WorldWideScience

Sample records for capsaicin

  1. Capsaicin for Rhinitis.

    Science.gov (United States)

    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

  2. Capsaicin, Nociception and Pain.

    Science.gov (United States)

    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

  3. Persistent Respiratory Symptoms following Prolonged Capsaicin Exposure

    Directory of Open Access Journals (Sweden)

    K Nugent

    2013-10-01

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

  4. The role of capsaicin in dermatology.

    Science.gov (United States)

    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

  5. Capsaicin in Idiopathic Rhinitis A Hot Topic

    OpenAIRE

    van Rijswijk, J B

    2005-01-01

    textabstractIn chapter I the currently known causes for nonallergic noninfectious rhinitis and possible treatments are summarised. Also possible pathophysiological mechanisms underlying idiopathic rhinitis (IR) are discussed. In chapter II the aims of the studies are presented. This thesis comprises studies aimed at the therapeutic potential and safety of intranasal capsaicin in IR patients, developing a patient and physician friendly, effective intranasal capsaicin treatment regimen for IR a...

  6. Capsaicin induced cough in cryptogenic fibrosing alveolitis

    OpenAIRE

    Doherty, M.; Mister, R; Pearson, M.; Calverley, P.

    2000-01-01

    BACKGROUND—Cough is a common and troublesome symptom in cryptogenic fibrosing alveolitis (CFA) but the mechanisms responsible are not known. The cough threshold to inhaled capsaicin is increased in asthma and chronic obstructive pulmonary disease (COPD) where lung volumes are increased, but the relationship between cough response and symptom intensity has not been studied in CFA where lung volumes are reduced.
METHODS—Capsaicin challenge tests were performed on 15 subject...

  7. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction.

    Science.gov (United States)

    Sun, Fang; Xiong, Shiqiang; Zhu, Zhiming

    2016-01-01

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

  8. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction

    Directory of Open Access Journals (Sweden)

    Fang Sun

    2016-04-01

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

  9. The Effect of Capsaicin on Salivary Gland Dysfunction.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2014-12-28

    The dietary compound capsaicin is responsible for the "hot and spicy" taste of chili peppers and pepper extracts. It is a valuable pharmacological agent with several therapeutic applications in controlling pain and inflammation. Emerging studies show that it displays potent anti-tumor activity in several human cancers. On a more basic research level, capsaicin has been used as a ligand to activate several types of ion-channel receptors. The pharmacological activity of capsaicin-like compounds is dependent on several factors like the dose, the route of administration and most importantly on its concentration at target tissues. The present review describes the current knowledge involving the metabolism and bioavailability of capsaicinoids in rodents and humans. Novel drug delivery strategies used to improve the bioavailability and therapeutic index of capsaicin are discussed in detail. The generation of novel capsaicin-mimetics and improved drug delivery methods will foster the hope of innovative applications of capsaicin in human disease. PMID:25307998

  12. Bioavailability of capsaicin and its implications for drug delivery

    OpenAIRE

    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...

  13. An Overview about Versatile Molecule Capsaicin

    Directory of Open Access Journals (Sweden)

    Arora R

    2011-10-01

    Full Text Available Capsaicin is a pungent highly domesticated fat soluble alkaloid having its origin from Bolvia and Brazil. It is biosynthesized via phenylpropanoid pathway and branched chain fatty acid pathway. Mostly found in trans isomeric form. Its pungent analogues are synthesized using amidation reactions catalyzed by lipases and non-pungent analogues using acyl chain lengths and different substituent in aromatic ring. It acts by binding TRPV1 and shows wide applications in relief from pain, breast and prostate cancer, obesity, heart diseases and hair loses. Its increased intake may cause lesions of liver and kidney along with gastric cancer. A review is made of capsaicin research focusing mainly on its origin, biosynthesis, chemistry and pharmacology, including its toxicological aspects.

  14. [Capsaicin in treatment of neuropathic pain].

    Science.gov (United States)

    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

  15. Capsaicin-induced neurogenic inflammation in pig skin

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  16. Integrating TRPV1 Receptor Function with Capsaicin Psychophysics

    Directory of Open Access Journals (Sweden)

    Gregory Smutzer

    2016-01-01

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

  17. Gastroprotection induced by capsaicin in healthy human subjects

    Institute of Scientific and Technical Information of China (English)

    Gyula Mózsik; János Szolcsányi; István Rácz

    2005-01-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  20. Late sensory function after intraoperative capsaicin wound instillation

    DEFF Research Database (Denmark)

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

    2010-01-01

    BACKGROUND: Intense capsaicin-induced C-fiber stimulation results in reversible lysis of the nerve soma, thereby making capsaicin wound instillation of potential interest for the treatment of post-operative pain. Clinical histological and short-term sensory studies suggest that the C-fiber function...... is partly re-established after skin injection of capsaicin. However, no study has evaluated the long-term effects of wound instillation of purified capsaicin on sensory functions. METHODS: Patients included in a double-blind placebo-controlled randomized study of the analgesic effect of capsaicin...... after groin hernia repair were examined by quantitative sensory testing before, 1 week and 2 years post-operatively. The primary endpoint was occurrence of hyperalgesia/allodynia. The secondary endpoints were acute and late sensory changes between the two patient groups. Patients were blinded to the...

  1. Antioxidant and antibacterial properties of capsaicine microemulsions

    OpenAIRE

    CRISTIAN DIMA; GIGI COMAN; MIHAELA COTÂRLEŢ; PETRU ALEXE; ŞTEFAN DIMA

    2013-01-01

    The aim of this study was to prepare capsaicin microemulsions and to assess their antioxidant and antibacterial properties. Pseudoternare phase diagrams were made and were highlighted O/W/S/CoS weight ratios corresponding to microemulsion states. The oil phase (O) was soybean oil and for the aqueous phase (W) was used a mixture of water and glycerol in a ratio of 4:1 (wt/wt). As a surfactant (S) was used Tween 40 and cosurfactant (CoS) was ethanol in the mass ratio S:CoS = 2:1. Viscosimetr...

  2. Treatment of notalgia paresthetica with capsaicin.

    Science.gov (United States)

    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

  3. Characterization of capsaicin induced responses in mice vas deferens

    DEFF Research Database (Denmark)

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

    2011-01-01

    isolated preparations. The present study sets out to study and characterize the capsaicin as well as CGRP-induced responses in isolated mouse vas deferens. The effects of capsaicin and CGRP family of peptides were studied on electrically-induced twitch responses in the absence or presence of transient...... receptor potential cation channel vanilloid subfamily member 1 (TRPV1) antagonist and CGRP receptor antagonists. Twitch responses were attenuated by capsaicin (1nM-30nM) and CGRP family of peptides. The potency order was CGRP>intermedin-long (IMDL)~[Cys(Et)(2,7)]aCGRP~adrenomedullin (AM)>[Cys(ACM)(2,7)]a...

  4. Suramin affects capsaicin responses and capsaicin-noxious heat interactions in rat dorsal root ganglia neurones

    Czech Academy of Sciences Publication Activity Database

    Vlachová, Viktorie; Lyfenko, Alla; Vyklický st., Ladislav; Orkand, R. K.

    2002-01-01

    Roč. 51, č. 2 (2002), s. 193-198. ISSN 0862-8408 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : dorsal root ganglia neurones * vanilloid receptor * capsaicin -noxious heat Subject RIV: ED - Physiology Impact factor: 0.984, year: 2002

  5. Capsaicin Content and Pungency of Different Capsicum spp. Cultivars

    Directory of Open Access Journals (Sweden)

    K. SANATOMBI

    2008-08-01

    Full Text Available Six chilli cultivars belonging to three species of Capsicum: Capsicum annuum L. (cvs 'Meiteimorok' and 'Haomorok', Capsicum frutescens L. (cvs 'Uchithi' and 'Mashingkha' and Capsicum chinense Jacq. (cvs 'Umorok' and 'Chiengpi' are economically important food crops. The capsaicin content and pungency in scoville heat unit (SHU of these six chilli cultivars were determined by high-performance liquid chromatography (HPLC. The capsaicin content and pungency of the chillies varied depending upon the genotype. Among the six chilli cultivars studied, the cultivar 'Umorok' had the highest capsaicin content (2.06%, and was also the most pungent of with 329.100 SHU while the cultivar 'Haomorok' had the least capsaicin content (0.17% with a corresponding pungency of 26.000 SHU.

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  7. EFFECT OF CAPSAICIN ON SUBSTANCE P IN PSORIASIS VULGARIS

    Institute of Scientific and Technical Information of China (English)

    王万卷; 谭升顺

    2003-01-01

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

  8. Capsaicin-induced Thermal Enhancement on Target Tissues in Hyperthermia

    Directory of Open Access Journals (Sweden)

    Peng Zeng

    2011-04-01

    Full Text Available Local thermal enhancement in target tissue is of great interest in tumor hyperthermia. In this study, we proposed a brand-new thermal enhancement protocol for tumor hyperthermia using heat generated from thermoge-nesis evoked by capsaicin, which can safely deliver a totally localized heating to target tissue. A healthy male volunteer was recruited, whose partial areas of the dorsum of hand and posterior aspect of forearm were smeared with 1% (w/w capsaicin solution, to determine the increase of ther-mogenesis in human body. In addition, animal experiments on healthy Kunming (KM mice (20-22g were performed to test the feasibility and efficacy of capsaicin-induced thermal enhancement. These KM mice were first locally smeared with, subcutaneous or intraperitoneal injected of the same capsaicin solution, and then heated by near infrared laser. Preliminary experiments on the volunteer showed an effec-tive temperature increase in the skin area. Animal experi-ments indicated that distinct thermal enhancement in heat-ing effect, and that the thermal enhancement induced by intraperitoneal injection of capsaicin is more obvious than the other two ways. Thus capsaicin can be used as a poten-tial therapeutic adjuvant to locally enhance heating effects in target tissue during tumor hyperthermia.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-03-15

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

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

    International Nuclear Information System (INIS)

    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 [3H]dihydrocapsaicin was observed in the jejunum. These results suggested that capsaicin and its analogs were absorbed by a nonactive process in jejunum. [3H]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 [3H]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

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

    Science.gov (United States)

    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

  12. Responses of primate spinomesencephalic tract cells to intradermal capsaicin.

    Science.gov (United States)

    Dougherty, P M; Schwartz, A; Lenz, F A

    1999-01-01

    The responses of 32 spinomesencephalic tract cells to intradermal capsaicin were examined in anesthetized monkeys. Wide dynamic range (n = 20) and nociceptive specific (n = 6) cells showed two types of excitatory responses to intradermal injection of capsaicin. The first excitatory response shown by the majority of wide dynamic range (n = 13) and nociceptive specific (n = 4) cells was consistent with their sensitization by capsaicin. The cells showed an acute and prolonged increase in ongoing activity with capsaicin injection. Responses to mechanical stimuli were substantially increased after capsaicin and an expansion of receptive field was often observed. The responses of the same cells to excitatory amino acid agonists applied locally by iontophoresis also increased. All cells showing sensitization were antidromically activated from periaqueductal gray regions dorsal to the sulcus limitans. Electrical stimulation at these sites did not affect the ongoing or evoked discharges of these cells. The second excitatory response of wide dynamic range (n = 5) and nociceptive specific (n = 1) cells was a novel pattern not consistent with sensitization. These cells nevertheless showed an acute and prolonged increase in background activity after capsaicin injection. Yet, there was no change or a decrease in responses to cutaneous stimuli, no evidence for change in receptive field size and no increase in responses to locally released excitatory amino acids. These cells projected to regions in the periaqueductal gray ventral to the sulcus limitans. Electrical stimulation at these sites produced a decrease in spontaneous activity of the same cell. Low threshold mesencephalic-projecting neurons (n = 6) showed a single inhibitory pattern (n = 4) of responses to capsaicin. The injection produced an acute decrease in spontaneous activity that was sustained for at least 30 min after injection. The responses to cutaneous stimuli and to excitatory amino acids were also substantially

  13. Distinct Modulations of Human Capsaicin Receptor by Protons and Magnesium through Different Domains*

    OpenAIRE

    Wang, Shu; Poon, Kinning; Oswald, Robert E.; Chuang, Huai-hu

    2010-01-01

    The capsaicin receptor (TRPV1) is a nonselective cation channel that integrates multiple painful stimuli, including capsaicin, protons, and heat. Protons facilitate the capsaicin- and heat-induced currents by decreasing thermal threshold or increasing agonist potency for TRPV1 activation (Tominaga, M., Caterina, M. J., Malmberg, A. B., Rosen, T. A., Gilbert, H., Skinner, K., Raumann, B. E., Basbaum, A. I., and Julius, D. (1998) Neuron 21, 531–543). In the presence of saturating capsaicin, rat...

  14. Similar itch and nociceptive sensations evoked by punctate cutaneous application of capsaicin, histamine and cowhage

    OpenAIRE

    Sikand, Parul; Shimada, Steven G.; Green, Barry G.; LaMotte, Robert H.

    2009-01-01

    Itch evoked by cowhage or histamine is reduced or blocked by capsaicin desensitization, suggesting that pruriceptive neurons are capsaicin-sensitive. Topical capsaicin can evoke both nociceptive sensations and itch, whereas intradermal injection of capsaicin evokes only burning pain. To dissociate the pruritic and nociceptive sensory effects caused by the chemical activation of sensory neurons, chemicals were applied in a punctiform manner to the skin of the forearm using individual, heat-ina...

  15. Extraction of capsaicin from hot peppers and determination of its antioxidant properties

    OpenAIRE

    Koleva Gudeva, Liljana; Janevik-Ivanovska, Emilija; Gulaboski, Rubin; Trajkova, Fidanka; Maksimova, Viktorija

    2013-01-01

    Capsaicin is one of the major constituent of the group of capsaicinoids which can be found only in the species of genus Capsicum, fam. Solananceae. Its characteristic chemical structure and the properties that capsaicin possess enforce its use in the field of pharmaceutical, food and agricultural chemistry. Capsacinoids are group of phenol amides from which capsaicin takes 69%, and the others capsaicinoids are represented with lower concentrations. Capsaicin,8-methyl-N-vanillyl-6-nonenamide, ...

  16. Intramuscular and intradermal injection of capsaicin: a comparison of local and referred pain

    DEFF Research Database (Denmark)

    Witting, Nanna; Svensson, Peter; Gottrup, Hanne; Arendt-Nielsen, Lars; Jensen, Troels Staehelin

    2000-01-01

    The present study compared capsaicin-induced muscle and skin pain in humans. Twelve healthy subjects received, in a randomised, balanced order, 3 intramuscular (i.m.) injections into the brachioradial muscle: capsaicin 100 microg/1 ml, capsaicin 100 microg/20 microl or 1 ml solvent (Tween 80), and...

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

    Science.gov (United States)

    2010-07-01

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

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

    Science.gov (United States)

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

    2000-12-01

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

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

    International Nuclear Information System (INIS)

    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. Natural Capsaicin in Capsicum chinense: Concentration vs. Origin

    Science.gov (United States)

    Capsaicin [N-vanillyl-8-methyl-6-(E) noneamide] is the most pungent of the group of compounds known as capsaicinoids in chili peppers. A survey was conducted to screen fruits of 307 hot pepper accessions of Capsicum chinense selected from the USDA germplasm collection for their major capsaicinoids c...

  1. Binding of Capsaicin to the TRPV1 Ion Channel.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  4. Nano-encapsulation of capsaicin on lipid vesicle and evaluation of their hepatocellular protective effect.

    Science.gov (United States)

    Giri, Tapan Kumar; Mukherjee, Payel; Barman, Tapan Kumar; Maity, Subhasis

    2016-07-01

    The intention of the study was to evaluate the effectiveness of nanocapsulated food constituent capsaicin in protection of liver oxidative stress. We had prepared phospholipid vesicle (nanoliposome) by formation of thin lipid film followed by hydration when the mean vesicle diameter was found to be 277.7nm. Protection from sodium fluoride (NaF) induced oxidative stress by capsaicin loaded nanoliposomal formulation were tested in rats where a single dose of capsaicin in free and nanoliposome forms were administered after two hour of exposure to NaF. Membrane in hepatic cells were damaged by NaF and it was evaluated by estimating reactive oxygen species (ROS), lipid peroxidation, and catalase activity when it was observed that free capsaicin produced mild protection whereas liposomal capsaicin exerted a significant result. This can be suggested that liposome encapsulating capsaicin acts as a promising therapeutic agent in reducing liver oxidative stress produced by different stress factors. PMID:27032489

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

    OpenAIRE

    Kawakami, Shinpei; Sato, Hajime; Akihiro T Sasaki; 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 visce...

  6. Human responses to inhaled capsaicin are not inhibited by granisetron.

    OpenAIRE

    Choudry, N B; McEwan, J. R.; Lavender, E A; Williams, A J; Fuller, R. W.

    1991-01-01

    Cough is a common respiratory symptom, the mechanism of which is poorly understood. In this study the role of 5-HT3 receptors was investigated. Capsaicin-induced cough and increase in airways resistance were measured in six male volunteers before and after infusion with granisetron 160 micrograms kg-1 or placebo. Neither cough nor the increase in respiratory resistance was altered by the active treatment. These results suggest that 5-HT3 receptors are not involved in these two respiratory res...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Shaherin Basith

    2016-07-01

    Full Text Available Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neuro-protective functions. Moreover, emerging data indicate its clinical significance in treating vascular-related diseases, metabolic syndrome, and gastro-protective effects. The dearth of potent drugs for management of such disorders necessitates the urge for further research into the pharmacological aspects of capsaicin. This review summarizes the historical background, source, structure and analogues of capsaicin, and capsaicin-triggered TRPV1 signaling and desensitization processes. In particular, we will focus on the therapeutic roles of capsaicin and its analogues in both normal and pathophysiological conditions.

  10. The effects of Hot Pepper Extract and Capsaicin on Adipocyte Metabolism

    Directory of Open Access Journals (Sweden)

    Ching Sheng, Chu

    2008-03-01

    Full Text Available Objectives : The purpose of this study is to investigate the effects of hot pepper extract and capsaicin on the adipogenesis in 3T3-L1 cells, lipolysis in rat epididymal adipocytes and histological changes in porcine adipose tissue. Methods : Inhibiton of preadipocyte differentiation and/or stimulation of lipolysis play important roles in reducing obesity. 3T3-L1 preadipocytes were differentiated with adipogenic reagents by incubating for 3 days in the absence or presence of hot pepper extract or capsaicin ranging from 0.01 to 1㎎/㎖. The effects of hot pepper extract and capsaicin on adipogenesis were examined by measuring GPDH activity and by Oil Red O staining. Mature adipocytes from rat epididymal fat pad was incubated with hot pepper extract or capsaicin ranging from 0.01 to 1㎎/㎖ for 3 hrs. The effects of hot pepper extract and capsaicin on lipolysis were examined by measuring free glycerol released. Fat tissue from pig skin was injected with hot pepper extract or capsaicinCFP ranging from 0.1 to 10㎎/㎖ to examine the effects of hot pepper extract and capsaicin on histological changes under light microscopy. Results : The following results were obtained from present study on adipogenesis of preadipocytes, lipolysis of adipocytes and histological changes in fat tissue. 1. Hot pepper extract and capsaicin inhibited adipogenic differentiation at the concentration of 0.1 and 0.01㎎/㎖, respectively, indicating that capsaicin was more effective in inhibiting adipogenesis than hot pepper extract. 2. Hot pepper extract and capsaicin decreased the activity of glycerol-3-phosphate dehydrogenase(GPDH at the concentration of 0.1 and 0.01㎎/㎖, respectively, indicating that capsaicin was more effective in inhibiting adipogenic differentiation than hot pepper extract. 3. Hot pepper extract and capsaicin increased glycerol release at the concentration of 0.1㎎/㎖. There was no difference in lipolytic activity between hot pepper extract and

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

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

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

  12. Capsaicin: A Potent Inhibitor of Carbonic Anhydrase Isoenzymes

    Directory of Open Access Journals (Sweden)

    Betul Arabaci

    2014-07-01

    Full Text Available Carbonic anhydrase (CA, EC 4.2.1.1 is a zinc containing metalloenzyme that catalyzes the rapid and reversible conversion of carbon dioxide (CO2 and water (H2O into a proton (H+ and bicarbonate (HCO3– ion. On the other hand, capsaicin is the main component in hot chili peppers and is used extensively used in spices, food additives and drugs; it is responsible for their spicy flavor and pungent taste. There are sixteen known CA isoforms in humans. Human CA isoenzymes I, and II (hCA I and hCA II are ubiquitous cytosolic isoforms. In this study, the inhibition properties of capsaicin against the slow cytosolic isoform hCA I, and the ubiquitous and dominant rapid cytosolic isozymes hCA II were studied. Both CA isozymes were inhibited by capsaicin in the micromolar range. This naturally bioactive compound has a Ki of 696.15 µM against hCA I, and of 208.37 µM against hCA II.

  13. CCK enhances response to gastric distension by acting on capsaicin-insensitive vagal afferents

    NARCIS (Netherlands)

    van de Wall, EHEM; Duffy, P; Ritter, RC

    2005-01-01

    Capsaicin treatment destroys vagal afferent C fibers and markedly attenuates reduction of food intake and induction of hindbrain Fos expression by CCK. However, both anatomical and electrophysiological data indicate that some gastric vagal afferents are not destroyed by capsaicin. Because CCK enhanc

  14. EFFECTS OF CAPSAICIN ON RAT SCIATIC NERVE IN VINCRISTINE-INDUCED NEUROPATHIC PAIN MODEL

    Directory of Open Access Journals (Sweden)

    Thanaa A. El-Masry *, Magda E. El Sayaad , Ibrahim A. Gaaboub and Wafaa M. Fouda

    2013-02-01

    Full Text Available Capsaicin, the pungent ingredient of red pepper, is used topically to treat different types of neuropathic pain, in rat model of vincristine induced neuropathic pain we tried to investigate the effect of capsaicin on sciatic nerve through electrophysiological and histopathological studies. We found that treatment of animals with vincristine results in significant decrease in sciatic nerve conduction velocity and degeneration of the nerve fibers, where combined treatment of vincristine and capsaicin showed highly significant decrease in sciatic nerve conduction velocity and degeneration of the nerve fibers compared with that treated with vincristine only. In new trial, we tried to investigate the effect of direct capsaicin titration on sciatic nerve fibers that results in nearly abolishment of nerve conduction velocity. All of these findings may illustrate the mechanism of capsaicin effect through afferent nerves degeneration.

  15. Spatial and Temporal Effects of Capsaicin and Menthol on Intraoral Somatosensory Sensitivity

    DEFF Research Database (Denmark)

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

    2015-01-01

    AIMS: To assess the spatial and temporal sensory effects of the topical application of capsaicin and menthol on the gingiva of healthy volunteers. METHODS: Capsaicin, menthol, and saline (control) were applied topically on the gingiva in the maxillary premolar area of healthy volunteers for 15......PT values, the number of hypersensitive or hyposensitive test sites, and the coordinates of the center of gravity (COG) of somatosensory sensitivity. RESULTS: The mean ± SEM VAS score of pain intensity produced by the application of capsaicin (4.6 ± 0.5) was significantly higher than that produced by...... menthol (0.3 ± 0.2) and saline (0.1 ± 0.1) (P < .001). Capsaicin induced local desensitization to all stimuli (P < .047) , and at the application site, capsaicin induced significant desensitization to 512 mN stimuli (P = .003). Menthol did not induce significant somatosensory changes (P > .147), and...

  16. Extraction of capsaicins in aerosol defense sprays from fabrics.

    Science.gov (United States)

    Spicer, Oliver; Almirall, José R

    2005-08-15

    The use of aerosol defense sprays has increased as a means of self-defense and as a weapon in the commission of a crime. The residue of these sprays is often left behind as physical evidence on a victim's clothing or personal belongings. As the popularity of self-defense weaponry increases, so does the likelihood that it will be encountered in forensic casework. The extraction, recovery from fabrics, and identification of residue from defense sprays is described. The commonly used extraction method of liquid-liquid extraction is compared to solid phase microextraction (SPME) to recover capsaicin and dihydrocapsaicin from cotton swabs. The use of SPME resulted in lower limits of detection and greater recovery efficiency when compared to solvent extraction. SPME also provided more consistent recovery and less variability when compared to solvent extraction. The effect of use of various types of evidence packages on the preservation of this type of evidence is also reported. The collection and analysis of hand swabs after normal discharge of pepper spray canisters was studied indicating the low persistence of these compounds on the hands of the person conducting the spraying. Finally, the results of a real case whereby solvent-solvent extraction did not provide the necessary sensitivity for extracting the capsaicin compounds on the garments of a victim of an alleged spraying and the SPME extraction provided the recovery and identification of the compounds is also presented. PMID:18970178

  17. Enhanced itch elicited by capsaicin in a chronic itch model.

    Science.gov (United States)

    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; Liu, Qin; Tang, Zongxiang

    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

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

    Science.gov (United States)

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

    2014-01-01

    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 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

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

    Directory of Open Access Journals (Sweden)

    A A Oyagbemi

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shengzhang Lin

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zai-Fa Hong

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

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

    Science.gov (United States)

    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

  3. [The response of the blood proteins to ablation of the capsaicin-sensitive nerves].

    Science.gov (United States)

    Kostina, N E; Spiridonov, V K

    2005-07-01

    Effects of neurotoxic doses of capsaicin (150 mg/kg) on the protein content in electrophoretic fractions (PAAG) in the Wistar rat plasma were studied. In early period (7 days) after administration of capsaicin, an increase of the alpha1-, alpha2-globulins and a decrease of the albumin, gamma-globulins, were observed. After 14-30 days, increase of the albumin and decrease of the alpha1-, gammay-globulins were detected. The ablation of the capsaicin-sensitive nerves abrogated the changes of positive and negative acute phase reactants induced by zymosan and diminished the content of gamma-globulins. PMID:16206619

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

    DEFF Research Database (Denmark)

    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......'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...

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

    Indian Academy of Sciences (India)

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

    2013-09-01

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

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

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    We examined the effect of the subcutaneous infiltration of ketamine, lidocaine and saline before injury on capsaicin-induced pain and hyperalgesia. Twelve healthy volunteers participated in two separate, randomized, double-blind, placebo-controlled crossover experiments. In experiment 1, 100...... micrograms capsaicin was injected intradermally in one volar forearm 10 min after the skin had been pretreated with lidocaine 20.0 mg in 2.0 ml or 0.9% saline 2.0 ml at the capsaicin injection site. In experiment 2, a similar capsaicin test was given 10 min after the skin had been pretreated with ketamine 5...... brush stimuli, and areas of brush-evoked and punctate-evoked hyperalgesia. Lidocaine reduced all measures compared with placebo (P < 0.001), whereas ketamine failed to change any measures. Pain scores and areas of hyperalgesia were not affected when the contralateral site was infiltrated with ketamine...

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

    DEFF Research Database (Denmark)

    Elberling, Jesper; Dirksen, Asger; Johansen, Jeanne Duus;

    2006-01-01

    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...

  9. A capsaicin (8%) patch in the treatment of severe persistent inguinal postherniorrhaphy pain

    DEFF Research Database (Denmark)

    Bischoff, Joakim M; Ringsted, Thomas K; Petersen, Marian; Sommer, Claudia; Uçeyler, Nurcan; Werner, Mads U

    2014-01-01

    BACKGROUND: Persistent pain after inguinal herniorrhaphy is a disabling condition with a lack of evidence-based pharmacological treatment options. This randomized placebo-controlled trial investigated the efficacy of a capsaicin 8% cutaneous patch in the treatment of severe persistent inguinal...... postherniorrhaphy pain. METHODS: Forty-six patients with persistent inguinal postherniorrhaphy pain were randomized to receive either a capsaicin 8% patch or a placebo patch. Pain intensity (Numerical Rating Scale [NRS 0-10]) was evaluated under standardized conditions (at rest, during movement, and during pressure...... application. The primary outcome was comparisons of summed pain intensity differences (SPIDs) between capsaicin andplacebo treatments at 1, 2 and 3 months after patch application (significance level P < 0.01). RESULTS: The maximum difference in SPID, between capsaicin and placebo treatments, was observed at 1...

  10. Capsaicin-induced neurogenic inflammation in the skin in patients with symptoms induced by odorous chemicals

    DEFF Research Database (Denmark)

    Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger; Serup, Jørgen; Elberling, Jesper

    2011-01-01

    Intradermal injection of capsaicin induces the axonal release of neuropeptides, vasodilatation and flare, e.g. neurogenic inflammation. The spatial profile of neurogenic inflammation in the skin has been studied in various experimental models. Polarization spectroscopy imaging introduced recently...

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

    NARCIS (Netherlands)

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

    1998-01-01

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

  12. A study to investigate capsaicin-induced pressure response in vagotomized rats

    Directory of Open Access Journals (Sweden)

    Abhaya Dutta

    2013-01-01

    Conclusions: These observations implicate the existence of mechanisms other than adrenergic, angiotensinergic, or Ca 2+ channel-dependent mechanisms for mediating the capsaicin-induced intermediate hypertensive response in vagotomized animals.

  13. Capsaicin induces "brite" phenotype in differentiating 3T3-L1 preadipocytes.

    Directory of Open Access Journals (Sweden)

    Ritesh K Baboota

    Full Text Available 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.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.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.Our findings suggest the dual modulatory role of capsaicin in adipogenesis. Capsaicin inhibits adipogenesis in 3T3-L1 via TRPV1 activation and induces brown-like phenotype whereas

  14. Capsaicin and Dihydrocapsaicin Determination in Chili Pepper Genotypes Using Ultra-Fast Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Magaji G. Usman

    2014-05-01

    Full Text Available Research was carried out to estimate the levels of capsaicin and dihydrocapsaicin that may be found in some heat tolerant chili pepper genotypes and to determine the degree of pungency as well as percentage capsaicin content of each of the analyzed peppers. A sensitive, precise, and specific ultra fast liquid chromatographic (UFLC system was used for the separation, identification and quantitation of the capsaicinoids and the extraction solvent was acetonitrile. The method validation parameters, including linearity, precision, accuracy and recovery, yielded good results. Thus, the limit of detection was 0.045 µg/kg and 0.151 µg/kg for capsaicin and dihydrocapsaicin, respectively, whereas the limit of quantitation was 0.11 µg/kg and 0.368 µg/kg for capsaicin and dihydrocapsaicin. The calibration graph was linear from 0.05 to 0.50 µg/g for UFLC analysis. The inter- and intra-day precisions (relative standard deviation were <5.0% for capsaicin and <9.9% for dihydrocapsaicin while the average recoveries obtained were quantitative (89.4%–90.1% for capsaicin, 92.4%–95.2% for dihydrocapsaicin, indicating good accuracy of the UFLC method. AVPP0705, AVPP0506, AVPP0104, AVPP0002, C05573 and AVPP0805 showed the highest concentration of capsaicin (12,776, 5,828, 4,393, 4,760, 3,764 and 4,120 µg/kg and the highest pungency level, whereas AVPP9703, AVPP0512, AVPP0307, AVPP0803 and AVPP0102 recorded no detection of capsaicin and hence were non-pungent. All chili peppers studied except AVPP9703, AVPP0512, AVPP0307, AVPP0803 and AVPP0102 could serve as potential sources of capsaicin. On the other hand, only genotypes AVPP0506, AVPP0104, AVPP0002, C05573 and AVPP0805 gave a % capsaicin content that falls within the pungency limit that could make them recommendable as potential sources of capsaicin for the pharmaceutical industry.

  15. The effect of codeine on the Urge-to-Cough response to inhaled capsaicin

    OpenAIRE

    Davenport, P.W.; Bolser, D. C.; Vickroy, T.; Berry, R.B.; Martin, A. D.; Hey, John A; Danzig, M.

    2006-01-01

    We have shown previously in normal subjects that a sensory measure, the Urge-to-Cough rating, increases at concentrations of inhaled capsaicin that are lower than those necessary to elicit reflex cough. This finding suggests that the Urge-to-Cough may represent an index of the cough response. Research on cough in the human has most often employed challenge with inhaled capsaicin to induce reflex cough. Current measures of cough sensitivity in the human provide no information regarding the int...

  16. Influence of neonatally administered capsaicin on baroreceptor and chemoreceptor reflexes in the adult rat.

    OpenAIRE

    Bond, S. M.; Cervero, F; McQueen, D S

    1982-01-01

    1 Baroreceptor and chemoreceptor reflex activity was studied in anaesthetized adult rats which had been treated neonatally with a single injection of capsaicin (50 mg/kg s.c.). 2 Pressor responses to bilateral carotid artery occlusion were significantly lower in capsaicin-treated rats compared with vehicle-treated controls. Pressor responses to intravenously injected noradrenaline were similar in the two groups of rats. 3 Resting respiratory minute volume and tidal volume were lower in anaest...

  17. Capsaicin (8%) patch increases multiple electrical nociceptive thresholds in healthy human subjects

    OpenAIRE

    Doll, R.J.; Buitenweg, J.R.; Amerongen, van, H.; Hay, J. L.; Groeneveld, G J; Veltink, P.H.

    2013-01-01

    Thresholds are dependent on stimulus properties and are related to different mechanisms in the nociceptive system. Measuring multiple thresholds enables a detailed observation of peripheral and central nociceptive processing. In this study, a model of capsaicin defunctionalization was used to investigate the effect on multiple simultaneously measured electrical nociceptive perception thresholds.With the presented data, increased electrical perception thresholds were observed due to capsaicin....

  18. Cannabinoid inhibition of the capsaicin-induced calcium response in rat dorsal root ganglion neurones

    OpenAIRE

    Millns, Paul J; Chapman, Victoria; Kendall, David A.

    2001-01-01

    Cannabinoids have marked inhibitory effects on somatosensory processing, which may arise from actions at both peripheral and central cannabinoid receptors. Here, the effect of a synthetic cannabinoid agonist HU210 on capsaicin-evoked responses in adult rat dorsal root ganglion (DRG) neurones was studied. The vanilloid capsaicin produced a concentration-related increase in intracellular calcium in DRG neurones, which was significantly inhibited by HU210 (1 μM). The cannabinoid CB1 receptor ant...

  19. Capsaicin and Dihydrocapsaicin Determination in Chili Pepper Genotypes Using Ultra-Fast Liquid Chromatography

    OpenAIRE

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

    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 paramet...

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

    OpenAIRE

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

    2015-01-01

    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 involv...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  2. Determination of Capsaicin and Dihydrocapsaicin in Capsicum Fruit Samples using High Performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Ayman Abdel Ghafar

    2011-10-01

    Full Text Available The aim of the present study was to determine the content of capsaicin and dihydrocapsaicin in Capsicum samples collected from city markets in Riyadh (Saudi Arabia, calculate their pungency in Scoville heat units (SHU and evaluate the average daily intake of capsaicin for the population of Riyadh. The investigated samples consisted of hot chillies, red chillies, green chillies, green peppers, red peppers and yellow peppers. Extraction of capsaicinoids was done using ethanol as solvent, while high performance liquid chromatography (HPLC was used for separation, identification and quantitation of the components. The limit of detection (LOD of the method was 0.09 and 0.10 µg/g for capsaicin and dihydrocapsaicin, respectively, while the limit of quantification (LOQ was 0.30 and 0.36 µg/g for capsaicin and dihydrocapsaicin, respectively. Hot chillies showed the highest concentration of capsaicin (4249.0 ± 190.3 µg/g and the highest pungency level (67984.60 SHU, whereas green peppers had the lowest detected concentration (1.0 ± 0.9 µg/g; green peppers, red peppers and yellow peppers were non pungent. The mean consumption of peppers for Riyadh city population was determined to be 15.5 g/person/day while the daily capsaicin intake was 7.584 mg/person/day.

  3. Respiratory action of capsaicin microinjected into the nucleus of the solitary tract: involvement of vanilloid and tachykinin receptors

    OpenAIRE

    Mazzone, Stuart B.; Geraghty, Dominic P

    1999-01-01

    The respiratory response to microinjection of capsaicin into the commissural nucleus of the solitary tract (cNTS) of urethane-anaesthetized rats was investigated in the absence and presence of the competitive vanilloid (capsaicin) antagonist, capsazepine, and selective tachykinin NK1, NK2 and NK3 antagonists (RP 67580, SR 48968 and SR 142801, respectively).Microinjection of capsaicin reduced respiratory frequency but not tidal volume (VT), leading to an overall reduction in minute ventilation...

  4. Study on vasoactive intestinal polypeptide receptor 1 gene translation in psoriatic epidermis with the topical treatment of capsaicin ointment

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To investigate the mechanism of capsaicin in treating active psoriasis vulgaris.Methods A total of 42 patients with active psoriasis vulgaris diagnosed by histology and clinical features were given either placebo or 0.025% capsaicin ointment four times daily for 30 days randomly by double-blind method.Vasoactive intestinal polypeptide receptor 1(VIPR1)gene translation in active psoriatic lesions before and after treatment with capsaicin ointment was detected by in situ hybridization.Results There ...

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

    Science.gov (United States)

    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. PMID:20925121

  6. Capsaicin-induced apoptosis is regulated by endoplasmic reticulum stress- and calpain-mediated mitochondrial cell death pathways

    International Nuclear Information System (INIS)

    Capsaicin, a pungent compound found in hot chili peppers, induces apoptotic cell death in various cell lines, however, the precise apoptosis signaling pathway is unknown. Here, we investigated capsaicin-induced apoptotic signaling in the human breast cell line MCF10A and found that it involves both endoplasmic reticulum (ER) stress and calpain activation. Capsaicin inhibited growth in a dose-dependent manner and induced apoptotic nuclear changes in MCF10A cells. Capsaicin also induced degradation of tumor suppressor p53; this effect was enhanced by the ER stressor tunicamycin. The proteasome inhibitor MG132 completely blocked capsaicin-induced p53 degradation and enhanced apoptotic cell death. Capsaicin treatment triggered ER stress by increasing levels of IRE1, GADD153/Chop, GRP78/Bip, and activated caspase-4. It led to an increase in cytosolic Ca2+, calpain activation, loss of the mitochondrial transmembrane potential, release of mitochondrial cytochrome c, and caspase-9 and -7 activation. Furthermore, capsaicin-induced the mitochondrial apoptotic pathway through calpain-mediated Bid translocation to the mitochondria and nuclear translocation of apoptosis-inducing factor (AIF). Capsaicin-induced caspase-9, Bid cleavage, and AIF translocation were blocked by calpeptin, and BAPTA and calpeptin attenuated calpain activation and Bid cleavage. Thus, both ER stress- and mitochondria-mediated death pathways are involved in capsaicin-induced apoptosis.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Peng X

    2015-08-01

    Full Text Available Xinsheng Peng,1* Yanfang Zhou,1* Ke Han,2,3 Lingzhen Qin,3 Linghui Dian,1 Ge Li,4 Xin Pan,3 Chuanbin Wu3 1Guangdong Medical University, Dongguan, 2The Second Affiliated Hospital of Guangzhou Medical University, 3School of Pharmaceutical Sciences, Sun Yat-Sen University, 4Guangzhou Neworld Pharmaceuticals Co. Ltd., Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this work Abstract: Phytantriol- and glycerol monooleate-based cubosomes were produced and characterized as a targeted and sustained transdermal delivery system for capsaicin. The cubosomes were prepared by emulsification and homogenization of phytantriol (F1, glycerol monooleate (F2, and poloxamer dispersions, characterized for morphology and particle size distribution by transmission electron microscope and photon correlation spectroscopy. Their Im3m crystallographic space group was confirmed by small-angle X-ray scattering. An in vitro release study showed that the cubosomes provided a sustained release system for capsaicin. An in vitro diffusion study conducted using Franz diffusion cells indicated that the skin retention of capsaicin from cubosomes in the stratum corneum was much higher (2.75±0.22 µg versus 4.32±0.13 µg, respectively than that of capsaicin cream (0.72±0.13 µg. The stress testing showed that the cubosome formulations were stable under strong light and high temperature for up to 10 days. After multiapplications on mouse skin, the irritation of capsaicin cubosomes and cream was light with the least amount of side effects. Overall, the present study demonstrated that cubosomes may be a suitable skin-targeted and sustained delivery system for the transdermal administration of capsaicin. Keywords: cubosomes, skin-targeted delivery, capsaicin

  9. Asthma exacerbation related with inhalation of hot peppers extract (capsaicin

    Directory of Open Access Journals (Sweden)

    Erkan Ceylan

    2013-09-01

    Full Text Available Objectives: In this study we aimed to prospectively investigate,asthma provoking factors and among thesefactors the place of Hot pepper (Isot during August-Septembermonths which are time period for processing isot.Methods: In this study, 73 female patients with exacerbationof asthma who applied to Chest Diseases OutpatientClinic and emergency department in the period of August-September (2010 were evaluated prospectively.Results: Seventy-three asthmatic female patients, meansage 34.7±6.1 (22-43 years were included. Patients withexacerbation of asthma provoking factors are; inhalationof isot pepper 28.8%, infections 23.3%, irregular use ofdrugs 16.4%, exposure to biomass and cigarette smoke13.7%, allergens 9.6%, emotional factors 5%, and gastroesophagealreflux 2.7%, physical exercise 1.4%.Conclusion: We observed that the most important asthmaprovoking factor was the inhalation of isot extract inasthmatic female patients in August-September (2010period in Sanliurfa. J Clin Exp Invest 2013; 4 (3: 331-334Key words: Asthma, hot pepper, Isot, capsaicin, Sanliurfa

  10. A study on the comparison of antioxidant effects between hot pepper extract and capsaicin

    Directory of Open Access Journals (Sweden)

    Hyeon Min Gang

    2008-03-01

    Full Text Available Objective : The objective of this study was to compare the antioxidant effects of hot pepper extract and capsaicin. Methods : In vitro, antioxidant activities were examined by DPPH radical scavenging activity, total antioxidant capacity(TAC, oxygen radical scavenging capacity(ORAC, inhibition of induced lipid peroxidation using liver mitochonria and total phenolic contents. Results : 1. DPPH free radical scavenging actiivities at the concentrations of both 1 and 10㎎/㎖ were 1.2 to 1.9 times higher in capsaicin than in hot pepper extract. The concentration of capsaicin required for 50% radical scavenging was lower than that of hot pepper extract(3.9 vs 5.9㎎/㎖, indicating that capsaicin had higher DPPH radical scavenging activity than hot pepper extract. 2. Total antioxidant capacities of capsaicin at the concentrations of 0.1 and 1mg/ml(13.8 and 41.3 nmol Trolox equivalent were not significantly different from those at the concentrations of 1 and 10㎎/㎖(11.4 and 41.2nmol Trolox equivalent, indicating that capsaicin showed 10 times higher ABTS radical scavenging activity compared to hot pepper extract. 3. ORAC of capsaicin at the concentrations of 1, 5, 10 and 100 mg/ml were 0.04, 0.17, 0.29 and 1.74nmol gallic acid equivalent, respectively. On the other hand, ORAC of hot pepper extract at the concentrations of 1, 5, 10 and 100㎍/㎖ were 0.15, 0.44, 0.75 and 2.49nmol gallic acid equivalent, respectively, indicating that capsaicin showed higher peroxyl radical scavenging activity than hot pepper extract. 4. Inhibition of lipid peroxidation caused by hot pepper extract at the concentrations of 1 and 10mg/㎖ were 12.2 and 61.4%, respectively. Inhibition of lipid peroxidation caused by capsaicin at the concentrations of 1 and 10㎎/㎖l were 64.0 and 96.8%, respectively. Thus capsaicin showed 10 times stronger effect in inhibiton of lipid peroxidation than hot pepper extract. 5. Total phenolic contents of hot pepper extract at the

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

    OpenAIRE

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

    2011-01-01

    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 intraepitheli...

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

    Energy Technology Data Exchange (ETDEWEB)

    Bynke, G.

    1983-06-01

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

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

    Science.gov (United States)

    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

  14. Capsaicin-capped silver nanoparticles: its kinetics, characterization and biocompatibility assay

    Science.gov (United States)

    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.

  15. CAPSAICIN AND ASCORBIC ACID VARIABILITY IN CHILLI AND PAPRIKA CULTIVARS AS REVEALED BY HPLC ANALYSIS

    Directory of Open Access Journals (Sweden)

    Samuel Tilahun

    2013-08-01

    Full Text Available Capsaicin and ascorbic acid contents of seven Indian peppers varieties/accessions from Capsicum annuum (CA 97, CCH, K1, KTPL19, Arka Abhir and Bayadagi Kaddi and C. frutescens (CF1 species were determined using High Performance Liquid Chromatography (HPLC. Based on their pungency value, all the chilli accession/varieties (CA 97, CCH, K1, and CF 1 were classified as highly pungent peppers. The accession CF1 showed the highest concentration of capsaicin (445mg 100g -1 DW with corresponding pungency value of 71,200 SHUs and Arka Abhir variety showed the lowest capsaicin concentration (29mg 100g -1 DW with 4,672 SHUs of pungency value. Similarly, Bayadaggi kaddi variety showed the highest ascorbic acid content (189 mg/100 FW and the accession CA 97 showed the lowest ascorbic acid contents (55.3 mg/100 FW. The variability in capsaicin and ascorbic acid content presented in the pepper germplasm can be exploited for breeding cultivars with improved nutritional qualities. Moreover, CF1and Bayadagi kaddi can be used as a potential source for capsaicin and vitamin C, respectively.

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

    Directory of Open Access Journals (Sweden)

    Gangabhagirathi R

    2015-06-01

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

  17. Capsaicin sensitizes TRAIL-induced apoptosis through Sp1-mediated DR5 up-regulation: Involvement of Ca2+ influx

    International Nuclear Information System (INIS)

    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.

