ganglion ipsilateral to the lesioned infraorbital nerve. This antiallodynic effect was reversed by both the opioid receptor antagonist naloxone and the peripherally acting antagonist naloxone methiodide. Our data demonstrate that the local overproduction of PA-derived peptides in trigeminal ganglion sensory neurons evoked a potent antiallodynic effect through the stimulation of mainly peripherally located opioid receptors and suggest that targeted delivery of endogenous opioids may be of interest for the treatment of some severe forms of neuropathic pain. PMID:15771963

  7. Comparison of the inhibitory action of synthetic capsaicin analogues with various NADH-ubiquinone oxidoreductases.

    PubMed

    Satoh, T; Miyoshi, H; Sakamoto, K; Iwamura, H

    1996-01-11

    Capsaicin is a new naturally occurring inhibitor of proton-pumping NADH-ubiquinone oxidoreductase (NDH-1), that competitively acts against ubiquinone. A series of capsaicin analogues was synthesized to examine the structural factors required for the inhibitory action and to probe the structural property of the ubiquinone catalytic site of various NADH-ubiquinone reductases, including non-proton-pumping enzyme (NDH-2), from bovine heart mitochondria, potato tuber (Solanum tuberosum, L) mitochondria and Escherichia coli (GR 19N) plasma membranes. Some synthetic capsaicins were fairly potent inhibitors of each of the three NDH-1 compared with the potent rotenone and piericidin A. Synthetic capsaicin analogues inhibited all three NDH-1 activities in a competitive manner against an exogenous quinone. The modification both of the substitution pattern and of the number of methoxy groups on the benzene ring, which may be superimposable on the quinone ring of ubiquinone, did not drastically affect the inhibitory potency. In addition, alteration of the position of dipolar amide bond unit in the molecule and chemical modifications of this unit did not change the inhibitory potency, particularly with bovine heart and potato tuber NDH-1. These results might be explained assuming that the ubiquinone catalytic site of NDH-1 is spacious enough to accommodate a variety of structurally different capsaicin analogues in a dissimilar manner. Regarding the moiety corresponding to the alkyl side chain, a rigid diphenyl ether structure was more inhibitory than a flexible alkyl chain. Structure-activity studies and molecular orbital calculations suggested that a bent form is the active conformation of capsaicin analogues. On the other hand, poor correlations between the inhibitory potencies determined with the three NDH-1 suggested that the structural similarity of the ubiquinone catalytic sites of these enzymes is rather poor. The sensitivity to the inhibition by synthetic capsaicins

  8. Clinical Characteristics of Patients with Trigeminal Neuralgia Referred to Neurosurgery

    PubMed Central

    Siqueira, Silvia RDT; Teixeira, Manoel J; Siqueira, José TT

    2009-01-01

    Objectives To investigate the clinical characteristics of patients with trigeminal neuralgia referred to surgery in a center of reference. Methods We evaluated the general characteristics of 395 patients with trigeminal neuralgia referred to neurosurgery as treatment. They corresponded to 2 samples of 1984 and 2004. The EDOF-HC protocol (Orofacial Pain Questionnaire) and the medical profile were used. Results In the first study (1984), with 290 patients, the higher prevalence was: women (57.3%), white (95.5%), with mean age of 62.5. The most affected trigeminal branches were the maxillary and/or mandibular branches (65.5%), and the right side was the most affected (57.6%). From the second study (2004), with 105 patients, 57.1% were women, 75.2% white, with a mean age of 60.8. The maxillary and/or mandibular branches (79.0%) and the right side (69.5%) were the most affected. Both samples had neurological abnormalities and systemic diseases (mainly cardiovascular). Conclusions General characteristics of these patients were similar to other samples of trigeminal neuralgia. Neurological findings were also present in patients with no previous surgical treatment for TN. Hypertension and cardiac diseases were also frequent and make the monitoring of the patients during crises necessary. PMID:19756195

  9. Pain. Part 2a: Trigeminal Anatomy Related to Pain.

    PubMed

    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.

  10. Intranasal trigeminal sensitivity in subjects with allergic rhinitis.

    PubMed

    Doerfler, H; Hummel, T; Klimek, L; Kobal, G

    2006-01-01

    Trigeminal nerve endings of the human nasal mucosa are activated by chemical, physical or thermal stimuli. Activation of these A(delta) and C fibers can be quantified through the recording of chemo-somatosensory event-related potentials (ERP). The aim of this study was to investigate whether allergy-related activation of trigeminal nerve endings leads to changes in their responsiveness to intranasal trigeminal stimulation. Gaseous carbon dioxide (CO(2)) stimuli were applied in three sessions (baseline, after NaCl solution and after allergen application) to the nasal mucosa of 13 subjects with allergic rhinitis. Chemo-somatosensory ERP were recorded, and subjects rated the intensity of rhinitis symptoms. Administration of allergen produced a significant shortening of chemo-somatosensory ERP peak latencies P1 and N1. Observed changes of latencies were in line with rhinitis symptoms subjects indicated during the session. In addition, there was a negative relation between the general symptom score and ERP peak latencies, obtained both at baseline and after allergen exposure. In conclusion, it is hypothesized that in patients suffering from allergic rhinitis, nasal itching and sneezing after allergen exposure are, at least in part, clinical correlates of the activation of trigeminal nerve endings due to local inflammatory mechanisms. The correlations between ERP latencies and the patients' symptoms indicate that ERP latencies may possess a predictive value of the subjects' responsiveness to allergens.