  18. Capsaicin, from Hot to Not; Can New Pain-Relieving Drugs Be Derived from This Substance Known to Cause Pain?

    Science.gov (United States)

    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…

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

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Petersen, Karin Lottrup

    2006-01-01

    /capsaicin sensitization, and heat pain detection thresholds. There was a trend toward smaller areas of secondary hyperalgesia in women. After adjusting for estimated gender differences in forearm surface area, areas to brush but not von Frey hair stimulation after capsaicin sensitization were larger in women. Peak pain......, but not total pain, during prolonged noxious thermal stimulation was higher in women. There was no gender difference in pain ratings during capsaicin sensitization or in heat pain detection thresholds. The results provided only limited support to the hypothesis that gender differences in clinical pain...... syndromes can be explained by enhanced central sensitization in women. PERSPECTIVE: Our findings suggest that gender differences in nociceptive transmission and neuronal sensitization are small and provide only limited support to the hypothesis that gender differences in acute and chronic pain syndromes can...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    Patients with multiple chemical sensitivity and eczema patients with airway symptoms elicited by odorous chemicals have enhanced cough reflex to capsaicin when applying the tidal breathing method. The aims of the present study were to test whether the capsaicin induced cough reflex was enhanced...... 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...

  1. Improvement of symptoms of non-allergic chronic rhinitis by local treatment with capsaicin.

    Science.gov (United States)

    Lacroix, J S; Buvelot, J M; Polla, B S; Lundberg, J M

    1991-09-01

    Sixteen adult patients suffering from severe chronic non-allergic rhinitis with nasal vasoconstrictor abuse for more than a year, received, under local anaesthesia, an intranasal spray of capsaicin (3.3 x 10(-3) mol), the pungent agent in hot pepper, once weekly for 5 weeks. The subjective intensity of their nasal obstruction, rhinorrhoea and sneezing frequency were evaluated throughout the study and the vascular effects of capsaicin on the nasal mucosa were recorded by anterior rhinomanometry and laser Doppler flowmetry. Calcitonin gene-related peptide (CGRP) is a vasodilator agent present in sensory nerves and may play a major role in the vascular component of neurogenic inflammation. Therefore, the nasal mucosa content of CGRP-like immunoreactivity (CGRP-LI) was determined by radioimmunoassay in biopsies obtained before and after the capsaicin treatment. Intra-nasal capsaicin application evoked a larger vascular response in patients with rhinitis than in controls (P less than 0.05). Both nasal vascular responses and subjective discomfort following capsaicin were markedly reduced after the fifth application (P less than 0.01). In parallel, a 50% reduction of the CGRP-LI content in the nasal biopsies was observed. All symptoms were significantly improved throughout a 6 month follow-up period. No significant side-effects occurred and weaning from nasal vasoconstrictor agents was possible. Both the subjective symptom score and objective measurements of vascular reactivity suggest that repeated intra-nasal capsaicin application could be beneficial for patients with chronic rhinitis, possibly by reducing hyperreactive nasal reflexes. PMID:1742652

  2. Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

    International Nuclear Information System (INIS)

    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 β 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

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

    Directory of Open Access Journals (Sweden)

    Carsten Zschenderlein

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

  4. Capsaicin cough sensitivity and the association with clinical parameters in bronchiectasis.

    Directory of Open Access Journals (Sweden)

    Wei-jie Guan

    Full Text Available BACKGROUND: Cough hypersensitivity has been common among respiratory diseases. OBJECTIVE: To determine associations of capsaicin cough sensitivity and clinical parameters in adults with clinically stable bronchiectasis. METHODS: We recruited 135 consecutive adult bronchiectasis patients and 22 healthy subjects. History inquiry, sputum culture, spirometry, chest high-resolution computed tomography (HRCT, Leicester Cough Questionnaire scoring, Bronchiectasis Severity Index (BSI assessment and capsaicin inhalation challenge were performed. Cough sensitivity was measured as the capsaicin concentration eliciting at least 2 (C2 and 5 coughs (C5. RESULTS: Despite significant overlap between healthy subjects and bronchiectasis patients, both C2 and C5 were significantly lower in the latter group (all P<0.01. Lower levels of C5 were associated with a longer duration of bronchiectasis symptoms, worse HRCT score, higher 24-hour sputum volume, BSI and sputum purulence score, and sputum culture positive for P. aeruginosa. Determinants associated with increased capsaicin cough sensitivity, defined as C5 being 62.5 µmol/L or less, encompassed female gender (OR: 3.25, 95%CI: 1.35-7.83, P<0.01, HRCT total score between 7-12 (OR: 2.57, 95%CI: 1.07-6.173, P = 0.04, BSI between 5-8 (OR: 4.05, 95%CI: 1.48-11.06, P<0.01 and 9 or greater (OR: 4.38, 95%CI: 1.48-12.93, P<0.01. CONCLUSION: Capsaicin cough sensitivity is heightened in a subgroup of bronchiectasis patients and associated with the disease severity. Gender and disease severity, but not sputum purulence, are independent determinants of heightened capsaicin cough sensitivity. Current testing for cough sensitivity diagnosis may be limited because of overlap with healthy subjects but might provide an objective index for assessment of cough in future clinical trials.

  5. The Anticancer Role of Capsaicin in Experimentallyinduced Lung Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Pandi Anandakumar

    2015-06-01

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

  6. Activation of TRPV1 by dietary capsaicin improves endothelium-dependent vasorelaxation and prevents hypertension

    DEFF Research Database (Denmark)

    Yang, Dachun; Luo, Zhidan; Ma, Shuangtao;

    2010-01-01

    Some plant-based diets lower the cardiometabolic risks and prevalence of hypertension. New evidence implies a role for the transient receptor potential vanilloid 1 (TRPV1) cation channel in the pathogenesis of cardiometabolic diseases. Little is known about impact of chronic TRPV1 activation on the...... regulation of vascular function and blood pressure. Here we report that chronic TRPV1 activation by dietary capsaicin increases the phosphorylation of protein kinase A (PKA) and eNOS and thus production of nitric oxide (NO) in endothelial cells, which is calcium dependent. TRPV1 activation by capsaicin...

  7. Comparison of prophylactic or therapeutic dietary administration of capsaicin for reduction of Salmonella in broiler chickens.

    Science.gov (United States)

    Orndorff, B W; Novak, C L; Pierson, F W; Caldwell, D J; McElroy, A P

    2005-12-01

    In three experiments the effects of prophylactic or therapeutic dietary inclusion of capsaicin, the pungent component of peppers, were evaluated as a nonantibiotic alternative for reduction of Salmonella in broiler chickens through culture and morphologic assessment of cecal tissue. Expt. 1 evaluated the effects of 0 or 10 ppm purified capsaicin (CAP) in the starter phase (days 1-16) on chicks challenged with Salmonella Enteritidis (SE) on day of age. Therapeutic inclusion of 10 ppm purified CAP increased (P capsaisin differentially affects broiler susceptibility to Salmonella. PMID:16404994

  8. Loss of capsaicin-induced meningeal neurogenic sensory vasodilatation in diabetic rats.

    Science.gov (United States)

    Dux, M; Rosta, J; Pintér, S; Sántha, P; Jancsó, G

    2007-11-30

    Neuropathic alterations of sensory nerves involved in the mediation of neurogenic inflammation of the meninges may contribute to the increased incidence of headaches in diabetics. In the rat, activation of capsaicin-sensitive nociceptors, which express the transient receptor potential vanilloid type 1 (TRPV1) receptor, induces meningeal vasodilatation, a significant component of neurogenic inflammation, through the release of calcitonin gene-related peptide (CGRP). This study examines the effects of streptozotocin-induced diabetes on TRPV1 receptor-mediated neurogenic sensory vasodilatation, CGRP release and nerve fiber density in the rat dura mater. In a cranial window preparation, epidural application of capsaicin (10(-7) M) produced distinct vasodilatory responses in control animals as measured by laser Doppler flowmetry. In diabetic rats, capsaicin-induced vasodilatation was reduced or even abolished 6, but not 2 or 4 weeks after diabetes induction. In contrast, vasoconstriction, a non-neurogenic response to capsaicin at a higher concentration (10(-5) M), was not altered in diabetic rats. The vasodilatory effects of histamine (10(-5) M), acetylcholine (10(-4) M) and CGRP (10(-5) M) were similar in control, diabetic and insulin-treated diabetic animals. In diabetic rats, a significant decrease in the capsaicin-evoked release of CGRP and reduction in the density of TRPV1-immunoreactive (IR) nerves were demonstrated. Treatment of the diabetic rats with insulin restored both the vasodilatory response and the capsaicin-induced CGRP release toward control values. In conclusion, this study revealed a marked impairment of meningeal TRPV1-IR nerves in streptozotocin diabetic rats by showing reduced neurogenic sensory vasodilatation, decreased capsaicin-evoked CGRP release and reduction in the number of TRPV1-IR nerve fibers of the dura mater. The findings suggest that capsaicin-sensitive afferents may play an important role in meningeal nociceptor function and their

  9. Ultraviolet radiation-induced lipid peroxidation in liposomal membrane: modification by capsaicin

    International Nuclear Information System (INIS)

    Ultraviolet-radiation has been reported to cause lipid peroxidation in the liposomal membrane. In the present study, treatment with capsaicin, (8-methyl-n-vanillyl-6-nonenamide), the pungent principle of red hot pepper, was shown to modify UV-induced lipid peroxidation in the liposomal membrane. Treatment with low doses of capsaicin (less than 0.1 μg/mL of phosphatidyl choline liposome) produced a significant increase in UV-induced lipid peroxidation, while high doses (0.1-0.5 μg/mL of PC liposome) caused a significant decrease of UV-induced peroxidation

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

    Science.gov (United States)

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

    2015-02-25

    Atherosclerosis is a chronic inflammatory vascular disease. It is characterized by endothelial dysfunction, lipid accumulation, leukocyte activation, and the production of inflammatory mediators and reactive oxygen species (ROS). Capsaicin, a biologically active compound of the red pepper and chili pepper, has several anti-oxidant, anti-inflammatory, anti-cancer, and hypolipidemic biological effects. However, its protective effects on foam cell formation and endothelial injury induced by oxidized low-density lipoprotein (oxLDL) remain unclear. In this study, we evaluated the anti-oxidative activity of capsaicin, and determined the mechanism by which capsaicin rescues human umbilical vein endothelial cells (HUVECs) from oxLDL-mediated dysfunction. The anti-oxidative activity of capsaicin was defined by Apo B fragmentation and conjugated diene production of the copper-mediated oxidation of LDL. Capsaicin repressed ROS generation, as well as subsequent mitochondrial membrane potential collapse, cytochrome c expression, chromosome condensation, and caspase-3 activation induced by oxLDL in HUVECs. Capsaicin also protected foam cell formation in macrophage RAW 264.7 cells. Our results suggest that capsaicin may prevent oxLDL-induced cellular dysfunction and protect RAW 264.7 cells from LDL oxidation. PMID:25603234

  11. Development, Characterization and Skin Interaction of Capsaicin-Loaded Microemulsion-Based Nonionic Surfactant.

    Science.gov (United States)

    Duangjit, Sureewan; Chairat, Wisuta; Opanasopit, Praneet; Rojanarata, Theerasak; Panomsuk, Suwannee; Ngawhirunpat, Tanasait

    2016-01-01

    The aim of this study was to develop novel microemulsions (MEs) for the transdermal delivery of capsaicin. Microemulsion-based nonionic surfactants consisting of isopropyl myristate as the oil phase, various nonionic surfactants as the surfactant (S), various glycols or alcohol as the co-surfactant (CoS), and reverse osmosis water as the aqueous phase were formulated. Based on the optimal ME obtained from Design Expert, MEs containing a fixed concentration of oil, water or surfactant were prepared while varying the amounts of the other two fractions. The results indicated that the skin permeation flux of low dose capsaicin (0.15% (w/w)) was significantly higher for the selected ME than the commercial product and capsaicin in ethanol (control) by approximately two- and four-fold, respectively. We successfully demonstrated the feasibility of the transdermal delivery of capsaicin-loaded ME using a low concentration of nonionic surfactant and ethanol. Moreover, the optimization using computer program helped to simplify the development of a pharmaceutical product. PMID:27040633

  12. Resiniferatoxin and its analogs provide novel insights into the pharmacology of the vanilloid (capsaicin) receptor

    Energy Technology Data Exchange (ETDEWEB)

    Szallasi, A.; Blumberg, P.M. (National Institutes of Health, Bethesda, MD (USA))

    1990-01-01

    Capsaicin, the pungent constituent of chili peppers, represents the paradigm for the capsaicinoids or vanilloids, a family of compounds shown to stimulate and then desensitize specific subpopulations of sensory receptors, including C-polymodal nociceptors, A-delta mechanoheat nociceptors and warm receptors of the skin, as well as enteroceptors of thin afferent fibers. An exciting recent advance in the field has been the finding that resiniferatoxin (RTX), a naturally occurring diterpene containing a homovanillic acid ester, a key structural motif of capsaicin, functions as an ultrapotent capsaicin analog. For most of the responses characteristic of capsaicin, RTX is 100-10,000 fold more potent. Structure/activity analysis indicates, however, that RTX and related homovanillyl-diterpene esters display distinct spectra of activity. Specific ({sup 3}H)RTX binding provides the first direct proof for the existence of vanilloid receptors. We expect that the RTX class of vanilloids will promote rapid progress in understanding of vanilloid structure/activity requirements and mechanism.

  13. 75 FR 22788 - Garlic Oil and Capsaicin; Registration Review Proposed Decisions; Notice of Availability

    Science.gov (United States)

    2010-04-30

    ... AGENCY Garlic Oil and Capsaicin; Registration Review Proposed Decisions; Notice of Availability AGENCY... decisions. Garlic oil is the volatile oil extracted from the bulb of the garlic plant or the entire plant. Garlic oil is used as a repellent for the control of insects, mites, birds, deer, rabbits and...

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

    Science.gov (United States)

    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.

  15. Comparison of the effects of pelargonic acid vanillylamide and capsaicin on human vanilloid receptors.

    Science.gov (United States)

    Weiser, Thomas; Roufogalis, Basil; Chrubasik, Sigrun

    2013-07-01

    Pelargonic acid vanillylamide is like capsaicin a natural capsaicinoid from chili peppers and commonly used in food additives to create a hot sensation, even in self-defense pepper sprays and as an alternative to capsaicin in medical products for topical treatment of pain. Although the chemical structures of both compounds are similar, preclinical data suggest that capsaicin is the more potent compound. We therefore performed voltage-clamp recordings using cells transfected with the human vanilloid receptor TRPV1 in order to assess the responses of pelargonic acid vanillylamide and capsaicin at the receptor level. We provide evidence that at the molecular target TRPV1, the concentration-response curves, kinetics of current activation, as well as inhibition by the competitive antagonist capsazepine were not significantly different between the two capsaicinoids. We suggest that the different effects of the two capsaicinoids observed in previous studies may rather be due to different physicochemical or pharmacokinetic properties than to different pharmacological profiles at the receptor level. PMID:22961689

  16. Resiniferatoxin and its analogs provide novel insights into the pharmacology of the vanilloid (capsaicin) receptor

    International Nuclear Information System (INIS)

    Capsaicin, the pungent constituent of chili peppers, represents the paradigm for the capsaicinoids or vanilloids, a family of compounds shown to stimulate and then desensitize specific subpopulations of sensory receptors, including C-polymodal nociceptors, A-delta mechanoheat nociceptors and warm receptors of the skin, as well as enteroceptors of thin afferent fibers. An exciting recent advance in the field has been the finding that resiniferatoxin (RTX), a naturally occurring diterpene containing a homovanillic acid ester, a key structural motif of capsaicin, functions as an ultrapotent capsaicin analog. For most of the responses characteristic of capsaicin, RTX is 100-10,000 fold more potent. Structure/activity analysis indicates, however, that RTX and related homovanillyl-diterpene esters display distinct spectra of activity. Specific [3H]RTX binding provides the first direct proof for the existence of vanilloid receptors. We expect that the RTX class of vanilloids will promote rapid progress in understanding of vanilloid structure/activity requirements and mechanism

  17. Reaction to topical capsaicin in spinal cord injury patients with and without central pain

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Pedersen, Louise H.; Terkelsen, Astrid J.;

    2007-01-01

    above the level of a spinal cord injury which already is hyperexcitable, would cause enhanced responses in patients with central pain at the level of injury compared to patients without neuropathic pain and healthy controls. Touch, punctuate stimuli, cold stimuli and topical capsaicin was applied above...

  18. Cardiovascular effects of substance P and capsaicin microinjected into the nucleus tractus solitarii of the rat

    NARCIS (Netherlands)

    Lukovic, L.; Jong, Wybren de; Wied, D. de

    1987-01-01

    This report deals with the effect of substance P (SP) and capsaicin on blood pressure and heart rate after administration into different sites of the nucleus tractus solitarii (NTS) of urethane-anesthetized rats. Microinjection of SP at 6 different coordinates throughout the NTS showed 3 sites where

  19. Capsaicin Cough Sensitivity and the Association with Clinical Parameters in Bronchiectasis

    OpenAIRE

    Guan, Wei-jie; Gao, Yong-hua; Xu, Gang; Lin, Zhi-ya; Tang, Yan; Li, Hui-min; Lin, Zhi-min; Zheng, Jin-ping; Chen, Rong-chang; Zhong, Nan-Shan

    2014-01-01

    Background Cough hypersensitivity has been common among respiratory diseases. Objective To determine associations of capsaicin cough sensitivity and clinical parameters in adults with clinically stable bronchiectasis. Methods We recruited 135 consecutive adult bronchiectasis patients and 22 healthy subjects. History inquiry, sputum culture, spirometry, chest high-resolution computed tomography (HRCT), Leicester Cough Questionnaire scoring, Bronchiectasis Severity Index (BSI) assessment and ca...

  20. Comparison between Chemical Senses Thresholds for Capsaicin and Dihydrocapsaicin in Aqueous Solutions and Identification of the Area of Burning Sensation

    Directory of Open Access Journals (Sweden)

    D.J. Schneider

    2014-01-01

    Full Text Available In the present study, the pungency detection thresholds for capsaicin and dihydrocapsaicin in aqueous solutions containing an emulsifier (polysorbate 80 were determined and compared. Thresholds were measured for 21 students (12 chili “users” and 9 “non users” using a 3-Alternative Forced Choice sensory test with ascending concentrations of capsaicin and dihydrocapsaicin (0.025, 0.045, 0.090, 0.180 and 0.360 ppm, respectively. In addition, the panelists were asked where the irritation occurred (throat, tongue or both. The group Best Estimate Thresholds were 0.080 and 0.049 ppm for capsaicin and dihydrocapsaicin, respectively and differed significantly. Chili “users” and “non users” did not differ significantly in their perception of capsaicin and dihydrocapsaicin, suggesting that no desensitization effects occur. In accordance with previous studies, in most cases the first irritation was experienced in the throat.

  1. Molecularly imprinted polymers with synthetic dummy templates for the preparation of capsaicin and dihydrocapsaicin from chili peppers.

    Science.gov (United States)

    Ma, Xiuli; Ji, Wenhua; Chen, Lingxiao; Wang, Xiao; Liu, Jianhua; Wang, Xueyong

    2015-01-01

    In this work, dummy molecularly imprinted polymers with high selectivity and affinity to capsaicin and dihydrocapsaicin are designed using N-vanillylnonanamide as a dummy template. The performance of dummy molecularly imprinted polymers and nonimprinted polymers was evaluated using adsorption isotherms, adsorption kinetics, and selective recognition capacity. Dummy molecularly imprinted polymers were found to exhibit good site accessibility, taking just 20 min to achieve adsorption equilibrium; they were also highly selective toward capsaicin and dihydrocapsaicin. We successfully used dummy molecularly imprinted polymers as a specific sorbent for selectively enriching capsaicin and dihydrocapsaicin from chili pepper samples. In a scaled-up experiment, the selective recovery of capsaicinoids was calculated to be 77.8% using solid-phase extraction. To the best of our knowledge, this is the first example of the use of N-vanillylnonanamide as a dummy template in molecularly imprinted polymers to simultaneously enrich capsaicin and dihydrocapsaicin. PMID:25348490

  2. Protein kinase C phosphorylation sensitizes but does not activate the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1)

    OpenAIRE

    Bhave, Gautam; HU, HUI-JUAN; Glauner, Kathi S.; Zhu, Weiguo; Wang, Haibin; Brasier, D. J.; Oxford, Gerry S; Gereau, Robert W.

    2003-01-01

    Protein kinase C (PKC) modulates the function of the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1). This modulation manifests as increased current when the channel is activated by capsaicin. In addition, studies have suggested that phosphorylation by PKC might directly gate the channel, because PKC-activating phorbol esters induce TRPV1 currents in the absence of applied ligands. To test whether PKC both modulates and gates the TRPV1 function by direct phosphorylation, w...

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

    OpenAIRE

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fang Li

    2006-03-01

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

  5. Inactivation of capsaicin-sensitive nerves reduces pulmonary remodeling in guinea pigs with chronic allergic pulmonary inflammation

    OpenAIRE

    C.M. Prado; G.Z. da Rocha; E.A. Leick-Maldonado; C.M. Starling; V.L. Capelozzi; M. A. Martins; I.F.L.C. Tibério

    2011-01-01

    Pulmonary remodeling is an important feature of asthma physiopathology that can contribute to irreversible changes in lung function. Although neurokinins influence lung inflammation, their exact role in the extracellular matrix (ECM) remodeling remains to be determined. Our objective was to investigate whether inactivation of capsaicin-sensitive nerves modulates pulmonary ECM remodeling in animals with chronic lung inflammation. After 14 days of capsaicin (50 mg/kg, sc) or vehicle administrat...

  6. Intraluminal capsaicin does not affect fluid and electrolyte absorption in the human jejunum but does cause pain

    OpenAIRE

    Hammer, J.; Hammer, H; Eherer, A; Petritsch, W; Holzer, P.; Krejs, G

    1998-01-01

    Background—Stimulation of sensory nerves with capsaicin regulates ion transport in the small intestine in animal experiments. 
Aim—To investigate whether sensory nerves that are stimulated by capsaicin administration influence fluid and electrolyte absorption in the human jejunum in vivo. 
Method—Intestinal perfusion studies were performed in 12 healthy subjects using a four lumen tube with a proximal occlusion balloon and a plasma-like electrolyte solution. After an init...

  7. Improved oral bioavailability of capsaicin via liposomal nanoformulation: preparation, in vitro drug release and pharmacokinetics in rats.

    Science.gov (United States)

    Zhu, Yuan; Wang, Miaomiao; Zhang, Jiajia; Peng, Wei; Firempong, Caleb Kesse; Deng, Wenwen; Wang, Qilong; Wang, Shicheng; Shi, Feng; Yu, Jiangnan; Xu, Ximing; Zhang, Weiming

    2015-04-01

    This study innovatively prepared an effective capsaicin-loaded liposome, a nanoformulation with fewer irritants, for oral administration. The in vitro and in vivo properties of the liposomal encapsulation were investigated and the potential possibility of oral administration evaluated. The liposomal agent composed of phospholipid, cholesterol, sodium cholate and isopropyl myristate was prepared using film-dispersion method. A level A in vitro-in vivo correlation (IVIVC) was established for the first time, which demonstrated an excellent IVIVC of both formulated and free capsaicin in oral administration. Physicochemical characterizations including mean particle size, zeta (ζ) potential and average encapsulation efficiency of capsaicin-loaded liposome were found to be 52.2 ± 1.3 nm, -41.5 ± 2.71 mv and 81.9 ± 2.43 %, respectively. In vivo, liposomal encapsulation allowed a 3.34-fold increase in relative bioavailability compared to free capsaicin. The gastric mucosa irritation studies indicated that the liposomal system was a safe carrier for oral administration. These results support the fact that capsaicin, an effective drug for the treatment of neuropathic pain, could be encapsulated in liposome for improved oral bioavailability. The excellent IVIVC of capsaicin-loaded liposome could also be a promising tool in liposomal formulation development with an added advantage of reduced animal testing. PMID:25231341

  8. The effects of cellulase on capsaicin production in freely suspended cells and immobilized cell cultures of capsicum annuum

    International Nuclear Information System (INIS)

    The effect of different concentrations of cellulase on the production of capsaicin in freely suspended cell and immobilized cell cultures of Kahramanmara pepper seeds (Capsicum annuum L.) were studied. Calluses were obtained from in vitro germinated hypocotyl explants of pepper seedlings and cell suspensions were prepared from these calluses. Immobilized cell suspension cultures with calcium alginate and free cell suspension cultures were obtained by using cell suspensions. Elicitor such as cellulase (5-30 micro g/ml), was applied both for the free and immobilized cell suspensions and control group without elicitor was prepared. The concentration of capsaicin in freely suspended cells, immobilized cells and their filtrates were identified by HPLC after extraction with ethyl acetate. It was found that the immobilization process had an increasing effect on the capsaicin accumulation. The concentration of capsaicin in the immobilized cells for both control groups and elicitor added samples was higher than the free cells. In general, capsaicin concentration in the filtrate for free cells was higher than the immobilized cells. When all the cellulase and the sampling hours were compared, the highest capsaicin concentration for the immobilized cells was determined as 362,91 micro g/ml f.w. at the 24th hour for 30 micro g/ml cellulase applied samples. (author)

  9. Effects of capsaicin, green tea and CH-19 sweet pepper on appetite and energy intake in humans in negative and positive energy balance

    DEFF Research Database (Denmark)

    Reinbach, Helene Christine; Smeets, A.; Martinussen, Torben;

    2009-01-01

    Summary Background & aims Bioactive ingredients have been shown to reduce appetite and energy intake. The magnitude of these effects might depend on energy balance why it was investigated how capsaicin, green tea, CH-19 sweet pepper as well as green tea and capsaicin affect appetite and energy...... intake during respectively negative and positive energy balance. Methods 27 subjects were randomized to three weeks of negative and three weeks of positive energy balance during which capsaicin, green tea, CH-19 sweet pepper, capsaicin + green tea or placebo was ingested on ten separate test days while...... the effects on appetite, energy intake, body weight and heart rate were assessed. Results CH-19 sweet pepper and a combination of capsaicin and green tea reduced energy intake during positive energy balance. Capsaicin and green tea suppressed hunger and increased satiety more during negative than...

  10. Manipulation of culture strategies to enhance capsaicin biosynthesis in suspension and immobilized cell cultures of Capsicum chinense Jacq. cv. Naga King Chili.

    Science.gov (United States)

    Kehie, Mechuselie; Kumaria, Suman; Tandon, Pramod

    2014-06-01

    Manipulation of culture strategies was adopted to study the influence of nutrient stress, pH stress and precursor feeding on the biosynthesis of capsaicin in suspension and immobilized cell cultures of C. chinense. Cells cultured in the absence of one of the four nutrients (ammonium and potassium nitrate for nitrate and potassium stress, potassium dihydrogen orthophosphate for phosphorus stress, and sucrose for sugar stress) influenced the accumulation of capsaicin. Among the stress factors studied, nitrate stress showed maximal capsaicin production on day 20 (505.9 ± 2.8 μg g(-1) f.wt) in immobilized cell, whereas in suspension cultures the maximum accumulation (345.5 ± 2.9 μg g(-1) f.wt) was obtained on day 10. Different pH affected capsaicin accumulation; enhanced accumulation of capsaicin (261.6 ± 3.4 μg g(-1) f.wt) was observed in suspension cultures at pH 6 on day 15, whereas in case of immobilized cultures the highest capsaicin content (433.3 ± 3.3 μg g(-1) f.wt) was obtained at pH 5 on day 10. Addition of capsaicin precursors and intermediates significantly enhanced the biosynthesis of capsaicin, incorporation of vanillin at 100 μM in both suspension and immobilized cell cultures resulted in maximum capsaicin content with 499.1 ± 5.5 μg g(-1) f.wt on day 20 and 1,315.3 ± 10 μg g(-1) f.wt on day 10, respectively. Among the different culture strategies adopted to enhance capsaicin biosynthesis in cell cultures of C. chinense, cells fed with vanillin resulted in the maximum capsaicin accumulation. The rate of capsaicin production was significantly higher in immobilized cells as compared to freely suspended cells. PMID:24141419

  11. Prostaglandin I2 enhances cough reflex sensitivity to capsaicin in the asthmatic airway

    OpenAIRE

    Ishiura, Yoshihisa; Fujimura, Masaki; Nobata, Kouichi; Oribe, Yoshitaka; Abo, Miki; Myou, Shigeharu

    2007-01-01

    Inflammatory mediators are involved in the pathogenesis of airway inflammation, but the role of prostaglandin I2 (PGI2) remains obscure. This study was designed to investigate the role of PGI2 in cough reflex sensitivity of the asthmatic airway, which is characterized by chronic eosinophilic airway inflammation. The effect of beraprost, a chemically and biologically stable analogue of PGI2, on cough response to inhaled capsaicin was examined in 21 patients with stable asthma in a randomized, ...

  12. In vivo and in vitro content of capsaicin in pepper(Capsicum annuum L.)

    OpenAIRE

    Koleva Gudeva, Liljana; Spasenoski, Mirko; Rafajlovska, Vesna

    2004-01-01

    From all groups of biological active-secondary metabolites, in the species of genus Capsicum the most importance have the alkaloids capsaicinoides, which are present only in the cultivars of genus Capsicum, and only they are responsible for the pungent of pepper. From all capsaicinoides only two compounds with 80-90% are responsible for the pungent of papper, and they are capsaicin and dihidrocapsaicin.

  13. Activity-dependent targeting of TRPV1 with a pore-permeating capsaicin analog

    OpenAIRE

    Hui LI; Wang, Shu; Chuang, Alexander Y.; Cohen, Bruce E.; Chuang, Huai-hu

    2011-01-01

    The capsaicin receptor TRPV1 is the principal transduction channel for nociception. Excessive TRPV1 activation causes pathological pain. Ideal pain mangement requires selective inhibition of hyperactive pain-sensing neurons, but sparing normal nociception. We sought to determine whether it is possible to use activity-dependent TRPV1 agonists to identify nerves with excessive TRPV1 activity, as well as exploit the TRPV1 pore to deliver charged anesthetics for neuronal silencing. We synthesized...

  14. Activation of TRPV1 by Dietary Capsaicin Improves Endothelium-Dependent Vasorelaxation and Prevents Hypertension

    OpenAIRE

    Yang, Dachun; Luo, Zhidan; Ma, Shuangtao; Wong, Wing Tak; Ma, Liqun; Zhong, Jian; He, Hongbo; Zhao, Zhigang; Cao, Tingbing; Yan, Zhencheng; Liu, Daoyan; Arendshorst, William J.; Yu HUANG; Tepel, Martin; Zhu, Zhiming

    2010-01-01

    Some plant-based diets lower the cardiometabolic risks and prevalence of hypertension. New evidence implies a role for the transient receptor potential vanilloid 1 (TRPV1) cation channel in the pathogenesis of cardiometabolic diseases. Little is known about impact of chronic TRPV1 activation on the regulation of vascular function and blood pressure. Here we report that chronic TRPV1 activation by dietary capsaicin increases the phosphorylation of protein kinase A (PKA) and eNOS and thus produ...

  15. Cough sensitivity and extrathoracic airway responsiveness to inhaled capsaicin in chronic cough patients.

    OpenAIRE

    Cho, You Sook; Lee, Chang-Keun; Yoo, Bin; Moon, Hee-Bom

    2002-01-01

    Enhanced cough response has been frequently observed in chronic cough. Recently, extrathoracic airway constriction to inhaled histamine was demonstrated in some chronic cough patients. However, relation between extrathoracic airway hyperresponsiveness (EAHR) and cough sensitivity determined by capsaicin inhalation is unclear in each etiological entity of chronic cough. Seventy-seven patients, with dry cough persisting for 3 or more weeks, normal spirometry and chest radiography, and 15 contro...

  16. Effect of Capsaicin Supplementation on Performance of and Physiological Response to Repeated Sprinting

    OpenAIRE

    Opheim, Maximilian Nicholas

    2010-01-01

    Aim: Fatigue during team sports requiring multiple sprints can result from the combined effects of metabolic, mechanical, neurological, and immune factors. The purpose of this study was to investigate the influence of capsaicin on performance of and the physiological response to an exercise test simulating the fitness demands of team sport game conditions. Methods: This study was a placebo-controlled, crossover design. Nineteen healthy male experienced athletes age 18-30 yr consumed eith...

  17. Cardiovascular effects of substance P and capsaicin microinjected into the nucleus tractus solitarii of the rat

    OpenAIRE

    Lukovic, L.; Jong, Wybren de; Wied, D. de

    1987-01-01

    This report deals with the effect of substance P (SP) and capsaicin on blood pressure and heart rate after administration into different sites of the nucleus tractus solitarii (NTS) of urethane-anesthetized rats. Microinjection of SP at 6 different coordinates throughout the NTS showed 3 sites where SP administration evoked changes in blood pressure and heart rate. The most sensitive sites where application of SP into the NTS evoked dose-dependent hypotension and bradycardia were at the level...

  18. Capsaicin reduces postoperative hyperalgesic responses in the rat model of surgical pain

    Czech Academy of Sciences Publication Activity Database

    Paleček, Jiří; Pospíšilová, Eva

    San Diego : American Physiological Society, 2005. s. 42-43. [International Congress of Physiological Sciences /35./. 31.03.2005-05.04.2005, San Diego] R&D Projects: GA ČR(CZ) GA309/03/0752; GA ČR(CZ) GD305/03/H148 Institutional research plan: CEZ:AV0Z5011922 Keywords : capsaicin Subject RIV: ED - Physiology

  19. Capsaicin reduces postoperative hyperalgesic responses in the rat model of surgical pain

    Czech Academy of Sciences Publication Activity Database

    Pospíšilová, Eva; Paleček, Jiří

    Seattle : IASP Press, 2005. s. 57-57. ISBN 0-931092-64-7. [22th World Congress on Pain. 21.08.2005-26.08.2005, Sydney] R&D Projects: GA ČR(CZ) GD305/03/H148; GA ČR(CZ) GA309/03/0752 Institutional research plan: CEZ:AV0Z5011922 Keywords : capsaicin Subject RIV: ED - Physiology

  20. Capsaicin treatment differentially affects feeding suppression by bombesin-like peptides

    OpenAIRE

    Ladenheim, Ellen E; Knipp, Susan

    2007-01-01

    Peripheral administration of bombesin (BN) and the related mammalian peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB), suppress food intake in rats. To examine whether all BN-like peptides utilize the same neural pathways to reduce feeding, rats were treated on postnatal day 2 with the injection vehicle or capsaicin, a neurotoxin that damages a subset of visceral afferent fibers. When rats reached adulthood, we compared the ability of a dose range of systemically administered ...

  1. A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1

    OpenAIRE

    Zhang, Ning; Inan, Sadeet; Cowan, Alan; Sun, Ronghua; Wang, Ji Ming; Rogers, Thomas J.; Caterina, Michael; Oppenheim, Joost J.

    2005-01-01

    Pain, a critical component of host defense, is one hallmark of the inflammatory response. We therefore hypothesized that pain might be exacerbated by proinflammatory chemokines. To test this hypothesis, CCR1 was cotransfected into human embryonic kidney (HEK)293 cells together with transient receptor potential vanilloid 1 (TRPV1), a cation channel required for certain types of thermal hyperalgesia. In these cells, capsaicin and anandamide induced Ca2+ influx mediated by TRPV1. When CCR1:TRPV1...

  2. A Bivalent Tarantula Toxin Activates the Capsaicin Receptor, TRPV1, by Targeting the Outer Pore Domain

    OpenAIRE

    Bohlen, Christopher J.; Priel, Avi; Zhou, Sharleen; King, David; Siemens, Jan; Julius, David

    2010-01-01

    Toxins have evolved to target regions of membrane ion channels that underlie ligand binding, gating, or ion permeation, and have thus served as invaluable tools for probing channel structure and function. Here we describe a peptide toxin from the Earth Tiger tarantula that selectively and irreversibly activates the capsaicin- and heat-sensitive channel, TRPV1. This high avidity interaction derives from a unique tandem repeat structure of the toxin that endows it with an antibody-like bivalenc...

  3. Effects of action of ultrasound with capsaicin in the treatment of post traumatic pathology

    Directory of Open Access Journals (Sweden)

    Ioan OSWALD

    2007-05-01

    Full Text Available There are numerous methods of administering drugs to the body,both passive and active. A recent review of the literature on phonophoresis reports that 75 % of the studies reviewed reported positive effects, ultrasound energy with drugs like gel or cream can travel through body tissue. Capsaicin was the active ingredient in hot chilli peppers has selection actions on unmyelinated C fibres and thinly myelinated A primary sensory neurones.

  4. The effects of Hot Pepper Extract and Capsaicin on Adipocyte Metabolism

    OpenAIRE

    Ching Sheng, Chu; Ki Rok, Kwon; Tae Jin, Rhim; Dong Heui, Kim

    2008-01-01

    Objectives : The purpose of this study is to investigate the effects of hot pepper extract and capsaicin on the adipogenesis in 3T3-L1 cells, lipolysis in rat epididymal adipocytes and histological changes in porcine adipose tissue. Methods : Inhibiton of preadipocyte differentiation and/or stimulation of lipolysis play important roles in reducing obesity. 3T3-L1 preadipocytes were differentiated with adipogenic reagents by incubating for 3 days in the absence or presence of hot pepper ...

  5. Resiniferatoxin and piperine: capsaicin-like stimulators of oxygen uptake in the perfused rat hindlimb.

    Science.gov (United States)

    Eldershaw, T P; Colquhoun, E Q; Bennett, K L; Dora, K A; Clark, M G

    1994-01-01

    The naturally occurring capsaicin-like molecules, resiniferatoxin (RTX, Euphorbia spp.) and piperine (Piper nigrum), each stimulated oxygen uptake (VO2) in association with increased vascular resistance in a concentration-dependent manner when infused into the perfused rat hindlimb. 5 microM glyceryl trinitrate (GTN, a nitrovasodilator) significantly blocked the oxygen and pressure responses to both RTX and piperine, indicating a close relationship between changes in VO2 and the vasoconstriction. Concentrations greater than those required for maximal VO2 resulted in an inhibition of VO2, although perfusion pressure continued to increase. Time course studies showed that both RTX and piperine at high doses resulted in a tri-phasic response. An initial phase of transient VO2 stimulation was followed by a second phase of inhibition. A third phase involving an often larger but transient stimulation of VO2 followed removal of the agents and continued after the pressure returned to basal. The actions of RTX and piperine were similar to those of other active capsaicin-like molecules tested previously in this system, including capsaicinoids (Capsicum spp.), gingerols (Zingiber officinale), and shogoals (Zingiber officinale). RTX was the most potent, and piperine the least potent of this series. Although receptor involvement has yet to be unequivocally established, the data are consistent with the presence of a functional capsaicin-like (vanilloid) receptor in the vasculature of the rat hindlimb that mediates vasoconstriction and oxygen uptake. These findings may have implications for the future development of thermogenic agents. PMID:8035653

  6. Costs and benefits of capsaicin-mediated control of gut retention in dispersers of wild chilies.

    Science.gov (United States)

    Tewksbury, Joshua J; Levey, Douglas J; Huizinga, Meribeth; Haak, David C; Traveset, Anna

    2008-01-01

    A fundamental way in which animal-dispersed plants can influence the viability and distribution of dispersed seeds is through control of retention time in the guts of dispersers. Using two species of wild chilies and their dispersers, we examined how chemical and physical properties of fruits and seeds mediate this interaction. Capsicum chacoense is polymorphic for pungency, occurs in Bolivia, and is dispersed mostly by elaenias. Capsicum annuum is not polymorphic, occurs in Arizona (USA), and is dispersed mostly by thrashers. We first tested whether capsaicin, the substance responsible for the pungency of chilies, affects gut retention time of seeds in primary dispersers. Capsaicin slowed gut passage of seeds but did so in a manner that differed greatly between bird species because the constipative effects of capsaicin occurred only after an 80-minute time lag. Elaenias in Bolivia held only 6% of C. chacoense seeds for > 80 minutes, whereas thrashers in Arizona held 78% of C. annuum seeds for > 80 minutes. Next we examined the effects of retention time on seed viability and germination. Increased retention resulted in a greater proportion of seeds germinating in C. annuum, had no effects on non-pungent C. chacoense, and had negative effects on pungent C. chacoense. These divergent effects are explained by differences in seed coat morphology: seed coats of pungent C. chacoense are 10-12% thinner than those of the other two types of seeds. Thus, longer retention times damaged seeds with the thinnest seed coats. In C. annuum, seed viability remained high regardless of retention time, but germination increased with retention, suggesting a role for scarification. Thus, in C. annuum, fruit chemistry appears well matched with seed morphology and disperser physiology: capsaicin extends gut retention for most seeds, resulting in greater seed scarification and higher germination rates. Increased retention of pungent C. chacoense seeds is detrimental, but because the primary

  7. Simultaneous determination of capsaicin and dihydrocapsaicin for vegetable oil adulteration by immunoaffinity chromatography cleanup coupled with LC-MS/MS.

    Science.gov (United States)

    Ma, Fei; Yang, Qingqing; Matthäus, Bertrand; Li, Peiwu; Zhang, Qi; Zhang, Liangxiao

    2016-05-15

    Capsaicin and dihydrocapsaicin were selected as adulteration markers to authenticate vegetable oils. In this study, a method of immunoaffinity chromatography (IAC) combined with liquid chromatography-tandem mass spectrometry was established for the determination of capsaicin and dihydrocapsaicin in vegetable oils. In this method, immunosorbents were obtained by covalently coupling highly specific capsaicinoid polyclonal antibodieswith CNBr-activated Sepharose 4B, and then packed into a polyethylene column. In this paper, the major parameters affecting IAC extraction efficiency, including loading, washing and eluting conditions, were also investigated. The IAC column displayed high selectivity for capsaicin and dihydrocapsaicin with the maximum capacity of 240ng. The limit of detection (LOD) and limit of quantification (LOQ) for capsaicin were calculated as 0.02 and 0.08μgkg(-1), and for dihydrocapsaicin were 0.03 and 0.10μgkg(-1). The recoveries of capsaicin and dihydrocapsaicin in oil samples were in the range of 87.3-95.2% with the relative standard deviation (RSD) of less than 6.1%. The results indicated that capsaicinoid compounds could not be found in edible vegetable oils. Therefore, the proposed method is simple, reliable and adequate for routine monitoring of capsaicinoid compounds in vegetable oils and has an excellent potential for detection of adulteration with inedible waste oil. PMID:26739369

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-02-15

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Fidias E. Leon-Sarmiento

    2005-09-01

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

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

    Science.gov (United States)

    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. PMID:26963851

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

    Directory of Open Access Journals (Sweden)

    Pilou L H R Janssens

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

  14. Post-operative pain behavior in rats is reduced after single high-concentration capsaicin application

    Czech Academy of Sciences Publication Activity Database

    Pospíšilová, Eva; Paleček, Jiří

    2006-01-01

    Roč. 125, č. 3 (2006), s. 233-243. ISSN 0304-3959 R&D Projects: GA ČR(CZ) GA305/06/1115; GA ČR(CZ) GD305/03/H148; GA ČR(CZ) GA309/03/0752; GA MŠk(CZ) LC554 Grant ostatní: MYORES(XE) 511978 Institutional research plan: CEZ:AV0Z50110509 Keywords : capsaicin * TRPV1 * surgical pain Subject RIV: ED - Physiology Impact factor: 4.836, year: 2006

  15. Elevating concentrations of capsaicin and dihydrocapsaicin in hot peppers using recycled waste.

    Science.gov (United States)

    Antonious, George F

    2015-01-01

    Five Capsicum accessions (PI 435916 and PI 438614 from Capsicum chinense; PI 370004 and Grif 9354 from C. baccatum and PI 438649 from C. annuum) were selected from the U.S. Department of Agriculture-Agricultural Research Service Capsicum germplasm collection to study the impact of four soil management practices: yard waste (YW), sewage sludge (SS), chicken manure (CM) and no-mulch (NM) bare soil on fruit concentrations of capsaicin and dihydrocapsaicin, yield, plant size and mature fruit characteristics (fruit weight, length, width, and wall-thickness) of plants grown under these practices. Regardless of soil treatments, PI 438614 and PI 435916 contained the greatest concentrations of total capsaicinoids (capsaicin and dihydrocapsaicin). Fruits of plants grown in soil mixed with SS contained the greatest concentrations of total capsaicinoids. Fruits of plants grown in SS or CM contained the greatest fruit weight. PI 438649 produced the greatest fruit weight, length and wall-thickness. The total marketable yield expressed as weight of fruit plants was significantly higher in soils mixed with SS and CM compared to those mixed with YW and NM soils. PMID:25996816

  16. Infringement of the barriers of cancer via dietary phytoconstituents capsaicin through novel drug delivery system.

    Science.gov (United States)

    Giri, Tapan Kumar; Alexander, Amit; Ajazuddin; Barman, Tapan Kumar; Maity, Subhasis

    2016-01-01

    Cancer is the major cause of fatality and the number of new cases is increasing incessantly. Conventional therapies and existing anticancer agents cause serious side effects and expand the patient's lifespan by a few years. There is the need to exploit alternative anticancer agents and novel drug delivery system to deliver these agents to the tumor site for the prevention of cancer. Recently, biologically active compounds isolated from plants used for the management of cancer have been the heart of interest. Capsaicin is a major pungent agent present in the chili peppers that is heavily consumed in the world. Capsaicin has demonstrated effectiveness as an anticancer agent, but a restraining factor is its pungency, extremely low aqueous solubility, and poor oral bioavailability which impede its use as an anticancer agent. Many technologies have been developed and applied to conquer this drawback. We bring to light the benefits of this phytoconstituent for treating different types of cancer. We also discussed some of the delivery approaches that have already made an impact by either delivering a drug to target tissue or increasing its bioavailability by many folds. PMID:26036845

  17. Acid potentiation of the capsaicin receptor determined by a key extracellular site.

    Science.gov (United States)

    Jordt, S E; Tominaga, M; Julius, D

    2000-07-01

    The capsaicin (vanilloid) receptor, VR1, is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. The response of VR1 to capsaicin or noxious heat is dynamically potentiated by extracellular protons within a pH range encountered during tissue acidosis, such as that associated with arthritis, infarction, tumor growth, and other forms of injury. A molecular determinant for this important physiological activity was localized to an extracellular Glu residue (E600) in the region linking the fifth transmembrane domain with the putative pore-forming region of the channel. We suggest that this residue serves as a key regulatory site of the receptor by setting sensitivity to other noxious stimuli in response to changes in extracellular proton concentration. We also demonstrate that protons, vanilloids, and heat promote channel opening through distinct pathways, because mutations at a second site (E648) selectively abrogate proton-evoked channel activation without diminishing responses to other noxious stimuli. Our findings provide molecular evidence for stimulus-specific steps in VR1 activation and offer strategies for the development of novel analgesic agents. PMID:10859346

  18. The Preparation of Capsaicin-Chitosan Microspheres (CCMS Enteric Coated Tablets

    Directory of Open Access Journals (Sweden)

    Jian Chen

    2013-12-01

    Full Text Available This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%, plasticisers (TEC and DBS, dosage of plasticiser (10%, 20% and 30% and coating weight (2%, 3% and 5% were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8 revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs.

  19. [Surfactant and water balance of lung in intracerebral hemorrhage at conditions of capsaicin blockade of vagus nerve].

    Science.gov (United States)

    Urakova, M A; Bryndina, I G

    2015-03-01

    It is known that intracranial hemorrhage (ICH) is accompanied by the development of neurogenic pulmonary edema and insufficiency of surfactant function. The present study was undertaken for evaluation of the role of vagal afferents in the mechanisms of ICH effects on pulmonary surfactant and water balance of the lung. We explored the surface activity and biochemical composition of surfactant, as well as blood supply, total, intravascular and extravascular fluid content in lung after ICH, simulated by intraventricular administration of autologous blood against the background of bilateral blockade of capsaicin-sensitive vagal affere its. The blockade was caused by the capsaicin application (50 mcmol) on the cervical part of the nerves. Intracerebralhemorrhage was accompanied by the decrease of surfactant activity which appeared by the enhancement of minimal, maximal and static surface tension of bronchoalveolar lavage fluid (BAL), the reduction of total phospholipids including their main fraction phosphatidylcholine, the increase of lysophosphatidyicholine content and hyperhydration of the lung. The level of total proteins in BAL elevated, confirmed the enhanced permeability of the alveolar-blood barrier. The exhaustion of neuropeptides in capsaicin-sensitive vagal afferents led to the partial restoration of surface active properties of lung, normalization of phospholipids and protein contents and water balance parameters. The obtained results suggest that capsaicin-sensitive vagal afferents play a pivotal role in the disturbances of surfactant function and water balance of the lung after ICH. PMID:26016324

  20. The effects of capsaicin and acidity on currents generated by noxious heat in cultured neonatal rat dorsal root ganglion neurones

    Czech Academy of Sciences Publication Activity Database

    Vlachová, Viktorie; Lyfenko, Alla; Orkand, R. K.; Vyklický st., Ladislav

    2001-01-01

    Roč. 533, č. 3 (2001), s. 717-728. ISSN 0022-3751 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : capsaicin * dorsal root ganglion neurones * neonatal rat Subject RIV: FH - Neurology Impact factor: 4.476, year: 2001

  1. Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Feldt-Rasmussen, Ulla; Rasmussen, Åse K.;

    2006-01-01

    affected. Recently, attention has been drawn to female patients whether they also show signs of nerve involvement. An early sign of the disease is painful small-fibre neuropathy. The aim of this study was to evaluate a small-fibre dysfunction in female Fabry patients by using capsaicin applied topically...

  2. Electrochemical sensing platform amplified with a nanobiocomposite of L-phenylalanine ammonia-lyase enzyme for the detection of capsaicin.

    Science.gov (United States)

    Sabela, Myalowenkosi I; Mpanza, Thabani; Kanchi, Suvardhan; Sharma, Deepali; Bisetty, Krishna

    2016-09-15

    The present study involves the development of a sensitive electrochemical biosensor for the determination of capsaicin extracted from chilli fruits, based on a novel signal amplification strategy using enzyme technology. For the first time, platinum electrode modified with multiwalled carbon nanotubes where phenylalanine ammonia-lyase enzyme was immobilized using nafion was characterized by attenuated total reflectance infrared spectroscopy, transmittance electron microscopy and thermo-gravimetric analysis supported by computational methods. Cyclic and differential pulse voltammetry measurements were performed to better understand the redox mechanism of capsaicin. The performance of the developed electrochemical biosensor was tested using spiked samples with recoveries ranging from 98.9 to 99.6%. The comparison of the results obtained from bare and modified platinum electrodes revealed the sensitivity of the developed biosensor, having a detection limit (S/N=3) of 0.1863µgmL(-1) and electron transfer rate constant (ks) of 3.02s(-1). Furthermore, adsorption and ligand-enzyme docking studies were carried out to better understand the redox mechanisms supported by density functional theory calculations. These results revealed that capsaicin forms hydrogen bonds with GLU355, GLU541, GLU586, ARG and other amino acids of the hydrophobic channel of the binding sites thereby facilitating the redox reaction for the detection of capsaicin. PMID:27104584

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

    Science.gov (United States)

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

    2015-12-17

    The distribution of spinal primary afferent terminals labeled transganglionically with the choleratoxin B subunit (CTB) or its conjugates changes profoundly after perineural treatment with capsaicin. Injection of CTB conjugated with horseradish peroxidase (HRP) into an intact nerve labels somatotopically related areas in the ipsilateral dorsal horn with the exceptions of the marginal zone and the substantia gelatinosa, whereas injection of this tracer into a capsaicin-pretreated nerve also results in massive labeling of these most superficial layers of the dorsal horn. The present study was initiated to clarify the role of C-fiber primary afferent neurons in this phenomenon. In L5 dorsal root ganglia, analysis of the size frequency distribution of neurons labeled after injection of CTB-HRP into the ipsilateral sciatic nerve treated previously with capsaicin or resiniferatoxin revealed a significant increase in the proportion of small neurons. In the spinal dorsal horn, capsaicin or resiniferatoxin pretreatment resulted in intense CTB-HRP labeling of the marginal zone and the substantia gelatinosa. Electron microscopic histochemistry disclosed a dramatic, ∼10-fold increase in the proportion of CTB-HRP-labeled unmyelinated dorsal root axons following perineural capsaicin or resiniferatoxin. The present results indicate that CTB-HRP labeling of C-fiber dorsal root ganglion neurons and their central terminals after perineural treatment with vanilloid compounds may be explained by their phenotypic switch rather than a sprouting response of thick myelinated spinal afferents which, in an intact nerve, can be labeled selectively with CTB-HRP. The findings also suggest a role for GM1 ganglioside in the modulation of nociceptor function and pain. PMID:26520849

  4. C-fiber-related EEG-oscillations induced by laser radiant heat stimulation of capsaicin-treated skin

    Directory of Open Access Journals (Sweden)

    Claudia Domnick

    2009-03-01

    Full Text Available Claudia Domnick1, Michael Hauck1,2,3, Kenneth L Casey3, Andreas K Engel1, Jürgen Lorenz1,3,41Department of Neurophysiology and Pathophysiology; 2Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 3Department of Neurology, University of Michigan, Ann Arbor, MI, USA; 4Faculty of Life Sciences, Hamburg University of Applied Sciences, Hamburg, GermanyAbstract: Nociceptive input reaches the brain via two different types of nerve fibers, moderately fast A-delta and slowly conducting C-fibers, respectively. To explore their distinct roles in normal and inflammatory pain we used laser stimulation of normal and capsaicin treated skin at proximal and distal arm sites in combination with time frequency transformation of electroencephalography (EEG data. Comparison of phase-locked (evoked and non-phase-locked (total EEG to laser stimuli revealed three significant pain-related oscillatory responses. First, an evoked response in the delta-theta band, mediated by A-fibers, was reduced by topical capsaicin treatment. Second, a decrease of total power in the alpha-to-gamma band reflected both an A- and C-nociceptor-mediated response with only the latter being reduced by capsaicin treatment. Finally, an enhancement of total power in the upper beta band was mediated exclusively by C-nociceptors and appeared strongly augmented by capsaicin treatment. These findings suggest that phase-locking of brain activity to stimulus onset is a critical feature of A-delta nociceptive input, allowing rapid orientation to salient and potentially threatening events. In contrast, the subsequent C-nociceptive input exhibits clearly less phase coupling to the stimulus. It may primarily signal the tissue status allowing more long-term behavioral adaptations during ongoing inflammatory events that accompany tissue damage.Keywords: C-fibers, oscillations, EEG, laser, capsaicin, inflammatory pain

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

    Directory of Open Access Journals (Sweden)

    Andrei Zakharov

    2015-07-01

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

  6. Is physician supervision of the capsaicin 8% patch administration procedure really necessary? An opinion from health care professionals

    Directory of Open Access Journals (Sweden)

    Kern KU

    2013-07-01

    Full Text Available Kai-Uwe Kern,1 Janice England,2 Andrea Roth-Daniek,3 Till Wagner3 1Institute for Pain Medicine/Pain Practice, Wiesbaden, Germany; 2Pain Medicine and Anaesthesia, The Christie National Health Service Foundation Trust, Manchester, UK; 3Pain Therapy and Palliative Care Department, Medizinisches Zentrum Städteregion Aachen, Aachen, Germany Abstract: Neuropathic pain is difficult to treat and can have a severe effect on quality of life. The capsaicin 8% patch is a novel treatment option that directly targets the source of peripheral neuropathic pain. It can provide pain relief for up to 12 weeks in patients with peripheral neuropathic pain. Treatment with the capsaicin 8% patch follows a clearly defined procedure, and patch application must be carried out by a physician or a health care professional under the supervision of a physician. Nonetheless, in our experience, nurses often take the lead role in capsaicin 8% patch application without the involvement of a physician. We believe that the nurse's key role is of benefit to the patients, as he or she may be better placed, because of time constraints and patient relationships, to support the patient through the application procedure than a physician. Moreover, a number of frequently prescribed drugs, including botulinum toxin and infliximab, can be administered by health care professionals without the requirement for physician supervision. Here we argue that current guidance should be amended to remove the requirement for physician supervision during application of the capsaicin 8% patch. Keywords: capsaicin, neuropathic pain, topical, health care professional, physician, nurse

  7. Adlea (ALGRX-4975), an injectable capsaicin (TRPV1 receptor agonist) formulation for longlasting pain relief.

    Science.gov (United States)

    Remadevi, Radhika; Szallisi, Arpad

    2008-02-01

    Anesiva Inc is developing Adlea (ALRGX-4975) - an injectable preparation of capsaicin, a TRPV1 (transient receptor potential vanilloid subfamily 1) receptor agonist - for the potential management of pain associated with osteoarthritis, tendonitiand postsurgical conditions, as well as for neuropathic pain occurring secondary to nerve injury. Adlea functions by desensitizing those neurons that conduct a long-lasting, throbbing form of pain. In phase II clinical trials, a single injection of Adlea significantly reduced pain levels in patients following total knee arthroplasty (TKA) or bunionectomy, and reduced pain in patients with osteoarthritis (OA) or Morton's neuroma. Phase II trials are ongoing to test Adlea in patients who are undergoing total hip arthroplasty or arthroscopic shoulder surgery and in patients with knee OA. Phase III clinical trials for the compound have been slated to begin in 2008 in patients following TKA or bunionectomy. Adlea appears to exhibit promise as a new medication in the treatment of conditions of chronic neuropathic pain. PMID:18240098

  8. Capsaicin - the Hot and Spicy Diet Turned Mild and Effective by Glycosylation

    Directory of Open Access Journals (Sweden)

    Henrik Toft Simonsen

    2009-01-01

    Full Text Available Shimoda and co-workers published a paper on the pharmacological properties of glycosides of the peppery compound capsaicin (1 and its derivative 8-nordihydrocapsaicin (2. In their paper they conclude that the β-glucoside and β-maltoside of 1 and the β-glucoside of 2 still have the same potent anti-obese activity but further studies are needed to determine the physiological effect. Shimoda et al.1 use glycosylation to make a drug candidate more water soluble to promote their research for new drug candidates within the chemical group of capsaicinoids. Their findings support that this is a plausible way to enhance both bioavailability and “drug-likeliness” properties of drug candidates. This is indeed an interesting approach which should be pursued further and by many more.

  9. N-[(1,3-Benzodioxol-5-ylmethyl]benzenesulfonamide: an analogue of capsaicin

    Directory of Open Access Journals (Sweden)

    Stella H. Maganhi

    2013-11-01

    Full Text Available The title compound, C14H13NO4S, an analogue of capsaicin, differs from the latter by having a 1,3-benzodioxole ring rather than a 2-methoxyphenol moiety, and having a benzenesulfonamide group instead of an aliphatic amide chain. The five-membered ring is in an envelope conformation with the methylene C atom lying 0.221 (6 Å out of the plane formed by the other four atoms. The dihedral angle between the phenyl ring and the mean plane of the 1,3-benzodioxole fused-ring system is 84.65 (4°. In the crystal, molecules aggregate into supramolecular layers in the ac plane through C—H...O, N—H...O and C—H...π interactions.

  10. STUDIES OF THE POSSIBILITY OF OBTAINING ECOLOGICALLY BASED CREAM CAPSAICIN IN THE TREATMENT OF RHEUMATIC DISEASE

    Directory of Open Access Journals (Sweden)

    Olimpia PANDIA

    2014-06-01

    Full Text Available Since herbal medicine makes strides to improve or cure of diseases or serious diseases to human, wherepreparations obtained by chemical are replaced successfully with herbal preparations obtained herbs, aromatic orthose of spontaneous. Thus, in this paper, several attempts are made to prepare a capsaicin based creams antrheumatic. This product is an environmentally friendly product, 100% vegetable produced in the laboratory as abase flossing a chilli extract obtained from private household, beeswax, distilled water, alcohol and peppermint oil.By obtaining this cream was intended to improve or cure people suffering from rheumatism, to relieve pain causedby arthritis, you know, is a readily available even at home, easy to manage, with immediate good results withoutside effects.

  11. Capsaicin-loaded vesicular systems designed for enhancing localized delivery for psoriasis therapy.

    Science.gov (United States)

    Gupta, Ruchi; Gupta, Madhu; Mangal, Sharad; Agrawal, Udita; Vyas, Suresh Prasad

    2016-05-01

    The aim of the current investigation is to evaluate the potential of capsaicin (CAP)-containing liposomes, niosomes and emulsomes in providing localized and controlled delivery, to improve the topical delivery of drug. CAP-bearing systems were prepared by the film hydration method and compared through various in vitro and in vivo parameters. The TEM photographs suggested that the carrier systems were spherical in shape and nanometric in size range. Skin retention studies of CAP from in vitro and in vivo experiments revealed significantly higher accumulation of drug in the case of the emul-gel formulation. Based on the results, we concluded that the emul-gel may be a potential approach for the topical delivery of CAP, for an effective therapy for psoriasis. PMID:25465045

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

    Science.gov (United States)

    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

  13. Phenylpyrazolone derivatives inhibit gastric emptying in rats by a capsaicin-sensitive afferent pathway

    Directory of Open Access Journals (Sweden)

    A.M. Vinagre

    2009-11-01

    Full Text Available Dipyrone (Dp, 4-aminoantipyrine (AA and antipyrine (At administered iv and Dp administered icv delay gastric emptying (GE in rats. The participation of capsaicin (Cps-sensitive afferent fibers in this phenomenon was evaluated. Male Wistar rats were pretreated sc with Cps (50 mg/kg or vehicle between the first and second day of life and both groups were submitted to the eye-wiping test. GE was determined in these animals at the age of 8/9 weeks (weight: 200-300 g. Ten minutes before the study, the animals of both groups were treated iv with Dp, AA or At (240 μmol/kg, or saline; or treated icv with Dp (4 μmol/animal or saline. GE was determined 10 min after treatment by measuring % gastric retention (GR of saline labeled with phenol red 10 min after orogastric administration. Percent GR (mean ± SEM, N = 8 in animals pretreated with Cps and treated with Dp, AA or At (35.8 ± 3.2, 35.4 ± 2.2, and 35.6 ± 2%, respectively did not differ from the GR of saline-treated animals pretreated with vehicle (36.8 ± 2.8% and was significantly lower than in animals pretreated with vehicle and treated with the drugs (52.1 ± 2.8, 66.2 ± 4, and 55.8 ± 3%, respectively. The effect of icv administration of Dp (N = 6 was not modified by pretreatment with Cps (63.3 ± 5.7% compared to Dp-treated animals pretreated with vehicle (62.3 ± 2.4%. The results suggest the participation of capsaicin-sensitive afferent fibers in the delayed GE induced by iv administration of Dp, AA and At, but not of icv Dp.

  14. A novel method of selective ablation of afferent renal nerves by periaxonal application of capsaicin.

    Science.gov (United States)

    Foss, Jason D; Wainford, Richard D; Engeland, William C; Fink, Gregory D; Osborn, John W

    2015-01-15

    Renal denervation has been shown to lower arterial pressure in some hypertensive patients, yet it remains unclear whether this is due to ablation of afferent or efferent renal nerves. To investigate the role of afferent renal nerves in arterial pressure regulation, previous studies have used methods that disrupt both renal and nonrenal afferent signaling. The present study was conducted to develop and validate a technique for selective ablation of afferent renal nerves that does not disrupt other afferent pathways. To do this, we adapted a technique for sensory denervation of the adrenal gland by topical application of capsaicin and tested the hypothesis that exposure of the renal nerves to capsaicin (renal-CAP) causes ablation of afferent but not efferent renal nerves. Renal-CAP had no effect on renal content of the efferent nerve markers tyrosine hydroxylase and norepinephrine; however, the afferent nerve marker, calcitonin gene-related peptide was largely depleted from the kidney 10 days after intervention, but returned to roughly half of control levels by 7 wk postintervention. Moreover, renal-CAP abolished the cardiovascular responses to acute pharmacological stimulation of afferent renal nerves. Renal-CAP rats showed normal weight gain, as well as cardiovascular and fluid balance regulation during dietary sodium loading. To some extent, renal-CAP did blunt the bradycardic response and increase the dipsogenic response to increased salt intake. Lastly, renal-CAP significantly attenuated the development of deoxycorticosterone acetate-salt hypertension. These results demonstrate that renal-CAP effectively causes selective ablation of afferent renal nerves in rats. PMID:25411365

  15. Capsaicin cough sensitivity is related to the older female predominant feature in chronic cough patients

    Science.gov (United States)

    Song, Woo-Jung; Kim, Ju-Young; Jo, Eun-Jung; Lee, Seung-Eun; Kim, Min-Hye; Yang, Min-Suk; Kang, Hye-Ryun; Park, Heung-Woo; Chang, Yoon-Seok; Min, Kyung-Up

    2014-01-01

    Purpose The present study aimed to examine the age and gender distributions among chronic cough patients referred to a tertiary cough clinic in Korea, and to investigate clinical factors related to the demographic findings. Methods Study participants were unselectively recruited from adult chronic cough patients who attended the cough clinic for the first time during one year. To validate their representativeness, their age and gender distributions were compared to the entire chronic cough population, or with those presenting with other chronic disease. Data from the baseline investigations were analyzed to identify clinical factors related to the demographic findings. Results A total of 272 chronic cough patients were included. They had a middle-aged female predominant feature (mean age: 52.8±15.7 years and female 69.1%). Their age and gender distributions were almost identical to the entire chronic cough population, but were distinct from patients with hypertension. Among clinical factors, the older female predominance was associated with enhanced capsaicin cough sensitivity, and also with the presence of 'cough by cold air' symptom. Allotussia and laryngeal paresthesia were highly common in chronic cough patients, affecting 94.8% and 86.8% of them, respectively. Conclusions The present study demonstrated older female predominance among adult chronic cough patients attending a referral cough clinic in Korea. The demographic features were significantly associated with the capsaicin cough responses and also potentially with allotussia (particularly cold air as the trigger). These findings suggest a role of cough reflex sensitization in the pathophysiology of chronic cough in adults. PMID:25228996

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

    Directory of Open Access Journals (Sweden)

    Kevin Gamber

    2015-02-01

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

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

    OpenAIRE

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

    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 ...

  18. Histone deacetylase inhibitory activity of hydroxycapsaicin, a synthetic derivative of capsaicin, and its cytotoxic effects against human colon cancer cell lines

    OpenAIRE

    SENAWONG, THANASET; WONGPHAKHAM, PAWEENA; SAIWICHAI, THUSSANEE; PHAOSIRI, CHANOKBHORN; KUMBOONMA, PAKIT

    2015-01-01

    Capsaicin possesses cytotoxic/anticancer activity and shares some common structural features, including a benzene ring and a long hydrophobic carbon tail, with the histone deacetylase (HDAC) inhibitors trichostatin A and suberoylanilide hydroxamic acid. The aims of this study were to investigate HDAC inhibitory and cytotoxic activities of a synthetic derivative of capsaicin, hydroxycapsaicin (6-hydroxy-N-(4-hydroxy-3-methoxybenzyl)-8-methylnonenamide), in colon cancer cell lines. Hydroxycapsa...

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

    Directory of Open Access Journals (Sweden)

    Zachary Rex Gallaher

    2011-02-01

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

  20. Capsaicin production by Alternaria alternata, an endophytic fungus from Capsicum annum; LC-ESI-MS/MS analysis.

    Science.gov (United States)

    Devari, Shekaraiah; Jaglan, Sundeep; Kumar, Manjeet; Deshidi, Ramesh; Guru, Santosh; Bhushan, Shashi; Kushwaha, Manoj; Gupta, Ajai P; Gandhi, Sumit G; Sharma, Jai P; Taneja, Subhash C; Vishwakarma, Ram A; Shah, Bhahwal Ali

    2014-02-01

    Alternaria alternata, an endophytic fungus capable of producing capsaicin (1) was isolated from Capsicum annum. The endophyte was found to produce capsaicin upto three generations. Upscaling of the fermentation broth led to the isolation of one known and one compound characterized as 2,4-di-tert-butyl phenol (2) and alternariol-10-methyl ether (3) respectively. Compound 1 and 3 were identified and quantified using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) system through multiple reaction monitoring (MRM). Furthermore, compound 3 displayed a range of cytotoxicity against a panel of human cancer cell lines and was found to induce apoptosis evidenced by Hoechst staining and loss of mitochondrial-membrane potential in HL-60 cells. PMID:24378219

  1. Self-reported sleep duration associated with distraction analgesia, hyperemia, and secondary hyperalgesia in the heat-capsaicin nociceptive model

    OpenAIRE

    Campbell, Claudia M.; Bounds, Sara C.; Simango, Mpepera B.; Witmer, Kenneth R.; Campbell, James N.; Edwards, Robert R.; Haythornthwaite, Jennifer A; Smith, Michael T.

    2010-01-01

    Although sleep deprivation is known to heighten pain sensitivity, the mechanisms by which sleep modifies nociception are largely unknown. Few studies of sleep-pain interactions have utilized quantitative sensory testing models that implicate specific underlying physiologic mechanisms. One possibility, which is beginning to receive attention, is that differences in sleep may alter the analgesic effects of distraction. We utilized the heat-capsaicin nociceptive model to examine whether self-rep...

  2. NMDA receptors are involved in the antidepressant-like effects of capsaicin following amphetamine withdrawal in male mice.

    Science.gov (United States)

    Amiri, Shayan; Alijanpour, Sakineh; Tirgar, Fatemeh; Haj-Mirzaian, Arya; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Rastegar, Mojgan; Ghaderi, Marzieh; Ghazi-Khansari, Mahmoud; Zarrindast, Mohammad-Reza

    2016-08-01

    Amphetamine withdrawal (AW) is accompanied by diminished pleasure and depression which plays a key role in drug relapse and addictive behaviors. There is no efficient treatment for AW-induced depression and underpinning mechanisms were not well determined. Considering both transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and N-Methyl-d-aspartate (NMDA) receptors contribute to pathophysiology of mood and addictive disorders, in this study, we investigated the role of TRPV1 and NMDA receptors in mediating depressive-like behaviors following AW in male mice. Results revealed that administration of capsaicin, TRPV1 agonist, (100μg/mouse, i.c.v.) and MK-801, NMDA receptor antagonist (0.005mg/kg, i.p.) reversed AW-induced depressive-like behaviors in forced swimming test (FST) and splash test with no effect on animals' locomotion. Co-administration of sub-effective doses of MK-801 (0.001mg/kg, i.p.) and capsaicin (10μg/mouse, i.c.v) exerted antidepressant-like effects in behavioral tests. Capsazepine, TRPV1 antagonist, (100μg/mouse, i.c.v) and NMDA, NMDA receptor agonist (7.5mg/kg, i.p.) abolished the effects of capsaicin and MK-801, respectively. None of aforementioned treatments had any effect on behavior of control animals. Collectively, our findings showed that activation of TRPV1 and blockade of NMDA receptors produced antidepressant-like effects in male mice following AW, and these receptors are involved in AW-induced depressive-like behaviors. Further, we found that rapid antidepressant-like effects of capsaicin in FST and splash test are partly mediated by NMDA receptors. PMID:27167081

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

    Directory of Open Access Journals (Sweden)

    Nicole Schöbel

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

  4. Capsaicin stimulates the non-store-operated Ca2+ entry but inhibits the store-operated Ca2+ entry in neutrophils

    International Nuclear Information System (INIS)

    Rat neutrophils express the mRNA encoding for transient receptor potential (TRP) V1. However, capsaicin-stimulated [Ca2+]i elevation occurred only at high concentrations (≥100 μM). This response was substantially decreased in a Ca2+-free medium. Vanilloids displayed similar patterns of Ca2+ 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 Ca2+ response was not affected by 8-bromo-cyclic ADP-ribose (8-Br-cADPR), the ryanodine receptor blocker, but was slightly attenuated by 1-[6-[17β-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-[β-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365), the blocker of receptor-gated and store-operated Ca2+ (SOC) channels, 2-aminoethyldiphenyl borate (2-APB), the blocker of D-myo-inositol 1,4,5-trisphospahte (IP3) receptor and Ca2+ influx, and by ruthenium red, a blocker of TRPV channels, and enhanced by the Ca2+ channels blocker, cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL-12330A) and Na+-deprivation. In addition, capsaicin had no effect on the plasma membrane Ca2+-ATPase activity or the production of nitric oxide (NO) and reactive oxygen intermediates (ROI) or on the total thiols content. Capsaicin (≥100 μM) inhibited the cyclopiazonic acid (CPA)-induced store-operated Ca2+ entry (SOCE). In the absence of external Ca2+, the robust Ca2+ entry after subsequent addition of Ca2+ 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 activates a TRPV1-independent non-SOCE pathway in neutrophils. The reorganization of the actin cytoskeleton is

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

    Directory of Open Access Journals (Sweden)

    Esmaeal Tamaddonfard

    2015-08-01

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

  6. Tolerability of NGX-4010, a capsaicin 8% patch for peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Peppin JF

    2011-11-01

    Full Text Available John F Peppin1, Kristine Majors2, Lynn R Webster3, David M Simpson4, Jeffrey K Tobias5, Geertrui F Vanhove51The Pain Treatment Center of the Bluegrass, Lexington, KY, USA; 2Integrated Clinical Trial Services, Inc, West Des Moines, IA, USA; 3Lifetree Clinical Research and Pain Clinic, Salt Lake City, UT, USA; 4Mount Sinai Medical Center, New York, NY, USA; 5NeurogesX, Inc, San Mateo, CA, USABackground/purpose: NGX-4010 (QUTENZA™; NeurogesX Inc, San Mateo, CA, a capsaicin 8% dermal patch, is licensed in the European Union for the treatment of peripheral neuropathic pain (PNP in nondiabetic adults and in the United States for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN. While NGX-4010 treatment is associated with a low risk of systemic adverse events, patch application-related pain is common and may be managed with local cooling and/or oral analgesics. This article characterizes the tolerability of NGX-4010 and will help to guide any pain management.Methods: This integrated analysis of tolerability data collected from the NGX-4010 clinical study program included 1696 patients with PNP. Patch application-related pain on the treatment day was captured as Numeric Pain Rating Scale (NPRS “pain now” scores while “average pain for the past 24 hours” NPRS scores were analyzed for 7 days following treatment. Other tolerability assessments included the percentage of patients completing ≥90% of the intended treatment duration and patients using medication for patch application-related pain.Results: The mean maximum change in “pain now” NPRS scores from pretreatment levels during and after patch application was 2.6 for all patients. This pain was transient and resolved following patch removal. Mean “average pain for the past 24 hours” NPRS scores returned to baseline by the evening of the treatment day for patients with PHN, and the evening of day 2 for patients with human immunodeficiency virus

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

    Science.gov (United States)

    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

  8. Involvement of capsaicin-sensitive afferent nerves in the proteinase-activated receptor 2-mediated vasodilatation in the rat dura mater.

    Science.gov (United States)

    Dux, M; Rosta, J; Sántha, P; Jancsó, G

    2009-07-01

    Neurogenic inflammation of the dura mater encephali has been suggested to contribute to the mechanisms of meningeal nociception and blood flow regulation. Recent findings demonstrated that the rat dura mater is innervated by trigeminal capsaicin-sensitive peptidergic nociceptive afferent nerves which mediate meningeal vascular responses through activation of the transient receptor potential vanilloid type 1 (TRPV1) receptor. The present work explored the functional significance of the capsaicin-sensitive subpopulation of dural afferent nerves via their contribution to the meningeal vascular responses evoked through activation of the proteinase-activated receptor 2 (PAR-2). The vascular responses of the dura mater were studied by laser Doppler flowmetry in a rat open cranial window preparation. Topical applications of trypsin, a PAR-2-activator, or Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-NH(2)), a selective PAR-2 agonist peptide, resulted in dose-dependent increases in meningeal blood flow. The SLIGRL-NH(2)-induced vasodilatation was significantly reduced following capsaicin-sensitive afferent nerve defunctionalization by prior systemic capsaicin treatment and by pretreatment of the dura mater with the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37). Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME) an unspecific inhibitor of nitric oxide (NO) production, but not 1-(2-trifluoromethylphenyl) imidazole (TRIM), a neuronal NO synthase inhibitor, also inhibited the vasodilator response to SLIGRL-NH(2). The vasodilator responses elicited by very low concentrations of capsaicin (10 nM) were significantly enhanced by prior application of SLIGRL-NH(2). The present findings demonstrate that activation of the PAR-2 localized on capsaicin-sensitive trigeminal nociceptive afferent nerves induces vasodilatation in the dural vascular bed by mechanisms involving NO and CGRP release. The results indicate that the PAR-2-mediated activation and

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

    Directory of Open Access Journals (Sweden)

    Talbot Sébastien

    2012-01-01

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

  10. Liposomal topical capsaicin in post-herpetic neuralgia: a safety pilot study

    Directory of Open Access Journals (Sweden)

    Manoel Jacobsen Teixeira

    2015-03-01

    Full Text Available Topical treatments have gained popularity for general use as an adjunct to systemic drugs in neuropathic pain, but their use produces variable clinical results and local adverse events. Objective To evaluate the safety and analgesic effect of a formulation of liposomal capsaicin (LC (0.025% in patients with post herpetic neuralgia (PHN. Method Patients who remained symptomatic after first-and second-line treatment were randomized to receive LC for six weeks in a placebo-controlled, crossover design study. Clinical assessment was performed at baseline, in the second, fourth and sixth week of treatment. Results Thirteen patients completed both treatment periods. Visual Analog Scale (VAS was significantly decreased after the end of the study (p = 0.008, however the effect of treatment was not significant (p = 0.076. There was no difference on global impression of change and other pain characteristics. LC was safe and well tolerated. However, at the concentration used, its analgesic effects were marginal and not significant.

  11. Development of Organogel-Derived Capsaicin Nanoemulsion with Improved Bioaccessibility and Reduced Gastric Mucosa Irritation.

    Science.gov (United States)

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

    2016-06-15

    Capsaicin (CAP) is the major active component in chili peppers with health-promoting benefits. However, the low bioavailability and irritating quality of CAP greatly limit its applications in functional foods. The objective of this study was to develop a food-grade nanoemulsion to increase the dissolution and bioaccessibility of CAP and to alleviate its irritating effects. To achieve this goal, CAP was first dissolved in medium-chain triacylglycerol (MCT), followed by the addition of sucrose stearate S-370 as organogelator to develop CAP-loaded organogel. The oil-in-water (O/W) emulsion was formed using organogel as the oil phase and Tween 80 as the emulsifier. After ultrasonication treatment, droplet sizes of emulsion were decreased to 168 nm with enhanced dissolution rate and bioaccessibility. In vivo study further confirmed the reduced rat gastric mucosa irritation caused by CAP. The organogel-derived nanoemulsion was proved to be an effective delivery system for CAP-based functional food products. PMID:27170269

  12. Central pain mechanisms following combined acid and capsaicin perfusion of the human oesophagus.

    Science.gov (United States)

    Brock, Christina; Andresen, Trine; Frøkjaer, Jens Brøndum; Gale, Jeremy; Olesen, Anne Estrup; Arendt-Nielsen, Lars; Drewes, Asbjørn Mohr

    2010-03-01

    Visceral afferents originating from different gut-segments converge at the spinal level. We hypothesized that chemically-induced hyperalgesia in the oesophagus could provoke widespread visceral hypersensitivity and also influence descending modulatory pain pathways. Fifteen healthy volunteers were studied at baseline, 30, 60 and 90 min after randomized perfusion of the distal oesophagus with either saline or 180 ml 0.1M HCl+2mg capsaicin. Electro-stimulation of the oesophagus, 8 cm proximal to the perfusion site, rectosigmoid electrical stimulation and rectal mechanical and heat stimulations were used. Evoked brain potentials were recorded after electrical stimulations before and after oesophageal perfusion. After the perfusion, rectal hyperalgesia to heat (Pelectro-stimulation was observed in both the oesophagus (Pelectro-stimulation in oesophagus were reduced by 13% after perfusion (P=0.01). Evoked brain potentials to rectosigmoid stimulations showed decreased latencies and amplitudes of P1, N1 and P2 (P<0.05), whereas oesophagus-evoked brain potentials were unaffected after perfusion. In conclusion, modality-specific hyperalgesia was demonstrated in the lower gut following chemical sensitization of the oesophagus, reflecting widespread central hyperexcitability. Conversely, hypoalgesia to electrical stimulation, decreases in referred pain and latencies of evoked brain potentials was seen. This outcome may reflect a counterbalancing activation of descending inhibitory pathways. As these findings are also seen in the clinical setting, the model may be usable for future basic and pharmacological studies. PMID:19541517

  13. Application of Design Expert for the investigation of capsaicin-loaded microemulsions for transdermal delivery.

    Science.gov (United States)

    Duangjit, Sureewan; Chairat, Wisuta; Opanasopit, Praneet; Rojanarata, Theerasak; Ngawhirunpat, Tanasait

    2016-09-01

    Our previous study reported that the Design Expert® Software showed a beneficial role in the development of microemulsions (ME) for transdermal drug delivery. To fully confirm the reproducibility and the reliability of simultaneous optimal ME formulations, the optimal ME formulations predicted by the Design Expert® Software were experimentally formulated and verified for their skin permeability. Ternary phase diagrams were used to predict the optimal ME area, and the ME formulations selected from outside this area were considered as candidate ME systems. Our ME systems were formulated with isopropyl myristate (IPM) as the oil phase, cocamide diethanolamine (DEA) as the surfactant, ethanol as a co-surfactant and water as the aqueous phase. The droplet size, size distribution, electrical conductivity, pH, drug content and skin permeability of the candidate ME systems were monitored. Our findings indicated that the skin permeability of the optimal ME and all of the candidate ME formulations was significantly greater than that of the commercial capsaicin (CAP) product. Our study succeeded in predicting and developing the ME systems for the transdermal delivery of CAP. The simplex lattice design used in this study is experimentally useful for the development of pharmaceutical formulations. PMID:25996630

  14. The capsaicin receptor TRPV1 is a crucial mediator of the noxious effects of mustard oil.

    Science.gov (United States)

    Everaerts, Wouter; Gees, Maarten; Alpizar, Yeranddy A; Farre, Ricard; Leten, Cindy; Apetrei, Aurelia; Dewachter, Ilse; van Leuven, Fred; Vennekens, Rudi; De Ridder, Dirk; Nilius, Bernd; Voets, Thomas; Talavera, Karel

    2011-02-22

    Mustard oil (MO) is a plant-derived irritant that has been extensively used in experimental models to induce pain and inflammation. The noxious effects of MO are currently ascribed to specific activation of the cation channel TRPA1 in nociceptive neurons. In contrast to this view, we show here that the capsaicin receptor TRPV1 has a surprisingly large contribution to aversive and pain responses and visceral irritation induced by MO. Furthermore, we found that this can be explained by previously unknown properties of this compound. First, MO has a bimodal effect on TRPA1, producing current inhibition at millimolar concentrations. Second, it directly and stably activates mouse and human recombinant TRPV1, as well as TRPV1 channels in mouse sensory neurons. Finally, physiological temperatures enhance MO-induced TRPV1 stimulation. Our results refute the dogma that TRPA1 is the sole nocisensor for MO and motivate a revision of the putative roles of these channels in models of MO-induced pain and inflammation. We propose that TRPV1 has a generalized role in the detection of irritant botanical defensive traits and in the coevolution of multiple mammalian and plant species. PMID:21315593

  15. The role of nitric oxide in the phosphorylation of cyclic adenosine monophosphate-responsive element-binding protein in the spinal cord after intradermal injection of capsaicin.

    Science.gov (United States)

    Wu, Jing; Fang, Li; Lin, Qing; Willis, William D

    2002-06-01

    We investigated the involvement of nitric oxide (NO) in the phosphorylation of cyclic adenosine monophosphate-responsive element-binding protein (CREB) in the spinal cord of rats during central sensitization after intradermal capsaicin injection. CREB and phosphorylated CREB (p-CREB) were measured by immunoblotting. The level of p-CREB increased by 20 minutes, peaked between 20 and 60 minutes after capsaicin injection, and started to decrease after 150 minutes. CREB itself did not show an obvious change after capsaicin injection. The p-CREB expression on the ipsilateral side of the spinal dorsal horn, but not on the contralateral side, increased significantly after capsaicin injection. The increase in p-CREB induced by capsaicin injection was partially blocked by pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, administered through a microdialysis fiber placed across the spinal cord. D-NAME, an inactive form of L-NAME, had no effect. CREB phosphorylation, not the level of CREB, was induced within 20 minutes by microdialysis administration of SIN-1, an NO donor. These results indicate that CREB phosphorylation in the spinal cord results from both endogenous and exogenous NO release and that p-CREB may play a role in central sensitization or in longer-term changes in gene expression induced by strong peripheral noxious stimulation. PMID:14622772

  16. Effect of capsaicin on the health of gastrointestinal tract%辣椒素对胃肠道健康的影响

    Institute of Scientific and Technical Information of China (English)

    苏昕峰; 文红丽; 刘雄

    2011-01-01

    As an important spice, the hot pepper has the important physiological function for human. The "hot" mainly dues to capsaicin in the hot pepper. Capsaicin has broad pharmacological effects, lots of researches has been made to explore the effects of capsaicin to the health of gastrointestinal. In order to make better use of capsaicin,this paper summarized the effects that made by capsaicin to gastrointestinal and their mechanisms.%辣椒是重要的香辛料,对人体有重要的生理作用.辣椒主要的辛辣成分是辣椒素,辣椒素药理作用广泛,国内外开展了大量关于辣椒素对胃肠道健康作用方面的研究.本文就辣椒素对胃肠道健康的影响及其机制进行了综述,以期为辣椒素的科学利用提供参考.

  17. Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.

    Science.gov (United States)

    Joe, Bina; Nagaraju, Anitha; Gowda, Lalitha R; Basrur, Venkatesha; Lokesh, Belur R

    2014-01-01

    Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I. PMID:25299597

  18. Effect of gibberellin, auxin and kinetin treatments combined with foliar applied NPK on the yield of Capsicum annuum L. fruits and their capsaicin content

    Directory of Open Access Journals (Sweden)

    Tomasz J. Nowak

    2013-12-01

    Full Text Available The Wrocław version of hydroponic culture was applied. Under optimal conditions of root fertilization the plants were sprayed with growth regulators sueh as gibberellins, auxins and kinetins, and .their mixtures. Each growth regulator treatment was applied with or without NPK added. The influence of these treatments on the fresh and dry weight of the fruit, percentage of ripe fruits and content and yield of capsaicin was studied. The highest yield of fruits and capsaicin. was obtained from plants sprayed with gibberellic acid and kinetin (in concentrations of 10 and 5 mg/l, respectively together with NPK foliar application. No influence of ,growth regulators and foliar-applied NPK was noted on capsaicin content and dry weight of fruits.

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

    Science.gov (United States)

    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

  20. Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-κB translocation and ROS production in synoviocytes

    International Nuclear Information System (INIS)

    Highlights: ► Moderate extracellular acidification regulates intracellular Ca2+ mobilization. ► Moderate acidification activates NF-κB nuclear translocation in synoviocytes. ► Moderate acidification depresses the ROS production induced by capsaicin. ► 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 Ca2+ 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 Ca2+ entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca2+ release from intracellular stores. The nuclear translocation of NF-κB 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-κB. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca2+ mobilization, activating NF-κB nuclear translocation and depressing ROS production.

  1. Phα1β toxin prevents capsaicin-induced nociceptive behavior and mechanical hypersensitivity without acting on TRPV1 channels.

    Science.gov (United States)

    Castro-Junior, Celio J; Milano, Julie; Souza, Alessandra H; Silva, Juliana F; Rigo, Flávia K; Dalmolin, Geruza; Cordeiro, Marta N; Richardson, Michael; Barros, Alexandre G A; Gomez, Renato S; Silva, Marco A R; Kushmerick, Christopher; Ferreira, Juliano; Gomez, Marcus V

    2013-08-01

    Phα1β toxin is a peptide purified from the venom of the armed spider Phoneutria nigriventer, with markedly antinociceptive action in models of acute and persistent pain in rats. Similarly to ziconotide, its analgesic action is related to inhibition of high voltage activated calcium channels with more selectivity for N-type. In this study we evaluated the effect of Phα1β when injected peripherally or intrathecally in a rat model of spontaneous pain induced by capsaicin. We also investigated the effect of Phα1β on Ca²⁺ transients in cultured dorsal root ganglia (DRG) neurons and HEK293 cells expressing the TRPV1 receptor. Intraplantar or intrathecal administered Phα1β reduced both nocifensive behavior and mechanical hypersensitivity induced by capsaicin similarly to that observed with SB366791, a specific TRPV1 antagonist. Peripheral nifedipine and mibefradil did also decrease nociceptive behavior induced by intraplantar capsaicin. In contrast, ω-conotoxin MVIIA (a selective N-type Ca²⁺ channel blocker) was effective only when administered intrathecally. Phα1β, MVIIA and SB366791 inhibited, with similar potency, the capsaicin-induced Ca²⁺ transients in DRG neurons. The simultaneous administration of Phα1β and SB366791 inhibited the capsaicin-induced Ca²⁺ transients that were additive suggesting that they act through different targets. Moreover, Phα1β did not inhibit capsaicin-activated currents in patch-clamp recordings of HEK293 cells that expressed TRPV1 receptors. Our results show that Phα1β may be effective as a therapeutic strategy for pain and this effect is not related to the inhibition of TRPV1 receptors. PMID:23597507

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-20

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

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

    Institute of Scientific and Technical Information of China (English)

    Kazuhiro Fukushima; Yoko Aoi; Shinichi Kato; Koji Takeuchi

    2006-01-01

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

  4. Chronic alteration in phosphatidylinositol 4,5-biphosphate levels regulates capsaicin and mustard oil responses.

    Science.gov (United States)

    Patil, Mayur J; Belugin, Sergei; Akopian, Armen N

    2011-06-01

    There is an agreement that acute (in minutes) hydrolysis and accumulation of phosphatidylinositol 4,5-bisphosphate (PIP(2) ) modulate TRPV1 and TRPA1 activities. Because inflammation results in PIP(2) depletion, persisting for long periods (hours to days) in pain models and in the clinic, we examined whether chronic depletion and accumulation of PIP(2) affect capsaicin (CAP) and mustard oil (MO) responses. In addition, we wanted to evaluate whether the effects of PIP(2) depend on TRPV1 and TRPA1 coexpression and whether the PIP(2) actions vary in expression cells vs. sensory neurons. Chronic PIP(2) production was stimulated by overexpression of phosphatidylinositol-4-phosphate-5-kinase, and PIP(2) -specific phospholipid 5'-phosphatase was selected to reduce plasma membrane levels of PIP(2) . Our results demonstrate that CAP (100 nM) responses and receptor tachyphylaxis are not significantly influenced by chronic changes in PIP(2) levels in wild-type (WT) or TRPA1 null-mutant sensory neurons as well as CHO cells expressing TRPV1 alone or with TRPA1. However, low concentrations of CAP (20 nM) produced a higher response after PIP(2) depletion in cells containing TRPV1 alone but not TRPV1 together with TRPA1. MO (25 μM) responses were also not affected by PIP(2) in WT sensory neurons and cells coexpressing TRPA1 and TRPV1. In contrast, PIP(2) reduction leads to pronounced tachyphylaxis to MO in cells with both channels. Chronic effect of PIP(2) on TRPA1 activity depends on presence of the TRPV1 channel and cell type (CHO vs. sensory neurons). In summary, chronic alterations in PIP(2) levels regulate magnitude of CAP and MO responses as well as MO tachyphylaxis. This regulation depends on coexpression profile of TRPA1 and TRPV1 and cell type. PMID:21337373

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    GABA-A receptor positive allosteric modulators (PAMs) mediate robust analgesia in animal models of pathological pain, in part via enhancing injury-induced loss of GABA-A-α2 and -α3 receptor function within the spinal cord. As yet, a lack of clinically suitable tool compounds has prevented this...... concept being tested in humans. Prior to assessing the efficacy of GABA-A receptor PAMs in a human volunteer pain model we have compared compounds capable of variously modulating GABA-A receptor function in comparable rat models of capsaicin-induced acute nocifensive flinching behaviour and secondary...