  11. Cryotherapy in the management of paroxysmal trigeminal neuralgia.

    PubMed Central

    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. PMID:3585363

  12. [Anaysis on acupoint selection rule of acupuncture for trigeminal neuralgia].

    PubMed

    Tao, Shengyu; Xu, Wen; Gao, Zhao; Dong, Qin

    2016-02-01

    The characteristics and rules of acupoint selection of acupuncture for trigeminal neuralgia were analyzed. By searching CNKI, VIP, WF, literature regarding acupuncture for trigeminal neuralgia from 1980 to 2013 was collected to establish an acupuncture prescription database. The data mining technology was applied to analyze the characteristics and rules of the acupoint selection. As a result, a total of 180 papers were included, involving 148 acupoints. It was found that the acupoints that had high frequency of selection included Hegu (LI 4), Xiaguan (ST 7), Fengchi (GB 20) and trigger points. The acupoints selected were distributed in 14 meridians, in which yangming meridian of hand-foot had a frequency of 41. 58%. The special acupoints including crossing points, yuan-primary points and five-shu points were widely used, accounting for 65. 9%. As for the branch of trigeminal nerve, the top-3 selected acupoints were Yangbai (GB 14), Yuyao (EX-HN 4), Cuanzhu (BL 2) in the first branch, Sibai (ST 2), Quanlian (SI 18), Yingxiang (LI 20) in the second branch, Jiache (ST 6), Xiaguan (ST 7), Dicang (ST 4) in the third branch. In conclusion, it is believed that the clinical treatment of trigeminal neural gia focuses on local acupoints in combination with nerve distribution-based acupoints and distal acupoints, also the special acupoints are emphasized. PMID:27348932

  13. Chronic dysphagia and trigeminal anesthesia after trichloroethylene exposure

    SciTech Connect

    Lawrence, W.H.; Partyka, E.K.

    1981-12-01

    A patient is described who inhaled trichloroethylene fumes while working in a closed underground pit. At the time of exposure he developed dysphagia, dysarthria and dyspnea. Assessment of his condition 11 years after the incident indicated major damage of cranial nerves, particularly the trigeminal, chronic involvement of the bulbar cranial nerves, and resultant esophageal and pharnygeal motility impairment. (JMT)

  14. Trigeminal neuralgia: a personal review and nursing implications.

    PubMed

    McConaghy, D J

    1994-04-01

    The facial pain of trigeminal neuralgia, also known as tic douloureux, has been described as the most excruciating pain known to man. The etiology of this disease is unknown, although some contributing factors have been identified. Medical treatment includes carbamazepine and other medications. Surgical options are microvascular decompression, percutaneous radiofrequency rhizotomy, balloon gangliolysis and temporary nerve lesions.

  15. Locomotor corollary activation of trigeminal motoneurons: coupling of discrete motor behaviors.

    PubMed

    Hänzi, Sara; Banchi, Roberto; Straka, Hans; Chagnaud, Boris P

    2015-06-01

    During motor behavior, corollary discharges of the underlying motor commands inform sensory-motor systems about impending or ongoing movements. These signals generally limit the impact of self-generated sensory stimuli but also induce motor reactions that stabilize sensory perception. Here, we demonstrate in isolated preparations of Xenopus laevis tadpoles that locomotor corollary discharge provokes a retraction of the mechanoreceptive tentacles during fictive swimming. In the absence of sensory feedback, these signals activate a cluster of trigeminal motoneurons that cause a contraction of the tentacle muscle. This corollary discharge encodes duration and strength of locomotor activity, thereby ensuring a reliable coupling between locomotion and tentacle motion. The strict phase coupling between the trigeminal and spinal motor activity, present in many cases, suggests that the respective corollary discharge is causally related to the ongoing locomotor output and derives at least in part from the spinal central pattern generator; however, additional contributions from midbrain and/or hindbrain locomotor centers are likely. The swimming-related retraction might protect the touch-receptive Merkel cells on the tentacle from sensory over-stimulation and damage and/or reduce the hydrodynamic drag. The intrinsic nature of the coupling of tentacle retraction to locomotion is an excellent example of a context-dependent, direct link between otherwise discrete motor behaviors.