  6. Simultaneous Determination of Piperine, Capsaicin, and Dihydrocapsaicin in Korean Instant-Noodle (Ramyun) Soup Base Using High-Performance Liquid Chromatography with Ultraviolet Detection.

    Science.gov (United States)

    Shim, You-Shin; Kim, Jong-Chan; Jeong, Seung-Weon

    2016-01-01

    A simultaneous analytical method for piperine, capsaicin, and dihydrocapsaicin in Korean instant-noodle soup base using HPLC was validated in terms of precision, accuracy, sensitivity, and linearity. The HPLC separation was performed on a reversed-phase C18 column (5 μm particle size, 4.6 mm id, 250 mm length) using a UV detector fixed at 280 nm. The LOD and LOQ of the HPLC analyses ranged from 0.25 to 1.03 mg/kg. The intraday and interday precisions of the individual piperine, capsaicin, and dihydrocapsaicin were noodles based on their levels of spiciness. PMID:26822681

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

    Directory of Open Access Journals (Sweden)

    Abu Bakar Ali Asad

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

  8. Roles of TRPV1 and neuropeptidergic receptors in dorsal root reflex-mediated neurogenic inflammation induced by intradermal injection of capsaicin

    Directory of Open Access Journals (Sweden)

    Zou Xiaoju

    2007-10-01

    Full Text Available Abstract Background Acute cutaneous neurogenic inflammation initiated by activation of transient receptor potential vanilloid-1 (TRPV1 receptors following intradermal injection of capsaicin is mediated mainly by dorsal root reflexes (DRRs. Inflammatory neuropeptides are suggested to be released from primary afferent nociceptors participating in inflammation. However, no direct evidence demonstrates that the release of inflammatory substances is due to the triggering of DRRs and how activation of TRPV1 receptors initiates neurogenic inflammation via triggering DRRs. Results Here we used pharmacological manipulations to analyze the roles of TRPV1 and neuropeptidergic receptors in the DRR-mediated neurogenic inflammation induced by intradermal injection of capsaicin. The degree of cutaneous inflammation in the hindpaw that followed capsaicin injection was assessed by measurements of local blood flow (vasodilation and paw-thickness (edema of the foot skin in anesthetized rats. Local injection of capsaicin, calcitonin gene-related peptide (CGRP or substance P (SP resulted in cutaneous vasodilation and edema. Removal of DRRs by either spinal dorsal rhizotomy or intrathecal administration of the GABAA receptor antagonist, bicuculline, reduced dramatically the capsaicin-induced vasodilation and edema. In contrast, CGRP- or SP-induced inflammation was not significantly affected after DRR removal. Dose-response analysis of the antagonistic effect of the TRPV1 receptor antagonist, capsazepine administered peripherally, shows that the capsaicin-evoked inflammation was inhibited in a dose-dependent manner, and nearly completely abolished by capsazepine at doses between 30–150 μg. In contrast, pretreatment of the periphery with different doses of CGRP8–37 (a CGRP receptor antagonist or spantide I (a neurokinin 1 receptor antagonist only reduced the inflammation. If both CGRP and NK1 receptors were blocked by co-administration of CGRP8–37 and spantide I

  9. Capsaicin from chili (Capsicum spp. inhibits vascular smooth muscle cell proliferation [v1; ref status: indexed, http://f1000r.es/4yk

    Directory of Open Access Journals (Sweden)

    Rongxia Liu

    2015-01-01

    Full Text Available Accelerated vascular smooth muscle cell (VSMC proliferation is implied in cardiovascular disease and significantly contributes to vessel lumen reduction following surgical interventions such as percutaneous transluminal coronary angioplasty or bypass surgery. Therefore, identification and characterization of compounds and mechanisms able to counteract VSMC proliferation is of potential therapeutic relevance. This work reveals the anti-proliferative effect of the natural product capsaicin from Capsicum spp. by quantification of metabolic activity and DNA synthesis in activated VSMC. The observed in vitro activity profile of capsaicin warrants further research on its mechanism of action and potential for therapeutic application.

  10. The effect of wound instillation of a novel purified capsaicin formulation on postherniotomy pain: A double-blind, randomized, placebo-controlled study

    DEFF Research Database (Denmark)

    Aasvang, Eske Kvanner; Hansen, J.B.; Malmstrom, J.;

    2008-01-01

    BACKGROUND: Acute postoperative pain is common after most surgical procedures. Despite the availability of many analgesic options, postoperative pain management is often unsatisfactory. Purified capsaicin (ALGRX 4975 98% pure) has demonstrated prolong inhibition of C-fiber function in in vitro......, preclinical, and clinical studies, and may be an effective adjunct to postoperative pain management. METHODS: We performed a single-center, randomized, double-blind, placebo-controlled study of the analgesic efficacy of a single intraoperative wound instillation of 1000 mu g ultrapurified capsaicin (ALGRX...

  11. Sputtering effect of low-energy ions on biological target: The analysis of sputtering product of urea and capsaicin

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Lili [Key Laboratory of Ion Beam Bio-Engineering, Institute of Technical Biology and Agriculture Engineering of Chinese Academy of Sciences, Shushanhu Road 350, Hefei 230031 (China); Xu, Xue [Rice Research Institute, Anhui Academy of Agricultural Sciences, Nongke South Road 40, Hefei 230031 (China); Wu, Yuejin, E-mail: yjwu@ipp.ac.cn [Key Laboratory of Ion Beam Bio-Engineering, Institute of Technical Biology and Agriculture Engineering of Chinese Academy of Sciences, Shushanhu Road 350, Hefei 230031 (China)

    2013-08-01

    Sputtering is a process whereby atoms are ejected from a solid target material due to bombardment of the target by energetic particles. Recent years, ion implantation was successfully applied to biological research based on the fragments sputtering and form open paths in cell structure caused by ion sputtering. In this study, we focused on urea and chilli pepper pericarp samples implanted with N{sup +} and Ar{sup +} ions. To investigate the sputtering effect, we designed a collecting unit containing a disk sample and a glass pipe. The urea content and capsaicin content recovered from glass pipes were adopted to represent the sputtering product. The result of urea showed that the sputtering effect is positively correlated with the ion energy and dose, also affected by the ion type. The result of capsaicin was different from that of urea at 20 keV and possibly due to biological complex composition and structure. Therefore the sputtering yield depended on both the parameters of incident ions and the state of target materials. The sputtering yield of urea was also simulated by computational method achieved through the TRIM program. The trajectories of primary and recoiled atoms were calculated on the basis of the binary collision approximation using Monte Carlo method. The experimental results were much higher than the calculated results. The possible explanation is that in the physical model the target were assumed as a disordered lattice and independent atoms, which is much less complicated than that of the biological models.

  12. Sputtering effect of low-energy ions on biological target: The analysis of sputtering product of urea and capsaicin

    Science.gov (United States)

    Zhang, Lili; Xu, Xue; Wu, Yuejin

    2013-08-01

    Sputtering is a process whereby atoms are ejected from a solid target material due to bombardment of the target by energetic particles. Recent years, ion implantation was successfully applied to biological research based on the fragments sputtering and form open paths in cell structure caused by ion sputtering. In this study, we focused on urea and chilli pepper pericarp samples implanted with N+ and Ar+ ions. To investigate the sputtering effect, we designed a collecting unit containing a disk sample and a glass pipe. The urea content and capsaicin content recovered from glass pipes were adopted to represent the sputtering product. The result of urea showed that the sputtering effect is positively correlated with the ion energy and dose, also affected by the ion type. The result of capsaicin was different from that of urea at 20 keV and possibly due to biological complex composition and structure. Therefore the sputtering yield depended on both the parameters of incident ions and the state of target materials. The sputtering yield of urea was also simulated by computational method achieved through the TRIM program. The trajectories of primary and recoiled atoms were calculated on the basis of the binary collision approximation using Monte Carlo method. The experimental results were much higher than the calculated results. The possible explanation is that in the physical model the target were assumed as a disordered lattice and independent atoms, which is much less complicated than that of the biological models.

  13. Sputtering effect of low-energy ions on biological target: The analysis of sputtering product of urea and capsaicin

    International Nuclear Information System (INIS)

    Sputtering is a process whereby atoms are ejected from a solid target material due to bombardment of the target by energetic particles. Recent years, ion implantation was successfully applied to biological research based on the fragments sputtering and form open paths in cell structure caused by ion sputtering. In this study, we focused on urea and chilli pepper pericarp samples implanted with N+ and Ar+ ions. To investigate the sputtering effect, we designed a collecting unit containing a disk sample and a glass pipe. The urea content and capsaicin content recovered from glass pipes were adopted to represent the sputtering product. The result of urea showed that the sputtering effect is positively correlated with the ion energy and dose, also affected by the ion type. The result of capsaicin was different from that of urea at 20 keV and possibly due to biological complex composition and structure. Therefore the sputtering yield depended on both the parameters of incident ions and the state of target materials. The sputtering yield of urea was also simulated by computational method achieved through the TRIM program. The trajectories of primary and recoiled atoms were calculated on the basis of the binary collision approximation using Monte Carlo method. The experimental results were much higher than the calculated results. The possible explanation is that in the physical model the target were assumed as a disordered lattice and independent atoms, which is much less complicated than that of the biological models

  14. The effect of dietary curcumin and capsaicin on hepatic fetuin-A expression and fat accumulation in rats fed on a high-fat diet.

    Science.gov (United States)

    Seyithanoğlu, Muhammed; Öner-İyidoğan, Yıldız; Doğru-Abbasoğlu, Semra; Tanrıkulu-Küçük, Sevda; Koçak, Hikmet; Beyhan-Özdaş, Şule; Koçak-Toker, Necla

    2016-05-01

    Effects of curcumin (turmeric) and capsaicin (red pepper) on hepatic fat accumulation and fetuin-A expression in rats fed high-fat diet (HFD) is aimed to be investigated. Male Sprague-Dawley rats received HFD (60% of total calories from fat) and 0.15 g capsaicin/kg HFD and/or 1.5 g curcumin/kg HFD for 16 weeks. Hepatic AMPK, p-AMPK and fetuin-A expressions were determined by western blotting, liver lipid levels were measured with colorimetric methods and serum fetuin-A, insulin, leptin and adiponectin levels were detected using commercial ELISA kits. HFD increased hepatic lipid levels, fetuin-A expression and serum leptin, insülin and fetuin-A levels. Curcumin and capsaicin treatments significantly reduced hepatic fat accumulation and leptin levels; liver fetuin-A expression was decreased significantly by the curcumin treatment. Curcumin and capsaicin treatments attenuated hepatic fat accumulation and increased leptin levels related to inflammation. The suppression of hepatic fetuin-A expression is observed to be especially sensitive to curcumin. PMID:26706937

  15. Tolerability of the capsaicin 8% patch following pretreatment with lidocaine or tramadol in patients with peripheral neuropathic pain: A multicentre, randomized, assessor-blinded study

    NARCIS (Netherlands)

    Jensen, T.S.; Hoye, K.; Fricova, J.; Vanelderen, P.J.L.; Ernault, E.; Siciliano, T.; Marques, S.

    2014-01-01

    BACKGROUND: Application of the capsaicin 8% patch is associated with treatment-related discomfort. Consequently, pretreatment for 60 min with anaesthetic cream is recommended; however, this may be uncomfortable and time consuming. METHODS: We conducted a multicentre, randomized (1:1), assessor-blind

  16. Cost-Effectiveness of Capsaicin 8% Patch Compared with Pregabalin for the Treatment of Patients with Peripheral Neuropathic Pain in Scotland

    Science.gov (United States)

    Mankowski, Colette; Patel, Sachin; Trueman, David; Bentley, Anthony; Poole, Chris

    2016-01-01

    We evaluated the cost-effectiveness of capsaicin 8% patch (QUTENZA™) versus pregabalin in patients with PNP from the perspective of the National Health Service (NHS) and Personal and Social Services in Scotland, UK. A decision-tree cost-effectiveness model was developed for non-diabetic patients with peripheral neuropathic pain (PNP) who were pregabalin-naïve and had not achieved adequate pain relief or tolerated conventional first- or second-line treatments. Patients entering the model received either a single application of capsaicin 8% patch or titrated daily dosing with pregabalin; after 8 weeks patients were classified as responders, non-responders, or were assumed to discontinue treatment due to intolerable adverse events. Responders continued to receive baseline treatment at intervals observed in clinical practice. Non-responders and those who discontinued treatment were assumed to receive last-line therapy (duloxetine). The base-case time horizon was 2 years. Model inputs for effectiveness, discontinuations and health-state utilities were taken from a head-to-head non-inferiority study (ELEVATE, NCT01713426). Other inputs were obtained from published sources or clinical expert opinion. Costs were expressed in GBP 2013/14. Results were presented as incremental cost-effectiveness ratios (ICER), i.e. cost per quality-adjusted life-year (QALY) gained. Model assumptions were tested with scenario analyses. Parameter uncertainty was tested using one-way and probabilistic sensitivity analyses. Compared with dose-optimized pregabalin, capsaicin 8% patch was the dominant treatment strategy (total cost difference, –£11; total QALY gain, 0.049). Capsaicin 8% patch was also the dominant treatment strategy versus pregabalin in 6 out of 7 scenario analyses. The model was most sensitive to variation in time to capsaicin 8% patch retreatment (maximum ICER, £7,951/QALY at lower-bound 95% confidence interval). At a willingness-to-pay threshold of £20,000/QALY, the

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

    Science.gov (United States)

    Ferreira, Adilson Kleber; Tavares, Maurício Temotheo; Pasqualoto, Kerly Fernanda Mesquita; de Azevedo, Ricardo Alexandre; Teixeira, Sarah Fernandes; Ferreira-Junior, Wilson Alves; Bertin, Ariane Matiello; de-Sá-Junior, Paulo Luiz; Barbuto, José Alexandre Marzagão; Figueiredo, Carlos Rogério; Cury, Yara; Damião, Mariana Celestina Frojuello Costa Bernstorff; Parise-Filho, Roberto

    2015-09-01

    Capsaicin, the primary pungent component of the chili pepper, has antitumor activity. Herein, we describe the activity of RPF151, an alkyl sulfonamide analogue of capsaicin, against MDA-MB-231 breast cancer cells. RPF151 was synthetized, and molecular modeling was used to compare capsaicin and RPF151. Cytotoxicity of RPF151 on MDA-MB-231 was also evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis, by flow cytometry, and Western blot analysis of cycle-related proteins were used to evaluate the antiproliferative mechanisms. Apoptosis was evaluated by phosphatidyl-serine externalization, cleavage of Ac-YVAD-AMC, and Bcl-2 expression. The production of reactive oxygen species was evaluated by flow cytometry. RPF151 in vivo antitumor effects were investigated in murine MDA-MB-231 model. This study shows that RPF151 downregulated p21 and cyclins A, D1, and D3, leading to S-phase arrest and apoptosis. Although RPF151 has induced the activation of TRPV-1 and TRAIL-R1/DR4 and TRAIL-2/DR5 on the surface of MDA-MB-231 cells, its in vivo antitumor activity was TRPV-1-independent, thus suggesting that RPF151 should not have the same pungency-based limitation of capsaicin. In silico analysis corroborated the biological findings, showing that RPF151 has physicochemical improvements over capsaicin. Overall, the activity of RPF151 against MDA-MB-231 and its lower pungency suggest that it may have a relevant role in cancer therapy. PMID:25894379

  18. The μ opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway

    Directory of Open Access Journals (Sweden)

    Roberts-Thomson Sarah J

    2006-07-01

    Full Text Available Abstract Background The vanilloid receptor 1 (TRPV1 is critical in the development of inflammatory hyperalgesia. Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA pathway to potentiate TRPV1-mediated capsaicin responses. Such regulation may have significance in inflammatory pain. However, few functional receptor interactions that inhibit PKA-mediated potentiation of TRPV1 responses have been described. Results In the present studies we investigated the hypothesis that the μ opioid receptor (MOP agonist morphine can modulate forskolin-potentiated capsaicin responses through a cAMP-dependent PKA pathway. HEK293 cells were stably transfected with TRPV1 and MOP, and calcium (Ca2+ responses to injection of the TRPV1 agonist capsaicin were monitored in Fluo-3-loaded cells. Pre-treatment with morphine did not inhibit unpotentiated capsaicin-induced Ca2+ responses but significantly altered capsaicin responses potentiated by forskolin. TRPV1-mediated Ca2+ responses potentiated by the direct PKA activator 8-Br-cAMP and the PKC activator Phorbol-12-myristate-13-acetatewere not modulated by morphine. Immunohistochemical studies confirmed that the TRPV1 and MOP are co-expressed on cultured Dorsal Root Ganglion neurones, pointing towards the existence of a functional relationship between the G-protein coupled MOP and nociceptive TRPV1. Conclusion The results presented here indicate that the opioid receptor agonist morphine acts via inhibition of adenylate cyclase to inhibit PKA-potentiated TRPV1 responses. Targeting of peripheral opioid receptors may therefore have therapeutic potential as an intervention to prevent potentiation of TRPV1 responses through the PKA pathway in inflammation.

  19. Capsaicin increases sensation of fullness in energy balance, and decreases desire to eat after dinner in negative energy balance.

    Science.gov (United States)

    Janssens, Pilou L H R; Hursel, Rick; Westerterp-Plantenga, Margriet S

    2014-06-01

    Addition of capsaicin (CAPS) to the diet has been shown to increase satiety; therefore, CAPS is of interest for anti-obesity therapy. We investigated the effects of CAPS on appetite profile and ad libitum energy intake in relation to energy balance. Fifteen subjects (seven women and eight men, age: 29.7 ± 10.8yrs, BMI: 23.3 ± 2.9 kg/m(2)) underwent four conditions in a randomized crossover design in 36 hour sessions in a respiration chamber; they received 100% of their daily energy requirements in the conditions "100%Control" and "100%CAPS", and 75% of their daily energy requirements in the conditions "75%Control" and "75%CAPS", followed by an ad libitum dinner. In the 100%CAPS and 75%CAPS conditions, CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units) with every meal. Satiety (P < 0.05) and fullness (P = 0.01) were measured every waking hour and before and after every meal using visual analogue scales, and were higher in the 100%CAPS versus 100%Control condition. After dinner desire to eat, satiety and fullness did not differ between 75%CAPS and 100%Control, while desire to eat was higher (P < 0.05) and satiety (P = 0.06) and fullness (P = 0.06) tended to be lower in the 75%Control versus 100%Control condition. Furthermore, ad libitum intake (P = 0.07) and overconsumption (P = 0.06) tended to decrease in 100%CAPS versus 100%Control. In energy balance, addition of capsaicin to the diet increases satiety and fullness, and tends to prevent overeating when food intake is ad libitum. After dinner, capsaicin prevents the effects of the negative energy balance on desire to eat. PMID:24630935

  20. Capsaicin on the viability of random-pattern skin flaps in rats Capsaicina na viabilidade de retalhos isquêmicos randômicos em ratos

    Directory of Open Access Journals (Sweden)

    Gustavo Roberto de Godoy

    2010-10-01

    Full Text Available PURPOSE: To evaluate the effects of capsaicin on the viability of ischemic random-pattern skin flaps in rats. METHODS:Forty EPM1-Wistar rats were randomized into two groups of 20 animals each, the capsaicin group and the control group. A random-pattern skin flap measuring 10 x 4cm was raised and a plastic barrier was placed between the flap and the donor site. After the surgical procedure, the control group was treated with an inert vehicle in the form of a cream applied uniformly to a rayon bandage which, in turn, was applied to the surface of the skin flap. The capsaicin group was treated in the same way, but in this case capsaicin was added to the cream. This procedure was repeated for two consecutive days. RESULTS: There was a significantly smaller amount of flap necrosis in the capsaicin group (35.07% than in the control group (44.75% (p=0.035. CONCLUSION:Topical administration of capsaicin improved the viability of ischemic random-pattern skin flaps in rats.OBJETIVO: Avaliar os efeitos da capsaicina na viabilidade de retalhos isquêmicos randômicos em ratos. MÉTODOS: Quarenta ratos EPM1-Wistar foram distribuídos ao acaso em dois grupos de 20 animais cada, um grupo capsaicina e um grupo controle. Um retalho isquêmico randômico medindo 10 x 4cm foi elevado e uma barreira plástica foi colocada entre o retalho e a área doadora. Após o procedimento cirúrgico, o grupo controle foi tratado com um veículo inerte sob a forma creme aplicado uniformemente sobre uma atadura de rayon, que, por sua vez, foi aplicada à superfície do retalho. O grupo capsaicina foi tratado da mesma forma, porém a capsaicina foi adicionada ao creme. Este procedimento foi repetido por dois dias consecutivos. RESULTADOS: Houve uma quantidade significativamente menor da necrose do retalho no grupo capsaicina (35,07% comparado ao grupo controle (44,75% (p=0,035. CONCLUSÃO: A administração tópica da capsaicina melhorou a viabilidade de retalhos isquêmicos rand

  1. Functional MRI brain imaging studies using the Contact Heat Evoked Potential Stimulator (CHEPS in a human volunteer topical capsaicin pain model

    Directory of Open Access Journals (Sweden)

    Shenoy R

    2011-10-01

    Full Text Available Ravikiran Shenoy1, Katherine Roberts1, Anastasia Papadaki2, Donald McRobbie2, Maarten Timmers3, Theo Meert3, Praveen Anand11Peripheral Neuropathy Unit, Hammersmith Hospital, Imperial College London; 2Imaging Sciences Department, Charing Cross Hospital, London, United Kingdom; 3Johnson and Johnson Pharmaceutical Research and Development, Beerse, BelgiumAbstract: Acute application of topical capsaicin produces spontaneous burning and stinging pain similar to that seen in some neuropathic states, with local hyperalgesia. Use of capsaicin applied topically or injected intradermally has been described as a model for neuropathic pain, with patterns of activation in brain regions assessed using functional magnetic resonance imaging (fMRI and positron emission tomography. The Contact Heat Evoked Potential Stimulator (CHEPS is a noninvasive clinically practical method of stimulating cutaneous A-delta nociceptors. In this study, topical capsaicin (1% was applied to the left volar forearm for 15 minutes of twelve adult healthy human volunteers. fMRI scans and a visual analog pain score were recorded during CHEPS stimulation precapsaicin and postcapsaicin application. Following capsaicin application there was a significant increase in visual analog scale (mean ± standard error of the mean; precapsaicin 26.4 ± 5.3; postcapsaicin 48.9 ± 6.0; P < 0.0001. fMRI demonstrated an overall increase in areas of activation, with a significant increase in the contralateral insular signal (mean ± standard error of the mean; precapsaicin 0.434 ± 0.03; postcapsaicin 0.561 ± 0.07; P = 0.047. The authors of this paper recently published a study in which CHEPS-evoked A-delta cerebral potential amplitudes were found to be decreased postcapsaicin application. In patients with neuropathic pain, evoked pain and fMRI brain responses are typically increased, while A-delta evoked potential amplitudes are decreased. The protocol of recording fMRI following CHEPS stimulation

  2. Influence of increased doses of microelements in hydroponic nutrient solution on the yield of Capsicum annuum L. fruits and their capsaicin content

    Directory of Open Access Journals (Sweden)

    Tomasz J. Nowak

    2013-12-01

    Full Text Available The Wrocław version of hydroponic culture was applied. The content of particular microelements (Cu, B, Mn, Mo, Zn or several of them jointly was increased ten times (to 6 mg/l as compared to the standard composition of the nutrient solution. It was found that the yield of fruits and of capsaicin per plant was significantly higher with 10 times increased content of Cu and B or Cu+B+Mo or Cu+Mn+Mo or B+Mn+Mo. Moreover, Cu and Mn applied alone or in combinations with other microelements in 10-fold increased proportion caused a marked increase of capsaicin content in the dry matter of the fruit. It is suggested that the proportions of microelements should be chosen individually for each plant species and for each type of agroclimatic conditions

  3. Quantitative determination of capsaicin, a transient receptor potential channel vanilloid 1 agonist, by liquid chromatography quadrupole ion trap mass spectrometry: evaluation of in vitro metabolic stability.

    Science.gov (United States)

    Beaudry, Francis; Vachon, Pascal

    2009-02-01

    Capsaicin is the most abundant pungent molecule present in red peppers and it is widely used for food flavoring, in pepper spray in self-defense devices and more recently in ointments for the relief of neuropathic pain. Capsaicin is a selective agonist of transient receptor potential channel, vanilloid subfamily member 1. A selective and sensitive quantitative method for the determination of capsaicin by LC-ESI/MS/MS was developed. The method consisted of a protein precipitation extraction followed by analysis using liquid chromatography electrospray quadrupole ion trap mass spectrometry. The chromatographic separation was achieved using a 100 x 2 mm C(18) Waters Symmetry column combined with a gradient mobile phase composed of acetonitrile and 0.1% formic acid aqueous solution at a flow rate of 220 microL/min. The mass spectrometer was operating in full-scan MS/MS mode using two-segment analysis. An analytical range of 10-5000 ng/mL was used in the calibration curve constructed in rat plasma. The interbatch precision and accuracy observed were 6.5, 6.7, 5.3 and 101.2, 102.7, 103.5% at 50, 500 and 5000 ng/mL, respectively. An in vitro metabolic stability study was performed in rat, dog and mouse liver microsomes and the novel analytical method was adapted and used to determine intrinsic clearance of capsaicin. Results suggest very rapid degradation with T(1/2) ranging from 2.3 to 4.1 min and high clearance values suggesting that drug bioavailability will be considerably reduced, consequently affecting drug response and efficacy. PMID:18816461

  4. Determination of capsaicin, dihydrocapsaicin, and nonivamide in self-defense weapons by liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Reilly, C A; Crouc, D J; Yost, G S; Fatah, A A

    2001-04-01

    Sensitive and selective liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods for the analysis of capsaicin, dihydrocapsaicin, and nonivamide in pepper spray products have been developed. Chromatographic separation of the capsaicinoid analogues was achieved using a reversed-phase HPLC column and a stepwise gradient of methanol and distilled water containing 0.1% (v/v) formic acid. Identification and quantification of the capsaicinoids was achieved by electrospray ionization single-stage mass spectrometry monitoring the protonated molecules of the internal standard (m/z 280), capsaicin (m/z 306), dihydrocapsaicin (m/z 308), and nonivamide (m/z 294) or by tandem mass spectrometry monitoring the appropriate precursor-to-product-ion transitions. The plot of concentration versus peak area ratio was linear over the range of 10-750 ng/ml using LC-MS and 10-500 ng/ml using LC-MS-MS. However, to accurately quantify the capsaicinoids in the pepper spray products calibration curves between 10 and 1000 ng were constructed and fit using a weighted quadratic equation. Using the quadratic curve, the accuracy of the assay ranged from 91 to 102% for all analytes. The intra-assay precision (RSD) for capsaicin was 2% at 25 ng/ml, 10% at 500 ng/ml, and 3% at 800 ng/ml. The inter-assay precision (RSD) for capsaicin was 6% at 25 ng/ml, 6% at 500 ng/ml, and 9% at 800 ng/ml. Similar values for inter- and intra-assay precision were experimentally obtained for both dihydrocapsaicin and nonivamide. The analysis of selected pepper spray products demonstrated that the capsaicinoid concentration in the products ranged from 0.7 to 40.5 microg/microl. PMID:11330795

  5. Calcium-Dependent and Independent Mechanisms of Capsaicin Receptor (TRPV1)-Mediated Cytokine Production and Cell Death in Human Bronchial Epithelial Cells

    OpenAIRE

    Reilly, Christopher A.; Johansen, Mark E.; Lanza, Diane L.; Lee, Jeewoo; Lim, Ju-Ok; Yost, Garold S.

    2005-01-01

    Activation of the capsaicin receptor (VR1 or TRPV1) in bronchial epithelial cells by capsaicinoids and other vanilloids promotes pro-inflammatory cytokine production and cell death. The purpose of this study was to investigate the role of TRPV1-mediated calcium flux from extracellular sources as an initiator of these responses and to define additional cellular pathways that control cell death. TRPV1 antagonists and reduction of calcium concentrations in treatment solutions attenuated calcium ...

  6. Differential inhibitory effects of opioids on cigarette smoke, capsaicin and electrically-induced goblet cell secretion in guinea-pig trachea.

    OpenAIRE

    Kuo, H. P.; Rohde, J. A.; Barnes, P. J.; Rogers, D. F.

    1992-01-01

    1. Goblet cell secretion in guinea-pig airways is under neural control. Opioids have previously been shown to inhibit neurogenic plasma exudation and bronchoconstriction in guinea-pig airways. We have now examined the effects of morphine and opioid peptides on tracheal goblet cell secretion induced by either electrical stimulation of the cervical vagus nerves, exogenous capsaicin, or acute inhalation of cigarette smoke. The degree of goblet cell secretion was determined by a morphometric meth...

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

    OpenAIRE

    Giuseppe Spaziano; Livio Luongo; Francesca Guida; Stefania Petrosino; Maria Matteis; Enza Palazzo; Nikol Sullo; Vito de Novellis; Vincenzo Di Marzo; Francesco Rossi; Sabatino Maione; Bruno D’Agostino

    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 cha...

  8. Considerable Variability in the Efficacy of 8% Capsaicin Topical Patches in the Treatment of Chronic Pruritus in 3 Patients with Notalgia Paresthetica

    OpenAIRE

    Andersen, Hjalte Holm; Sand, Carsten; Elberling, Jesper

    2016-01-01

    Notalgia paresthetica (NP) is a focal neuropathic itch con- dition manifesting in intense chronic or recurrent episodic itch in a hyperpigmented, macular, uni- or bilateral skin area located below and/or medially to the scapulae. Achieving satisfactory relieve in NP patients is challenging. In this case-series three female NP patients were treated with 8% capsaicin patches following a spatial quantification of their alloknetic area with a von Frey filament. The use of a von Frey filament in o...

  9. Calcium-dependent desensitization of vanilloid receptor TRPV1: a mechanism possibly involved in analgesia induced by topical application of capsaicin

    Czech Academy of Sciences Publication Activity Database

    Vyklický st., Ladislav; Nováková-Toušová, Karolina; Benedikt, Jan; Samad, Abdul; Touška, Filip; Vlachová, Viktorie

    2008-01-01

    Roč. 57, Suppl.3 (2008), S59-S68. ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GA305/06/0319 Institutional research plan: CEZ:AV0Z50110509 Keywords : TRPV1 receptors * capsaicin * analgesia Subject RIV: ED - Physiology Impact factor: 1.653, year: 2008

  10. Topical delivery of anti-TNFα siRNA and capsaicin via novel lipid-polymer hybrid nanoparticles efficiently inhibits skin inflammation in vivo

    OpenAIRE

    Desai, Pinaki R.; Marepally, Srujan; Patel, Apurva R.; Voshavar, Chandrashekhar; Chaudhuri, Arabinda; Singh, Mandip

    2013-01-01

    The barrier properties of the skin pose a significant but not insurmountable obstacle for development of new effective anti-inflammatory therapies. The objective of this study was to design and evaluate therapeutic efficacy of anti-nociception agent Capsaicin (Cap) and anti-TNFα siRNA (siTNFα) encapsulated cyclic cationic head Lipid-Polymer hybrid Nanocarriers (CyLiPns) against chronic skin inflammatory diseases. Physico-chemical characterizations including hydrodynamic size, surface potentia...

  11. Enhancing antibiofouling performance of Polysulfone (PSf) membrane by photo-grafting of capsaicin derivative and acrylic acid

    Science.gov (United States)

    Wang, Jian; Sun, Haijing; Gao, Xueli; Gao, Congjie

    2014-10-01

    Biofouling is a critical issue in membrane water and wastewater treatment. Herein, antibiofouling PSf membrane was prepared by UV-assisted graft polymerization of acrylic acid (AA) and a capsaicin derivative, N-(5-methyl-3-tert-butyl-2-hydroxy benzyl) acrylamide (MBHBA), on PSf membrane. AA and MBHBA were used as hydrophilic monomer and antibacterial monomer separately. The membranes were characterized by FTIR-ATR, contact angle, SEM, AFM, cross-flow filtration unit, antifouling and antibacterial measurements. Verification of MBHBA and AA that photo-chemically grafted onto the PSf membrane surface is confirmed by carbonyl stretching vibration at ∼1655 cm-1 and ∼1730 cm-1, separately. The increasing AA concentration accelerates the graft-polymerization of MBHBA and resulted in a more hydrophilic surface. Consequently, antifouling property of the membranes was improved on a large level. The flux recovery rate can achieve 100% during the cyclic test, which may be attributed to the more hydrophilic and smooth surface, as well as the decreased membrane pore size. Most importantly, the presence of AA in graft co-polymer does not affect the antibacterial activity of MBHBA. That may be induced by the increasing chain length and flexibility of the grafted polymer chains.

  12. Collateral sprouting of uninjured primary afferent A-fibers into the superficial dorsal horn of the adult rat spinal cord after topical capsaicin treatment to the sciatic nerve.

    Science.gov (United States)

    Mannion, R J; Doubell, T P; Coggeshall, R E; Woolf, C J

    1996-08-15

    That terminals of uninjured primary sensory neurons terminating in the dorsal horn of the spinal cord can collaterally sprout was first suggested by Liu and Chambers (1958), but this has since been disputed. Recently, horseradish peroxidase conjugated to the B subunit of cholera toxin (B-HRP) and intracellular HRP injections have shown that sciatic nerve section or crush produces a long-lasting rearrangement in the organization of primary afferent central terminals, with A-fibers sprouting into lamina II, a region that normally receives only C-fiber input (Woolf et al., 1992). The mechanism of this A-fiber sprouting has been thought to involve injury-induced C-fiber transganglionic degeneration combined with myelinated A-fibers being conditioned into a regenerative growth state. In this study, we ask whether C-fiber degeneration and A-fiber conditioning are both necessary for the sprouting of A-fibers into lamina II. Local application of the C-fiber-specific neurotoxin capsaicin to the sciatic nerve has previously been shown to result in C-fiber damage and degenerative atrophy in lamina II. We have used B-HRP to transganglionically label A-fiber central terminals and have shown that 2 weeks after topical capsaicin treatment to the sciatic nerve, the pattern of B-HRP staining in the dorsal horn is indistinguishable from that seen after axotomy, with lamina II displaying novel staining in the identical region containing capsaicin-treated C-fiber central terminals. These results suggest that after C-fiber injury, uninjured A-fiber central terminals can collaterally sprout into lamina II of the dorsal horn. This phenomenon may help to explain the pain associated with C-fiber neuropathy. PMID:8756447

  13. Blockage of the neurokinin 1 receptor and capsaicin-induced ablation of the enteric afferent nerves protect SCID mice against T-cell-induced chronic colitis

    DEFF Research Database (Denmark)

    Gad, Monika; Pedersen, Anders Elm; Kristensen, Nanna Ny; Fernandez, Carmen de Felipe; Claesson, Mogens H

    2009-01-01

    BACKGROUND: The neurotransmitter substance P (SP) released by, and the transient receptor potential vanilloid (TRPV1), expressed by afferent nerves, have been implicated in mucosal neuro-immune-regulation. To test if enteric afferent nerves are of importance for the development of chronic colitis......, we examined antagonists for the high-affinity neurokinin 1 (NK-1) SP receptor and the TRPV1 receptor agonist capsaicin in a T-cell transfer model for chronic colitis. METHODS: Chronic colitis was induced in SCID mice by injection of CD4(+)CD25(-) T cells. The importance of NK-1 signaling and TRPV1...

  14. Single high-concentration capsaicin application prevents c-Fos expression in spinothalamic and postsynaptic dorsal column neurons after surgical incision

    Czech Academy of Sciences Publication Activity Database

    Uchytilová, Eva; Špicarová, Diana; Paleček, Jiří

    2015-01-01

    Roč. 19, č. 10 (2015), s. 1496-1505. ISSN 1090-3801 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LH12058; GA ČR(CZ) GPP303/12/P510; GA MŠk(CZ) EE2.3.30.0025; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : pain * spinothalamic * capsaicin * TRPV1 * PSDC Subject RIV: FH - Neurology Impact factor: 2.928, year: 2014

  15. Aumento del umbral tusígeno en sujetos sanos con el uso de Levodropropizina INCREASE OF THE COUGH THRESHOLD TO CAPSAICIN IN HEALTHY ADULTS BY ADMINISTERING LEVODROPROPIZINE

    Directory of Open Access Journals (Sweden)

    Patricia Schönffeldt G.

    2005-09-01

    Full Text Available Se diseñó un estudio aleatorio prospectivo, doble ciego cruzado contra placebo, para estudiar la reproducibilidad y las modificaciones del umbral tusígeno (UT inducido por capsaicina, luego de administrar placebo y Levodropropizina (un nuevo antitusivo sintético. Se determinó el UT basal (logaritmo de la concentración de capsaicina que induce al menos dos toses consecutivas en 20 voluntarios adultos sanos, no fumadores de ambos sexos con edad promedio de 34,9 años (rango: 18 a 57 años. El promedio del UT basal fue 2,240 µM (± 0,060 ES, sin haber diferencias significativas por sexo o edad (p: ns. En 11 de 18 sujetos el UT aumentó de 2,358 µM (± 0,044 ES con placebo a 2,469 µM (± 0,057 ES con Levodropropizina (p = 0,01. Dos sujetos fueron excluidos por presentar una enfermedad intercurrente no relacionada con el estudio. No hubo efectos adversos significativos. Conclusión: La capsaicina indujo reproduciblemente el reflejo tusígeno en 20 voluntarios sanos, y la Levodropropizina administrada por vía oral aumentó el umbral tusígenoA randomized, prospective, double blind and placebo controlled study was designed to evaluate in 20 non smoker healthy adult volunteers the reproducibility and modification of cough threshold (CT induced by capsaicin after placebo and Levodropropizine (a new synthetic drug. Adult volonteers of both sexes, mean age 34.9 years old (range: 18-57 years, inhaled increasing concentrations of capsaicin to determine the basal CT: log concentration of capsaicin that induced at least two consecutive coughs. The basal CT was 2.240 µM (± 0.060 SE, without differences by sex or age (p: ns, In 11 out of 18 subjects the CT increased from 2.358 (± 0,044 SE on placebo to 2.469 µM (± 0.057 after Levodropropizine (p = 0.01. Two subjects were excluded due to intercurrent disease, not related to the study. No significant adverse reactions were reported during the study. Conclusion: Capsaicin induced reproducible

  16. Considerable Variability in the Efficacy of 8% Capsaicin Topical Patches in the Treatment of Chronic Pruritus in 3 Patients with Notalgia Paresthetica.

    Science.gov (United States)

    Andersen, Hjalte H; Sand, Carsten; Elberling, Jesper

    2016-02-01

    Notalgia paresthetica (NP) is a focal neuropathic itch condition manifesting in intense chronic or recurrent episodic itch in a hyperpigmented, macular, uni- or bilateral skin area located below and/or medially to the scapulae. Achieving satisfactory relieve in NP patients is challenging. In this case-series three female NP patients were treated with 8% capsaicin patches following a spatial quantification of their alloknetic area with a von Frey filament. The use of a von Frey filament in order to delimit the precise area of itch sensitization and thus patch application, proved clinically feasible. Although 8% topical capsaicin relieved itch in all three patients, the duration of the effectiveness varied greatly from only 3 days to >2 months. The treatment was well tolerated in the patients and there appear to be no significant hindrances to applying this treatment with NP as an indication, although it may only exhibit satisfactory effectiveness in certain patients. Placebo-controlled double-blinded trials are needed to confirm the effectiveness of the treatment and assess predictive parameters of the treatment outcome. PMID:26848223

  17. Protein kinases mediate increment of the phosphorylation of cyclic AMP -responsive element binding protein in spinal cord of rats following capsaicin injection

    Directory of Open Access Journals (Sweden)

    Li Junfa

    2005-09-01

    Full Text Available Abstract Background Strong noxious stimuli cause plastic changes in spinal nociceptive neurons. Intracellular signal transduction pathways from cellular membrane to nucleus, which may further regulate gene expression by critical transcription factors, convey peripheral stimulation. Cyclic AMP-responsive element binding protein (CREB is a well-characterized stimulus-induced transcription factor whose activation requires phosphorylation of the Serine-133 residue. Phospho-CREB can further induce gene transcription and strengthen synaptic transmission by the activation of the protein kinase cascades. However, little is known about the mechanisms by which CREB phosphorylation is regulated by protein kinases during nociception. This study was designed to use Western blot analysis to investigate the role of mitogen-activated protein (MAP/extracellular signal-regulated kinase (ERK kinase (MEK 1/2, PKA and PKC in regulating the phosphorylation of CREB in the spinal cord of rats following intraplantar capsaicin injection. Results We found that capsaicin injection significantly increased the phosphorylation level of CREB in the ipsilateral side of the spinal cord. Pharmacological manipulation of MEK 1/2, PKA and PKC with their inhibitors (U0126, H89 and NPC 15473, respectively significantly blocked this increment of CREB phosphorylation. However, the expression of CREB itself showed no change in any group. Conclusion These findings suggest that the activation of intracellular MAP kinase, PKA and PKC cascades may contribute to the regulation of phospho-CREB in central nociceptive neurons following peripheral painful stimuli.

  18. Synthesis of tris(quinoline)monochloroplatinum(II) Chloride and its Activity Alone and in Combination with Capsaicin and Curcumin in Human Ovarian Cancer Cell Lines.

    Science.gov (United States)

    Arzuman, Laila; Beale, Philip; Yu, Jun Q; Huq, Fazlul

    2016-06-01

    Currently used platinum drugs fail to provide long-term cure for ovarian cancer mainly because of acquired drug resistance. With the idea that the difference may translate into an altered spectrum of activity, monofunctional planaramineplatinum(II) complex tris(quinoline)monochloro-platinum chloride (coded as LH5) was synthesized and investigated for its activity against human ovarian A2780, cisplatin-resistant A2780 (A2780(cisR)) and ZD0473-resistnat A2780 (A2780(ZD0473R)) cancer cell lines alone and in combination with the phytochemicals capsaicin (Caps) and curcumin (Cur) as a function of concentration and sequence of administration. Cell viability was quantified using the MTT reduction assay, while combination was used as a quantitative measure of the combined drug action. LH5 is found to be more active than cisplatin (CS) against both resistant cell lines. Combination of LH5 with capsaicin showed synergism in all three cell lines, with the bolus being most synergistic. Lack of association between the levels of platinum accumulation and platinum-DNA with cytotoxicity can be seen to indicate that binding with DNA may not be the main determinant of activity of LH5. Greater activity of LH5 compared to cisplatin, especially against the resistant cell lines, indicates that the compound may have the potential for development as a novel anticancer drug and that its combination with phytochemicals can serve to further enhance drug efficacy. PMID:27272792

  19. Pharmacodynamic analysis of the analgesic effect of capsaicin 8% patch (QutenzaTM in diabetic neuropathic pain patients: detection of distinct response groups

    Directory of Open Access Journals (Sweden)

    Martini C

    2012-03-01

    Full Text Available Christian Martini1,*, Ashraf Yassen2,*, Erik Olofsen1, Paul Passier2, Malcom Stoker3, Albert Dahan1 1Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands; 2Global Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Europe, Leiderdorp, The Netherlands; 3Global Medical Sciences, Astellas Pharma Global Development Europe, Leiderdorp, The Netherlands*These authors contributed equally to this workAbstract: Treatment of chronic pain is associated with high variability in the response to pharmacological interventions. A mathematical pharmacodynamic model was developed to quantify the magnitude and onset/offset times of effect of a single capsaicin 8% patch application in the treatment of painful diabetic peripheral neuropathy in 91 patients. In addition, a mixture model was applied to objectively match patterns in pain-associated behavior. The model identified four distinct subgroups that responded differently to treatment: 3.3% of patients (subgroup 1 showed worsening of pain; 31% (subgroup 2 showed no change; 32% (subgroup 3 showed a quick reduction in pain that reached a nadir in week 3, followed by a slow return towards baseline (16% ± 6% pain reduction in week 12; 34% (subgroup 4 showed a quick reduction in pain that persisted (70% ± 5% reduction in week 12. The estimate of the response-onset rate constant, obtained for subgroups 1, 3, and 4, was 0.76 ± 0.12 week-1 (median ± SE, indicating that every 0.91 weeks the pain score reduces or increases by 50% relative to the score of the previous week (= t½. The response-offset rate constant could be determined for subgroup 3 only and was 0.09 ± 0.04 week-1 (t½ 7.8 weeks. The analysis allowed separation of a heterogeneous neuropathic pain population into four homogenous subgroups with distinct behaviors in response to treatment with capsaicin. It is argued that this model-based approach may have added value in analyzing

  20. Synthesis, characterization, in silico approach and in vitro antiproliferative activity of RPF151, a benzodioxole sulfonamide analogue designed from capsaicin scaffold

    Science.gov (United States)

    Tavares, Maurício T.; Pasqualoto, Kerly F. M.; van de Streek, Jacco; Ferreira, Adilson K.; Azevedo, Ricardo A.; Damião, Mariana C. F. C. B.; Rodrigues, Cecilia P.; de-Sá-Júnior, Paulo L.; Barbuto, José A. M.; Parise-Filho, Roberto; Ferreira, Fabio F.

    2015-05-01

    RPF151, an alkylsulfonamide capsaicin analogue, was synthesized by a simple and efficient one-step methodology. The compound was characterized by 1H and 13C NMR, elemental analysis, IR and melting point. The crystal structure of RPF151 was determined by X-ray powder diffraction and its experimental arrangement was compared to the lowest-energy conformer from molecular dynamics simulation. The computational and experimental findings regarding the RPF151 structural arrangement have corroborated with one another. The compound was also tested in vitro against human umbilical vein endothelial cells (HUVEC) in order to verify its antiproliferative activity. RPF151 has significantly reduced the growth of HUVEC cells at 10 μM, suggesting that it probably would act on the angiogenesis process. RPF151 can be considered, then, as a promising anticancer lead for designing novel antitumor agents as potential drug candidates.

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

    Science.gov (United States)

    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. PMID:26048309

  2. The involvement of Smac/DIABLO, p53, NF-kB and MAPK pathways in apoptosis of keratinocytes from perilesional vitiligo skin: protective effects of curcumin and capsaicin

    OpenAIRE

    Becatti, M; F. Prignano; Fiorillo, C>; L. Pescitelli; P. Nassi; T Lotti; N. TADDEI

    2010-01-01

    Oxidative stress has been suggested as the initial pathogenetic event in melanocyte degeneration in vitiligo. Our previous results indicate that keratinocytes from perilesional skin show the features of damaged cells. In the present study, biopsies were taken from the perilesional skin of 12 patients suffering from nonsegmental vitiligo. The intracellular pathways involved in keratinocyte damage and apoptosis and the antioxidant protection of curcumin and capsaicin in these cells were investi...

  3. Capsaicina tópica en el tratamiento del dolor neuropático Topical capsaicin for the management of neuropathic pain

    Directory of Open Access Journals (Sweden)

    M. A. Vidal

    2004-07-01

    sensación de quemazón en la zona de aplicación, que tiende a desaparecer después de la primera semana. Esta sensación de quemazón constituye, junto con la limitada efectividad clínica, la principal limitación de la aplicación tópica de capsaicina. La principal indicación del uso de la capsaicina tópica es la de coadyuvante de los antidepresivos y anticonvulsivantes en el tratamiento de los diversos cuadros de dolor neuropático, ya que como terapia única parece ser insuficiente. Es una opción a tener en cuenta en los pacientes añosos afectos de dolor neuropático, con lo que disminuiremos la incidencia de efectos secundarios sistémicos y de interacciones medicamentosas.Neuropathic pain is one of the most complex painful syndromes and one of the most difficult to treat. It is a symptom resulting from neurological damage (peripheral, central or both affecting the pain nervous transmission system. Several drugs have been used, but none of them has resulted effective enough and their side effects frequently deter the continuation of the treatment. It can show up in different situations, all of which are more frequent in aged patients. A powerful analgesic with as little number ofside effects as possible is needed. This paper is a bibliographic review performed through the Medline data base of the treatment with topical capsaicin in different cases of neuropathic pain: postherpetic neuralgia, diabetic neuropathy, neuropathic pain associated to AIDS, trigeminal neuralgia, post-mastectomy painful syndromes and regional complex pain. The topical administration of capsaicin 0.075%, has shown to be effective for the management of dysesthesic pain and hence it is a therapeutic alternative for this type of pain. Its mechanism of action appears to be based on the selective stimulation of the neurons of amyelinic fibers C, causing the release of substance P and perhaps of other neurotransmitters; and finally, a depletion of substance P, which would disturb pain

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-02-01

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

  5. 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

    International Nuclear Information System (INIS)

    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.

  6. Tolerability of NGX-4010, a capsaicin 8% patch, in conjunction with three topical anesthetic formulations for the treatment of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Webster LR

    2012-01-01

    Full Text Available Lynn R Webster1, John F Peppin2, Frederick T Murphy3,4, Jeffrey K Tobias5, Geertrui F Vanhove51Lifetree Clinical Research and Pain Clinic, Lifetree Medical Inc, Salt Lake City, UT, USA; 2Clinical Research Division, The Pain Treatment Center of the Bluegrass, Lexington, KY, USA; 3Altoona Center for Clinical Research, Duncansville, PA, USA; 4University of Pennsylvania, School of Medicine, Philadelphia, PA, USA; 5NeurogesX Inc, San Mateo, CA, USABackground: The objective of this study was to assess the safety, tolerability, and preliminary efficacy of NGX-4010, a capsaicin 8% patch, following pretreatment with three different topical anesthetics in patients with peripheral neuropathic pain.Methods: This open-label, multicenter study enrolled 117 patients with post-herpetic neuralgia, HIV-associated distal sensory polyneuropathy, or painful diabetic neuropathy. Patients received pretreatment with one of three lidocaine 4%-based topical anesthetics (L.M.X.4® [Ferndale Laboratories Inc, Ferndale, MI], Topicaine® Gel [Estela Basso, Jupiter, FL], or Betacaine Enhanced Gel 4 [Tiberius Inc, Tampa, FL] for 60 minutes followed by a single 60- or 90-minute NGX-4010 application, and were followed for 12 weeks. Tolerability and safety measures included “pain now” Numeric Pain Rating Scale (NPRS scores, dermal assessments, medication use for treatment-related pain, adverse events (AEs, clinical laboratory parameters, physical examinations, and vital signs. The primary efficacy variable was the percentage change in mean NPRS scores for “average pain for the past 24 hours” from baseline to weeks 2 through 12.Results: Treatment with NGX-4010 following pretreatment with any of the three topical anesthetics was generally safe and well tolerated. Nearly all patients completed ≥90% of the planned NGX-4010 application duration. The most common treatment-related AEs, application-site burning and application-site pain, were transient, mostly mild or moderate

  7. 辣椒素对微波辐射所致小鼠血液系统损伤的保护作用%Protective Effects of Capsaicin on Blood System Injured by Microwave Radiation in Mice

    Institute of Scientific and Technical Information of China (English)

    王瀚; 余智操; 魏卫; 李渊; 陈杨; 贾易臻; 梁向艳; 于军

    2012-01-01

    Objective To study the protective effects of capsaicin on the mice' s hematopoietic system injuries induced by microwave radiation.Methods Mice were randomly divided into control,radiation and capsaicin groups.The radiation group was exposed to 2450 MHz and 65 mW/cm2 microwave radiation 8 h per day for 3 consecutive days.The capsaicin group was treated with the same microwave radiation exposure as that of the radiation group,in addition 0.2 mL of 2.5 g/L capsaicin were poured into the stomach of mice twice a day.The count of red blood cells (RBCs),polychromatic erythrocyte micronucleus rate,serum superoxide dis-mutase (SOD) and erythropoietin (EPO) of each mouse were analyzed.Results The micronucleus rates increased and SOD and EPO decreased in the modeling group.While,in the capsaicin group,the micronucleus rates decreased to normal,EPO and counting of RBC increased obviously and SOD recovered to normal.Conclusion Capsaicin has a protective effect on the mouse' s blood system injuries caused by microwave radiation.The mechanism may be related to the capsaicin's antioxidalion function and the promotion of EPO secretion.%目的 研究辣椒素对微波辐射所致小鼠血液系统损伤的保护作用.方法 将小鼠随机分为3组:对照组;辐射组,用频率为2450 MHz、功率密度为65 mW/cm2的微波辐射,连续3d,每天8h;辣椒素组,在与辐射组相同的辐射下每天2次辣椒素灌胃,浓度为2.5 g/L,体积为0.2 mL.检测小鼠的红细胞(RBC)计数、嗜多染红细胞微核率、血清超氧化物歧化酶(SOD)与促红细胞生成素(EPO).结果 辐射组微核率升高,SOD,EPO降低,辣椒素组微核率下降至正常,EPO明显上升,RBC计数也明显上升,同时SOD也回升至正常.结论 辣椒素对微波所致小鼠血液系统损伤有保护作用,其机制可能与辣椒素的抗氧化作用和促进EPO分泌有关.

  8. Effect of foliar fertilization of Capsicum annuum L. together with optimal root fertilization in hydroponic culture on fruit yield and its capsaicin content

    Directory of Open Access Journals (Sweden)

    Tomasz J. Nowak

    2013-12-01

    Full Text Available The Wrocław version of hydroponic culture was applied. The optimal dose of mineral nutrient solution for root-fertilizing was found to be 19,6g and 22,4g of mineral salts per one plant during the whole vegetation season. In a separate experiment plants with optimal root fertilization were sprayed with multicomponent solutions of mineral salts. The sprays were applied weekly for 15 weeks. The concentrations of solutions for spraying were: 0,28, 0,84 and 1,4 per cent. The greatest increase of fruit yield was noted after the 0,84 per cent solution. At optimal concentration of spray solution (0,84% chelating agents added (EDTA or humate had no effect. Addition of the chelating agents to the 1,4% solution attennated its inhibitory effect. The humate gave a better effect than EDTA. A tenfold increase of microelements content (6 mg/l of each instead of 0,6 mg/l in 0,28 per cent spray solution produced a marked increase of the yield of fruits and of their capsaicin content.

  9. Cannabinoid CB(1) receptor activation stimulates neurite outgrowth and inhibits capsaicin-induced Ca(2+) influx in an in vitro model of diabetic neuropathy.

    Science.gov (United States)

    Zhang, Fan; Challapalli, Sarat C; Smith, Paula J W

    2009-08-01

    Cannabinoid CB(1) receptors mediate, in part, the neuroprotectant properties of endocannabinoids, and altered signalling via the CB(1) receptor may contribute to the pathogenesis of diabetic neuropathy. We investigated CB(1) receptor function in PC12 cells differentiated into a neuronal phenotype with nerve growth factor (NGF, 50 ng/ml) in 5.5 and 50 mM concentrations of glucose. High glucose was associated with impaired NGF-induced neurite outgrowth (P HU210 (0.03-3 microM) increased neurite length in a concentration-dependent manner (P HU210 (1 microM) inhibited capsaicin-induced calcium transients to a similar degree in cells cultured in high glucose (40%) versus normal (43%) (P HU210-mediated rescue of neurite outgrowth and inhibition of calcium influx was blocked by the selective CB(1) antagonist AM251 (1 microM), but not by the selective CB(2) antagonist AM630 (1 microM), confirming the role of CB(1) receptors. High glucose treatment did not significantly elevate endocannabinoid levels. These results suggest that high glucose concentrations are associated with decreased expression, but preserved function of CB(1) receptors in nerve cells. PMID:19501110

  10. Capsaicin consumption, Helicobacter pylori CagA status and IL1B-31C>T genotypes: a host and environment interaction in gastric cancer.

    Science.gov (United States)

    López-Carrillo, Lizbeth; Camargo, M Constanza; Schneider, Barbara G; Sicinschi, Liviu A; Hernández-Ramírez, Raúl U; Correa, Pelayo; Cebrian, Mariano E

    2012-06-01

    Gastric cancer (GC) has been associated with a complex combination of genetic and environmental factors. In contrast to most countries, available information on GC mortality trends showed a gradual increase in Mexico. Our aim was to explore potential interactions among dietary (chili pepper consumption), infectious (Helicobacter pylori) and genetic factors (IL1B-31 genotypes) on GC risk. The study was performed in three areas of Mexico, with different GC mortality rates. We included 158 GC patients and 317 clinical controls. Consumption of capsaicin (Cap), the pungent active substance of chili peppers, was estimated by food frequency questionnaire. H. pylori CagA status was assessed by ELISA, and IL1B-31 genotypes were determined by TaqMan assays and Pyrosequencing in DNA samples. Multivariate unconditional logistic regression was used to estimate potential interactions. Moderate to high Cap consumption synergistically increased GC risk in genetically susceptible individuals (IL1B-31C allele carriers) infected with the more virulent H. pylori (CagA+) strains. The combined presence of these factors might explain the absence of a decreasing trend for GC in Mexico. However, further research on gene-environment interactions is required to fully understand the factors determining GC patterns in susceptible populations, with the aim of recommending preventive measures for high risk individuals. PMID:22414649

  11. Oral ingestion of Capsaicin, the pungent component of chili pepper, enhances a discreet population of macrophages and confers protection from autoimmune diabetes.

    Science.gov (United States)

    Nevius, E; Srivastava, P K; Basu, S

    2012-01-01

    Vanilloid receptor 1 (VR1) is expressed on immune cells as well as on sensory neurons. Here we report that VR1 can regulate immunological events in the gut in response to its ligand Capsaicin (CP), a nutritional factor, the pungent component of chili peppers. Oral administration of CP attenuates the proliferation and activation of autoreactive T cells in pancreatic lymph nodes (PLNs) but not other lymph nodes, and protects mice from development of type 1 diabetes (T1D). This is a general phenomenon and not restricted to one particular strain of mice. Engagement of VR1 enhances a discreet population of CD11b(+)/F4/80(+) macrophages in PLN, which express anti-inflammatory factors interleukin (IL)-10 and PD-L1. This population is essential for CP-mediated attenuation of T-cell proliferation in an IL-10-dependent manner. Lack of VR1 expression fails to inhibit proliferation of autoreactive T cells, which is partially reversed in (VR1(+/+) → VR1(-/-)) bone marrow chimeric mice, implying the role of VR1 in crosstalk between neuronal and immunological responses in vivo. These findings imply that endogenous ligands of VR1 can have profound effect on gut-mediated immune tolerance and autoimmunity by influencing the nutrient-immune interactions. PMID:22113584

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

    Directory of Open Access Journals (Sweden)

    Yamaguchi Asuka

    2006-05-01

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

  13. Synthesis, characterization, in silico approach and in vitro antiproliferative activity of RPF151, a benzodioxole sulfonamide analogue designed from capsaicin scaffold

    DEFF Research Database (Denmark)

    Tavares, Mauricio T.; Pasqualoto, Kerly F. M.; van de Streek, Jacco;

    2015-01-01

    ) in order to verify its antiproliferative activity. RPF151 has significantly reduced the growth of HUVEC cells at 10 μM, suggesting that it probably would act on the angiogenesis process. RPF151 can be considered, then, as a promising anticancer lead for designing novel antitumor agents as potential......RPF151, an alkylsulfonamide capsaicin analogue, was synthesized by a simple and efficient one-step methodology. The compound was characterized by 1H and 13C NMR, elemental analysis, IR and melting point. The crystal structure of RPF151 was determined by X-ray powder diffraction and its experimental...

  14. Effect of capsaicin on intestinal permeation of P-glycoprotein substrate rhodamine 123 and fluorescein sodium in rats%辣椒素对P-糖蛋白和细胞旁途经转运透过的作用

    Institute of Scientific and Technical Information of China (English)

    梁倩莹; 段炼; 庄志铨; 赵博欣; 刘媛; 王胜奇; 杨富恒; 刘思佳; 李国锋

    2015-01-01

    目的:通过研究P-糖蛋白(P-gp)底物罗丹明123(R123)在空肠、回肠和结肠转运时辣椒素的作用,探究辣椒素对肠粘膜上P-gp功能的影响。方法使用体外扩散池法技术,分别取SD雄性大鼠的空肠、回肠和结肠肠段标本,计算各肠段中吸收方向(mucosa to serosa, M-S)和分泌方向(serosa to mucosa, S-M)R123的表观渗透速率(Papp)。用荧光分光光度计测定R123和荧光素钠(CF)在接收室中的浓度。结果在辣椒素作用下,R123经空肠粘膜透过时,吸收方向与空白组相比显著增高,分泌方向显著降低,但其在回肠及结肠M-S组及S-M组表观渗透系数Papp与空白组相比均没有显著性差异。CF经空肠粘膜透过时,M-S组及S-M组Papp与空白组相比均显著增高;经回肠和结肠粘膜透过与空白组相比没有显著性差异。结论辣椒素影响P-gp底物R123和细胞旁转运药物CF经肠粘膜透过的作用具有肠段差异性,对R123和CF的影响仅存在于空肠,表明辣椒素是一种较弱的P-gp抑制剂和粘膜通道改善剂。可能与P-gp和紧密连接在肠粘膜上的逐渐变化的分布有关。%Objective To investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 (R123) across the jejunum, ileum and colon membranes of rats. Methods The permeability of R123 or fluorescein sodium (CF) across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient (Papp). Results Compared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal (M-S) direction and decreased its permeability in the serosal-to-mucosal (S-M) direction, but produced no obvious effect on R123 transport across the ileum or colon membranes

  15. Analysis and QTLs Identification of Pepper Fruit Capsaicin Content under Different Cultivation Conditions%不同栽培条件下辣椒果实辣椒素含量的分析与QTL定位

    Institute of Scientific and Technical Information of China (English)

    王宁; 张正海; 王立浩; 张宝玺

    2016-01-01

    利用辣味辣椒Perennial(Capsicum annuum)和无辣味辣椒83-58种内重组自交系群体构建的辣椒种内遗传图谱,以温室和露地栽培条件下无辣味辣椒77013A与重组自交系群体各株系杂交F1果实的辣椒素和二氢辣椒素含量作为表型性状进行分析。结果表明,温室和露地栽培条件下辣椒素和二氢辣椒素的含量和比值差异明显。对露地和温室栽培条件下辣椒果实辣椒素和二氢辣椒素含量、总和及其比值进行了QTL定位,共获得16个关于辣椒素和二氢辣椒素含量的QTL位点,分布在辣椒第2、4、12号染色体上,2号染色体上同时控制辣椒素、二氢辣椒素、二者比值和辣椒素总量的主效QTL位点cap2.1、dhp2.1、C/D2.1和(C+D)2.1,均在露地和温室被检测到,其LOD值大于5.0,贡献率为20.2%~76.6%,侧翼标记均为BD76366和Pun1,12号染色体上调控辣椒素总量的微效QTL也在温室和露地同时被检测到,其他QTL位点未在两种环境下同时定位到。%In the present study,we constructed an intraspecific genetic map by using a recombinant inbred lines crossed by pungent pepper ‘Perennial’(Capsicum annuum) and non-pungent pepper ‘83-58’,and analyzed capsaicin and dihydrocapsaicin contents investigated on a test cross progeny by non-pungent pepper ‘77013A ’and RILs (‘83-58’בPerennial’) both in greenhouse and open fields. And the differences in capsaicin content,dihydrocapsaicin content,total capsaicinoids and capsaicin/dihydrocapsaicin ratio between greenhouse and open fields were obvious. We did QTL mapping on them and found 16 QTLs located in chromosome 2,4 and 12. The major QTLcap2.1,dhp2.1,C/D2.1and (C+D)2.1 on chromosome 2 that controlling capsaicin content,dihydrocapsaicin content,total capsaicinoids content and capsaicin/dihydrocapsaicin ratio, was detected in both greenhouse and open fields. The LOD was above 5.0,accounting for 20.2%-76.6% of the

  16. Influence of pregnancy and labor on the occurrence of nerve fibers expressing the capsaicin receptor TRPV1 in human corpus and cervix uteri

    Directory of Open Access Journals (Sweden)

    Irestedt Lars

    2008-02-01

    Full Text Available Abstract Background Cervical ripening is a prerequisite for a normal obstetrical outcome. This process, including labor, is a painful event that shares features with inflammatory reactions where peripheral nociceptive pathways are involved. The capsaicin and heat receptor TRPV1 is a key molecule in sensory nerves involved in peripheral nociception, but little is known regarding its role in the pregnant uterus. Therefore, the aim of this study was to investigate human corpus and cervix uteri during pregnancy and labor and non-pregnant controls for the presence of TRPV1. Methods We have investigated human uterine corpus and cervix biopsies at term pregnancy and parturition. Biopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n = 8, in labor (n = 8 and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 8. Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial frozen sections were examined immunohistochemically using specific antibodies to TRPV1 and nerve markers (neurofilaments/peripherin. Results In cervix uteri, TRPV1-immunoreactive fibers were scattered throughout the stroma and around blood vessels, and appeared more frequent in the sub-epithelium. Counts of TRPV1-immunoreactive nerve fibers were not significantly different between the three groups. In contrast, few TRPV1-immunoreactive fibers were found in nerve fascicles in the non-pregnant corpus, and none in the pregnant corpus. Conclusion In this study, TRPV1 innervation in human uterus during pregnancy and labor is shown for the first time. During pregnancy and labor there was an almost complete disappearance of TRPV1 positive nerve fibers in the corpus. However, cervical innervation remained throughout pregnancy and labor. The difference in TRPV1 innervation between the corpus and the cervix is thus very marked. Our data suggest that TRPV1 may be involved in pain mechanisms associated with

  17. Tolerability of NGX-4010, a capsaicin 8% dermal patch, following pretreatment with lidocaine 2.5%/prilocaine 2.5% cream in patients with post-herpetic neuralgia

    Directory of Open Access Journals (Sweden)

    Webster Lynn R

    2011-12-01

    Full Text Available Abstract Background Post-herpetic neuralgia (PHN is a common type of neuropathic pain that can severely affect quality of life. NGX-4010, a capsaicin 8% dermal patch, is a localized treatment that can provide patients with significant pain relief for up to 3 months following a single 60-minute application. The NGX-4010 application can be associated with application-site pain and in previous clinical trials pretreatment with a topical 4% lidocaine anesthetic was used to enhance tolerability. The aim of the current investigation was to evaluate tolerability of NGX-4010 after pretreatment with lidocaine 2.5%/prilocaine 2.5% anesthetic cream. Methods Twenty-four patients with PHN were pretreated with lidocaine 2.5%/prilocaine 2.5% cream for 60 minutes before receiving a single 60-minute application of NGX-4010. Tolerability was assessed by measuring patch application duration, the proportion of patients completing over 90% of the intended treatment duration, application site-related pain using the Numeric Pain Rating Scale (NPRS, and analgesic medication use to relieve such pain. Safety was assessed by monitoring adverse events (AEs and dermal irritation using dermal assessment scores. Results The mean treatment duration of NGX-4010 was 60.2 minutes and all patients completed over 90% of the intended patch application duration. Pain during application was transient. A maximum mean change in NPRS score of +3.0 was observed at 55 minutes post-patch application; pain scores gradually declined to near pre-anesthetic levels (+0.71 within 85 minutes of patch removal. Half of the patients received analgesic medication on the day of treatment; by Day 7, no patients required medication. The most common AEs were application site-related pain, erythema, edema, and pruritus. All patients experienced mild dermal irritation 5 minutes after patch removal, which subsequently decreased; at Day 7, no irritation was evident. The maximum recorded dermal assessment

  18. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to capsaicin and maintenance of body weight after weight loss (ID 2039, 2041, 2042), increase in carbohydrate oxidation (ID 2040), and contribution to normal hair growth

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to capsaicin and contribution to the maintenance or achievement of a normal body weight, increase in carbohydrate oxidation, and contribution to normal hair growth. The scientific substantiation is based on the information provided by the Member States in the consolidated list of...

  19. Capsaicin Stimulation on Autonomic Nervous System in Human by Heart Rate Variability Analysis%心率变异性分析评价辣椒素致痛对自主神经活动的影响

    Institute of Scientific and Technical Information of China (English)

    周芳; 房泽; 张健; 申岱

    2015-01-01

    目的:探讨心率变异性分析对辣椒素疼痛模型进行评价的可行性。方法:22~27岁健康志愿者36名,取平静状态20 min ECG信号中较稳定的一段长度5 min信号作为对照;以浸透0.5 mL辣椒素溶液的棉纸片覆盖下唇唇红位置,继续记录20 min心电信号,选取较稳定的一段长度5 min;记录涂抹辣椒素后的VAS评分;用Matlab R2006a编程软件分析所采集到的ECG信号,计算平静状态下(T0)和辣椒素刺激状态下(T1)的心率变异性(HRV)指标,进行统计学分析。结果:视觉模拟评分(VAS)平均(63.36±11.21),可评价为中度疼痛;心率在T1时期较T0时期增加,无统计学意义。HRV时域分析指标NN间期标准差(SDNN)、相邻NN间期差的均方根(RMSSD)在T1期均较T0期明显升高;HRV频域分析指标总功率(TP)、低频功率(LF)、高频功率(HF)以及LF/HF在T1期均较T0期明显升高;散点图分析结果:散点图短轴(SD1)和散点图长轴(SD2)在T1时期较T0时期均明显升高。结论:用辣椒素建立疼痛模型是可行的,且操作简单,易于实施;HRV分析有可能在疼痛的量化评价中具有一定权衡作用。%Objective To verify the feasibility of the capsaicin pain model and to discuss the quantitative analysis of pain by heart rate variability. Methods Approved by the ethics committee, thirty-six healthy vol⁃unteers were selected with the age of 22 to 27 years. The volunteers lied on their back and calmed down for 20 minutes. Then capsaicin solution was daubed on their lips. Observation was taken for another 20 minutes. VAS scores were recorded after capsaicin stimulation. The ECG signals were analyzed by Matlab R2006a. The heart rate variability indicators of volunteers at the T0 (state of calm) and T1 (stimulated by capsaicin) were recorded. The differences between the two groups were compared and the results statistically analyzed. The

  20. 4.8%鱼藤酮·辣椒碱悬浮剂对环境生物的毒性%Evaluation of Rotenone·Capsaicin 4.8% SC to Environmental Biology

    Institute of Scientific and Technical Information of China (English)

    刘哲鹏; 倪德浩; 陆丽芳; 吴长兴; 赵学平

    2011-01-01

    [Aims] Rotenone was a natural plant toxin which used as a commercial insecticide for centuries by peoples. It is chemically unstable and breaks down rapidly in the environment, yielding watersoluble non-toxic products. Fish are acutely sensitive to rotenone poisoning. In a previous study, research was focus on rotenone. Here, the acute toxicity of the rotenone · capsaicin 4.8% SC was studied and the safety was evaluated. [Results] The LD50 of rotenone · capsaicin 4.8% SC to bee, bird(female/male), zebra fish and silkworm was 271.2, 40.9(35.6), 0.0116 and 3.58 mg/L respectively. [Conclusions] The results demonstrated that the suspension was low toxic to bee. In actually uses rotenone · capsaicin 4.8% SC was low risk to birds. The product was highly toxic to silkworm and fish. When it was used in fields, it was avoid strictly the pesticide liquid neither falling to the mulberry leaves nor pouring into river.%[目的]测定4.8%鱼藤酮·辣椒碱悬浮剂对蜜蜂、鹌鹑、斑马鱼和家蚕4种生物的半数致死量,评价其安全性.[结果]4.8%鱼藤酮·辣椒碱悬浮剂对蜜蜂、雌(雄)鹌鹑、斑马鱼和家蚕LD50值分别为271.2、40.9(35.6)、0.0116、3.58 mg/L.[结论]4.8%鱼藤酮·辣椒碱悬浮剂对蜜蜂低毒,在实际使用过程中对鸟类急性中毒风险较小.对家蚕高毒,对鱼类剧毒,使用时远离桑园,在桑园附近农田使用时注意施药方式和风向,避免药液飘落到桑叶上.要严格避免药液流入水域对鱼类造成危害.

  1. Síndrome de boca ardiente: Eficacia de la aplicación tópica de capsaicina. Estudio piloto Burning mouth syndrome: Clinical study about efficacy of topical capsaicin application. Pilot study

    Directory of Open Access Journals (Sweden)

    S. León Espinosa

    2004-12-01

    Full Text Available El síndrome de boca ardiente es un cuadro clínico complejo en el que el paciente manifiesta una sensación de escozor o ardor intrabucal sin que aparezcan lesiones clínicas objetivables. Objetivo: Valorar la eficacia mediante la aplicación de un gel de capsaicina a una concentración de 0.025 mg., en pacientes con síndrome de boca ardiente. Pacientes y método: Se estudiaron a un grupo de 29 pacientes a los que se les realiza un protocolo de recogida de datos que incluye anamnesis, historia médica, exploración bucal y pruebas complementarias. A 15 de dichos pacientes se les prescribe un gel de capsaicina y se les realiza un seguimiento durante varias semanas. Resultados: La eficacia de la capsaicina es relativamente baja, solo un 13% de los pacientes refiere una mejoría importante (con una disminución de mas de 3 puntos en las escalas analógico-visuales y un 6% mejoría parcial (disminución menor de 3 puntos con este tratamiento. Discusión: La estomatodinia es un cuadro clínico multifactorial que precisa de una mayor investigación tanto de su etiología como de su manejo terapéutico. Es de suma importancia realizar un correcto diagnóstico y explicar este al paciente para poder mantener unas metas realistas sobre las posibilidades de éxito.Burning mouth syndrome is a complex clinical condition, patients show a sensation of irritation or intraoral heat without objetivable clinical injuries. Objective: to value the effectiveness of a capsaicin 0,025% gel application in patients with burning mouth syndrome. Patients and methods: 29 patients with burning mouth syndrome was examined by means of anamnesis, medical history, oral explortation and complementary tests. 15 of these patients were administered a capsaicin gel and were examined for several weeks. Results: the effectiveness of capsaicin is relatively low, only 13% of patients refer an important improvement ( with a reduction more tha 3 points in the visual alalogical scales and

  2. Inhalation injury after capsaicin exposure.

    Science.gov (United States)

    Miller, James Jason; Skolnick, Judah

    2006-03-01

    Pepper spray is defined as a non-lethal agent used in riot control and personal self-defense. Oleoresin capsicum (OC), derived from the fruit of plants in the Capsicum genus, commonly referred to as hot peppers or chilies, is the active agent used in many of these defense sprays. Although generally assumed to be safe and effective, the consequences of OC cannot be predicted with certainty. Nationwide there have been numerous reports of pepper spray-related injuries, including officers injured in pepper spray-related training exercises. This report details one officer's experience. PMID:16578994

  3. Capsaicina al 8% para controlar el dolor neuropático periférico: una estrategia basada en casos clínicos Capsaicin al 8% for the management of peripheral neuropathic pain: a strategy based on clinic cases

    Directory of Open Access Journals (Sweden)

    A. Bhaskar

    2013-02-01

    Full Text Available La reunión multidisciplinar organizada por Astellas tuvo lugar en Milán el 28 de agosto de 2012. Alrededor de 150 médicos invitados, especializados en el dolor, procedentes de toda Europa y con conocimientos o experiencia en el uso de los parches de capsaicina al 8 % para tratar el dolor neuropático (DN periférico, asistieron a la reunión para escuchar la presentación de distintos casos clínicos tratados con el parche de capsaicina al 8%, por parte de un grupo de ponentes europeos expertos en la clínica del dolor. El objetivo de la reunión era compartir experiencia clínica real sobre el uso del parche de capsaicina al 8% para controlar el DN siguiendo un formato interactivo y dando a los asistentes la oportunidad de intercambiar experiencia práctica directa con el uso de este medicamento. La reunión estuvo presidida por el Dr. Arun Bhaskar del Reino Unido. Este inauguró la reunión dando la bienvenida a los delegados, presentando a los ponentes, resumiendo los objetivos de la reunión y realizando una demostración del ThoughtSort, el software que por grupos a través de un iPad, hizo posible que todos los participantes de la sesión pudiesen interactuar. Los detalles de los casos clínicos que se presentaron en la reunión y que se resumen en este artículo responden a las opiniones personales de los ponentes.The Astellas peer-to-peer meeting took place in Milan on the evening of Tuesday 28 August, 18:00-20:00. Approximately 150 invited pain physicians from across Europe, all with some knowledge or experience of using the high-dose capsaicin patch to treat peripheral neuropathic pain (NP, attended the meeting to hear an expert European faculty of practising physicians present different case studies involving treatment with high-dose capsaicin. The objective of the meeting was to share real-world experience in the use of high-dose capsaicin for the management of NP in an interactive format to provide delegates with the opportunity

  4. Determination of capsaicin and dihydrocapsaicin in fruits of Capsicum annuum by HPLC%HPLC 法测定不同产地辣椒中辣椒素和二氢辣椒素的含量

    Institute of Scientific and Technical Information of China (English)

    曹莉; 黄多临

    2016-01-01

    Objective To establish an HPLC method for determination of capsaicin and dihydrocapsaicin in fruits of Capsicum ann-uum,and compare the quality of the different areas of Capsicum annuum.Methods The HPLC system consisting of Agilent Eclipse SB C18 (250mm ×4.6mm,5μm) column and a solution system of methanol -water (50 ∶50),The detection UV wavelength was at 280nm,the flow rate was 1.0ml·min -1 ,the column temperature was 25 ℃.Results The contents of capsaicin and dihydrocapsaicin in fruits of Capsicum annuum from different habitats are significantly different.Conclusion The method is simple,rapid and accurate, and can be used for the quality control of Capsicum annuum L.%目的:采用反相高效液相法测定不同产地辣椒中辣椒素和二氢辣椒素的含量。方法:采用安捷伦 Eclipse SB C18色谱柱(250mm ×4.6mm;5μm),流动相为甲醇-水(50∶50),流速为1.0ml /min,检测波长280nm,柱温25℃。结果:各产地辣椒中均含有辣椒素和二氢辣椒素,目不同产地的含量差别较大。结论:该方法准确、简便、可行,可作为辣椒药材的含量测定方法。

  5. Uso del parche de capsaicina 8% para el tratamiento del dolor por infusión de treprostinil subcutáneo Using the 8% capsaicin patch for treatment of pain by subcutaneous infusion of treprostinil

    Directory of Open Access Journals (Sweden)

    J. M. Trinidad

    2012-06-01

    Hypertension is a low-prevalence disease (15 cases per 1 million inhabitants, but is nevertheless a serious process with high mortality. Treprostinil is a new drug for the PH treatment, it is a prostacyclin with a half-life of 2-3 hours, which permits subcutaneous administration with rapid absorption and 100% bioavailability. The issue with treprostini is the high rate of drop-outs due to pain at the injection site. Aims: to reduce the rate of drop-outs due to pain at the injection site with the use of Treprostinil Methods: we searches in PubMed and Tripdatabase, fore terms, "capsaicin", "qutenza", "treprostinil", and "pulmonary hypertension", finding no related publication. The treatment with capsaicin 8% patch, was performed for one hour, according to the protocol, the peri-umbilical abdominal area (injection site was delimited and the patch administered for one hour. Results: erythema at the administration site was subsequently observed, albeit with no further incidents. Good treatment tolerance and discharge. In the control after 1 month, the patient reported changing the injection site to the treated area with a very striking reduction in pain (VAS 2-3 that enabled him to lead a normal life. The patient's satisfaction is very high, and he requires no coadjuvant or rescue treatment. At the 3-month control, the patient continues with the same level of analgesia Conclusions: capsaicin 8% patch could be a valid alternative to be considered in the analgesic control of patients on treatment with subcutaneous treprostinil.

  6. Wounding effects of capsaicin, a new irritant riot control agent: an overview%新型控暴剂辣椒素的致伤效应研究进展

    Institute of Scientific and Technical Information of China (English)

    骆媛,; 王永安

    2011-01-01

    新型控暴剂辣椒素作为催泪瓦斯的主要组分,已被广泛装备于军队及警察部门,用于制止暴力犯罪和各种恐怖活动等.辣椒素可引起流泪、喷嚏、咳嗽等强烈不适症状或受累器官的疼痛,导致中毒人员暂时性失能.虽然辣椒素被认为是相对安全的控暴剂,但其诱发的严重并发症甚至死亡等中毒事件,不得不使人们重新认识其安全性.目前国内外对辣椒素的致伤效应研究非常有限,相关医学防护急救措施更是缺乏,本文将就辣椒素的毒理学作用及防护措施研究进展作一综述.%Capsaicin,a new irritant agent as the main component of tear gas or pepper spray,is being widely used by army or police forces to aid in arresting aggressive individuals. When applied in the form of a spray,it quickly produces lacrimation, sneezing,cough,as well as pain in some organ after stimulation,that can cause exposed persons incapacitated. In general,pepper spray appears to be a relatively safe weapon with small risk,but serious complications and even deaths have been reported, and raises questions and concerns regarding its health effects and safety. Not enough is known concerning the toxic effects of this riot control agent thus far,and also lack of medical protective measures. This article will review the toxicological effects of the new irritant agent capsaicin,and the research progress of its medical protective measures.

  7. Effect of duration of postherpetic neuralgia on efficacy analyses in a multicenter, randomized, controlled study of NGX-4010, an 8% capsaicin patch evaluated for the treatment of postherpetic neuralgia

    Directory of Open Access Journals (Sweden)

    Rauck Richard

    2010-10-01

    Full Text Available Abstract Background Postherpetic neuralgia (PHN is a painful and difficult to treat complication of acute herpes zoster. Current treatment options provide only partial relief and are often limited by poor tolerability. We evaluated the safety and efficacy of a single 60-minute application of NGX-4010, an 8% capsaicin patch, in patients with PHN. Methods This multicenter, double-blind, controlled study randomized 155 patients 2:1 to receive either NGX-4010 or a 0.04% capsaicin control patch. Patients were at least 18 years old with PHN for at least 3 months, and an average Numeric Pain Rating Scale (NPRS score of 3 to 9. The primary efficacy endpoint was the percentage change in NPRS score from baseline to weeks 2-8. Results The mean percent reduction in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 was greater in the NGX-4010 group (36.5% compared with control (29.9% although the difference was not significant (p = 0.296. PGIC analysis demonstrated that more NGX-4010 recipients considered themselves improved (much, or very much compared with control at weeks 8 and 12, but the differences did not reach statistical significance. Post hoc analyses of patients with PHN for at least 6 months showed significantly greater reductions in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 in NGX-4010 patients compared to controls (37.6% versus 23.4%; p = 0.0291. PGIC analysis in this subgroup demonstrated that significantly more NGX-4010 recipients considered themselves much or very much improved compared with control at week 12 (40% versus 20%; p = 0.0403;. Conclusions Although treatment appeared to be safe and well tolerated, a single 60-minute application of NGX-4010 failed to show efficacy in this study which included patients with PHN for less than 6 months. Large reductions in pain observed among control patients with pain for less than 6 months may have been due to spontaneous resolution of PHN

  8. Determination of equilibrium solubility of capsaicin in various liquid lipids by High performance liquid chromatography%高效液相色谱法测定辣椒碱在不同液态脂质中的平衡溶解度

    Institute of Scientific and Technical Information of China (English)

    郭一沙; 陈孝储; 张阳阳; 张莉; 陈莉

    2013-01-01

    目的测定辣椒碱在不同种类液态脂质中平衡溶解度,为进一步研究辣椒碱新剂型提供理论基础。方法建立高效液相色谱法(HPLC)测定辣椒碱在橄榄油、花生油、玉米油、葵花籽油、油酸、亚油酸、油酸乙酯、辛癸酸甘油酯以及肉豆蔻酸异丙酯等油类中的溶解度。结果25℃时,辣椒碱在不同液态脂质中的溶解度顺序为:油酸>油酸乙酯>肉豆蔻酸异丙酯>亚油酸>辛癸酸甘油酯>花生油>葵花籽油>玉米油>橄榄油。结论辣椒碱在单一脂类中的溶解度比在橄榄油、花生油、玉米油、葵花籽油等混合脂肪酸高。%Objective To determine the equilibrium solubility of capsaicin in various liquid lipids by high performance liquid chromatography (HPLC). Methods Capsaicin was solved in olive oil, peanut oil, corn oil, sunflower oil, oleic acid, linoleic acid, ethyl oleate, ODO, and IPM respectively. The values of equilibrium solubility of capsaicin in different liquid lipids were determined by HPLC. Results The liquid lipids in which capsaicin was solved with different values of equilibrium solubility at 25℃ (μg·mL-1) were arranged in descending order as oleic acid, ethyl oleate, Isopropyl myristate, linoleic acid, Caprylic/Capric Triglyceride, peanut oil, sunflower oil, corn oil, and olive oil. Conclusion The equilibrium solubility of capsaicin in pure liquid lipids like oleic acid tends to be higher than that in mixed lipids such as olive oil at 25℃.

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-04-22

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

  11. 辣椒素抑制胰腺癌裸鼠皮下移植瘤生长的实验研究%Capsaicin enhances the anti-tumor effect of gemcitabine on pancreatic cancer cell xenograft

    Institute of Scientific and Technical Information of China (English)

    刘南; 张兆伟; 孙刚

    2013-01-01

    目的 探讨辣椒素增强吉西他滨对胰腺癌T3M4细胞裸鼠移植瘤化疗作用及其机制.方法 建立耐药胰腺癌T3M4细胞的裸鼠皮下移植瘤动物模型,将荷瘤鼠随机分为:N组(生理盐水组),G组(吉西他滨,125 mg/kg),C组(辣椒素,20 mg/kg),G+C组(联合用药,吉西他滨80 mg/kg,辣椒素20 mg/kg).各组给药均采用腹腔注射的方法,每3d一次,共8次.实验过程中测量肿瘤体积.免疫组织化学法检测细胞增殖因子Ki-67、多药耐药蛋白P-gp和核转录因子NF-κB的表达.采用RT-PCR检测核转录因子NF-κB和多药耐药基因MDR1的表达.结果 末次用药1周后G+C组肿瘤体积和质量明显小于其他各组.免疫组织化学染色结果显示C组和G+C组的NF-κB和P-gp蛋白的表达量明显低于N组和G组.G+C组Ki-67的表达量明显低于其他各组.RT-PCR结果显示C组MDR1和NF-κB的表达水平明显低于N组和G组,G+C组NF-κB和MDR1的表达水平明显低于N组和G组.结论 辣椒素可以通过下调NF-κB的表达,抑制MDR1基因表达,有效地增强吉西他滨对胰腺癌T3M4细胞移植瘤的化疗作用.%Objective To investigate the enhanced effect of gemcitabine by capsaicin on T3M4 cell xenograft on athymic.Meethods The models of T3M4 cell xenograft on athymic mouse were established and randomized to four groups with intraperitoneal (IP)injection of different drugs (group N 0.9% sodium chloride),group G(gemcitabine,125 mg/kg),group C (capsaicin 20 mg/kg) and group G + C (gemcitabine 80 mg/kg and capsaicin 20 mg/kg in combination).The drugs were injected once every 3 days,8 times in all.The mice were sacrificed 1 week after the last injection.The tumor volume and tumor weight were measured during the drug therapy.Immunohistochemistry(IHC) was performed to detect the expression of NF-κB,P-gp and Ki-67,RT-PCR was performed to detect the expression of NF-κB and MDR1 mRNA.Results One week after the last administration,the mean tumor volume and tumor

  12. P物质抑制剂辣椒素和抗碱性成纤维细胞生长因子抗体联合应用对小鼠切口中胶原沉积的影响%Effects of inhibitory substance P, capsaicin and anti-basic fibroblast growth factor antibody on collagen deposition of excision scar formation in mice

    Institute of Scientific and Technical Information of China (English)

    肖丽玲; 刘宏伟; 张海伟; 杜彬; 郑佩娥

    2009-01-01

    目的 观察抗碱性成纤维细胞(bFGF)抗体和辣椒素对小鼠切口瘢痕组织中胶原沉积的影响,探讨它们对切口愈合期间瘢痕形成的作用.方法 建立小鼠背部切口愈合模型;应用不同种浓度(每只20、80 μg/0.1 ml)剂量的辣椒素组、抗bFGF抗体组(每只20、80μg/0.1 ml)、辣椒素(每只20μg/0.1 ml)+抗bFGF抗体(每只20 μg/0.1 ml)组作用于其切口瘢痕;于术后14 d切取切口瘢痕组织,采用Mason染色和计算机图像分析结合透射电镜来观察、分析切口瘢痕组织中胶原沉积情况.结果 低剂量的辣椒素(每只20 μg/0.1 ml)或抗bFGF抗体(每只20μg/0.1 ml)单独作用后14 d,切口瘢痕中胶原纤维分布的密度无明显变化;高剂量的辣椒素(每只80 μg/0.1 ml)或抗bFGF抗体(每只80 μg/0.1 ml)单独作用后14 d,切口瘢痕中胶原纤维分布的密度均明显减少;但低剂量的辣椒素(每只20 μg/0.1 ml)和抗bFGF抗体(每只20μg/0.1 ml)联合作用后14 d,切口瘢痕中胶原纤维分布的密度明显减少,显示了协同抑制作用.结论 辣椒素及抗bFGF抗体可抑制小鼠皮肤切口愈合过程中局部胶原的沉积,两者联合用药可协同抑制切口瘢痕的增生.%ObJective To observe the effects of inhibitory substance P (capsaicin) and anti-bas-ic fibroblast growth factor antibody on collagen deposition during excision scar formation and explore their effects on scar formation.Methods The excision injury model on the back of mice skin was developed,and the different final concentrations of capsaicin (20 and 80 μg/0.1 ml), anti-basic fibroblast growth fac-tor antibody (20 and 80 μg/0.1 ml),or capsaicin (20 μg/0.1 ml) in combination with anti-basic fibro-blast growth factor antibody (20 μg/0.1) were used in the excision injury.Results The high dose of capsaicin (80 μg/0.1 ml) or high anti-basic fibroblast growth factor antibody (80 μg/0.1 ml) markedly inhibited collagen deposition in the excision site, but low

  13. Anti-inflammatory and Analgesic Effects and Toxicity of Compound Diclofenac Capsaicin Cataplasms%复方双氯芬酸辣椒凝胶贴膏的抗炎镇痛作用与毒性反应

    Institute of Scientific and Technical Information of China (English)

    陈鹰; 陈湖海; 徐腾; 杜蓉; 李佳芝; 朱晓雯; 朱以良

    2012-01-01

    Objective: To stud) the anti-inflammatory and analgesic effects and toxicity of compound diclofenac capsaicin cataplasms ( CDCC ). Method: The anti-inflammatory and analgesic effects of CDCC on mice were researched by dimethyl-benzen induced ear oedema model, acetic acid induced writhing model and hot plate method. The acute toxicity of CDCC was studied in rats and the irritation test was observed in rabbits. Result: The ear swelling degree was inhibited significantly by CDCC. The writhing reaction induced by acetic acid was inhibited and the pain threshold induced by hot plate was raised significantly in mice. The dosage with no significant toxicity in rats was 200 mg穔g-1. Irritant symptoms were not significant in the integral skin, while mild irritation was shown in the damaged skin of rabbits. Conclusion: CDCC can be used in the treatment of local pain inflammation and the clinical dosages are safe, while attention should be paid for the use in damaged skin.%目的:研究复方双氯芬酸辣椒凝胶贴膏的抗炎镇痛作用及毒性反应.方法:采用二甲苯致炎法、醋酸扭体法和热板法,观察复方双氯芬酸辣椒凝胶贴膏局部给药对小鼠的抗炎镇痛作用.并考察大鼠的皮肤急性毒性和家兔皮肤刺激性.结果:复方双氯芬酸辣椒凝胶贴膏能显著抑制小鼠耳肿胀度,小鼠醋酸扭体反应和热板舔足反应;大鼠皮肤给药的无明显损害作用剂量为200 mg·kg-1,家兔皮肤给药对完整皮肤组无刺激性,对破损皮肤有轻度刺激性.结论:复方双氯芬酸辣椒凝胶贴膏可用于局部疼痛炎症的治疗,临床剂量下是安全的,但应慎用于破损皮肤.