  16. Trigeminally-mediated alteration of cardiorespiratory rhythms during nasal application of carbon dioxide in the rat.

    PubMed

    Yavari, P; McCulloch, P F; Panneton, W M

    1996-11-01

    Stimulation of the upper respiratory tract with air-borne irritants can result in dramatic alterations of cardiorespiratory rhythms that include apnea, bradycardia and selective peripheral vasoconstriction. Since carbon dioxide can stimulate receptors in the nasal passages, we wanted to determine if this odorless gas can induce the same autonomic changes as air-borne irritants. Passing 100% carbon dioxide through the nasal passages of rats anesthetized with chloralose-urethane produced apnea, a vagally-mediated bradycardia and a sympathetically-mediated increase in mean arterial blood pressure. Application of atropine blocked the bradycardia without affecting respiratory or blood pressure changes, while injection of prazosin eliminated blood pressure responses but did not affect heart rate or apnea. There were no significant autonomic responses to nasal application of 10, 25 or 50% carbon dioxide. The responses were mediated through the trigeminal innervation of the nasal mucosa since they could be blocked when the anesthetic procaine was applied to the nasal cavity. We conclude that these cardiorespiratory responses are due to stimulation of trigeminal nociceptors located within the nasal mucosa.

  17. RNA Sequencing of Trigeminal Ganglia in Rattus Norvegicus after Glyceryl Trinitrate Infusion with Relevance to Migraine

    PubMed Central

    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

  18. Insular cortex representation of dynamic mechanical allodynia in trigeminal neuropathic rats.

    PubMed

    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.

  19. Effects of capsaicin on nitric oxide synthase isoforms in prepubertal rat ovary.

    PubMed

    Zik, B; Altunbas, K; Tutuncu, S; Ozden, O; Ozguden Akkoc, C G; Peker, S; Sevimli, A

    2012-04-01

    Nitric oxide (NO) has emerged as an important intra-ovarian regulatory factor. We investigated effects of low dose capsaicin (CAP) treatment on the different NOS isoforms in prepubertal rat ovaries. Fifteen 21-day-old female Sprague-Dawley rats were divided randomly into three groups. The first group received no treatment, the second group received 0.5 mg/kg/day CAP dissolved in the vehicle, and the third group was treated with the vehicle only. The animals were euthanized by ether inhalation after 15 days and their ovaries were excised. Ovaries were fixed in 10% neutral buffered formalin and embedded in paraffin. Sections were processed for standard immunohistochemistry using the labeled streptavidin-biotin technique for expression of nNOS, eNOS and iNOS. We demonstrated that CAP induced expression of NOS isotypes including eNOS, iNOS and nNOS in prepubertal rat ovaries. CAP may lead to release of NO either directly from nerves or indirectly by evoking release from other cells via the action of neuropeptides that are released from afferent terminals and are involved in regulating female reproductive function.

  20. Controlled noxious chemical stimulation: responses of rat trigeminal brainstem neurones to CO2 pulses applied to the nasal mucosa.

    PubMed

    Anton, F; Peppel, P; Euchner, I; Handwerker, H O

    1991-02-25

    The nasal mucosa of halothane-anesthetized rats was stimulated with defined CO2 pulses. Recordings were performed from single trigeminal brainstem neurons to characterize their responses to this controlled chemical irritation. All cells examined with this stimulus displayed graded discharges to increasing concentrations of CO2. Enhanced responses were obtained in a group of neurons when the duration of the interstimulus interval was increased. The application of chemical irritants, notably mustard oil or acetic acid induced vigorous ongoing discharges in all cells tested. The CO2 stimulation method described here thus provides an ideal model for the quantitative physiological and pharmacological examination of chemically induced nociception.

  1. Stress-induced dura vascular permeability does not develop in mast cell-deficient and neurokinin-1 receptor knockout mice.

    PubMed

    Kandere-Grzybowska, Kristiana; Gheorghe, Daniela; Priller, Josef; Esposito, Pamela; Huang, Man; Gerard, Norma; Theoharides, Theoharis C

    2003-08-01

    Migraine headaches are often precipitated by stress and seem to involve neurogenic inflammation (NI) of the dura mater associated with the sensation of throbbing pain. Trigeminal nerve stimulation had been reported to activate rat dura mast cells and increase vascular permeability, effects inhibited by neonatal pretreatment with capsaicin implicating sensory neuropeptides, such as substance P (SP). The aim of the present study was to investigate NI, assessed by extravasation of 99-Technetium-gluceptate (99Tc-G), as well as the role of mast cells, SP and its receptor (NK-1R) in dura mater of mice in response to acute stress. Restraint stress for thirty min significantly increased 99Tc-G extravasation in the dura mater of C57BL mice. This effect was absent in W/W(v) mast cell-deficient mice and NK-1 receptor knockout mice (NK-1R-/-), but was unaltered in SP knockout mice (SP-/-). Acute restraint stress also resulted in increased dura mast cell activation in C57BL mice, but not in NK-1R-/- mice. These data demonstrate for the first time that acute stress triggers NI and mast cell activation in mouse dura mater through the activation of NK-1 receptors. The fact that SP-/- mice had intact vascular permeability response to stress indicates that some other NK-1 receptor agonist may substitute for SP. These results may help explain initial events in pathogenesis of stress-induced migraines.

  2. Nitrergic innervation of trigeminal and hypoglossal motoneurons in the cat.

    PubMed

    Pose, Ines; Fung, Simon; Sampogna, Sharon; Chase, Michael H; Morales, Francisco R

    2005-04-11

    The present study was undertaken to determine the location of trigeminal and hypoglossal premotor neurons that express neuronal nitric oxide synthase (nNOS) in the cat. Cholera toxin subunit b (CTb) was injected into the trigeminal (mV) or the hypoglossal (mXII) motor nuclei in order to label the corresponding premotor neurons. CTb immunocytochemistry was combined with NADPH-d histochemistry or nNOS immunocytochemistry to identify premotor nitrergic (NADPH-d(+)/CTb(+) or nNOS(+)/ CTb(+) double-labeled) neurons. Premotor trigeminal as well as premotor hypoglossal neurons were located in the ventro-medial medullary reticular formation in a region corresponding to the nucleus magnocellularis (Mc) and the ventral aspect of the nucleus reticularis gigantocellularis (NRGc). Following the injection of CTb into the mV, this region was found to contain a total of 60 +/- 15 double-labeled neurons on the ipsilateral side and 33 +/- 14 on the contralateral side. CTb injections into the mXII resulted in 40 +/- 17 double-labeled neurons in this region on the ipsilateral side and 16 +/- 5 on the contralateral side. Thus, we conclude that premotor trigeminal and premotor hypoglossal nitrergic cells coexist in the same medullary region. They are colocalized with a larger population of nitrergic cells (7200 +/- 23). Premotor neurons in other locations did not express nNOS. The present data demonstrate that a population of neurons within the Mc and the NRGc are the source of the nitrergic innervation of trigeminal and hypoglossal motoneurons. Based on the characteristics of nitric oxide actions and its diffusibility, we postulate that these neurons may serve to synchronize the activity of mV and mXII motoneurons. PMID:15804497

  3. Vascular and Psychophysical Effects of Topical Capsaicin Application to Orofacial Tissues

    PubMed Central

    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

  4. Enzymatic changes in phenylalanine ammonia-lyase, cinnamic-4-hydroxylase, capsaicin synthase, and peroxidase activities in capsicum under drought stress.

    PubMed

    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 increased as compared to the non-drought-stressed plants. A novel discovery was that PAL was the critical enzyme in capsaicinoid biosynthesis under drought stress because its activities and capsaicinoid increased across the different pungency levels of hot pepper cultivars examined.

  5. Effects of capsaicin on testis ghrelin expression in mice.

    PubMed

    Ilhan, T; Erdost, H

    2013-01-01

    Capsaicin (CAP), the active substance of red hot peppers, has been reported to stimulate development of the gonad. Ghrelin is an acylated polypeptide hormone that is secreted predominantly by endocrine cells of the stomach. There is evidence that ghrelin is involved in reproductive function. Ghrelin significantly inhibits testosterone secretion in a dose-dependent manner. We investigated the effect of CAP on ghrelin expression in testes of mice and on testosterone levels during pubertal and adult periods. We used a variety of morphometric, immunohistochemical and biochemical methods, and western blot analysis. The animals were divided into two age groups: puberty and adult. Control groups for both age groups were fed with standard diet and experimental groups were fed with a diet containing 0.02% CAP. Testes were collected quickly after sacrifice. After dehydration, the specimens were embedded in paraffin and 5 μm sections were cut, and Crossman's triple staining and immunohistochemical staining for ghrelin were applied. Immunohistochemical staining with ghrelin antibody for both age groups demonstrated immunoreaction especially in Leydig and Sertoli cells, but no reaction was observed in spermatogenic cells. Ghrelin immunoreaction was less intense in the experimental groups. Serum testosterone levels were increased in both experimental groups, especially in adults. More spermatocytes were observed in the experimental group compared to the control group. In both pubertal and adult experimental groups, the seminiferous epithelium was thick. CAP appears to enhance testicular cell proliferation and can affect the release of ghrelin and testosterone directly or indirectly.

  6. Decision-making in classic trigeminal neuralgia concurrent with a pontine cavernous malformation: Causal or coincidental association?

    PubMed

    Parise, Maud; Acioly, Marcus André; Vincent, Maurice; Gasparetto, Emerson Leandro

    2015-01-01

    Trigeminal neuralgia is classically associated with neurovascular compression of the trigeminal nerve, at the root entry zone (REZ). However, patients are occasionally affected by intra-axial involvement of trigeminal sensory fibers caused by demyelinating diseases, strokes and, rarely, pontine cavernous malformations. We discuss the management strategies and decision-making process in a 55-year-old patient, affected by trigeminal neuralgia with 2 potential causative mechanisms: a neurovascular conflict at the trigeminal REZ and an ipsilateral cavernous malformation at the pontine nucleus of the trigeminal nerve.

  7. Immunohistochemical expression of ghrelin in capsaicin-treated rat ovaries during the different developmental periods.