  14. Vasodilating effect of capsaicin on rat mesenteric artery and its mechanism%辣椒素对大鼠肠系膜阻力血管的舒张作用及其机制

    Institute of Scientific and Technical Information of China (English)

    陈强; 朱欢欢; 张媛媛; 张媛; 王利宏; 郑良荣

    2013-01-01

    目的:观测辣椒素(capsaicin,CAP)对大鼠肠系膜阻力血管的舒张作用,探讨其可能机制.方法:雄性Sprague-Dawley大鼠,取肠系膜动脉三级分支约2 mm长血管环,置于DMT 610M系统,记录张力变化.结果:CAP(10-9~10-5 mol/L)对苯肾上腺素(PE)预收缩的内皮完整血管和去内皮血管产生浓度依赖性的舒张作用,其中内皮完整组的血管舒张作用比去内皮组更明显,两者相比CAP在10-7~1O-5 mol/L时,差异有统计学意义(P<0.01).该舒张作用可被一氧化氮合酶抑制剂L-NAME和CGRP竞争性阻滞剂CGRP8-37阻断.CGRP(10-10~3×10-8 mol/L)对PE预收缩的内皮完整血管和去内皮血管产生浓度依赖性的舒张作用,其中内皮完整组的血管舒张作用比去内皮组更明显,两者相比CGRP在3×10-9~3×10-8 mol/L时,差异有统计学意义(P<0.05).P物质对PE预收缩的内皮完整血管无舒张作用.结论:CAP对大鼠肠系膜阻力动脉具有部分内皮依赖性舒张作用,该作用机制与其促进内皮一氧化氮合酶(NOS)途径有关;CAP的非内皮依赖性舒张血管效应与CGRP释放有关.%Objective: To investigate the vasodilating effect of capsaicin ( CAP) on rat mesenteric artery and its mechanism. Methods: The third branch of the superior mesenteric artery in male Sprague-Dawley rat(250 -350 g) was excised,the periadventitial fat and connective tissue were removed and the mesenteric artery was dissected into 2 mm rings. Each ring was placed in a 5 ml organ bath of DMT 610M system and the tension was recorded. Results: CAP( 10 -9 - 10 -5 mol/L) relaxed endothelium-intact and endothelium-denuded mesenteric artery pre-constricted by phenylephrine ( 10-5 mol/L ) , and the vasodilation in endothelium-intact mesenteric artery was stronger than that in endothelium-denuded one. Pretreatment with either L-NAME (3×10-4mol/L) , an inhibitor of nitric oxide synthase ( NOS), or CGRP8-37(2×10-6 mol/L),an antagonist of calcitonin gene

  15. Effects and mechanisms of capsaicin on gastric motility in water immersion restraint stress rats%辣椒素对浸水-束缚应激大鼠胃动力作用及机制研究

    Institute of Scientific and Technical Information of China (English)

    李泽培; 唐川康; 史孝敏; 彭燕

    2016-01-01

    Objective To investigate the effects and mechanisms of capsaicin (CAP) on gastric motility in water immersion restraint stress rats . MethodsForty male SD rats were randomly divided into 4 groups (n=10):normal control group, model group, model+CAP group, and CAP group. The model of water immersion restraint stress was created by injecting capsaicin 1mg/g for 4 consecutive weeks. At the end of the experiment, gastric emptying rate of phenol red was tested and the expression of c-kit and SCF mRNAs were evaluated in the gastric antrum tissues. Results: ① The gastric emptying rate in CAP group was significantly higher than that in the control and model groups ( P<0.05 ), and the gastric emptying rate in the model+CAP and control groups were significantly higher than that in the model group ( P< 0.05 ). ② The expression of c-kit mRNA in model group was significantly lower than that in the control group (P<0.05), and the expression of c-kit mRNA in CAP group was significantly higher than that in the model group ( P< 0.05 ). The expression of SCF mRNA in model+CAP and CAP groups was significantly higher than that in the control and model groups (P<0.05), and the expression of SCF mRNA in control group was significantly higher than that in the model group ( P< 0.05 ). ConclusionThe CAP fed for 4 weeks could improve the gastric emptying rate in the normal and WIRS rats. The effect of CAP on gastric motility may come from the altered expression of SCF, but have no obvious relationship with interstitial cells of Cajal and the expression of c-kit.%目的::研究辣椒素(CAP)对浸水束缚应激(模型)导致的大鼠胃动力障碍的作用及其机制。方法:选取雄性SPF级SD大鼠40只随机均分为对照组、模型组、模型组+CAP组和CAP组4组,每组10只。采用浸水束缚应激法建立胃动力障碍大鼠模型,胃管注入CAP 1 mg/g,连续4周。实验末测定大鼠胃酚红排空率,并取胃窦组织用RT-PCR方法检测c-kit m

  16. 辣椒素对大鼠面部皮肤降钙素基因相关肽和一氧化氮合酶阳性神经纤维的影响%Effect of capsaicin on calcitonin gene-related peptide and nitric oxide synthase-positive nerve fiber in rat facial skin

    Institute of Scientific and Technical Information of China (English)

    丁继固; 茹立强

    2005-01-01

    BACKGROUND: The effect of external application of capsaicin in the treatment of superficial pain has been recognized, but its effect against trigeminal neuralgia by direct action on the nerve ending or nerves in the hypodermis or deep tissues awaits intensive investigation.OBJECTIVE: To observes the effect of subcutaneous injection of capsaicin on calcitonin gene-related peptide (CGRP) and nitric oxide synthase(NOS)-positive nerve fibers in rat facial skin.SETTING: Teaching and Research Division of Anatomy, Xianning Medical College, and Department of Neurobiology, Tongji Medical College of Huazhong University of Science and Technology.MATERIALS: This experiment was conducted in the Laboratory of Neurobiology, Tongji Medical College, between October and December 2003.Twenty healthy Wistar rats of either sex with body mass of 120-170 g were used.METHODS: The rats received subcutaneous injection of capsaicin for treatment of the suborbital branch of the trigeminal nerve on the right side,with the left side serving as the control side. According to the doses of capsaicin applied, the rats were divided into 4 groups, namely 20, 30, 50and 100 μL capsaicin groups with 5 rats in each group. Twenty-four hours after the injections, samples were obtained and cut into slices for microscopic observation and the expressions of CGRP and NOS were examined immunohistochemically.MAIN OUTCOME MEASURES: [1] Changes of CGRP and NOS-positive nerve fibers on the experimental side and image analysis of the mean absorbance of CGRP and NOS; [2] changes of characteristic behaviors and body signs of the rats.RESULTS: Totally 20 rats entered the result analysis. [1] Behavioral change: A few minutes after subcutaneous injection of capsaicin, the rats exhibited a series of characteristic behavioral and symptomatic changes,which gradually diminished or even vanished with the increase of the doses. [2] Microscopic changes: On the experimental side, no obvious difference was noted in the

  17. Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin.

    Science.gov (United States)

    2007-01-01

    Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of

  18. 慢性咳嗽常见病因之间咳嗽敏感性的差异%Difference of Capsaicin Cough Sensitivity in Common Causes of Chronic Cough

    Institute of Scientific and Technical Information of China (English)

    陈如冲; 刘春丽; 罗炜; 赖克方; 钟南山

    2013-01-01

    Diseases between 2005 to 2010.Using a modified diagnostic algorithm of chronic cough,common causes were identified.Capsaicin cough provocation test was also performed in these patients to assess the cough threshold.The relations between cough reflex sensitivity and duration of cough,cough severity,pulmonary function,induced sputum cell counts were then investigated.Results Through the diagnostic algorithm of chronic cough,the current study evaluated 133 adult patients,including 24 cases with upper airway cough syndrome (UACS),26 patients with cough variant asthma (CVA),31 cases with eosinophilic bronchitis (EB),30 patients with atopic cough (AC),22 cases with gastroesophageal reflux induced cough (GERC).There were 30 healthy volunteers recruited as normal control.The cough threshold of LgC5 in AC,CVA,EB,GERC and UACS was 1.70 ± 0.70,2.12 ± 0.67,2.13 ± 0.69,1.69 ± 0.73,2.16 ± 0.66,respectively.The LgC5 of the normal group (2.63 ± 0.39) was higher than those in chronic cough groups (All P < 0.05).The LgC5 of AC and GERC were lower than CVA,EB and UACS (all P < 0.05).Duration and daytime score of cough showed positive correlations with LgC5 (r =-0.280,-0.168,all P < 0.05).Pulmonary function and differential cell count of induced sputum were not associated with LgC5 (all P > 0.05).Conclusions Different cause of chronic cough exhbit high cough reflex sensitivity to different extent.The difference of cough sensitivity may reflect the different pathogenesis among different causes,and may be related to the type of nerve fiber dominating the cough reflex.

  19. 固相萃取-超高效液相色谱-串联质谱快速检测食用油和地沟油中辣椒素和二氢辣椒素%Fast Determination of Capsaicin and Dihydrocapsaicin in Edible and Illegal Cooking Oils by Combination of Solid Phase Extraction and Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    赵琴; 胡艺凡; 许静; 冯钰锜

    2014-01-01

    A simple one step solid phase extraction(SPE) method based on hydrogen bond interaction for the separation and purification of capsaicin and dihydrocapsaicin from oils was developed.Several parameters influencing the extraction efficiency including the amount of sorbent,the type and volume of desorption solvent,the amount of oil in the sampling solution and the batch of sorbent material were investigated.Under the optimized conditions,a rapid and cost-effective method for the determination of capsaicin and dihydrocapsaicin in edible and illegal cooking oils was established by coupling with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis.The linear range of the proposed method was 0.01-100 ng/mL with satisfactory correlation coefficients(R2) between 0.9983 and 0.9998.The limits of detection for the target analytes were as low as 4.5 pg/mL.In addition,a satisfying reproducibility was achieved by evaluating the intra-and inter-day precisions with relative standard deviations (RSDs) less than 12.2% and 14.1%,respectively.Finally,the established method was successfully applied to the analysis of capsaicin and dihydrocapsaicin in a variety of edible and illegal cooking oils.Taken together,the SPE-UPLC-MS/MS method developed in current study provides a new option for the identification of illegal cooking oils.%采用基于氢键相互作用原理的固相萃取与超高效液相色谱-串联质谱联用技术,建立了食用油和地沟油中天然辣椒素和二氢辣椒素的快速分析方法.该方法中油脂样品经正己烷稀释后直接进行固相萃取.优化了一系列影响萃取效率的参数,包括固相萃取材料用量、解吸液种类、解吸液体积、上样液中油脂基质的含量等.在优化条件下,以上两种目标物在0.01~100 ng/mL范围内线性关系良好(R2>0.9983),检出限低至4.5 pg/mL,日内、日间相对标准偏差分别小于12.2%和14.1%.该方法已成功应用于多

  20. Capsaicin receptor immunoreactivity in the human trigeminal ganglion

    DEFF Research Database (Denmark)

    Hou, Mingyan; Uddman, Rolf; Tajti, Janos; Kanje, Martin; Edvinsson, Lars

    2002-01-01

    protons, and therefore it is suggested as a molecular integrator of chemical and physical stimuli that elicit pain. In the present study, indirect immunofluorescence detected a small number of neurons that are VR1 receptor immunoreactive (ir) (171 versus 1038 or 16% of all neuronal cell bodies) in the...

  1. The capsaicin receptor participates in artificial sweetener aversion.

    Science.gov (United States)

    Riera, Céline E; Vogel, Horst; Simon, Sidney A; Damak, Sami; le Coutre, Johannes

    2008-11-28

    Artificial sweeteners such as saccharin, aspartame, acesulfame-K, and cyclamate produce at high concentrations an unpleasant after-taste that is generally attributed to bitter and metallic taste sensations. To identify receptors involved with the complex perception of the above compounds, preference tests were performed in wild-type mice and mice lacking the TRPV1 channel or the T1R3 receptor, the latter being necessary for the perception of sweet taste. The sweeteners, including cyclamate, displayed a biphasic response profile, with the T1R3 mediated component implicated in preference. At high concentrations imparting off-taste, omission of TRPV1 reduced aversion. In a heterologous expression system the Y511A point mutation in the vanilloid pocket of TRPV1 did not affect saccharin and aspartame responses but abolished cyclamate and acesulfame-K activities. The results rationalize artificial sweetener tastes and off-tastes by showing that at low concentrations, these molecules stimulate the gustatory system through the hedonically positive T1R3 pathway, and at higher concentrations, their aversion is partly mediated by TRPV1. PMID:18804451

  2. Nitrate Promotes Capsaicin Accumulation in Capsicum chinense Immobilized Placentas

    OpenAIRE

    Aldana-Iuit, Jeanny G.; Enrique Sauri-Duch; María de Lourdes Miranda-Ham; Lizbeth A. Castro-Concha; Luis F. Cuevas-Glory; Vázquez-Flota, Felipe A.

    2015-01-01

    In chili pepper’s pods, placental tissue is responsible for the synthesis of capsaicinoids (CAPs), the compounds behind their typical hot flavor or pungency, which are synthesized from phenylalanine and branched amino acids. Placental tissue sections from Habanero peppers (Capsicum chinense Jacq.) were immobilized in a calcium alginate matrix and cultured in vitro, either continuously for 28 days or during two 14-day subculture periods. Immobilized placental tissue remained viable and metabol...

  3. Nitrate promotes capsaicin accumulation in Capsicum chinense immobilized placentas.

    Science.gov (United States)

    Aldana-Iuit, Jeanny G; Sauri-Duch, Enrique; Miranda-Ham, María de Lourdes; Castro-Concha, Lizbeth A; Cuevas-Glory, Luis F; Vázquez-Flota, Felipe A

    2015-01-01

    In chili pepper's pods, placental tissue is responsible for the synthesis of capsaicinoids (CAPs), the compounds behind their typical hot flavor or pungency, which are synthesized from phenylalanine and branched amino acids. Placental tissue sections from Habanero peppers (Capsicum chinense Jacq.) were immobilized in a calcium alginate matrix and cultured in vitro, either continuously for 28 days or during two 14-day subculture periods. Immobilized placental tissue remained viable and metabolically active for up to 21 days, indicating its ability to interact with media components. CAPs contents abruptly decreased during the first 7 days in culture, probably due to structural damage to the placenta as revealed by scanning electron microcopy. CAPs levels remained low throughout the entire culture period, even though a slight recovery was noted in subcultured placentas. However, doubling the medium's nitrate content (from 40 to 80 mM) resulted in an important increment, reaching values similar to those of intact pod's placentas. These data suggest that isolated pepper placentas cultured in vitro remain metabolically active and are capable of metabolizing inorganic nitrogen sources, first into amino acids and, then, channeling them to CAP synthesis. PMID:25710024

  4. Reducing agent dithiothreitol facilitates activity of the capsaicin receptor VR-1

    Czech Academy of Sciences Publication Activity Database

    Vyklický st., Ladislav; Lyfenko, Alla; Sušánková, Klára; Teisinger, Jan; Vlachová, Viktorie

    2002-01-01

    Roč. 111, č. 3 (2002), s. 435-441. ISSN 0306-4522 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : dorsal root ganglion neurone * HEK293 cell * sulfhydryl group Subject RIV: ED - Physiology Impact factor: 3.457, year: 2002

  5. A novel method of selective ablation of afferent renal nerves by periaxonal application of capsaicin

    OpenAIRE

    Foss, Jason D.; Wainford, Richard D.; Engeland, William C.; Fink, Gregory D.; Osborn, John W.

    2014-01-01

    Renal denervation has been shown to lower arterial pressure in some hypertensive patients, yet it remains unclear whether this is due to ablation of afferent or efferent renal nerves. To investigate the role of afferent renal nerves in arterial pressure regulation, previous studies have used methods that disrupt both renal and nonrenal afferent signaling. The present study was conducted to develop and validate a technique for selective ablation of afferent renal nerves that does not disrupt o...

  6. Sensitization of capsaicin and icilin responses in oxaliplatin treated adult rat DRG neurons

    Directory of Open Access Journals (Sweden)

    Anand Praveen

    2010-11-01

    Full Text Available Abstract Background Oxaliplatin chemotherapy induced neuropathy is a dose related cumulative toxicity that manifests as tingling, numbness, and chronic pain, compromising the quality of life and leading to discontinued chemotherapy. Patients report marked hypersensitivity to cold stimuli at early stages of treatment, when sensory testing reveals cold and heat hyperalgesia. This study examined the morphological and functional effects of oxaliplatin treatment in cultured adult rat DRG neurons. Results 48 hour exposure to oxaliplatin resulted in dose related reduction in neurite length, density, and number of neurons compared to vehicle treated controls, using Gap43 immunostaining. Neurons treated acutely with 20 μg/ml oxaliplatin showed significantly higher signal intensity for cyclic AMP immunofluorescence (160.5 ± 13 a.u., n = 3, P Conclusions Oxaliplatin treatment induces TRP sensitization mediated by increased intracellular cAMP, which may cause neuronal damage. These effects may be mitigated by co-treatment with adenylyl cyclase inhibitors, like CB2 agonists, to alleviate the neurotoxic effects of oxaliplatin.

  7. Costs and benefits of capsaicin-mediated control of gut retention in dispersers of wild chilies

    OpenAIRE

    Tewksbury, Joshua J.; Levey, Douglas J.; Huizinga, Meribeth; Haak, David C.; TRAVESET, ANNA

    2008-01-01

    A fundamental way in which animal-dispersed plants can influence the viability and distribution of dispersed seeds is through control of retention time in the guts of dispersers. Using two species of wild chilies and their dispersers, we examined how chemical and physical properties of fruits and seeds mediate this interaction. Capsicum chacoense is polymorphic for pungency, occurs in Bolivia, and is dispersed mostly by elaenias. Capsicum annuum is not polymorphic, occurs in Arizona (USA), an...

  8. Molecular target size of the vanilloid (capsaicin) receptor in pig dorsal root ganglia

    International Nuclear Information System (INIS)

    The size of the vanilloid receptor was examined by high-energy radiation inactivation analysis of the binding of [3H]resiniferatoxin to pig dorsal root ganglion membranes; it was found to be 270 ± 25 kDa. This value most likely represents the size of a receptor complex rather than of an individual subunit. Other ligand-gated cation channel complexes have reported molecular weights in this range, e.g. 300 kDa for the acetylcholine receptor

  9. Mechanisms of acute Ca 2+ dependent desensitization of TRPV1 ( capsaicin) receptor

    Czech Academy of Sciences Publication Activity Database

    Toušová, Karolina; Sušánková, Klára; Benedikt, Jan; Teisinger, Jan; Vyklický st., Ladislav; Vlachová, Viktorie

    Elsevier. Roč. 10, Suppl.1 (2006), S49-S49. ISSN 1090-3801. [Pain in Europe /5./. 12.09.2006 - 17.09.2006, Istanbul] Institutional research plan: CEZ:AV0Z50110509 Keywords : vanilloid * TRPV1 Subject RIV: ED - Physiology

  10. Electronic Nose Based Alternative Method for the Determination of Capsaicin in Hot Chili Pepper

    Science.gov (United States)

    Mohamed, E. I.; Andreoli, A.; Martinelli, E.; Candeloro, N.; Mantini, A.; di Natale, C.; de Lorenzo, A.

    2000-12-01

    The aim of the present study is to examine the EN aptitude to evaluate different pepper brands' freshness by repeated measurements of chosen pepper samples. This, in addition to study the possibility of differentiation and classification of Bell, Thai and Scotch Bonnet pepper brands, available in the Italian market.

  11. Molecular target size of the vanilloid (capsaicin) receptor in pig dorsal root ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Szallasi, A.; Blumberg, P.M. (National Cancer Institute, Bethesda, MD (USA))

    1991-01-01

    The size of the vanilloid receptor was examined by high-energy radiation inactivation analysis of the binding of ({sup 3}H)resiniferatoxin to pig dorsal root ganglion membranes; it was found to be 270 {plus minus} 25 kDa. This value most likely represents the size of a receptor complex rather than of an individual subunit. Other ligand-gated cation channel complexes have reported molecular weights in this range, e.g. 300 kDa for the acetylcholine receptor.

  12. Differential effect of intravenous S-ketamine and fentanyl on atypical odontalgia and capsaicin-evoked pain

    DEFF Research Database (Denmark)

    Baad-Hansen, Lene; Juhl, Gitte Irene; Jensen, Troels Staehelin;

    2007-01-01

    Atypical odontalgia (AO) is an intraoral pain condition of currently unknown mechanisms. In 10 AO patients and 10 matched healthy controls, we examined the effect of intravenous infusion of an N-methyl-D-aspartate (NMDA) receptor antagonist S-ketamine and a mu-opioid agonist fentanyl on spontaneous...... neuropathic pain conditions, fentanyl and S-ketamine in the present doses failed to attenuate AO pain....

  13. Capsaicin Synthesis Requires in Situ Phenylalanine and Valine Formation in in Vitro Maintained Placentas from Capsicum chinense.

    Science.gov (United States)

    Baas-Espinola, Fray M; Castro-Concha, Lizbeth A; Vázquez-Flota, Felipe A; Miranda-Ham, María L

    2016-01-01

    Capsaicinoids (CAP) are nitrogenous metabolites formed from valine (Val) and phenylalanine (Phe) in the placentas of hot Capsicum genotypes. Placentas of Habanero peppers can incorporate inorganic nitrogen into amino acids and have the ability to secure the availability of the required amino acids for CAP biosynthesis. In order to determine the participation of the placental tissue as a supplier of these amino acids, the effects of blocking the synthesis of Val and Phe by using specific enzyme inhibitors were analyzed. Isolated placentas maintained in vitro were used to rule out external sources' participation. Blocking Phe synthesis, through the inhibition of arogenate dehydratase, significantly decreased CAP accumulation suggesting that at least part of Phe required in this process has to be produced in situ. Chlorsulfuron inhibition of acetolactate synthase, involved in Val synthesis, decreased not only Val accumulation but also that of CAP, pointing out that the requirement for this amino acid can also be fulfilled by this tissue. The presented data demonstrates that CAP accumulation in in vitro maintained placentas can be accomplished through the in situ availability of Val and Phe and suggests that the synthesis of the fatty acid chain moiety may be a limiting factor in the biosynthesis of these alkaloids. PMID:27338325

  14. POTENTIATION OF PULMONARY REFLEX RESPONSE TO CAPSAICIN 24 HOURS FOLLOWING WHOLE-BODY ACROLEIN EXPOSURE IS MEDIATED BY TRPV1

    Science.gov (United States)

    Pulmonary C-fibers are stimulated by irritant air pollutants producing apnea, bronchospasm, and decrease in HR. C-fiber chemoreflex activation is mediated by TRPV1 and release of substance P. While acrolein has been shown to stimulate C-fibers, the persistence of acrolein effect...

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

    OpenAIRE

    Esmaeal Tamaddonfard; Sina Tamaddonfard; Salar Pourbaba

    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 induce...

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

    OpenAIRE

    Kondo E; Jinnouchi O; Ohnishi H.; Kawata I; Nakano S; Goda M; Kitamura Y; Abe K.; Hoshikawa H; Okamoto H; Takeda N

    2014-01-01

    Eiji Kondo,1,2 Osamu Jinnouchi,3 Hiroki Ohnishi,3 Ikuji Kawata,3 Seiichi Nakano,2 Masakazu Goda,1 Yoshiaki Kitamura,1 Koji Abe,1 Hiroshi Hoshikawa,4 Hidehiko Okamoto,5 Noriaki Takeda1 1Department of Otolaryngology, University of Tokushima School of Medicine, Tokushima, Japan; 2Department of Otolaryngology, Kochi National Hospital, Kochi, Japan; 3Department of Otolaryngology, Anan Kyoei Hospital, Anan, Japan; 4Department of Otolaryngology, Kagawa University School of Medicine, Kagawa, Japan; ...

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

    OpenAIRE

    du Jardin, Kristian G; Gregersen, Lise S; Røsland, Turid; Uggerhøj, Kathrine H; Petersen, Lars J.; Arendt-Nielsen, Lars; Gazerani, Parisa

    2013-01-01

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

  18. Local capsaicin and TRPV1 antagonist application attenuate postoperative hyperalgesic responses in the rat model of incisional pain

    Czech Academy of Sciences Publication Activity Database

    Pospíšilová, Eva; Paleček, Jiří

    Washington : Society for Neuroscience, 2005. [Society of Neuroscience - Annual Meeting /35./. 12.11.2005-16.11.2005, Washington, DC] R&D Projects: GA ČR(CZ) GA309/03/0752; GA ČR(CZ) GD305/03/H148 Institutional research plan: CEZ:AV0Z50110509 Keywords : TRPV1 receptors Subject RIV: ED - Physiology

  19. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.

    Science.gov (United States)

    Chuang, H H; Prescott, E D; Kong, H; Shields, S; Jordt, S E; Basbaum, A I; Chao, M V; Julius, D

    2001-06-21

    Tissue injury generates endogenous factors that heighten our sense of pain by increasing the response of sensory nerve endings to noxious stimuli. Bradykinin and nerve growth factor (NGF) are two such pro-algesic agents that activate G-protein-coupled (BK2) and tyrosine kinase (TrkA) receptors, respectively, to stimulate phospholipase C (PLC) signalling pathways in primary afferent neurons. How these actions produce sensitization to physical or chemical stimuli has not been elucidated at the molecular level. Here, we show that bradykinin- or NGF-mediated potentiation of thermal sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons. Diminution of plasma membrane phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) levels through antibody sequestration or PLC-mediated hydrolysis mimics the potentiating effects of bradykinin or NGF at the cellular level. Moreover, recruitment of PLC-gamma to TrkA is essential for NGF-mediated potentiation of channel activity, and biochemical studies suggest that VR1 associates with this complex. These studies delineate a biochemical mechanism through which bradykinin and NGF produce hypersensitivity and might explain how the activation of PLC signalling systems regulates other members of the TRP channel family. PMID:11418861

  20. Drug: D00250 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00250 Drug Capsaicin (JAN/USP); Zostrix (TN) C18H27NO3 305.1991 305.4119 D00250.gi...ULAR PAIN M02A TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN M02AB Capsaicin and similar agents M02AB01 Capsaicin D00250 Capsaicin..., LOCAL N01BX Other local anesthetics N01BX04 Capsaicin D00250 Capsaicin (JAN/USP) Target-based classificati..., member 1 (TRPV1) [HSA:7442] [KO:K05222] Capsaicin [ATC:M02AB01 N01BX04] D00250 Capsaicin (JAN/USP) CAS: 40

  1. Overexpression of artemin in the tongue increases expression of TRPV1 and TRPA1 in trigeminal afferents and causes oral sensitivity to capsaicin and mustard oil

    OpenAIRE

    Elitt, Christopher M.; Malin, Sacha A.; Koerber, H Richard; Davis, Brian M.; Albers, Kathryn M.

    2008-01-01

    Artemin, a member of the glial cell line-derived neurotrophic factor (GDNF) family, supports a subpopulation of trigeminal sensory neurons through activation of the Ret/GFRα3 receptor tyrosine kinase complex. In a previous study we showed that artemin is increased in inflamed skin of wildtype mice and that transgenic overexpression of artemin in skin increases TRPV1 and TRPA1 expression in dorsal root ganglia neurons. In this study we examined how transgenic overexpression of artemin in tongu...

  2. Effect of foliar fertilization of Capsicum annuum L. together with optimal root fertilization in hydroponic culture on fruit yield and its capsaicin content

    OpenAIRE

    Tomasz J. Nowak

    2013-01-01

    The Wrocław version of hydroponic culture was applied. The optimal dose of mineral nutrient solution for root-fertilizing was found to be 19,6g and 22,4g of mineral salts per one plant during the whole vegetation season. In a separate experiment plants with optimal root fertilization were sprayed with multicomponent solutions of mineral salts. The sprays were applied weekly for 15 weeks. The concentrations of solutions for spraying were: 0,28, 0,84 and 1,4 per cent. The greatest increase of f...

  3. Inhibitors of monoacylglycerol lipase, fatty-acid amide hydrolase and endocannabinoid transport differentially suppress capsaicin-induced behavioral sensitization through peripheral endocannabinoid mechanisms

    OpenAIRE

    Spradley, Jessica M.; Guindon, Josée; Hohmann, Andrea G.

    2010-01-01

    Monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH) degrade the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA), respectively. Pharmacological inhibition of these enzymes in the periphery may elucidate the role of endocannabinoids in controlling nociceptive transmission. We compared effects of the MGL inhibitor JZL184, the FAAH inhibitor URB597, and the endocannabinoid uptake inhibitor VDM11, administered locally in the paw, on behavioral hypersensitivities...

  4. Benzodiazepine-induced intestinal motor disturbances in rats: mediation by omega 2 (BZ2) sites on capsaicin-sensitive afferent neurones.

    OpenAIRE

    Bonnafous, C; Scatton, B; BUÉNO, L.

    1994-01-01

    1. The central and peripheral effects of the omega (benzodiazepine) site ligands, clonazepam, alpidem, zolpidem, triazolam, flumazenil, ethyl beta carboline-3-carboxylate (beta-CCE) and N-methyl beta carboline-3-carboxylate (beta-CCM) on intestinal myoelectrical activity were evaluated in conscious rats, chronically fitted with Nichrome electrodes implanted on the duodenum and jejunum. The localization of the omega (benzodiazepine) receptors involved in these effects was evaluated by use of s...

  5. Considerable variability in the efficacy of 8% capsaicin topical patches in the treatment of chronic pruritus in 3 patients with notalgia paresthetica

    DEFF Research Database (Denmark)

    Andersen, Hjalte Holm; Sand, Carsten; Elberling, Jesper

    2016-01-01

    Notalgia paresthetica (NP) is a focal neuropathic itch con- dition manifesting in intense chronic or recurrent episodic itch in a hyperpigmented, macular, uni- or bilateral skin area located below and/or medially to the scapulae. Achieving satisfactory relieve in NP patients is challenging...

  6. The role of TRPV1 receptors in cutaneous hypersensitivity following surgical incision and the effect of local capsaicin treatment on postoperative pain

    Czech Academy of Sciences Publication Activity Database

    Pospíšilová, Eva; Paleček, Jiří

    Fyziologický ústav AV ČR, v. v. i.. Roč. 55, č. 4 (2006), s. 55-55 ISSN 0862-8408. [Physiological Days /82./. 07.02.2006-09.02.2006, Prague] R&D Projects: GA ČR(CZ) GA309/03/0752; GA ČR(CZ) GA305/06/1115; GA ČR(CZ) GD305/03/H148; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z5011922 Keywords : postoperative pain Subject RIV: ED - Physiology

  7. 辣椒素经大鼠肠黏膜的区段透过特性%Study on permeability of capsaicin via different intestinal mucosa in rat

    Institute of Scientific and Technical Information of China (English)

    段炼; 李国锋; 孙亚彬; 周望梅; 李科

    2010-01-01

    目的 研究辣椒素经大鼠空肠、回肠和结肠黏膜的区段透过特性.方法 应用体外Ussing Chamber法,评价100 μg·mL-1辣椒素经空肠、回肠和结肠黏膜的经时吸收方向的累计透过量,并计算表观渗透系数,辣椒素在接收池中的浓度用HPLC法测定.结果 辣椒素经结肠和回肠的透过性显著高于空肠,在结肠的透过性也显著高于回肠.结论 辣椒素在大鼠肠黏膜中的透过性存在区段性差异,在空肠部位吸收最差,结肠部位吸收最好,可考虑将其制成结肠定位肠溶片.

  8. Capsaicin consumption, Helicobacter pylori CagA status and IL1B-31C > T genotypes: A host and environment interaction in gastric cancer

    OpenAIRE

    López-Carrillo, Lizbeth; Camargo, M. Constanza; Schneider, Barbara G.; Sicinschi, Liviu A.; Hernández-Ramírez, Raúl U.; Correa, Pelayo; Cebrian, Mariano E.

    2012-01-01

    Gastric cancer (GC) has been associated with a complex combination of genetic and environmental factors. In contrast to most countries, available information on GC mortality trends showed a gradual increase in Mexico. Our aim was to explore potential interactions among dietary (chili pepper consumption), infectious (Helicobacter pylori) and genetic factors (IL1B-31 genotypes) on GC risk. The study was performed in three areas of Mexico, with different GC mortality rates. We included 158 GC pa...

  9. Aumento del umbral tusígeno en sujetos sanos con el uso de Levodropropizina INCREASE OF THE COUGH THRESHOLD TO CAPSAICIN IN HEALTHY ADULTS BY ADMINISTERING LEVODROPROPIZINE

    OpenAIRE

    Patricia Schönffeldt G; Juan Céspedes G.; Ricardo Sepúlveda M.; M. Eugenia Salamanca H.

    2005-01-01

    Se diseñó un estudio aleatorio prospectivo, doble ciego cruzado contra placebo, para estudiar la reproducibilidad y las modificaciones del umbral tusígeno (UT) inducido por capsaicina, luego de administrar placebo y Levodropropizina (un nuevo antitusivo sintético). Se determinó el UT basal (logaritmo de la concentración de capsaicina que induce al menos dos toses consecutivas) en 20 voluntarios adultos sanos, no fumadores de ambos sexos con edad promedio de 34,9 años (rango: 18 a 57 años). El...

  10. Drug: D06455 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06455 Crude, Drug Capsicum tincture (JP16); Capsicum extract; Capsicum tincture (TN) Capsaicin...gory: 2649 Solanaceae (nightshade family) Capsicum seed and mature fruit (dried) Major component: Capsaicin

  11. CORRIGENDUM to J Exp Integr Med 2013; 3(3: 191-197 - ETB receptor activation as a mechanism of modulation of inflammatory pain and neurogenic inflammation in the temporomandibular joint of capsaicin-treated rats

    Directory of Open Access Journals (Sweden)

    Thiago E. V. Lemos

    2014-02-01

    Full Text Available The Publisher and the Editorial Board regrets to declare an obligatory modification in the author list of the above manuscript originally published in the July 2013 issue (Volume 3, Issue 3 of the Journal. Three months after publication in both print and online forms, the author in the third order of the first published version contacted the Editorial Board and declared that he did not participate to this work and requested his name to be removed from the author list. During submission, the Journal of Experimental and Integrative Medicine requests a clear statement that all authors are aware of the work, as was done for this particular article; thus, neither the Publisher nor the editors are responsible for this unwanted condition. This one-page publication corrects and updates the author list for the above-mentioned paper. The same correction was also done in the web page of the Journal (www.jeim.org/?mno=34844, however, the PDF-document remained unchanged as the same in the print version of the Journal. [J Exp Integr Med 2014; 4(1.000: 74-74

  12. Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy

    Directory of Open Access Journals (Sweden)

    Bountra Chas

    2007-05-01

    Full Text Available Abstract Background Transient receptor potential (TRP receptors expressed by primary sensory neurons mediate thermosensitivity, and may play a role in sensory pathophysiology. We previously reported that human dorsal root ganglion (DRG sensory neurons co-expressed TRPV1 and TRPV3, and that these were increased in injured human DRG. Related receptors TRPV4, activated by warmth and eicosanoids, and TRPM8, activated by cool and menthol, have been characterised in pre-clinical models. However, the role of TRPs in common clinical sensory neuropathies needs to be established. Methods We have studied TRPV1, TRPV3, TRPV4, and TRPM8 in nerves (n = 14 and skin from patients with nerve injury, avulsed dorsal root ganglia (DRG (n = 11, injured spinal nerve roots (n = 9, diabetic neuropathy skin (n = 8, non-diabetic neuropathic nerve biopsies (n = 6, their respective control tissues, and human post mortem spinal cord, using immunohistological methods. Results TRPV1 and TRPV3 were significantly increased in injured brachial plexus nerves, and TRPV1 in hypersensitive skin after nerve repair, whilst TRPV4 was unchanged. TRPM8 was detected in a few medium diameter DRG neurons, and was unchanged in DRG after avulsion injury, but was reduced in axons and myelin in injured nerves. In diabetic neuropathy skin, TRPV1 expressing sub- and intra-epidermal fibres were decreased, as was expression in surviving fibres. TRPV1 was also decreased in non-diabetic neuropathic nerves. Immunoreactivity for TRPV3 was detected in basal keratinocytes, with a significant decrease of TRPV3 in diabetic skin. TRPV1-immunoreactive nerves were present in injured dorsal spinal roots and dorsal horn of control spinal cord, but not in ventral roots, while TRPV3 and TRPV4 were detected in spinal cord motor neurons. Conclusion The accumulation of TRPV1 and TRPV3 in peripheral nerves after injury, in spared axons, matches our previously reported changes in avulsed DRG. Reduction of TRPV1 levels in nerve fibres in diabetic neuropathy skin may result from the known decrease of nerve growth factor (NGF levels. The role of TRPs in keratinocytes is unknown, but a relationship to changes in NGF levels, which is produced by keratinocytes, deserves investigation. TRPV1 represents a more selective therapeutic target than other TRPs for pain and hypersensitivity, particularly in post-traumatic neuropathy.

  13. Central sensitization in spinal cord injured humans assessed by reflex receptive fields

    DEFF Research Database (Denmark)

    Biurrun Manresa, José Alberto; Finnerup, Nanna Susanne Brix; Johannesen, Inger Lauge; Biering-Sørensen, Fin; Jensen, Troels Staehelin; Arendt-Nielsen, Lars; Andersen, Ole Kæseler

    2014-01-01

    OBJECTIVE: To investigate the effects of central sensitization, elicited by intramuscular injection of capsaicin, by comparing the reflex receptive fields (RRF) of spinally-intact volunteers and spinal cord injured volunteers that present presensitized spinal nociceptive mechanisms. METHODS...... after an intramuscular injection of capsaicin in the foot sole in order to induce central sensitization. RESULTS: Both groups presented RRF expansion and lowered NWR thresholds immediately after capsaicin injection, reflected by the enlargement of RRF sensitivity areas and RRF probability areas...

  14. TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice

    OpenAIRE

    Luo, Zhidan; Ma, Liqun; Zhao, Zhigang; He, Hongbo; Yang, Dachun; Feng, Xiaoli; Ma, Shuangtao; Chen, Xiaoping; Zhu, Tianqi; Cao, Tingbing; Liu, Daoyan; Nilius, Bernd; Yu HUANG; Yan, Zhencheng; Zhu, Zhiming

    2011-01-01

    Impaired aerobic exercise capacity and skeletal muscle dysfunction are associated with cardiometabolic diseases. Acute administration of capsaicin enhances exercise endurance in rodents, but the long-term effect of dietary capsaicin is unknown. The capsaicin receptor, the transient receptor potential vanilloid 1 (TRPV1) cation channel has been detected in skeletal muscle, the role of which remains unclear. Here we report the function of TRPV1 in cultured C2C12 myocytes and the effect of TRPV1...

  15. Light Intensity Affects Pungency of Hot Pepper (Capsicum annuum L.) Fruits

    Institute of Scientific and Technical Information of China (English)

    LV Chang-shan; WANG Jin-ling; YU Guang-jian

    2005-01-01

    This study was carried out both laboratory and field experiment to research the effects of three different light intensity on capsaicin content of hot pepper fruits during the growing stage, the varieties in the study were in different hot levels named No.4 Xiangyan (mid-hot) and No.3 Jingjianjiao (very hot). The study showed that capsaicin content increased accompanied with light intensity weakening. There was an inverse relationship between capsaicin content and peroxidase activity.

  16. Thermal and radiation resistance of stabilized LDPE

    Energy Technology Data Exchange (ETDEWEB)

    Zaharescu, T., E-mail: traian_zaharescu@yahoo.co [INCDIE ICPE CA, Department of Radiation Processing, 313 Splaiul Unirii, P.O. Box 149, Bucharest 030138 (Romania); Jipa, S. [INCDIE ICPE CA, Department of Radiation Processing, 313 Splaiul Unirii, P.O. Box 149, Bucharest 030138 (Romania); ' Valahia' University of Targoviste, Faculty of Sciences, Targoviste 130024 (Romania); Henderson, D. [Trinity College, Hartford, CT 06106 (United States); Kappel, W. [INCDIE ICPE CA, Department of Radiation Processing, 313 Splaiul Unirii, P.O. Box 149, Bucharest 030138 (Romania); Maris, D.A.; Maris, M. [' Ovidius' University, 7 Ilarie Voronca St, P.O. Box 8700, Constanta (Romania)

    2010-03-15

    The effect of capsaicin on the radiation stability of low density polyethylene was accomplished by applying the chemiluminescence procedure. The neat and modified polymer with 0.25% and 0.50% (w/w) capsaicin were exposed to gamma-irradiation in air receiving 10, 20 and 30 kGy. The synergistic effect due to the presence of metallic selenium was demonstrated. The significant improvement in oxidation induction time was obtained demonstrating the efficient antioxidant activity of capsaicin in LDPE. The simultaneous protection action of metallic selenium in LDPE/capsaicin systems brought about a supplementary enhancement in the oxidation resistance of irradiated samples.

  17. Thermal and radiation resistance of stabilized LDPE

    International Nuclear Information System (INIS)

    The effect of capsaicin on the radiation stability of low density polyethylene was accomplished by applying the chemiluminescence procedure. The neat and modified polymer with 0.25% and 0.50% (w/w) capsaicin were exposed to γ-irradiation in air receiving 10, 20 and 30 kGy. The synergistic effect due to the presence of metallic selenium was demonstrated. The significant improvement in oxidation induction time was obtained demonstrating the efficient antioxidant activity of capsaicin in LDPE. The simultaneous protection action of metallic selenium in LDPE/capsaicin systems brought about a supplementary enhancement in the oxidation resistance of irradiated samples.

  18. Environ: E00014 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available E00014 Capsicum (JP16/USP) Cayenne papper Crude drug; Medicinal herb Capsaicin [CPD...(dried) Major component: Capsaicin [CPD:C06866] Medicinal herbs [BR:br08322] Dicot plants: asterids Solanaceae (nightshade family) E00014 Cayenne papper ...

  19. Effects of Nitrogenous Fertilizer on Pungency of Hot Pepper (Capsicum annuum L.) Fruits

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The response of pungency of hot pepper fruits nitrogenous fertilizer on was invesigated. The results indicated that nitrogenous fertilizer had a significant effect on the capsaicin content of hot pepper fruits at 35 and 42 days after flowering;capsaicin content gradually decreased, while peroxidase activity increased with nitrogenous fertilizer increasing.

  20. TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice

    Institute of Scientific and Technical Information of China (English)

    Zhidan Luo; Tingbing Cao; Daoyan Liu; Bernd Nilius; Yu Huang; Zhencheng Yan; Zhiming Zhu; Liqun Ma; Zhigang Zhao; Hongbo He; Dachun Yang; Xiaoli Feng; Shuangtao Ma; Xiaoping Chen; Tianqi Zhu

    2012-01-01

    Impaired aerobic exercise capacity and skeletal muscle dysfunction are associated with cardiometabolic diseases.Acute administration of capsaicin enhances exercise endurance in rodents,but the long-term effect of dietary capsaicin is unknown.The capsaicin receptor,the transient receptor potential vanilloid 1(TRPV1)cation channel has been detected in skeletal muscle,the role of which remains unclear.Here we report the function of TRPV1 in cultured C2C12 myocytes and the effect of TRPV1 activation by dietary capsaicin on energy metabolism and exercise endurance of skeletal muscles in mice.In vitro,capsaicin increased cytosolic free calcium and peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α)expression in C2C12 myotubes through activating TRPV1.In vivo,PGC-1α in skeletal muscle was upregulated by capsaicin-induced TRPV1 activation or genetic overexpression of TRPV1 in mice.TRPV1 activation increased the expression of genes involved in fatty acid oxidation and mitochondrial respiration,promoted mitochondrial biogenesis,increased oxidative fibers,enhanced exercise endurance and prevented high-fat diet-induced metabolic disorders.Importantly,these effects of capsaicin were absent in TRPV1-deficient mice.We conclude that TRPV1 activation by dietary capsaicin improves energy metabolism and exercise endurance by upregulating PGC-1α in skeletal muscles.The present results indicate a novel therapeutic strategy for managing metabolic diseases and improving exercise endurance.

  1. TRPV1 stimulation triggers apoptotic cell death of rat cortical neurons

    International Nuclear Information System (INIS)

    Transient receptor potential vanilloid 1 (TRPV1) functions as a polymodal nociceptor and is activated by several vanilloids, including capsaicin, protons and heat. Although TRPV1 channels are widely distributed in the brain, their roles remain unclear. Here, we investigated the roles of TRPV1 in cytotoxic processes using TRPV1-expressing cultured rat cortical neurons. Capsaicin induced severe neuronal death with apoptotic features, which was completely inhibited by the TRPV1 antagonist capsazepine and was dependent on extracellular Ca2+ influx. Interestingly, nifedipine, a specific L-type Ca2+ channel blocker, attenuated capsaicin cytotoxicity, even when applied 2-4 h after the capsaicin. ERK inhibitor PD98059 and several antioxidants, but not the JNK and p38 inhibitors, attenuated capsaicin cytotoxicity. Together, these data indicate that TRPV1 activation triggers apoptotic cell death of rat cortical cultures via L-type Ca2+ channel opening, Ca2+ influx, ERK phosphorylation, and reactive oxygen species production.