    PubMed

    Tütüncü, Ş; İlhan, T; Özfiliz, N

    2016-01-01

    Red hot pepper is a plant that belongs to the Solanaceae family and is known as Capsicum annuum. Capsaicin is the active ingredient of cayenne pepper. Ghrelin is a hormone, which consists of polypeptide structure. Ghrelin also contributes to growth hormone secretion, energy balance, food intake and body weight regulator. The aim of this study was the localization and expression of ghrelin in the ovaries of rats treated with capsaicin during the postnatal development. Ninety female Sprague-Dawley rats (21 d) were used. The rats were randomly divided into 3 groups (n=30 each) as pubertal, post pubertal and adult. Each group was subdivided into three groups. The first subgroup (control) was given no injections. The second subgroup (vehicle) received only 0.3 cc solvent and the third subgroup (experiment) received subcutaneous injection of equal volume of capsaicin (1 mg/kg/d) for 42, 56, and 70 days. Ghrelin immunoreactivity was determined in ovarian follicular granulosa cells, interstitial cells and corpus luteal cells. A ghrelin immunopositive reaction located in the cytoplasm of cells in all groups. These results indicate that prolonged administration of low dose capsaicin does not affect ghrelin expression. However, follicular atresia was seen in lower rate in capsaicin treated group in comparison to other groups. PMID:27656230

  8. Immunohistochemical expression of ghrelin in capsaicin-treated rat ovaries during the different developmental periods

    PubMed Central

    Tütüncü, Ş.; İlhan, T.; Özfiliz, N.

    2016-01-01

    Red hot pepper is a plant that belongs to the Solanaceae family and is known as Capsicum annuum. Capsaicin is the active ingredient of cayenne pepper. Ghrelin is a hormone, which consists of polypeptide structure. Ghrelin also contributes to growth hormone secretion, energy balance, food intake and body weight regulator. The aim of this study was the localization and expression of ghrelin in the ovaries of rats treated with capsaicin during the postnatal development. Ninety female Sprague-Dawley rats (21 d) were used. The rats were randomly divided into 3 groups (n=30 each) as pubertal, post pubertal and adult. Each group was subdivided into three groups. The first subgroup (control) was given no injections. The second subgroup (vehicle) received only 0.3 cc solvent and the third subgroup (experiment) received subcutaneous injection of equal volume of capsaicin (1 mg/kg/d) for 42, 56, and 70 days. Ghrelin immunoreactivity was determined in ovarian follicular granulosa cells, interstitial cells and corpus luteal cells. A ghrelin immunopositive reaction located in the cytoplasm of cells in all groups. These results indicate that prolonged administration of low dose capsaicin does not affect ghrelin expression. However, follicular atresia was seen in lower rate in capsaicin treated group in comparison to other groups. PMID:27656230

  9. Capsaicin and the Treatment of Vulvar Vestibulitis Syndrome: A Valuable Alternative?

    PubMed Central

    Murina, Filippo; Radici, Gianluigi; Bianco, Vanda

    2004-01-01

    Objective To assess the efficacy of topical capsaicin in the treatment of vulvar vestibulitis syndrome. Study Design Thirty-three consecutive women referred for vulvar vestibulitis syndrome were treated with topical capsaicin 0.05 %. The capsaicin cream was applied twice a day for 30 days, then once a Day for 30 days, and finally 2 times a week for 4 months. Results In 19 patients (59%), improvement of symptoms was recorded, but no complete remission was observed. Symptoms recurred in all patients after the use of capsaicin cream was discontinued. A return to a twice-weekly topical application of the cream resulted in the improvement of symptoms. Severe burning was reported as the only side effect by all the patients. Conclusion Response to treatment was only partial, possibly due to the concentration of the compound being too low, or to the need for more frequent than daily applications. The therapeutic role of capsaicin should hence be confined to a last-choice medical approach. PMID:15775875

  10. Capsaicin-capped silver nanoparticles: its kinetics, characterization and biocompatibility assay

    NASA Astrophysics Data System (ADS)

    Amruthraj, Nagoth Joseph; Preetam Raj, John Poonga; Lebel, Antoine

    2015-04-01

    Capsaicin was used as a bio-reductant for the reduction of silver nitrate to form silver nanoparticles. The formation of the silver nanoparticles was initially confirmed by color change and Tyndall effect of light scattering. It was characterized with UV-visible spectroscopy, FTIR and TEM. Hemagglutination (H) test and H-inhibition assay were performed in the presence of AgNPs-capsaicin conjugates. The silver colloid solution after complete reduction turned into pale gray color. The characteristic surface plasmon resonance of silver nanoparticles (SNPs) was observed at 450 nm. Time taken for complete bio-reduction of silver nitrate and capping was found to be 16 hours. The amount of capsaicin required to reduce 20 ml of 1 mM silver nitrate solution was found to be 40 μg approximately. The FTIR results confirmed the capping of capsaicin on the silver metal. The particle size was within the range of 20-30 nm. The hemagglutination and H-inhibition test was negative for all the blood groups. The capsaicin-capped silver nanoparticles were compatible with blood cells in hemagglutination test implying biocompatibility as future therapeutic drug.

  11. Capsaicin Fluidifies the Membrane and Localizes Itself near the Lipid-Water Interface.

    PubMed

    Torrecillas, Alejandro; Schneider, Monika; Fernández-Martínez, Ana M; Ausili, Alessio; de Godos, Ana M; Corbalán-García, Senena; Gómez-Fernández, Juan C

    2015-10-21

    Capsaicin is the chemical responsible for making some peppers spicy hot, but additionally it is used as a pharmaceutical to alleviate different pain conditions. Capsaicin binds to the vanilloid receptor TRPV1, which plays a role in coordinating chemical and physical painful stimuli. A number of reports have also shown that capsaicin inserts in membranes and its capacity to modify them may be part of its molecular mode of action, affecting the activity of other membrane proteins. We have used differential scanning calorimetry, X-ray diffraction, (31)P NMR, and (2)H NMR spectroscopy to show that capsaicin increases the fluidity and disorder of 1,2-palmitoyl-sn-glycero-3-phosphocholine membrane models. By using (1)H NOESY MAS NMR based on proton-proton cross-peaks between capsaicin and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine resonances, we determined the location profile of this molecule in a fluid membrane concluding that it occupies the upper part of the phospholipid monolayer, between the lipid-water interface and the double bond of the acyl chain in position sn-2. This location explains the disorganization of the membrane of both the lipid-water interface and the hydrophobic palisade.

  12. Immunohistochemical expression of ghrelin in capsaicin-treated rat ovaries during the different developmental periods.

    PubMed

    Tütüncü, Ş; İlhan, T; Özfiliz, N

    2016-01-01

    Red hot pepper is a plant that belongs to the Solanaceae family and is known as Capsicum annuum. Capsaicin is the active ingredient of cayenne pepper. Ghrelin is a hormone, which consists of polypeptide structure. Ghrelin also contributes to growth hormone secretion, energy balance, food intake and body weight regulator. The aim of this study was the localization and expression of ghrelin in the ovaries of rats treated with capsaicin during the postnatal development. Ninety female Sprague-Dawley rats (21 d) were used. The rats were randomly divided into 3 groups (n=30 each) as pubertal, post pubertal and adult. Each group was subdivided into three groups. The first subgroup (control) was given no injections. The second subgroup (vehicle) received only 0.3 cc solvent and the third subgroup (experiment) received subcutaneous injection of equal volume of capsaicin (1 mg/kg/d) for 42, 56, and 70 days. Ghrelin immunoreactivity was determined in ovarian follicular granulosa cells, interstitial cells and corpus luteal cells. A ghrelin immunopositive reaction located in the cytoplasm of cells in all groups. These results indicate that prolonged administration of low dose capsaicin does not affect ghrelin expression. However, follicular atresia was seen in lower rate in capsaicin treated group in comparison to other groups.

  13. Immunohistochemical expression of ghrelin in capsaicin-treated rat ovaries during the different developmental periods

    PubMed Central

    Tütüncü, Ş.; İlhan, T.; Özfiliz, N.

    2016-01-01

    Red hot pepper is a plant that belongs to the Solanaceae family and is known as Capsicum annuum. Capsaicin is the active ingredient of cayenne pepper. Ghrelin is a hormone, which consists of polypeptide structure. Ghrelin also contributes to growth hormone secretion, energy balance, food intake and body weight regulator. The aim of this study was the localization and expression of ghrelin in the ovaries of rats treated with capsaicin during the postnatal development. Ninety female Sprague-Dawley rats (21 d) were used. The rats were randomly divided into 3 groups (n=30 each) as pubertal, post pubertal and adult. Each group was subdivided into three groups. The first subgroup (control) was given no injections. The second subgroup (vehicle) received only 0.3 cc solvent and the third subgroup (experiment) received subcutaneous injection of equal volume of capsaicin (1 mg/kg/d) for 42, 56, and 70 days. Ghrelin immunoreactivity was determined in ovarian follicular granulosa cells, interstitial cells and corpus luteal cells. A ghrelin immunopositive reaction located in the cytoplasm of cells in all groups. These results indicate that prolonged administration of low dose capsaicin does not affect ghrelin expression. However, follicular atresia was seen in lower rate in capsaicin treated group in comparison to other groups.

  14. Loss of inhibition by brain natriuretic peptide over P2X3 receptors contributes to enhanced spike firing of trigeminal ganglion neurons in a mouse model of familial hemiplegic migraine type-1.