  2. Inhibition of β-catenin signaling suppresses pancreatic tumor growth by disrupting nuclear β-catenin/TCF-1 complex: critical role of STAT-3.

    Science.gov (United States)

    Pramanik, Kartick C; Fofaria, Neel M; Gupta, Parul; Ranjan, Alok; Kim, Sung-Hoon; Srivastava, Sanjay K

    2015-05-10

    Aberrant activation of β-catenin/TCF signaling is related to the invasiveness of pancreatic cancer. In the present study, we evaluated the effect of capsaicin on β-catenin/TCF signaling. In a concentration and time-dependent study, we observed that capsaicin treatment inhibits the activation of dishevelled (Dsh) protein DvI-1 in L3.6PL, PanC-1 and MiaPaCa-2 pancreatic cancer cells. Capsaicin treatment induced GSK-3β by inhibiting its phosphorylation and further activated APC and Axin multicomplex, leading to the proteasomal degradation of β-catenin. Expression of TCF-1 and β-catenin-responsive proteins, c-Myc and cyclin D1 also decreased in response to capsaicin treatment. Pre-treatment of cells with MG-132 blocked capsaicin-mediated proteasomal degradation of β-catenin. To establish the involvement of β-catenin in capsaicin-induced apoptosis, cells were treated with LiCl or SB415286, inhibitors of GSK-3β. Our results reveal that capsaicin treatment suppressed LiCl or SB415286-mediated activation of β-catenin signaling. Our results further showed that capsaicin blocked nuclear translocation of β-catenin, TCF-1 and p-STAT-3 (Tyr705). The immunoprecipitation results indicated that capsaicin treatment reduced the interaction of β-catenin and TCF-1 in the nucleus. Moreover, capsaicin treatment significantly decreased the phosphorylation of STAT-3 at Tyr705. Interestingly, STAT-3 over expression or STAT-3 activation by IL-6, significantly increased the levels of β-catenin and attenuated the effects of capsaicin in inhibiting β-catenin signaling. Finally, capsaicin mediated inhibition of orthotopic tumor growth was associated with inhibition of β-catenin/TCF-1 signaling. Taken together, our results suggest that capsaicin-induced apoptosis in pancreatic cancer cells was associated with inhibition of β-catenin signaling due to the dissociation of β-catenin/TCF-1 complex and the process was orchestrated by STAT-3. PMID:25869100

  3. Partial Activation and Inhibition of TRPV1 Channels by Evodiamine and Rutaecarpine, Two Major Components of the Fruits of Evodia rutaecarpa.

    Science.gov (United States)

    Wang, Shenglan; Yamamoto, Satoshi; Kogure, Yoko; Zhang, Wensheng; Noguchi, Koichi; Dai, Yi

    2016-05-27

    Evodiamine (1) and rutaecarpine (2) are the two major components of Evodia rutaecarpa, which has long been used in traditional medicine for the treatment of many diseases. Using transient receptor potential vanilloid 1 (TRPV1)-expressing HEK293 cells and patch-clamp recording, the inhibitory actions of 1 and 2 against TRPV1 channels were investigated. The effects of these compounds against capsaicin- or proton-activated TRPV1 activities were evaluated. The results showed that, although 1 and 2 can activate TRPV1, the maximum response was 3.5- or 9-fold lower than that of capsaicin, respectively, suggesting partial agonism. In comparison to capsaicin, coadministration of 1 and capsaicin increased the half-maximal effective concentration (EC50) of capsaicin-activated TRPV1 currents as shown by a right shift in the dose-response curve, whereas coadministration of 1 with protons failed to inhibit the proton-induced current. Moreover, preadministration of 1, but not 2, inhibited both capsaicin- and proton-induced TRPV1 currents, which might involve channel desensitization. Taken together, 1 and 2 may share the same binding site with capsaicin and act as partial agonists (antagonists) of TRPV1. Evodiamine (1), but not rutaecarpine (2), can desensitize or competitively inhibit the activity of TRPV1. PMID:27159637

  4. Chemical study and anti-inflammatory activity of Capsicum chacoense and C. baccatum

    OpenAIRE

    Paula López; Susana Gorzalczany; Cristina Acevedo; Rosario Alonso; Graciela Ferraro

    2012-01-01

    Capsicum species, Solanaceae, have been used for centuries as food additives by populations of different regions of the world. Capsaicin (trans-methyl-N-vainillyl-nonenamide) is the main pungent compound extracted from the red hot pepper fruit (Capsicum spp.). The capsaicin content was determined by means of a HPLC method. The results showed that Capsicum chacoense Hunz., contains similar amounts of capsaicin (13.9 mg/100 g of dry fruit) in comparison with Capsicum baccatum L. (12.6 mg/100 g)...

  5. Sensory nerve desensitization by resiniferatoxin improves glucose tolerance and increases insulin secretion in Zucker Diabetic Fatty rats and is associated with reduced plasma activity of dipeptidyl peptidase IV

    DEFF Research Database (Denmark)

    Gram, Dorte X; Hansen, Anker J; Deacon, Carolyn F;

    2005-01-01

    Sensory nerve desensitization by capsaicin has been shown to improve the diabetic condition in Zucker Diabetic Fatty rats. However, administration of capsaicin to adult rats is associated with an increased mortality. Therefore, in this experiment, we examined the influence of resiniferatoxin, a...... tolerable analogue of capsaicin suitable for in vivo use, on the diabetic condition of Zucker Diabetic Fatty rats. A single subcutaneous injection of resiniferatoxin (0.01 mg/kg) to these rats was tolerable, with no mortality. When administered to early diabetic rats at 15 weeks of age, the further...

  6. Observation on Efficacy of Additional Capsaicin on the Basis of Mifepristone Combined with Misoprostol in Terminating Early Pregnancy%米非司酮配伍米索前列醇加用辣椒素终止早期妊娠的疗效观察

    Institute of Scientific and Technical Information of China (English)

    蔺瑾

    2015-01-01

    Objective:To observe the efficacy of additional capsalcin on the basis of mifepristone combined with misoprostol in terminating early pregnancy .Methods:A total of 400 women with gestational age at 10 weeks ,who wanted to terminate the pregnancy in the third people′s hospital of Yunan province from Feb 2012 to Feb 2014 ,were randomly divided into the control group and the study group ,with 200 cases in each group .Both the groups were given drug‐induced abortion with same dosage and method .The study group was added with capsalcin .The abortion rate ,the embryo sac discharge time ,vaginal bleeding time and menstruation recovery time of the two groups were compared with each other .Results:The complete abortion rate in the study group was higher than that in the control group(P<0 .05) .The embryo sac discharge time ,the vaginal bleeding time , menstruation recovery time in the study group were significantly shorter than those in the control group ( P< 0 .05 ) . Conclusions:For terminating early pregnancy ,capsalcin combined with abortion medications could shorten the period of vaginal bleeding ,decrease the uterine bleeding volume ,and improve the efficacy of drug‐induced abortion .%目的:观察米非司酮配伍米索前列醇加用辣椒素终止早期妊娠的疗效。方法:选择2012年2月—2014年2月在云南省第三人民医院就诊的孕龄在10周内要求终止妊娠的妇女400例,随机分为研究组和对照组,每组200例。2组均采用药物流产,服药剂量及方法相同;研究组加用辣椒素口服。比较2组的流产率、胚囊排出时间、阴道流血时间及月经复潮时间。结果:研究组完全流产率高于对照组(P<0.05);研究组胚囊排出时间、阴道流血时间及月经复潮时间均显著短于对照组(P<0.05)。结论:辣椒素配合流产药物终止早期妊娠能提高完全流产率,缩短阴道流血时间,减少子宫出血,提高药物流产的治疗效果。

  7. EFFECTS OF CAPSAICIN ON C-FOS PROTEIN EXPRESSION IN NEURONS OF DMV AND NTS AND GASTRIC ULCER OF RATS IN WATER IMMERSION-RESTRAINT STRESS%辣椒素对束缚-浸水应激大鼠DMV和NTS神经元c-fos蛋白表达和胃溃疡的影响

    Institute of Scientific and Technical Information of China (English)

    李兆平; 马晓丽; 张薇薇; 孙海基; 艾洪滨

    2008-01-01

    目的观察辣椒索对束缚-浸水应激大鼠脑于迷走运动背核(DMV)和孤束核(NTS)c-fos蛋白表达和胃溃疡的影响,并探讨c-fos蛋白在DMV和NTS表达与胃溃疡的关系.方法大鼠皮下注射辣椒素,束缚-浸水应激,免疫组织化学技术检测原癌基因c-fos在脑干的DMV和NTS的蛋白表达,计算胃溃疡的指数.结果与盐水对照组相比,注射辣椒索组DMV和NTS中c-fos阳性细胞数显著减少(P<0.01),胃溃疡指数明显降低(P<0.05).结论辣椒素抑制束缚-浸水应激大鼠DMV和NTS神经元c-fos蛋白表达和胃溃疡的,DMV,NTS及辣椒素敏感传入神经可能参与应激性胃溃疡的形成.

  8. Herpes Zoster (Shingles)

    Science.gov (United States)

    ... nervous system). Skin Treatments: Several creams, gels and sprays are being studied. These provide temporary relief from pain. Capsaicin, the chemical that makes chili peppers hot, has shown good preliminary results. In addition, ...

  9. Lipid conjugated prodrugs for enzyme-triggered liposomal drug delivery to tumors

    DEFF Research Database (Denmark)

    Clausen, Mads Hartvig

    2011-01-01

    accommodates therapeutic agents with otherwise unfavorable pharmacokinetic properties. We have designed and synthesized different prodrugs, including published examples using capsaicin, chlorambucil and all-trans retinoic acid as the cytotoxic agents. Currently, we are investigating more potent agents...

  10. 辣椒(Capsicum)

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    又名 African Chillies, African Pepper, Bird Pepper, Capsaicin, Capsicum Fruit, Cayenne, Chili Pepper, Garden Pepper, Goat's Pod, Grains Of Paradise, Green Bell Pepper, Green Chili Pepper, Hot Pepper, Hungarian . Pepper, Ici Fructus, Louisiana Long Pepper, Louisiana Sport Pepper,

  11. Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats

    DEFF Research Database (Denmark)

    Nelson, David W; Liu, Xiaowen; Holst, Jens Juul; Raybould, Helen E; Ney, Denise M

    2006-01-01

    in mucosal mass, protein, DNA, and histology. Both systemic and perivagal capsaicin significantly attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein, and DNA in rats fed orally. Villus height was significantly reduced in resected rats given capsaicin compared with...... of bioactive GLP-2 resulting from resection in orally fed rats. Ablation of spinal/splanchnic innervation by ganglionectomy failed to attenuate resection-induced adaptive growth. In TPN rats, capsaicin did not attenuate resection-induced mucosal growth. We conclude that vagal afferents are not...... essential for maximal resection-induced intestinal growth. Rats received systemic or perivagal capsaicin or ganglionectomy before 70% midjejunoileal resection or transection and were fed orally or by total parenteral nutrition (TPN) for 7 days after surgery. Growth of residual bowel was assessed by changes...

  12. Nitric Oxide Mediates the Central Sensitization of Primate Spinothalamic Tract Neurons

    Czech Academy of Sciences Publication Activity Database

    Lin, Q.; Paleček, Jiří; Palečková, V.; Peng, Y. B.; Wu, J.; Cui, M.; Willis, W. D.

    1999-01-01

    Roč. 81, č. 3 (1999), s. 1075-1085. ISSN 0022-3077 Institutional research plan: CEZ:AV0Z5011922 Keywords : NO * capsaicin * spinothalamic Subject RIV: FH - Neurology Impact factor: 3.935, year: 1999

  13. Vanilloid receptor expressed in the sarcoplasmic reticulum of rat skeletal muscle

    International Nuclear Information System (INIS)

    Vanilloid receptor subtype 1 (VR1) was cloned as a capsaicin receptor from neuronal cells of dorsal root ganglia. VR1 was subsequently found in a few non-neuronal tissues, including skeletal muscle [Onozawa et al., Tissue distribution of capsaicin receptor in the various organs of rats, Proc. Jpn. Acad. Ser. B 76 (2000) 68-72]. We confirmed the expression of VR1 in muscle cells using the RT-PCR method and Western blot analysis. Immunostaining studies with a confocal microscope and an electron microscope indicated that VR1 was present in the sarcoplasmic reticulum (SR), a store of Ca2+. The SR releases Ca2+ to cause a contraction when a muscle is excited. However, SR still releases a small amount of Ca2+ under relaxed conditions. We found that this leakage was enhanced by capsaicin and was antagonized by capsazepine, a capsaicin blocker, indicating that leakage of Ca2+ occurs through a channel composed of VR1

  14. Ultrasound Assisted Extraction of capsaicinoids from peppers

    OpenAIRE

    2008-01-01

    The development of a rapid, reproducible and simple method of extraction of the majority capsaicinoids (nordihydrocapsaicin, capsaicin, dihydrocapsaicin, homocapsaicin and homodihydrocapsaicin) present in hot peppers by the employment of ultrasound-assisted extraction is reported.

  15. Molecular basis for species-specific sensitivity to "hot" chili peppers.

    Science.gov (United States)

    Jordt, Sven-Eric; Julius, David

    2002-02-01

    Chili peppers produce the pungent vanilloid compound capsaicin, which offers protection from predatory mammals. Birds are indifferent to the pain-producing effects of capsaicin and therefore serve as vectors for seed dispersal. Here, we determine the molecular basis for this species-specific behavioral response by identifying a domain of the rat vanilloid receptor that confers sensitivity to capsaicin to the normally insensitive chicken ortholog. Like its mammalian counterpart, the chicken receptor is activated by heat or protons, consistent with the fact that both mammals and birds detect noxious heat and experience thermal hypersensitivity. Our findings provide a molecular basis for the ecological phenomenon of directed deterence and suggest that the capacity to detect capsaicin-like inflammatory substances is a recent acquisition of mammalian vanilloid receptors. PMID:11853675

  16. Comparison of the transport of QX-314 through TRPA1, TRPM8, and TRPV1 channels

    Directory of Open Access Journals (Sweden)

    Nakagawa H

    2013-03-01

    Full Text Available Hiroshi Nakagawa,1 Akio Hiura2 1Dentistry for Persons with Disability, Tokushima University Hospital, Tokushima, Japan; 2Department of Oral Histology, School of Dentistry, University of Tokushima, Tokushima, Japan Background: It has been demonstrated that N-ethyl-lidocaine (QX-314 can target the transient receptor protein vanilloid 1 (TRPV1 nociceptors when coadministered with capsaicin, resulting in a selective block of the nociceptors. Capsaicin is problematic in therapeutic use because it induces firing of nociceptors. The present study aimed to search for substitutes for capsaicin. We also examined the transportability of QX-314 into nociceptive neurons, through the pores of transient receptor potential ankyrin 1 (TRPA1, transient receptor potential melastatin-8 (TRPM8, and TRPV1. Methods: To investigate the effect on TRPA1, injections of a vehicle, allyl isothiocyanate (AITC, QX-314, or AITC/QX-314 were made into the hind paws of rats. The effects of menthol and capsaicin on the opening of TRPM8 and TRPV1 were also examined and compared with the potency of QX-314. To examine inhibition of the antinociceptive effect by capsaicin/QX-314, capsazepine (50 µg/mL; 10 µL was injected 30 minutes prior to capsaicin/QX-314 (10 µL injection. Thermal sensitivity was investigated by the Hargreaves method. 5(6-carboxyfluorescein (FAM-conjugated QX-314 was used as a tracer to examine how many and which kind of dorsal root ganglia accumulate this molecule. QX-314-FAM, capsaicin/QX-314-FAM, AITC/QX-314-FAM, and menthol/QX-314-FAM were injected into the paw. Two weeks after injections, dorsal root ganglia were removed and sectioned with a cryostat. Results: The capsaicin/QX-314 group induced longer withdrawal-response latency at 60 to 300 minutes after injection than the control. Both menthol only and menthol/QX-314 injections showed analgesia 10 to 60 minutes after injection. No significant difference was seen between the capsazepine/capsaicin/QX-314

  17. Direct activation of Transient Receptor Potential Vanilloid 1(TRPV1) by Diacylglycerol (DAG)

    OpenAIRE

    Oh Seog; Kim Yong; Park Chul-Kyu; Zhu Mei; Jung Sung; Woo Dong; Lee C Justin

    2008-01-01

    Abstract The capsaicin receptor, known as transient receptor potential channel vanilloid subtype 1 (TRPV1), is activated by a wide range of noxious stimulants and putative ligands such as capsaicin, heat, pH, anandamide, and phosphorylation by protein kinase C (PKC). However, the identity of endogenous activators for TRPV1 under physiological condition is still debated. Here, we report that diacylglycerol (DAG) directly activates TRPV1 channel in a membrane-delimited manner in rat dorsal root...

  18. Sensitizing effects of lafutidine on CGRP-containing afferent nerves in the rat stomach

    OpenAIRE

    Nishihara, Katsushi; Nozawa, Yoshihisa; Nakano, Motoko; Ajioka, Hirofusa; Matsuura, Naosuke

    2002-01-01

    Capsaicin sensitive afferent nerves play an important role in gastric mucosal defensive mechanisms. Capsaicin stimulates afferent nerves and enhances the release of calcitonin gene-related peptide (CGRP), which seems to be the predominant neurotransmitter of spinal afferents in the rat stomach, exerting many pharmacological effects by a direct mechanism or indirectly through second messengers such as nitric oxide (NO).Lafutidine is a new type of anti-ulcer drug, possessing both an antisecreto...

  19. Der Einfluß viszeraler afferenter Nervenfasern auf den postoperativen Ileus bei der Ratte

    OpenAIRE

    Meile, Tobias

    2003-01-01

    Der postoperative Ileus steht häufig einer schnellen Genesung der Patienten im Wege. Frühere Untersuchungen haben erkennen lassen, daß Capsaicin-sensible, afferente Nervenfasern bei der Induktion des postoperativen Ileus wahrscheinlich eine entscheidende Rolle spielen. Ratten in der vorliegenden Arbeit wurden Dehnungsmeßstreifen zur Registrierung der gastrointestinalen Motilität auf die Darmwand genäht. Capsaicin wurde entweder intraperitoneal oder intraluminal in das Zökum appliziert, gle...

  20. CB1 cannabinoid receptor stimulation modulates transient receptor potential vanilloid receptor 1 activities in calcium influx and substande P release in cultured rat dorsal root ganglion cells

    OpenAIRE

    Ohshita, Kyoko

    2005-01-01

    Cannabinoids have been reported to have analgesic properties in animals of acute nociception or of inflammatory and neuropathic pain models, but the mechanisms by which they exert such alleviative effects are not yet fully understood. We investigated whether the CB1- cannabinoid-receptor agonist HU210 modulates the capsaicin-induced 45Ca2+ influx and substance P like-immunoreactivity (SPLI) release in cultured rat dorsal root ganglion (DRG) cells. HU210 attenuated the capsaicin-induced 45Ca2+...

  1. Drug: D06388 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available [topical] ATC code: M02AB02 cis-isomer of Capsaicin [DR:D00250] transient receptor potential cation channel...CULO-SKELETAL SYSTEM M02 TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN M02A TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN M02AB Capsaic...in and similar agents M02AB02 Zucapsaicin D06388 Zucapsaicin (USAN/INN) Target-base

  2. Effects of dihydrocapsiate on adaptive and diet-induced thermogenesis with a high protein very low calorie diet: a randomized control trial

    OpenAIRE

    Zerlin Alona; Li Zhaoping; Lee TszYing; Heber David

    2010-01-01

    Abstract Background Dihydrocapsiate (DCT) is a natural safe food ingredient which is structurally related to capsaicin from chili pepper and is found in the non-pungent pepper strain, CH-19 Sweet. It has been shown to elicit the thermogenic effects of capsaicin but without its gastrointestinal side effects. Methods The present study was designed to examine the effects of DCT on both adaptive thermogenesis as the result of caloric restriction with a high protein very low calorie diet (VLCD) an...

  3. Environ: E00047 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available E00047 Capsicum tincture (JP16) Capsicum extract Crude drug Capsaicin [CPD:C06866],...ianside A [CPD:C17516], all-trans-beta-Carotene, Ascorbic acid [CPD:C00072], beta Carotene [CPD:C02094] Capsicum... annuum [TAX:4072] Same as: D06455 Solanaceae (nightshade family) Capsicum seed and mature fruit (dried) Major component: Capsaicin [CPD:C06866] ...

  4. Antiproliferative effects of TRPV1 ligands on nonspecific and enteroantigen-specific T cells from wild-type and Trpv1 KO mice

    DEFF Research Database (Denmark)

    Belmaáti, Mohammed-Samir; Diemer, Sanne; Hvarness, Tine; Baumann, Katrine; Pedersen, Anders Elm; Christensen, Rikke E; Claesson, Mogens H

    2014-01-01

    BACKGROUND: Treatment with the TRPV1 agonist, capsaicin, was previously shown to protect against experimental colitis in the severe combined immunodeficiency (SCID) T-cell transfer model. Here, we investigate trpv1 gene expression in lymphoid organs and cells from SCID and BALB/c mice to identify a...... potential target for the anti-inflammatory effect of capsaicin. METHODS: The trpv1 expression was studied by real-time PCR in lymphoid tissues and gut of untreated and capsaicin-treated colitic SCID mice. Effects of capsaicin and a TRPV1 antagonist on T cells were studied in vitro. RESULTS: In contrast to...... BALB/c mice, spleen, lymph nodes, and rectum of colitic and noncolitic SCID mice express trpv1 mRNA. Capsaicin treatment in vivo attenuated T-cell transfer colitis and capsaicin in vitro also attenuated T-cell proliferation induced by enteroantigen, mitogen, and anti-CD3/CD28 beads in BALB/c, C57BL/6...

  5. [Assessment of the Effect of Pain on Autonomic Nervous System in Human Body Using Heart Rate Variability Analysis].

    Science.gov (United States)

    Fu, Qingbiao; Liu, Chunlin; Zhang, Fang; Fang, Yi; Shen, Dai; Zhang, Jian

    2015-12-01

    The purpose of this study is to discuss the feasibility of establishing capsaicin pain model and the possibility to evaluate different degrees of pain by the heart rate variability (HRV). It also aims to investigate the changes of autonomic nervous activity of volunteers during the process of pain caused by capsaicin. A total of 30 volunteers were selected, who were physically and mentally healthy, into the study. To assess the effects of capsaicin on the healthy volunteers, we recorded the Visual Analogue Scale (VAS) scores after the capsaicin stimulus. Additionally, the electrocardiogram signals and HRV analysis index before and after stimulating were also recorded, respectively. More specifically, the HRV analysis indexes included the time domain index, the frequency domain index, and the nonlinear analysis index. The results demonstrated that the activity of the autonomic nerves was enhanced in the process of capsaicin stimulus, especially for the sympathetic nerve, which exhibited a significantly differences in HRV. In conclusion, the degree of pain can be reflected by the HRV. It is feasible to establish a capsaicin pain model. And in further experiments, HRV analysis could be used as a reference index for quantitative evaluation of pain. PMID:27079091

  6. Involvement of sensory neurons in bone defect repair in rats

    International Nuclear Information System (INIS)

    We investigated bone repair in sensory-denervated rats, compared with controls, to elucidate the involvement of sensory neurons. Nine-week-old male Wistar rats received subcutaneous injections of capsaicin to denervate sensory neurons. Rats treated with the same amount of vehicle served as controls. A standardized bone defect was created on the parietal bone. We measured the amount of repaired bone with quantitative radiographic analysis and the mRNA expressions of osteocalcin and cathepsin K with real-time polymerase chain reaction (PCR). Quantitative radiographic analysis showed that the standard deviations and coefficients of variation for the amount of repaired bone were much higher in the capsaicin-treated group than in the control group at any time point, which means that larger individual differences in the amount of repaired bone were found in capsaicin-treated rats than controls. Furthermore, radiographs showed radiolucency in pre-existing bone surrounding the standardized defect only in the capsaicin-treated group, and histological observation demonstrated some multinuclear cells corresponding to the radiolucent area. Real-time PCR indicated that there was no significant difference in the mRNA expression levels of osteocalcin and cathepsin K between the control group and the capsaicin-treated group. These results suggest that capsaicin-induced sensory denervation affects the bone defect repair. (author)

  7. Activation of CFTR-mediated CI-Transport by Capsaicinoids in Cell Culture Model

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xue-liang; HOU Ting-ting; GE Hong; SUN Juan-juan; YANG Hong; MA Tong-hui

    2009-01-01

    Previous studies reported that capsaicin potentiates ΔF508 mutant cystic fibrosis transmembrane conductance regulator(CFTR) channel gating defect by transfected cell-based assays.It has been postulated that orally ingested capsaicin may conceptually be used to develop a therapeutic strategy to treat gastrointestinal disorders in CF patients.We tried to reproduce and extend those pre-clinical data of previous studies.Cell-based fluorescence functional measurements in Fischer thyroid epithelial cells(FRT) expressing CFTR showed no effect of capsaicin on potentiating ΔF508-CFTR.while genistein showed a strongly positive activity.Studies show that capsaicin and dihydrocapsaicin activated cAMP-prestimulated wild-type CFTR in a dose-dependent manner with a maximal response of 70% of that activated by genistein,thus gave an apparent EC50 of (40.4±6.8)μmol/L and (150.2±7.4) μmol/L respectively.Preliminary study shows that the binding sites for capsaicin and dihydrocapsaicin may be probably partially overlapped with that for genistein because the maximal activation of wild-type CFTR with genistein is partially blocked by capsaicin and dihydrocapsaicin.

  8. Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells

    Directory of Open Access Journals (Sweden)

    Daniel Alvarez-Berdugo

    2014-01-01

    Full Text Available Purpose. TRPV1 is a multimodal channel mainly expressed in sensory neurons. We aimed to explore the pharmacodynamics of the TRPV1 agonists, capsaicin, natural capsaicinoids, and piperine in an in vitro bioassay using human PC-3 cells and to examine desensitization and the effect of the specific antagonist SB366791. Methods. PC-3 cells expressing TRPV1 were incubated with Fluo-4. Fluorescence emission changes following exposition to agonists with and without preincubation with antagonists were assessed and referred to maximal fluorescence following the addition of ionomycin. Concentration-response curves were fitted to the Hill equation. Results. Capsaicin and piperine had similar pharmacodynamics (Emax 204.8 ± 184.3% piperine versus 176.6 ± 35.83% capsaicin, P=0.8814, Hill coefficient 0.70 ± 0.50 piperine versus 1.59 ± 0.86 capsaicin, P=0.3752. In contrast, capsaicinoids had lower Emax (40.99 ± 6.14% capsaicinoids versus 176.6 ± 35.83% capsaicin, P<0.001. All the TRPV1 agonists showed significant desensitization after the second exposition and their effects were strongly inhibited by SB366791. Conclusion. TRPV1 receptor is successfully stimulated by capsaicin, piperine, and natural capsaicinoids. These agonists present desensitization and their effect is significantly reduced by a TRPV1-specific antagonist. In addition, PC-3 cell bioassays proved useful in the study of TRPV1 pharmacodynamics.

  9. Screening Capsicum accessions for capsaicinoids content.

    Science.gov (United States)

    Antonious, George F; Jarret, Robert L

    2006-01-01

    Ninety Capsicum accessions selected from the USDA Capsicum germplasm collection were screened for their capsaicinoids content using gas hromatography with nitrogen phosphorus detection (GC/NPD). Fresh fruits of Capsicum chinense, C. frutescens, C. baccatum, C. annuum, and C. pubescens were extracted with methanol and analyzed for capsaicin, dihydrocapsaicin, and nordihydrocapsaicin. Mass spectrometry of the fruit crude extracts indicated that the molecular ions at m/z 305, 307, and 293, which correspond to capsaicin, dihydrocapsaicin, and nordihydrocapsaicin, respectively, have a common benzyl cation fragment at m/z 137 that can be used for monitoring capsaicinoids in pepper fruit extracts. Capsaicin and dihydrocapsaicin were the dominant capsaicinoids detected. Capsaicin concentrations were typically greater than dihydrocapsaicin. Concentrations of total capsaicinoids varied from not detectable to 11.2 mg fruit(-1). Statistical analysis revealed that accession PI-441624 (C. chinense) had the highest capsaicin content (2.9 mg g(-1) fresh fruit) and accession PI-497984 (C. frutescens) had the highest dihydrocapsaicin content (2.3 mg g(-1) fresh fruit). Genebank accessions PI-439522 (C. frutescens) and PI-497984 contained the highest concentrations of total capsaicinoids. PMID:16785178

  10. NOX3 NADPH oxidase couples transient receptor potential vanilloid 1 to signal transducer and activator of transcription 1-mediated inflammation and hearing loss.

    Science.gov (United States)

    Mukherjea, Debashree; Jajoo, Sarvesh; Sheehan, Kelly; Kaur, Tejbeer; Sheth, Sandeep; Bunch, Jennifer; Perro, Christopher; Rybak, Leonard P; Ramkumar, Vickram

    2011-03-15

    Transient receptor potential vanilloid 1 (TRPV1) is implicated in cisplatin ototoxicity. Activation of this channel by cisplatin increases reactive oxygen species generation, which contribute to loss of outer hair cells in the cochlea. Knockdown of TRPV1 by short interfering RNA protected against cisplatin ototoxicity. In this study, we examined the mechanism underlying TRPV1-mediated ototoxicity using cultured organ of Corti transformed cells (UB/OC-1) and rats. Trans-tympanic injections of capsaicin produced transient hearing loss within 24 h, which recovered by 72 h. In UB/OC-1 cells, capsaicin increased NOX3 NADPH oxidase activity and activation of signal transducer and activator of transcription 1 (STAT1). Intratympanic administration of capsaicin transiently increased STAT1 activity and expression of downstream proinflammatory molecules. Capsaicin produced a transient increase in CD14-positive inflammatory cells into the cochlea, which mimicked the temporal course of STAT1 activation but did not alter the expression of apoptotic genes or damage to outer hair cells. In addition, trans-tympanic administration of STAT1 short interfering RNA protected against capsaicin-induced hearing loss. These data suggest that activation of TRPV1 mediates temporary hearing loss by initiating an inflammatory process in the cochlea via activation of NOX3 and STAT1. Thus, these proteins represent reasonable targets for ameliorating hearing loss. PMID:20712533

  11. Rational design and validation of a vanilloid-sensitive TRPV2 ion channel.

    Science.gov (United States)

    Yang, Fan; Vu, Simon; Yarov-Yarovoy, Vladimir; Zheng, Jie

    2016-06-28

    Vanilloids activation of TRPV1 represents an excellent model system of ligand-gated ion channels. Recent studies using cryo-electron microcopy (cryo-EM), computational analysis, and functional quantification revealed the location of capsaicin-binding site and critical residues mediating ligand-binding and channel activation. Based on these new findings, here we have successfully introduced high-affinity binding of capsaicin and resiniferatoxin to the vanilloid-insensitive TRPV2 channel, using a rationally designed minimal set of four point mutations (F467S-S498F-L505T-Q525E, termed TRPV2_Quad). We found that binding of resiniferatoxin activates TRPV2_Quad but the ligand-induced open state is relatively unstable, whereas binding of capsaicin to TRPV2_Quad antagonizes resiniferatoxin-induced activation likely through competition for the same binding sites. Using Rosetta-based molecular docking, we observed a common structural mechanism underlying vanilloids activation of TRPV1 and TRPV2_Quad, where the ligand serves as molecular "glue" that bridges the S4-S5 linker to the S1-S4 domain to open these channels. Our analysis revealed that capsaicin failed to activate TRPV2_Quad likely due to structural constraints preventing such bridge formation. These results not only validate our current working model for capsaicin activation of TRPV1 but also should help guide the design of drug candidate compounds for this important pain sensor. PMID:27298359

  12. Lack of sensorial innervation in the newborn female rats affects the activity of hypothalamic monoaminergic system and steroid hormone secretion during puberty.

    Science.gov (United States)

    Quiróz, Ubaldo; Morales-Ledesma, Leticia; Morán, Carolina; Trujillo, Angélica; Domínguez, Roberto

    2014-06-01

    There is evidence that sensory innervation plays a role regulating ovarian functions, including fertility.Since sensory denervation by means of capsaicin in newborn female rats results in a lower response togonadotropins, the present study analyzed the effects that sensory denervation by means of capsaicin in neonatal rats has on the concentration of monoamines in the anterior(AH) and medium (MH) hypothalamus, and on steroid hormone levels in serum. Groups of newborn female rats were injected subcutaneously with capsaicin and killed at 10, 20, and 30 days of age and on the first vaginal estrous.The concentrations of noradrenaline, dopamine, serotonin(5-HT), and their metabolites in the AH and MH were measured using HPLC, and the levels of estradiol (E),progesterone (P), testosterone (T), FSH, and luteinizing hormone using radioimmunoanalysis. The results show thatat 20 days of age, capsaicin-treated rats have lowernoradrenergic and serotonergic activities in the AH, and that the dopaminergic activity was lower in the MH. These results suggest that the sensorial system connections within the monoaminergic systems of the AH and MH are different.Capsaicin-treated animals had lower T, E, and P levels than in the control group, suggesting that the lower activity in the AH monoaminergic system and lower hormonesecretion could be explained by the blockade of information mediated by the sensory innervation (probably substance P), mainly between the ovary and the AH. PMID:24122121

  13. Oleoresin capsicum (pepper) spray and "in-custody deaths".

    Science.gov (United States)

    Steffee, C H; Lantz, P E; Flannagan, L M; Thompson, R L; Jason, D R

    1995-09-01

    Increasing use of oleoresin capsicum (OC) spray devices (i.e., pepper spray, pepper mace, OC, capsaicin) by law enforcement agencies as a means of sublethal force to control suspects has brought into question whether exposure to this noxious irritant (capsaicin) can cause or contribute to unexpected in-custody deaths. Capsaicin stimulates nociceptors in exposed mucous membranes to produce intense pain, particularly involving the conjunctiva, and generates systemic physiologic and behavioral responses consonant with such extreme discomfort. We describe two cases of in-custody death, both associated temporally with the use of pepper spray, to illustrate salient investigative considerations. As with any other in-custody death, a thorough autopsy and toxicologic analysis, coupled with evaluation of the premortem chain of events, postexposure symptomatology, and the extent of natural disease processes, will help to reveal the role of oleoresin capsicum spray as unrelated, contributory, or causative. PMID:7495257

  14. Chemical study and anti-inflammatory activity of Capsicum chacoense and C. baccatum

    Directory of Open Access Journals (Sweden)

    Paula López

    2012-04-01

    Full Text Available Capsicum species, Solanaceae, have been used for centuries as food additives by populations of different regions of the world. Capsaicin (trans-methyl-N-vainillyl-nonenamide is the main pungent compound extracted from the red hot pepper fruit (Capsicum spp.. The capsaicin content was determined by means of a HPLC method. The results showed that Capsicum chacoense Hunz., contains similar amounts of capsaicin (13.9 mg/100 g of dry fruit in comparison with Capsicum baccatum L. (12.6 mg/100 g and Capsicum annum L. (10.1 mg/100 g. Dichloromethane (CH2Cl2 and ethanol (EtOH extracts of C. chacoense elicited a 46% and 38 % of inhibition on the arachidonic acid (AA pathway in ear edema respectively while the CH2Cl2 and EtOH extracts of C. baccatum inhibited 52% and 35% the arachidonic acid response respectively.

  15. The effect of local vs remote experimental pain on motor learning and sensorimotor integration using a complex typing task.

    Science.gov (United States)

    Dancey, Erin; Murphy, Bernadette A; Andrew, Danielle; Yielder, Paul

    2016-08-01

    Recent work demonstrated that capsaicin-induced acute pain improved motor learning performance; however, baseline accuracy was very high, making it impossible to discern the impact of acute pain on motor learning and retention. In addition, the effects of the spatial location of capsaicin application were not explored. Two experiments were conducted to determine the interactive effects of acute pain vs control (experiment 1) and local vs remote acute pain (experiment 2) on motor learning and sensorimotor processing. For both experiments, somatosensory evoked potential (SEP) amplitudes and motor learning acquisition and retention (accuracy and response time) data were collected at baseline, after application, and after motor learning. Experiment 1: N11 (P Experiment 2: The P25 SEP peak decreased in the local group after application of capsaicin cream (P attention to the body part used in motor learning, contributing to our understanding of how the location of pain impacts somatosensory processing and the associated motor learning. PMID:27023419

  16. Evidence for regulatory diversity and auto-regulation at the TAC1 locus in sensory neurones

    Directory of Open Access Journals (Sweden)

    Ross Ruth

    2011-02-01

    Full Text Available Abstract The neuropeptide substance-P (SP is expressed from the TAC1 gene in sensory neurones where it acts as a key modulator of neurogenic inflammation. The promoter of TAC1 (TAC1prom plays a central role in the regulation of the TAC1 gene but requires the presence of a second regulatory element; ECR2, to support TAC1 expression in sensory neurones and to respond appropriately to signalling pathways such as MAPkinases and noxious induction by capsaicin. We examined whether the effect of capsaicin on ECR2-TAC1prom activity in larger diameter neurones was cell autonomous or non- cell autonomous. We demonstrate that TRPV1 is not expressed in all the same cells as SP following capsaicin induction suggesting the presence of a non-cell autonomous mechanism for TAC1 up-regulation following capsaicin induction. In addition, we demonstrate that induction of SP and ECR1-TAC1prom activity in these larger diameter neurones can be induced by potassium depolarisation suggesting that, in addition to capsaicin induction, transgene activity may be modulated by voltage gated calcium channels. Furthermore, we show that NK1 is expressed in all SP- expressing cells after capsaicin induction and that an agonist of NK1 can activate both SP and the transgene in larger diameter neurones. These observations suggest the presence of an autocrine loop that controls the expression of the TAC1 promoter in sensory neurones. In contrast, induction of the TAC1 promoter by LPS was not dependent on ECR2 and did not occur in large diameter neurones. These studies demonstrate the diversity of mechanisms modulating the activity of the TAC1 promoter and provide novel directions for the development of new anti-inflammatory therapies.

  17. Hippocampal plasticity after a vagus nerve injury in the rat

    Institute of Scientific and Technical Information of China (English)

    Giulia Ronchi; Vitaly Ryu; ong ling; Krzysztof Czaja

    2012-01-01

    Stimulation of the vagus nerve has been previously reported to promote neural plasticity and neurogenesis in the brain. Several studies also revealed plastic changes in the spinal cord after injuries to somatosensory nerves originating from both the brachial and lumbo-sacral plexuses. However, the neurogenic responses of the brain to the injury of the viscerosensory innervation are not as yet well understood. In the present study, we investigated whether cells in the dentate gyrus of the hippocampus respond to a chemical and physical damage to the vagus nerve in the adult rat. Intraperitoneal capsaicin administration was used to damage non-myelinated vagal afferents while subdiaphragmatic vagotomy was used to damage both the myelinated and non-myelinated vagal afferents. The 5-bromo-2-deoxyuridine (BrdU) incorporation together with cell-specific markers was used to study neural proliferation in subgranular zone, granule cell layer, molecular layer and hilus of the dentate gyrus. Microglia activation was determined by quantifying changes in the intensity of fluorescent staining with a primary antibody against ionizing calcium adapter-binding molecule 1. Results revealed that vagotomy decreased BrdU incorporation in the hilus 15 days after injury compared to the capsaicin group. Capsaicin administration decreased BrdU incorporation in the granular cell layer 60 days after the treatment. Capsaicin decreased the number of doublecortin-expressing cells in the dentate gyrus, whereas vagotomy did not alter the expression of doublecortin in the hippocampus. Both the capsaicin- and the vagotomy-induced damage to the vagus nerve decreased microglia activation in the hippocampus at 15 days after the injury. At 30 days post injury, capsaicin-treated and vagotomized rats revealed significantly more activated microglia. Our findings show that damage to the subdiaphragmatic vagus in adult rats is followed by microglia activation and long-lasting changes in the dentate gyrus

  18. Effects of vehicle on the uptake and elimination kinetics of capsaicinoids in human skin in vivo

    International Nuclear Information System (INIS)

    While the physiologic and molecular effects of capsaicinoids have been extensively studied in various model systems by a variety of administration routes, little is known about the uptake and elimination kinetic profiles in human skin following topical exposure. The present study evaluated the uptake and elimination kinetics of capsaicinoids in human stratum corneum following a single topical exposure to 3% solutions containing 55% capsaicin, 35% dihydrocapsaicin, and 10% other analogues prepared in three vehicles: mineral oil (MO), propylene glycol (PG), and isopropyl alcohol (IPA). Capsaicinoid solutions were evaluated simultaneously in a random application pattern on the volar forearms of 12 subjects using a small, single 150-μg dose. Capsaicin and dihydrocapsaicin were recovered from human skin using commercial adhesive discs to harvest stratum corneum from treated sites. Capsaicinoids were extracted from the stratum corneum-adhesive discs and quantified by liquid chromatography/mass spectroscopy (LC/MS). Both capsaicinoids were detected in stratum corneum 1 min after application with all vehicles and achieved a pseudo-steady state shortly thereafter. IPA delivered three times greater capsaicin and dihydrocapsaicin into the human stratum corneum than PG or MO at all time points investigated. The Cmax of capsaicin in IPA, PG, and MO was 16.1, 6.2, and 6.5 μg, respectively. The dihydrocapsaicin content was 60% of capsaicin with all vehicles. The estimated Thalf of capsaicin and dihydrocapsaicin in the three vehicles was similar (24 h). Thus, maximal cutaneous capsaicinoid concentrations were achieved quickly in the human stratum corneum and were concentration and vehicle dependent. In contrast, capsaicinoid half-life was long and vehicle independent

  19. The vanilloid receptor and hypertension

    Institute of Scientific and Technical Information of China (English)

    Donna H WANG

    2005-01-01

    Mammalian transient receptor potential (TRP) channels consist of six related protein sub-families that are involved in a variety of pathophysiological function, and disease development. The TRPV1 channel, a member of the TRPV sub-family, is identified by expression cloning using the "hot" pepper-derived vanilloid compound capsaicin as a ligand. Therefore, TRPV1 is also referred as the vanilloid receptor (VR1) or the capsaicin receptor. VR1 is mainly expressed in a subpopulation of primary afferent neurons that project to cardiovascular and renal tissues.These capsaicin-sensitive primary afferent neurons are not only involved in the perception of somatic and visceral pain, but also have a "sensory-effector" function.Regarding the latter, these neurons release stored neuropeptides through a calcium-dependent mechanism via the binding of capsaicin to VR1. The most studied sensory neuropeptides are calcitonin gene-related peptide (CGRP) and substance P (SP), which are potent vasodilators and natriuretic/diuretic factors. Recent evidence using the model of neonatal degeneration of capsaicin-sensitive sensory nerves revealed novel mechanisms that underlie increased salt sensitivity and several experimental models of hypertension. These mechanisms include insufficient suppression of plasma renin activity and plasma aldosterone levels subsequent to salt loading, enhancement of sympathoexcitatory response in the face of a salt challenge, activation of the endothelin- 1 receptor, and impaired natriuretic response to salt loading in capsaicin-pretreated rats. These data indicate that sensory nerves counterbalance the prohypertensive effects of several neurohormonal systems to maintain normal blood pressure when challenged with salt loading. The therapeutic utilities of vanilloid compounds, endogenous agonists,and sensory neuropeptides are also discussed.

  20. Transient receptor potential vanilloid type 1 receptor regulates glutamatergic synaptic inputs to the spinothalamic tract neurons of the spinal cord deep dorsal horn.

    Science.gov (United States)

    Kim, H; Cui, L; Kim, J; Kim, S J

    2009-05-01

    The spinothalamic tract (STT) neurons in the spinal dorsal horn play an important role in transmission and processing of nociceptive sensory information. Although transient receptor potential vanilloid type 1 (TRPV1) receptors are present in the spinal cord dorsal horn, their physiological function is not fully elucidated. In this study, we examined the role of TRPV1 in modulating neuronal activity of the STT neurons through excitatory and inhibitory synaptic inputs. Whole-cell patch-clamp recordings were performed on STT neurons labeled by a retrograde fluorescent tracer injected into the ventral posterior lateral (VPL) nucleus of the thalamus. Capsaicin (1 microM) increased the frequency of miniature excitatory postsynaptic currents (mEPSC) without changing the amplitude or decay time constant of mEPSC. In contrast, capsaicin had no distinct effect on GABAergic miniature inhibitory postsynaptic currents (mIPSC). Capsazepine (10 microM), a TRPV1 receptor antagonist, abolished the effect of capsaicin on mEPSCs. Capsazepine itself did not affect the baseline amplitude and frequency of mEPSC. The effect of capsaicin on mEPSC was also abolished by removal of external Ca(2+), but not by treatment with Cd(2+). Furthermore, capsaicin increased the firing activity of the STT neurons and this increase in neuronal activity by capsaicin was abolished in the presence of non-N-methyl-d-aspartic acid (NMDA) and NMDA receptor antagonists, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) and (R)-amino-5-phosphonovaleric acid (APV). These data suggest that activation of TRPV1 potentiates the glutamate release from excitatory terminals of primary afferent fibers and subsequently increases the neural activity of STT neurons of the rat spinal cord deep dorsal horn. PMID:19236908

  1. Repetitive trigeminal nociceptive stimulation in rats increases their susceptibility to cortical spreading depression.