    PubMed

    Marchenkova, Anna; van den Maagdenberg, Arn M J M; Nistri, Andrea

    2016-09-01

    Purinergic P2X3 receptors (P2X3Rs) play an important role in pain pathologies, including migraine. In trigeminal neurons, P2X3Rs are constitutively downregulated by endogenous brain natriuretic peptide (BNP). In a mouse knock-in (KI) model of familial hemiplegic migraine type-1 with upregulated calcium CaV2.1 channel function, trigeminal neurons exhibit hyperexcitability with gain-of-function of P2X3Rs and their deficient BNP-mediated inhibition. We studied whether the absent BNP-induced control over P2X3Rs activity in KI cultures may be functionally expressed in altered firing activity of KI trigeminal neurons. Patch-clamp experiments investigated the excitability of wild-type and KI trigeminal neurons induced by either current or agonists for P2X3Rs or transient receptor potential vanilloid-1 (TRPV1) receptors. Consistent with the constitutive inhibition of P2X3Rs by BNP, sustained pharmacological block of BNP receptors selectively enhanced P2X3R-mediated excitability of wild-type neurons without affecting firing evoked by the other protocols. This effect included increased number of action potentials, lower spike threshold and shift of the firing pattern distribution toward higher spiking activity. Thus, inactivation of BNP signaling transformed the wild-type excitability phenotype into the one typical for KI. BNP receptor block did not influence excitability of KI neurons in accordance with the lack of BNP-induced P2X3R modulation. Our study suggests that, in wild-type trigeminal neurons, negative control over P2X3Rs by the BNP pathway is translated into tonic suppression of P2X3Rs-mediated excitability. Lack of this inhibition in KI cultures results in a hyperexcitability phenotype and might contribute to facilitated trigeminal pain transduction relevant for migraine. PMID:27346147

  15. Capsaicin, from Hot to Not; Can New Pain-Relieving Drugs Be Derived from This Substance Known to Cause Pain?

    ERIC Educational Resources Information Center

    Rusterholz, David B.

    2006-01-01

    The systematic developments of synthetically modified structures related to capsaicin known to have pungent properties found in chili peppers that could be useful as analgesic drug are described. It is found that identification of the receptor for capsaicin and the mechanism of its action greatly contributed to an understanding of the role…

  16. Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage.

    PubMed

    He, Yifan; Zhu, Jihong; Huang, Fang; Qin, Liu; Fan, Wenguo; He, Hongwen

    2014-11-15

    The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that

  17. Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage

    PubMed Central

    He, Yifan; Zhu, Jihong; Huang, Fang; Qin, Liu; Fan, Wenguo; He, Hongwen

    2014-01-01

    The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that

  18. Molecular Cloning and Functional Characterization of Xenopus tropicalis Frog Transient Receptor Potential Vanilloid 1 Reveal Its Functional Evolution for Heat, Acid, and Capsaicin Sensitivities in Terrestrial Vertebrates*

    PubMed Central

    Ohkita, Masashi; Saito, Shigeru; Imagawa, Toshiaki; Takahashi, Kenji; Tominaga, Makoto; Ohta, Toshio

    2012-01-01

    The functional difference of thermosensitive transient receptor potential (TRP) channels in the evolutionary context has attracted attention, but thus far little information is available on the TRP vanilloid 1 (TRPV1) function of amphibians, which diverged earliest from terrestrial vertebrate lineages. In this study we cloned Xenopus tropicalis frog TRPV1 (xtTRPV1), and functional characterization was performed using HeLa cells heterologously expressing xtTRPV1 (xtTRPV1-HeLa) and dorsal root ganglion neurons isolated from X. tropicalis (xtDRG neurons) by measuring changes in the intracellular calcium concentration ([Ca2+]i). The channel activity was also observed in xtTRPV1-expressing Xenopus oocytes. Furthermore, we tested capsaicin- and heat-induced nocifensive behaviors of the frog X. tropicalis in vivo. At the amino acid level, xtTRPV1 displays ∼60% sequence identity to other terrestrial vertebrate TRPV1 orthologues. Capsaicin induced [Ca2+]i increases in xtTRPV1-HeLa and xtDRG neurons and evoked nocifensive behavior in X. tropicalis. However, its sensitivity was extremely low compared with mammalian orthologues. Low extracellular pH and heat activated xtTRPV1-HeLa and xtDRG neurons. Heat also evoked nocifensive behavior. In oocytes expressing xtTRPV1, inward currents were elicited by heat and low extracellular pH. Mutagenesis analysis revealed that two amino acids (tyrosine 523 and alanine 561) were responsible for the low sensitivity to capsaicin. Taken together, our results indicate that xtTRPV1 functions as a polymodal receptor similar to its mammalian orthologues. The present study demonstrates that TRPV1 functions as a heat- and acid-sensitive channel in the ancestor of terrestrial vertebrates. Because it is possible to examine vanilloid and heat sensitivities in vitro and in vivo, X. tropicalis could be the ideal experimental lower vertebrate animal for the study of TRPV1 function. PMID:22130664

  19. Solid cystic trigeminal schwannoma with intraorbital extension causing proptosis and vision loss

    PubMed Central

    Gupta, Pankaj; Sharma, Arvind; Singh, Jitendra

    2016-01-01

    Schwannomas are slowly growing, well capsulated, benign tumors. Involvement of vestibular nerve is most commonly followed by trigeminal nerve. Trigeminal schwannoma is rare entity, and cystic degeneration with intraorbital extension of trigeminal schwannoma is even rarer. These tumors occur in fourth and fifth decades of life and patients have variable presentation depending on which cranial compartment is involved. Orbital schwannoma usually presents with proptosis with or without vision loss. We are reporting such a rare case of solid cystic trigeminal schwannoma with intraorbital extension through superior orbital fissure that was removed surgically.

  20. Effect of beam channel plugging on the outcome of gamma knife radiosurgery for trigeminal neuralgia

    SciTech Connect

    Massager, Nicolas . E-mail: nmassage@ulb.ac.be; Nissim, Ouzi; Murata, Noriko; Devriendt, Daniel; Desmedt, Francoise; Vanderlinden, Bruno; Regis, Jean; Levivier, Marc

    2006-07-15

    Purpose: We studied the influence of using plugs for brainstem protection during gamma knife radiosurgery (GKR) of trigeminal neuralgia (TN), with special emphasis on irradiation doses delivered to the trigeminal nerve, pain outcomes, and incidence of trigeminal dysfunction. Methods and Materials: A GKR procedure for TN using an anterior cisternal target and a maximum dose of 90 Gy was performed in 109 patients. For 49 patients, customized beam channel blocking (plugs) were used to reduce the dose delivered to the brainstem. We measured the mean and integrated radiation doses delivered to the trigeminal nerve and the clinical course of patients treated with and without plugs. Results: We found that blocking increases the length of trigeminal nerve exposed to high-dose radiation, resulting in a significantly higher mean dose to the trigeminal nerve. Significantly more of the patients with blocking achieved excellent pain outcomes (84% vs. 62%), but with higher incidences of moderate and bothersome trigeminal nerve dysfunction (37% mild/10% bothersome with plugs vs. 30% mild/2% bothersome without). Conclusions: The use of plugs to protect the brainstem during GKR treatment for TN increases the dose of irradiation delivered to the intracisternal trigeminal nerve root and is associated with an important increase in the incidence of trigeminal nerve dysfunction. Therefore, beam channel blocking should be avoided for 90 Gy-GKR of TN.

  1. Solid cystic trigeminal schwannoma with intraorbital extension causing proptosis and vision loss

    PubMed Central

    Gupta, Pankaj; Sharma, Arvind; Singh, Jitendra

    2016-01-01

    Schwannomas are slowly growing, well capsulated, benign tumors. Involvement of vestibular nerve is most commonly followed by trigeminal nerve. Trigeminal schwannoma is rare entity, and cystic degeneration with intraorbital extension of trigeminal schwannoma is even rarer. These tumors occur in fourth and fifth decades of life and patients have variable presentation depending on which cranial compartment is involved. Orbital schwannoma usually presents with proptosis with or without vision loss. We are reporting such a rare case of solid cystic trigeminal schwannoma with intraorbital extension through superior orbital fissure that was removed surgically. PMID:27695572

  2. Chronic nerve growth factor administration increases the peripheral exocytotic activity of capsaicin-sensitive cutaneous neurons.

    PubMed

    Bowles, Walter R; Sabino, Ma'lou; Harding-Rose, Catherine; Hargreaves, Kenneth M

    2006-08-01

    Nerve growth factor (NGF) plays an important role in inflammation and pain and has been suggested to regulate the responsiveness and sensitivity of nociceptive fibers. However, no study has evaluated whether chronic NGF alters the exocytotic capacity of peripheral terminals of peptidergic fibers. To test this hypothesis, rats were injected subcutaneously every other day with either murine recombinant NGF (mNGF; 1.0 mg/kg) or vehicle for 7 days; or mNGF (0.1 mg/kg), mNGF (1 mg/kg) or vehicle every other day for 13 days. Treatment of rats with NGF over a 13-day period produced a significant increase in capsaicin-evoked iCGRP release from isolated biopsies of hindpaw skin, as assessed by in vitro superfusion and RIA. This effect was dose-dependent and exhibited a temporal requirement, because the enhancement was only observed after 13 days of treatment and was not evident after 7 days of treatment. This NGF enhancement of capsaicin-evoked iCGRP release was not due solely to increases in peripheral iCGRP content since only the 1mg/kg dose of NGF elevated cutaneous pools of iCGRP, whereas both doses significantly increased capsaicin-evoked peptide release. Moreover, NGF also enhanced capsaicin-evoked thermal hyperalgesia under similar dose- and time-related conditions. Collectively, the chronic administration of NGF not only increases capsaicin-evoked hyperalgesia, but also significantly primes peripheral fibers to enhanced peptidergic exocytosis following activation of the capsaicin receptor. Collectively, these data are consistent with the hypothesis that persistently elevated NGF levels may contribute to enhanced neurogenic regulation of inflammatory and wound healing processes in injured tissue.

  3. Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

    SciTech Connect

    Wang Junru; Zheng Huaien; Kulkarni, Ashwini; Ou Xuemei; Hauer-Jensen, Martin . E-mail: mhjensen@life.uams.edu

    2006-04-01

    Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor {beta} immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent.

  4. Trigeminal neuralgia: An insight into the current treatment modalities

    PubMed Central

    Punyani, Silky Rajesh; Jasuja, Vishal Ramesh

    2012-01-01

    Trigeminal neuralgia (TN) is one of the most excruciating pain syndromes afflicting the orofacial region. Trigeminal neuralgia may be primary i.e. idiopathic or secondary, resulting from trauma or a CNS lesion. Considering the agonizing nature of the disease and TN being the commonest of the neural maladies affecting the orofacial region it is important fo