    Science.gov (United States)

    Toriumi, Haruki; Shimizu, Toshihiko; Ebine, Taeko; Takizawa, Tsubasa; Kayama, Yohei; Koh, Anri; Shibata, Mamoru; Suzuki, Norihiro

    2016-05-01

    We examined the ability of trigeminal nerve activation to induce cortical spreading depression in rats. Capsaicin was injected into the bilateral plantar or whisker pad for either 4 or 6 days in rats. The number and duration of cortical spreading depressions induced by potassium were significantly increased in animals injected with capsaicin in the bilateral whisker pad compared with animals injected in the bilateral plantar or in controls, while administration of a GABAA receptor agonist decreased these effects. Repetitive nociceptive stimulation of the trigeminal nerve lowers the threshold for the induction of cortical spreading depression by altering GABAergic neuronal activity. PMID:26739227

  2. Antioxidants in Capsicum chinense: Variation among countries of origin

    Science.gov (United States)

    The worldwide search for sources of beneficial phytochemicals continues. In this vein, many pepper (Capsicum L.) species and their cultivars have not been analyzed for their concentrations of the health-promoting antioxidants ß-carotene, ascorbic acid, phenols, or capsaicin. Capsicum chinense has be...

  3. Direct activation of Transient Receptor Potential Vanilloid 1(TRPV1 by Diacylglycerol (DAG

    Directory of Open Access Journals (Sweden)

    Oh Seog

    2008-10-01

    Full Text Available Abstract The capsaicin receptor, known as transient receptor potential channel vanilloid subtype 1 (TRPV1, is activated by a wide range of noxious stimulants and putative ligands such as capsaicin, heat, pH, anandamide, and phosphorylation by protein kinase C (PKC. However, the identity of endogenous activators for TRPV1 under physiological condition is still debated. Here, we report that diacylglycerol (DAG directly activates TRPV1 channel in a membrane-delimited manner in rat dorsal root ganglion (DRG neurons. 1-oleoyl-2-acetyl-sn-glycerol (OAG, a membrane-permeable DAG analog, elicited intracellular Ca2+ transients, cationic currents and cobalt uptake that were blocked by TRPV1-selective antagonists, but not by inhibitors of PKC and DAG lipase in rat DRG neurons or HEK 293 cells heterologously expressing TRPV1. OAG induced responses were about one fifth of capsaicin induced signals, suggesting that OAG displays partial agonism. We also found that endogenously produced DAG can activate rat TRPV1 channels. Mutagenesis of rat TRPV1 revealed that DAG-binding site is at Y511, the same site for capsaicin binding, and PtdIns(4,5P2binding site may not be critical for the activation of rat TRPV1 by DAG in heterologous system. We propose that DAG serves as an endogenous ligand for rat TRPV1, acting as an integrator of Gq/11-coupled receptors and receptor tyrosine kinases that are linked to phospholipase C.

  4. Effektiv smertelindring af capsaicinplaster mod postherpetisk neuralgi

    DEFF Research Database (Denmark)

    Andersen, Hjalte Holm; Sand, Carsten; Elberling, Jesper

    2016-01-01

    svimmelhed. Derudover kan forbigående smertelindring opnås ned topikal lidocain- og/eller lav- dosis capsaicincreme [2]. Capsaicin er en transient re- ceptor potential cation channel V1 (TRPV1)-receptorago- nist, som i høje koncentrationer medfører ekstensiv depolarisering og reversibel defunktionalisering...

  5. The TRPA1 Activator Allyl Isothiocyanate (AITC) Contracts Human Jejunal Muscle: Pharmacological Analysis.

    Science.gov (United States)

    Sandor, Zsolt; Dekany, Andras; Kelemen, Dezsö; Bencsik, Timea; Papp, Robert; Bartho, Lorand

    2016-09-01

    The contractile effect of AITC (300 μM) on human jejunal longitudinal strips was inhibited by the TRPA1 antagonist HC 030031 and atropine or scopolamine, but was insensitive to tetrodotoxin, purinoceptor antagonists or capsaicin desensitization. It is concluded that TRPA1 activation stimulates a cholinergic mechanism in a tetrodotoxin-resistant manner. PMID:26928772

  6. Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Vijayalakshmi; Tripathi, Preeti [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Sharma, Sunil [Department of Radiation Oncology, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Moros, Eduardo G. [Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Zheng, Junying [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hauer-Jensen, Martin [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas (United States); Boerma, Marjan, E-mail: mboerma@uams.edu [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States)

    2014-01-01

    Purpose: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.

  7. Chronic Treatment with NGF Induces Spontaneous Fluctuations of Intracellular Ca(2+) in Icilin-Sensitive Dorsal Root Ganglion Neurons of the Rat

    Czech Academy of Sciences Publication Activity Database

    Kayano, T.; Kitamura, N.; Moriya, A.; Ozaki, Y.; Dayanithi, Govindan; Shibuya, I.

    2010-01-01

    Roč. 72, č. 12 (2010), s. 1531-1538. ISSN 0916-7250 Institutional research plan: CEZ:AV0Z50390703 Keywords : capsaicin * sensory neuron * TRPA1 Subject RIV: FH - Neurology Impact factor: 0.722, year: 2010

  8. Molekulární přístupy ke studiu periferních mechanismů nocicepce

    Czech Academy of Sciences Publication Activity Database

    Vyklický st., Ladislav; Vlachová, Viktorie; Lyfenko, Alla

    2001-01-01

    Roč. 4, č. 1 (2001), s. 19-26. ISSN 1212-0634 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : primary sensory neurones * membrane currents * capsaicin receptor Subject RIV: ED - Physiology

  9. Elicitation of Induced Resistance against Pectobacterium carotovorum and Pseudomonas syringae by Specific Individual Compounds Derived from Native Korean Plant Species

    Directory of Open Access Journals (Sweden)

    Choong-Min Ryu

    2013-10-01

    Full Text Available Plants have developed general and specific defense mechanisms for protection against various enemies. Among the general defenses, induced resistance has distinct characteristics, such as broad-spectrum resistance and long-lasting effectiveness. This study evaluated over 500 specific chemical compounds derived from native Korean plant species to determine whether they triggered induced resistance against Pectobacterium carotovorum supsp. carotovorum (Pcc in tobacco (Nicotiana tabacum and Pseudomonas syringae pv. tomato (Pst in Arabidopsis thaliana. To select target compound(s with direct and indirect (volatile effects, a new Petri-dish-based in vitro disease assay system with four compartments was developed. The screening assay showed that capsaicin, fisetin hydrate, jaceosidin, and farnesiferol A reduced the disease severity significantly in tobacco. Of these four compounds, capsaicin and jaceosidin induced resistance against Pcc and Pst, which depended on both salicylic acid (SA and jasmonic acid (JA signaling, using Arabidopsis transgenic and mutant lines, including npr1 and NahG for SA signaling and jar1 for JA signaling. The upregulation of the PR2 and PDF1.2 genes after Pst challenge with capsaicin pre-treatment indicated that SA and JA signaling were primed. These results demonstrate that capsaicin and jaceosidin can be effective triggers of strong induced resistance against both necrotrophic and biotrophic plant pathogens.

  10. Sequence Classification: 775646 [TMBETA-GENOME[Archive

    Lifescience Database Archive (English)

    Full Text Available Non-TMB TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|17543232|ref|NP_501172.1| osm-9 and Capsaicin re ... ceptor-Related (88.2 kD) (ocr -4) || http://www.ncbi.nlm.nih.gov/protein/17543232 ...

  11. Základní mezníky neurofyziologického výzkumu bolesti

    Czech Academy of Sciences Publication Activity Database

    Vyklický st., Ladislav; Vlachová, Viktorie

    2009-01-01

    Roč. 12, č. 1 (2009), s. 9-19. ISSN 1212-0634 R&D Projects: GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : nociception * pain * capsaicin Subject RIV: ED - Physiology

  12. NGF-induced hyperexcitability causes spontaneous fluctuations of intracellular Ca(2+) in rat nociceptive dorsal root ganglion neurons

    Czech Academy of Sciences Publication Activity Database

    Ozaki, Y.; Kitamura, N.; Tsutsumi, A.; Dayanithi, Govindan; Shibuya, I.

    2009-01-01

    Roč. 45, č. 3 (2009), s. 209-215. ISSN 0143-4160 Institutional research plan: CEZ:AV0Z50390512 Keywords : sensory neuron * capsaicin * TRPV1 Subject RIV: FH - Neurology Impact factor: 4.288, year: 2009

  13. Vaniloidní receptor: struktura jako klíč k poznání funkce

    Czech Academy of Sciences Publication Activity Database

    Sušánková, Klára; Vlachová, Viktorie

    -, č. 3 (2005), s. 139-143. ISSN 1212-0634 R&D Projects: GA ČR(CZ) GA305/03/0802; GA MŠk(CZ) LC554; GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z50110509 Keywords : primary sensory neuron * vanilloid receptor * capsaicin Subject RIV: ED - Physiology

  14. Desentizace kapsaicínového receptoru klinické aplikace

    Czech Academy of Sciences Publication Activity Database

    Vyklický st., Ladislav; Vlachová, Viktorie; Toušová, Karolina; Sušánková, Klára

    2006-01-01

    Roč. 9, Suppl. 2 (2006), s. 16-16. ISSN 1212-0634. [Česko-Slovenské dialogy o bolesti /8./. 18.10.2006 - 21.10.2006, České Budějovice] Institutional research plan: CEZ:AV0Z50110509 Keywords : TRPV1 * capsaicin Subject RIV: ED - Physiology

  15. Vaniloidní receptor TRPV1: aktivace, modulace a úloha v mechanizmech nocicepce

    Czech Academy of Sciences Publication Activity Database

    Vyklický st., Ladislav; Sušánková, Klára; Toušová, Karolina; Vlachová, Viktorie

    2004-01-01

    Roč. 11, č. 1-2 (2004), s. 17-32. ISSN 1212-4575 R&D Projects: GA ČR(CZ) GA305/03/0802; GA MŠk(CZ) LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : nociception * vanilloid receptor * capsaicin Subject RIV: ED - Physiology

  16. Analgetické účinky kapsaicinu - 10let hledání molekulárních mechanismů

    Czech Academy of Sciences Publication Activity Database

    Toušová, Karolina; Benedikt, Jan; Samad, Abdul; Vyklický st., Ladislav; Vlachová, Viktorie

    2007-01-01

    Roč. 11, Suppl.3 (2007), s. 62-63. ISSN 1212-6845 R&D Projects: GA MŠk(CZ) LC554; GA MŠk(CZ) 1M0517; GA ČR(CZ) GA305/06/0319 Institutional research plan: CEZ:AV0Z50110509 Keywords : nociception * vanilloid receptor * capsaicin Subject RIV: ED - Physiology

  17. Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

    International Nuclear Information System (INIS)

    Purpose: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity

  18. Effect of drying temperature on the nutritional and antioxidant qualities of cumari peppers from Pará (Capsicum chinense Jacqui)

    OpenAIRE

    Reis, R. C.; V. C. Castro; I. A. Devilla; C.A. Oliveira; Barbosa, L. S.; R. Rodovalho

    2013-01-01

    This study evaluated the proximate components, concentration of total polyphenols, antioxidant activity, and capsaicin and dihydrocapsaicin in the Cumari chili pepper from Pará, Brazil (Capsicum chinense Jacqui) both fresh and after subjected to three different drying temperatures. The results showed that the contents of ash and vitamin C for the dried pepper differed significantly (P

  19. Non-pungent jalapeno peppers: Weed control and yields

    Science.gov (United States)

    Unknown to most consumers, non-pungent jalapeno peppers are used for making commercial picante sauces (salsas). The non-pungent jalapeno peppers produce the required jalapeno flavor along with the appropriate texture necessary for picante sauce. Capsaicin is added during processing to produce the va...

  20. Molecules that amaze us

    CERN Document Server

    May, Paul

    2014-01-01

    Adenosine Triphosphate (ATP)Adrenaline/Epinephrine (Noradrenaline/Norepinephrine)Ammonium NitrateArtemisinin Aspirin Caffeine CapsaicinCarbon Dioxideβ-CaroteneChlorophyllCholesterolCisplatinCocaineDEETCF2Cl2DDTDigitalisDimethylmercuryDimethylsulfideDopamineEpibatidineEstradiolGlucoseGlycerolHeavy WaterHemeHexenalHydrogen PeroxideInsulin<

  1. Capsaicinoids: a spicy solution to the management of obesity?

    Science.gov (United States)

    Tremblay, A; Arguin, H; Panahi, S

    2016-08-01

    Capsaicin is the molecule that is responsible for the pungency of hot peppers. It stimulates the sympathoadrenal system that mediates the thermogenic and anorexigenic effects of capsaicinoids. Capsaicinoids have been found to accentuate the impact of caloric restriction on body weight loss. Some studies have also shown that capsinoids, the non-pungent analogs of capsaicinoids, increase energy expenditure. Capsaicin supplementation attenuates or even prevents the increase in hunger and decrease in fullness as well as the decrease in energy expenditure and fat oxidation, which normally result from energy restriction. These effects may postpone the occurrence of resistance to lose fat during a weight loss program and facilitate the maintenance of body weight in a postobese state. Evidence also highlights the plausibility of an indirect effect of capsaicin on energy balance via its analgesic effects, which may improve sleep and ultimately facilitate the regulation of energy balance. Although capsaicin intake appears to be a safe practice, further studies will be needed to ascertain the safety of regular long-term consumption. Taken together, these observations reinforce the idea that consumption of capsaicinoids and capsinoids may be helpful to facilitate obesity management. PMID:26686003

  2. Activation of sensory nerves participates in stress-induced histamine release from mast cells in rats.

    Science.gov (United States)

    Huang, Z L; Mochizuki, T; Watanabe, H; Maeyama, K

    1999-08-01

    To elucidate the mechanism by which stress induces rapid histamine release from mast cells, Wistar rats, pretreated as neonates with capsaicin, were subjected to immobilization stress for 2 h, and histamine release was measured in paws of anesthetized rats by using in vivo microdialysis after activation of sensory nerves by electrical or chemical stimulation. Immobilization stress studies indicated that in control rats stress induced a 2.7-fold increase in the level of plasma histamine compared to that in freely moving rats. Whereas pretreatment with capsaicin significantly decreased stress-induced elevation of plasma histamine. Microdialysis studies showed that electrical stimulation of the sciatic nerve resulted in a 4-fold increase of histamine release in rat paws. However, this increase was significantly inhibited in rats pretreated with capsaicin. Furthermore, injection of capsaicin into rat paw significantly increased histamine release in a dose-dependent manner. These results suggest that activation of sensory nerves participates in stress-induced histamine release from mast cells. PMID:10462124

  3. Real-Time Translocation and Function of PKCβII Isoform in Response to Nociceptive Signaling via the TRPV1 Pain Receptor

    Directory of Open Access Journals (Sweden)

    Basil D. Roufogalis

    2011-11-01

    Full Text Available Serine/threonine protein kinase C βII isoform (PKCβII or the pain receptor transient receptor potential vanilloid 1 (TRPV1 have been separately implicated in mediating heat hyperalgesia during inflammation or diabetic neuropathy. However, detailed information on the role of PKC βII in nociceptive signaling mediated by TRPV1 is lacking. This study presents evidence for activation and translocation of the PKC βII isoform as a signaling event in nociception mediated by activation of TRPV1 by capsaicin. We show that capsaicin induces translocation of cytosolic PKCβII isoform fused with enhanced green fluorescence protein (PKCβII-EGFP in dorsal root ganglion (DRG neurons. We also show capsaicin-induced translocation in Chinese Hamster Ovarian (CHO cells co-transfected with TRPV1 and PKCβII-EGFP, but not in CHO cells expressing PKCβII-EGFP alone. By contrast, the PKC activator phorbol-12-myristate-13-acetate (PMA induced translocation of PKCβII-EGFP which was sustained and independent of calcium or TRPV1. In addition PMA-induced sensitization of TRPV1 to capsaicin response in DRG neurons was attenuated by PKCβII blocker CGP 53353. Capsaicin response via TRPV1 in the DRG neurons was confirmed by TRPV1 antagonist AMG 9810. These results suggested a novel and potential signaling link between PKCβII and TRPV1. These cell culture models provide a platform for investigating mechanisms of painful neuropathies mediated by nociceptors expressing the pain sensing gene TRPV1, and its regulation by the PKC isoform PKCβII.

  4. Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain

    International Nuclear Information System (INIS)

    Utilizing 125I-BSA administered intravenously, a simple, reliable, and sensitive method was established for the detection of plasma protein extravasation in the dura of rats and guinea pigs following chemical, electrical, or immunological stimulation. Extravasated 125I-BSA or Evans blue was noted in the dura and conjunctiva but not in the temporalis muscle of saline-perfused rats following intravenous capsaicin, 1 mumol/kg. Capsaicin-induced extravasation was mediated by unmyelinated and small myelinated fibers since leakage did not develop in adult animals in whom these fibers were destroyed by capsaicin pretreatment (50 mg/kg) as neonates. An ipsilateral increase in Evans blue and 125I-BSA was found in the dura, eyelids, lips and gingival mucosa, and snout following electrical stimulation of the rat trigeminal ganglion. This increase was also C-fiber dependent. Among those peptides contained in perivascular afferent fibers and administered intravenously, substance P (SP) and neurokinin A (NKA), but not calcitonin gene-related peptide, caused a dose-dependent extravasation in the dura and conjunctiva of rats. Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva. Intravenous administration of 5-HT or bradykinin to normal adult rats or adult rats pretreated as neonates with capsaicin increased levels of 125I-BSA in both the dura and the conjunctiva. Histamine and prostaglandin E2, on the other hand, caused protein leakage in the conjunctiva but not in the dura of rats; however, histamine did induce extravasation in the dura of guinea pigs

  5. Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain

    Energy Technology Data Exchange (ETDEWEB)

    Markowitz, S.; Saito, K.; Moskowitz, M.A.

    1987-12-01

    Utilizing /sup 125/I-BSA administered intravenously, a simple, reliable, and sensitive method was established for the detection of plasma protein extravasation in the dura of rats and guinea pigs following chemical, electrical, or immunological stimulation. Extravasated /sup 125/I-BSA or Evans blue was noted in the dura and conjunctiva but not in the temporalis muscle of saline-perfused rats following intravenous capsaicin, 1 mumol/kg. Capsaicin-induced extravasation was mediated by unmyelinated and small myelinated fibers since leakage did not develop in adult animals in whom these fibers were destroyed by capsaicin pretreatment (50 mg/kg) as neonates. An ipsilateral increase in Evans blue and /sup 125/I-BSA was found in the dura, eyelids, lips and gingival mucosa, and snout following electrical stimulation of the rat trigeminal ganglion. This increase was also C-fiber dependent. Among those peptides contained in perivascular afferent fibers and administered intravenously, substance P (SP) and neurokinin A (NKA), but not calcitonin gene-related peptide, caused a dose-dependent extravasation in the dura and conjunctiva of rats. Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva. Intravenous administration of 5-HT or bradykinin to normal adult rats or adult rats pretreated as neonates with capsaicin increased levels of /sup 125/I-BSA in both the dura and the conjunctiva. Histamine and prostaglandin E2, on the other hand, caused protein leakage in the conjunctiva but not in the dura of rats; however, histamine did induce extravasation in the dura of guinea pigs.

  6. Antifouling Activity of Simple Synthetic Diterpenoids against Larvae of the Barnacle Balanus albicostatus Pilsbry

    Directory of Open Access Journals (Sweden)

    Dan-Qing Feng

    2010-11-01

    Full Text Available Five new pimarane diterpenoids 1-5 were synthesized using ent-8(14-pimarene-15R,16-diol as starting material. The structures were elucidated by means of extensive NMR and MS analysis. The antifouling activity against larval settlement of the barnacle Balanus albicostatus were evaluated using capsaicin as a positive control. Compounds 1-3 and 5 showed more potent antifouling activity than capsaicin. Compound 5, which exhibited almost the same antifouling activity as starting material, showed better stability than starting material. These compounds all showed antifouling activity in a non-toxic way against larval settlement of the barnacle B. albicostatus. Analysis of structure-activity relationships (SAR demonstrated that the substituents on the C-15 and C-16 position of pimarane diterpenoid were responsible for the antifouling activity.

  7. Development and validation of AccuTOF-DART™ as a screening method for analysis of bank security device and pepper spray components.

    Science.gov (United States)

    Pfaff, Allison M; Steiner, Robert R

    2011-03-20

    Analysis of bank security devices, containing 1-methylaminoanthraquinone (MAAQ) and o-chlorobenzylidenemalononitrile (CS), and pepper sprays, containing capsaicin, is a lengthy process with no specific screening technique to aid in identifying samples of interest. Direct Analysis in Real Time (DART™) ionization coupled with an Accurate Time of Flight (AccuTOF) mass detector is a fast, ambient ionization source that could significantly reduce time spent on these cases and increase the specificity of the screening process. A new method for screening clothing for bank dye and pepper spray, using AccuTOF-DART™ analysis, has been developed. Detection of MAAQ, CS, and capsaicin was achieved via extraction of each compound onto cardstock paper, which was then sampled in the AccuTOF-DART™. All results were verified using gas chromatography coupled with electron impact mass spectrometry. PMID:20643521

  8. Design and Synthesis of New Transient Receptor Potential Vanilloid Type-1 (TRPV1) Channel Modulators: Identification, Molecular Modeling Analysis, and Pharmacological Characterization of the N-(4-Hydroxy-3-methoxybenzyl)-4-(thiophen-2-yl)butanamide, a Small Molecule Endowed with Agonist TRPV1 Activity and Protective Effects against Oxidative Stress.

    Science.gov (United States)

    Aiello, Francesca; Badolato, Mariateresa; Pessina, Federica; Sticozzi, Claudia; Maestrini, Vanessa; Aldinucci, Carlo; Luongo, Livio; Guida, Francesca; Ligresti, Alessia; Artese, Anna; Allarà, Marco; Costa, Giosué; Frosini, Maria; Schiano Moriello, Aniello; De Petrocellis, Luciano; Valacchi, Giuseppe; Alcaro, Stefano; Maione, Sabatino; Di Marzo, Vincenzo; Corelli, Federico; Brizzi, Antonella

    2016-06-15

    4-(Thiophen-2-yl)butanoic acid was identified as a cyclic substitute of the unsaturated alkyl chain of the natural ligand, capsaicin. Accordingly, a new class of amides was synthesized in good yield and high purity and their molecular recognition against the target was investigated by means of docking experiments followed by molecular dynamics simulations, in order to rationalize their geometrical and thermodynamic profiles. The pharmacological properties of these new compounds were expressed as activation (EC50) and desensitization (IC50) potencies. Several compounds were found to activate TRPV1 channels, and in particular, derivatives 1 and 10 behaved as TRPV1 agonists endowed with good efficacy as compared to capsaicin. The most promising compound 1 was also evaluated for its protective role against oxidative stress on keratinocytes and differentiated human neuroblastoma cell lines expressing the TRPV1 receptor as well as for its cytotoxicity and analgesic activity in vivo. PMID:26942555

  9. Osthole inhibits histamine-dependent itch via modulating TRPV1 activity.

    Science.gov (United States)

    Yang, Niu-Niu; Shi, Hao; Yu, Guang; Wang, Chang-Ming; Zhu, Chan; Yang, Yan; Yuan, Xiao-Lin; Tang, Min; Wang, Zhong-Li; Gegen, Tana; He, Qian; Tang, Kehua; Lan, Lei; Wu, Guan-Yi; Tang, Zong-Xiang

    2016-01-01

    Osthole, an active coumarin isolated from Cnidium monnieri (L.) Cusson, has long been used in China as an antipruritic herbal medicine; however, the antipruitic mechanism of osthole is unknown. We studied the molecular mechanism of osthole in histamine-dependent itch by behavioral test, Ca(2+) imaging, and electrophysiological experiments. First, osthole clearly remitted the scratching behaviors of mice induced with histamine, HTMT, and VUF8430. Second, in cultured dorsal root ganglion (DRG) neurons, osthole showed a dose-dependent inhibitory effect to histamine. On the same neurons, osthole also decreased the response to capsaicin and histamine. In further tests, the capsaicin-induced inward currents were inhibited by osthole. These results revealed that osthole inhibited histamine-dependent itch by modulating TRPV1 activity. This study will be helpful in understanding how osthole exerts anti-pruritus effects and suggests that osthole may be a useful treatment medicine for histamine-dependent itch. PMID:27160770

  10. Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature

    DEFF Research Database (Denmark)

    Chen, L; Kaßmann, M; Sendeski, M; Tsvetkov, D; Marko, L; Michalick, L; Riehle, M; Liedtke, W B; Kuebler, W M; Harteneck, C; Tepel, Martin; Patzak, A; Gollasch, M

    2015-01-01

    AIM: Transient receptor potential vanilloid 1 (TRPV1) and vanilloid 4 (TRPV4) cation channels have been recently identified to promote endothelium-dependent relaxation of mouse mesenteric arteries. However, the role of TRPV1 and TRPV4 in the renal vasculature is largely unknown. We hypothesized...... that TRPV1/4 plays a role in endothelium-dependent vasodilation of renal blood vessels. METHODS: We studied the distribution of functional TRPV1/4 along different segments of the renal vasculature. Mesenteric arteries were studied as control vessels. RESULTS: The TRPV1 agonist capsaicin relaxed mouse...... mesenteric arteries with an EC50 of 25 nm, but large mouse renal arteries or rat descending vasa recta only at >100-fold higher concentrations. The vasodilatory effect of capsaicin in the low-nanomolar concentration range was endothelium-dependent and absent in vessels of Trpv1 -/- mice. The TRPV4 agonist...

  11. Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity

    DEFF Research Database (Denmark)

    Zhang, Li Li; Yan Liu, Dao; Ma, Li Qun;

    2007-01-01

    We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect...... of TRPV1 on cytosolic calcium was determined fluorometrically in 3T3-L1-preadipocytes and in human visceral fat tissue. Adipogenesis in stimulated 3T3-L1-preadipocytes was determined by oil red O-staining of intracellular lipid droplets, triglyceride levels, expression of peroxisome proliferator......-activated receptor-gamma, and expression of fatty acid synthase. Long-term feeding experiments were undertaken in wild-type mice and TRPV1 knockout mice. We detected TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans. In vitro, the TRPV1 agonist capsaicin dose-dependently induced...

  12. Pharmacological differences between the human and rat vanilloid receptor 1 (VR1)

    OpenAIRE

    Mcintyre, Peter; McLatchie, Linda M.; Chambers, Anne; Phillips, Elsa; Clarke, Melanie; Savidge, Jonathan; Toms, Christy; Peacock, Marcus; Shah, Kirti; Winter, Janet; Weerasakera, Natasha; Webb, Mike; Rang, Humphrey P; Bevan, Stuart; James, Iain F

    2001-01-01

    Vanilloid receptors (VR1) were cloned from human and rat dorsal root ganglion libraries and expressed in Xenopus oocytes or Chinese Hamster Ovary (CHO) cells.Both rat and human VR1 formed ligand gated channels that were activated by capsaicin with similar EC50 values. Capsaicin had a lower potency on both channels, when measured electrophysiologically in oocytes compared to CHO cells (oocytes: rat=1.90±0.20 μM; human=1.90±0.30 μM: CHO cells: rat=0.20±0.06 μM; human=0.19±0.08 μM).In CHO cell l...

  13. Topical Anti-Inflammatory Activity of Oil from Tropidurus hispidus (Spix, 1825).

    Science.gov (United States)

    Santos, Israel J M; Leite, Gerlânia O; Costa, José Galberto M; Alves, Romulo R N; Campos, Adriana R; Menezes, Irwin R A; Freita, Francisco Ronaldo V; Nunes, Maria Janeth H; Almeida, Waltécio O

    2015-01-01

    Tropidurus hispidus has been used in traditional medicine in several regions of Northeastern Region of Brazil. Its medicinal use involves the treatment of diseases such as warts, sore throat, tonsillitis, chicken pox, varicella, measles, asthma, alcoholism, and dermatomycosis. The present study evaluated the topical anti-inflammatory activity of Tropidurus hispidus fat in treating ear edema in an animal model. Oil from T. hispidus (OTH) was evaluated on its effect against experimental inflammation in mice. OTH was extracted from body fat located in the ventral region of Tropidurus hispidus using hexane as a solvent. We used the model of mouse ear edema induced by phlogistic agents, croton oil (single and multiple applications), arachidonic acid, phenol, capsaicin, and histamine, applied into the right ears of animals pretreated with acetone (control), dexamethasone, or OTH. OTH inhibited the dermatitis induced by all noxious agents, except capsaicin. This effect may be related to the fatty acids present in OTH. PMID:26664448

  14. Topical Anti-Inflammatory Activity of Oil from Tropidurus hispidus (Spix, 1825

    Directory of Open Access Journals (Sweden)

    Israel J. M. Santos

    2015-01-01

    Full Text Available Tropidurus hispidus has been used in traditional medicine in several regions of Northeastern Region of Brazil. Its medicinal use involves the treatment of diseases such as warts, sore throat, tonsillitis, chicken pox, varicella, measles, asthma, alcoholism, and dermatomycosis. The present study evaluated the topical anti-inflammatory activity of Tropidurus hispidus fat in treating ear edema in an animal model. Oil from T. hispidus (OTH was evaluated on its effect against experimental inflammation in mice. OTH was extracted from body fat located in the ventral region of Tropidurus hispidus using hexane as a solvent. We used the model of mouse ear edema induced by phlogistic agents, croton oil (single and multiple applications, arachidonic acid, phenol, capsaicin, and histamine, applied into the right ears of animals pretreated with acetone (control, dexamethasone, or OTH. OTH inhibited the dermatitis induced by all noxious agents, except capsaicin. This effect may be related to the fatty acids present in OTH.

  15. Genetic parameters and selection for resistance to bacterial spot in recombinant F6 lines of Capsicum annuum

    Directory of Open Access Journals (Sweden)

    Messias Gonzaga Pereira

    2009-01-01

    Full Text Available This study aimed to advance generations and select superior sweet pepper genotypes with resistance tobacterial spot, using the breeding method Single Seed Descent (SSD based on the segregating population derived from thecross between Capsicum annuum L. UENF 1421 (susceptible, non-pungent and UENF 1381 (resistant, pungent. Thesegregating F3 generation was grown in pots in a greenhouse until the F5 generation. The F6 generation was grown in fieldconditions. The reaction to bacterial spot was evaluated by inoculation with isolate ENA 4135 of Xanthomonas campestris pv.vesicatoria, based on a score scale and by calculating the area under the disease progress curve (AUDPC. The presence orabsence of capsaicin was also assessed. Eighteen F6 lines were bacterial leaf spot-resistant. Since no capsaicin was detectedin the F6 lines 032, 316, 399, 434, and 517, these will be used in the next steps of the sweet pepper breeding program.

  16. Where did the chili get its spice? Biogeography of capsaicinoid production in ancestral wild chili species.

    Science.gov (United States)

    Tewksbury, Joshua J; Manchego, Carlos; Haak, David C; Levey, Douglas J

    2006-03-01

    The biogeography of pungency in three species of wild chili in the chaco and surrounding highland habitats of southeastern Bolivia is described. We report that Capsicum chacoense, C. baccatum, and C. eximium are polymorphic for production of capsaicin and its analogs, such that completely pungent and completely nonpungent individuals co-occur in some populations. In C. chacoense, the density of plants and the proportion of pungent plants increased with elevation. Above 900 m, all individuals in all populations except two were pungent; nonpungent individuals in at least one of the two polymorphic populations were likely a result of spreading by humans. The occurrence of pungent and nonpungent individuals in three species of ancestral Capsicum and the geographic variation of pungency within species suggest that production of capsaicin and its analogs entails both costs and benefits, which shift from one locality to another. Determining the selection pressures behind such shifts is necessary to understand the evolution of pungency in chilies. PMID:16572297

  17. Capsaicinoids in the hottest pepper Bhut Jolokia and its antioxidant and antiinflammatory activities.

    Science.gov (United States)

    Liu, Yunbao; Nair, Muraleedharan G

    2010-01-01

    Hot peppers are known for medicinally important capsaicinoids. Bhut Jolokia, Capsicum chinense/Capsicum frutescens, is the hottest pepper in the world. However, its bioactivity and quantity of heat principles are not reported. We have now quantified capsaicin (C) and dihydrocapsaicin (DHC) in Bhut Jolokia and compared it with commonly consumed hot peppers, Jalapeno (Capsicum annuum) and Scotch Bonnet (Capsicum chinense). The concentration of C and DHC in Bhut Jolokia was 5.36%, which is about 338 and 18 times greater than in Scotch Bonnet and Jalapeno, respectively. We have also isolated capsaicin (C) and dihydrocapsaicin (DHC) in pure form and determined lipid peroxidation (LPO) and cyclooxygenase (COX-1 and -2) enzymes inhibitory concentrations. This is the first report of the quantification of C and DHC in Bhut Jolokia, comparison of capsaicinoids content in Bhut Jolokia with Jalapeno and Scotch Bonnet hot peppers and the COX and LPO inhibitory activities of C and DHC. PMID:20184029

  18. In vitro anticholinesterase activity of various alkaloids.

    Science.gov (United States)

    Orhan, Ilkay; Naz, Qamar; Kartal, Murat; Tosun, Fatma; Sener, Bilge; Choudhary, M Iqbal

    2007-01-01

    In the current study, a number of alkaloids including retamine, cytisine, and sparteine (quinolizidine-type), yohimbine and vincamine (indole-type), scopolamine and atropine (tropane-type), colchicine (tropolone-type), allantoin (imidazolidine-type), trigonelline (pyridine-type) as well as octopamine, synephrine, and capsaicin (exocyclic amine-type) were tested in vitro for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at 1 mg/ml concentration by the Ellman method using an ELISA microplate reader. Among the alkaloids tested, only capsaicin exerted a remarkable inhibitory effect towards both AChE and BChE [(62.7 +/- 0.79)% and (75.3 +/- 0.98)%, respectively]. While the rest of the alkaloids did not show any significant inhibition against AChE, three of the alkaloids, namely retamine, sparteine, and yohimbine, exerted a noteworthy anti-BChE effect as compared to galanthamine, the reference drug. PMID:18069241

  19. Functional and structural assessment of patients with and without persistent pain after thoracotomy

    DEFF Research Database (Denmark)

    Springer, J S; Karlsson, P; Madsen, C S;

    2016-01-01

    BACKGROUND: Persistent pain is frequent after thoracotomy, with a reported prevalence of up to 60%. It remains unclear why some patients develop pain, whereas others do not. We therefore examined patients with and without pain after thoracotomy to identify pathophysiological contributors to...... sensory testing according to the protocol of the German Research Network on Neuropathic Pain, measurement of capsaicin-evoked flare response, intradermal nerve density as determined by skin biopsies and laser- and heat-evoked potentials. RESULTS: Bedside testing revealed evoked pain in 16 of 20 patients....... SIGNIFICANCE: Evoked pain is more frequent in patients with pain. Assessment of intradermal nerve density, capsaicin-induced flare response and contact and laser heat-evoked potentials revealed no differences between pain patients and pain-free patients....

  20. A randomized, double-blind, positive-controlled, 3-way cross-over human experimental pain study of a TRPV1 antagonist (V116517) in healthy volunteers and comparison with preclinical profile

    DEFF Research Database (Denmark)

    Arendt-Nielsen, Lars; Harris, Steve; Whiteside, Garth T.;

    2016-01-01

    This experimental, translational, experimental pain, single-center, randomized, double-blind, single-dose, 3-treatment, 3-period cross-over proof-of-concept volunteer trial studied the efficacy of a novel TRPV1 antagonist (V116517) on capsaicin and UVB induced hyperalgesia. Heat and pressure pain...... after UVB were significantly (p<0.0001) reduced by celecoxib. Stimulus-response function in capsaicin treated areas showed significant differences between both celecoxib and placebo and between V116517 and placebo. The body temperature showed no change, and no side effects were reported for any of the...... demonstrated an alignment between two of the three end points tested.The TRPV1 antagonist showed a potent anti-hyperalgesic action without changing the body temperature but heat analgesia may be a potential safety issue....

  1. Involvement of nitric oxide (NO) in cough reflex sensitivity between non-sensitized and OVA-sensitized guinea pigs

    OpenAIRE

    Hori, Akihiro; Fujimura, Masaki; Ohkura, Noriyuki; Tokuda, Akira

    2011-01-01

    Background Exhaled nitric oxide (ENO) is elevated in bronchial asthma patients, and inhaled corticosteroid therapy lowers the elevated ENO levels in such patients. ENO appears to be an inflammatory marker, but its role in the pathophysiology of cough remains unclear. This study aimed to elucidate the relationship between NO and increased cough reflex sensitivity induced by allergic airway reactions. Methods Cough reflex sensitivity to inhaled capsaicin was observed under NO depletion caused b...

  2. METABOLISM OF CAPSAICINOIDS BY P450 ENZYMES: A REVIEW OF RECENT FINDINGS ON REACTION MECHANISMS, BIO-ACTIVATION, AND DETOXIFICATION PROCESSES

    OpenAIRE

    Reilly, Christopher A.; Yost, Garold S.

    2006-01-01

    Capsaicinoids are botanical irritants present in chili peppers. Chili pepper extracts and capsaicinoids are common dietary constituents and important pharmaceutical agents. Use of these substances in modern consumer products and medicinal preparations occurs worldwide. Capsaicinoids are the principals of pepper spray self-defense weapons and several over-the-counter pain treatments as well as the active component of many dietary supplements. Capsaicinoids interact with the capsaicin receptor ...

  3. Reactive formulations for a neutralization of toxic industrial chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, Mark D. (Albuqueruqe, NM); Betty, Rita G. (Rio Rancho, NM)

    2006-10-24

    Decontamination formulations for neutralization of toxic industrial chemicals, and methods of making and using same. The formulations are effective for neutralizing malathion, hydrogen cyanide, sodium cyanide, butyl isocyanate, carbon disulfide, phosgene gas, capsaicin in commercial pepper spray, chlorine gas, anhydrous ammonia gas; and may be effective at neutralizing hydrogen sulfide, sulfur dioxide, formaldehyde, ethylene oxide, methyl bromide, boron trichloride, fluorine, tetraethyl pyrophosphate, phosphorous trichloride, arsine, and tungsten hexafluoride.

  4. Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia

    OpenAIRE

    Garami, Andras; Shimansky, Yury P.; Pakai, Eszter; Oliveira, Daniela L.; Gavva, Narender R.; Romanovsky, Andrej A

    2010-01-01

    Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic...

  5. Genetic control of neuronal activity in mice conditionally expressing TRPV1

    OpenAIRE

    Arenkiel, Benjamin R.; Klein, Marguerita E; Davison, Ian G.; Katz, Lawrence C.; Ehlers, Michael D.

    2008-01-01

    Here we describe a knock-in mouse model for Cre-loxP–based conditional expression of TRPV1 in central nervous system neurons. Expression of Cre recombinase using biolistics, lentivirus or genetic intercrosses triggered heterologous expression of TRPV1 in a cell-specific manner. Application of the TRPV1 ligand capsaicin induced strong inward currents, triggered action potentials and activated stereotyped behaviors, allowing cell type–specific chemical genetic control of neuronal activity in vi...

  6. TRPV1 and Endocannabinoids: Emerging Molecular Signals that Modulate Mammalian Vision

    OpenAIRE

    Ryskamp, Daniel A.; Sarah Redmon; Jo, Andrew O.; David Križaj

    2014-01-01

    Transient Receptor Potential Vanilloid 1 (TRPV1) subunits form a polymodal cation channel responsive to capsaicin, heat, acidity and endogenous metabolites of polyunsaturated fatty acids. While originally reported to serve as a pain and heat detector in the peripheral nervous system, TRPV1 has been implicated in the modulation of blood flow and osmoregulation but also neurotransmission, postsynaptic neuronal excitability and synaptic plasticity within the central nervous system. In addition t...

  7. Conservation of Tubulin-Binding Sequences in TRPV1 throughout Evolution

    OpenAIRE

    Sardar, Puspendu; Kumar, Abhishek; Bhandari, Anita; Goswami, Chandan

    2012-01-01

    Background Transient Receptor Potential Vanilloid sub type 1 (TRPV1), commonly known as capsaicin receptor can detect multiple stimuli ranging from noxious compounds, low pH, temperature as well as electromagnetic wave at different ranges. In addition, this receptor is involved in multiple physiological and sensory processes. Therefore, functions of TRPV1 have direct influences on adaptation and further evolution also. Availability of various eukaryotic genomic sequences in public domain faci...

  8. Compartment-Specific Modulation of GABAergic Synaptic Transmission by TRPV1 Channels in the Dentate Gyrus

    OpenAIRE

    Chávez, Andrés E.; Hernández, Vivian M.; Rodenas-Ruano, Alma; Chan, C. Savio; Castillo, Pablo E.

    2014-01-01

    The transient receptor potential TRPV1 or vanilloid receptor is a nonselective ligand-gated channel highly expressed in primary sensory neurons where it mediates nociception. TRPV1 is also expressed in the brain where its activation depresses excitatory synaptic transmission. Whether TRPV1 also regulates inhibitory synapses in the brain is unclear. Here, using a combination of pharmacology, electrophysiology, and an in vivo knockdown strategy, we report that TRPV1 activation by capsaicin or b...

  9. Increase of TRPV1-Immunoreactivity in Dorsal Root Ganglia Neurons Innervating the Femur in a Rat Model of Osteoporosis

    OpenAIRE

    Yoshino, Kensuke; Suzuki, Miyako; Kawarai, Yuya; Sakuma, Yoshihiro; Inoue, Gen; Orita, Sumihisa; Yamauchi, Kazuyo; Aoki, Yasuchika; Ishikawa, Tetsuhiro; Miyagi, Masayuki; Kamoda, Hiroto; Kubota, Gou; Oikawa, Yasuhiro; Inage, Kazuhide; Sainoh, Takeshi

    2014-01-01

    Purpose Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, which can be activated by capsaicin and other noxious stimuli. Recently, an association between bone pain and TRPV1 has been reported. However, the influence of osteoporosis on TRPV1 in the sensory system innervating the femur has not been reported. Materials and Methods TRPV1-immunoreactive (ir) in dorsal root ganglia (DRG) neurons labeled with neurotracer [Fluoro-Gold (FG)] innervating th...

  10. Lipopolysaccharide-induced Pulpitis Up-regulates TRPV1 in Trigeminal Ganglia

    OpenAIRE

    Chung, M.-K.; Lee, J.; Duraes, G.; Ro, J. Y.

    2011-01-01

    Tooth pain often accompanies pulpitis. Accumulation of lipopolysaccharides (LPS), a product of Gram-negative bacteria, is associated with painful clinical symptoms. However, the mechanisms underlying LPS-induced tooth pain are not clearly understood. TRPV1 is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and hyperalgesia under inflammation or injury. Although TRPV1 is expressed in pulpal afferents, it is not known whether the application of LPS to teeth mod...

  11. TRPV1 splice variants: structure and function

    OpenAIRE

    Schumacher, Mark A; Eilers, Helge

    2010-01-01

    The capsaicin receptor (TRPV1) is a non-selective cation channel predominantly expressed in specialized sensory neurons that detect painful stimuli. Although its many functional roles continue to be revealed, it has been confirmed to play a critical role in the perception of peripheral inflammatory hyperalgesia and pain. TRPV1 not only is sensitized and/or activated under a wide range of conditions including inflammation and nerve injury but also undergoes changes in expressed levels in respo...

  12. A Hot New Twist to Hair Biology: Involvement of Vanilloid Receptor-1 (VR1/TRPV1) Signaling in Human Hair Growth Control

    OpenAIRE

    Bodó, Enikő; Bíró, Tamás; Telek, Andrea; Czifra, Gabriella; Griger, Zoltán; Tóth, Balázs I; Mescalchin, Alessandra; Ito, Taisuke; Bettermann, Albrecht; Kovács, László; Paus, Ralf

    2005-01-01

    The vanilloid receptor-1 (VR1, or transient receptor potential vanilloid-1 receptor, TRPV1) is activated by capsaicin, the key ingredient of hot peppers. TRPV1 was originally described on sensory neurons as a central integrator of various nociceptive stimuli. However, several human skin cell populations are also now recognized to express TRPV1, but with unknown function. Exploiting the human hair follicle (HF) as a prototypic epithelial-mesenchymal interaction system, we have characterized th...

  13. Identification of a Binding Motif in the S5 Helix That Confers Cholesterol Sensitivity to the TRPV1 Ion Channel*

    OpenAIRE

    Picazo-Juárez, Giovanni; Romero-Suárez, Silvina; Nieto-Posadas, Andrés; Llorente, Itzel; Jara-Oseguera, Andrés; Briggs, Margaret; McIntosh, Thomas J.; Simon, Sidney A.; Ladrón-de-Guevara, Ernesto; Islas, León D.; Rosenbaum, Tamara

    2011-01-01

    The TRPV1 ion channel serves as an integrator of noxious stimuli with its activation linked to pain and neurogenic inflammation. Cholesterol, a major component of cell membranes, modifies the function of several types of ion channels. Here, using measurements of capsaicin-activated currents in excised patches from TRPV1-expressing HEK cells, we show that enrichment with cholesterol, but not its diastereoisomer epicholesterol, markedly decreased wild-type rat TRPV1 currents. Substitutions in t...

  14. Epithelial TRPV1 Signaling Accelerates Gingival Epithelial Cell Proliferation

    OpenAIRE

    Takahashi, N; Matsuda, Y; Yamada, H; Tabeta, K; Nakajima, T; Murakami, S.; Yamazaki, K.

    2014-01-01

    Transient receptor potential cation channel subfamily V member 1 (TRPV1), a member of the calcium-permeable thermosensitive transient receptor potential superfamily, is a sensor of thermal and chemical stimuli. TRPV1 is activated by noxious heat (> 43°C), acidic conditions (pH < 6.6), capsaicin, and endovanilloids. This pain receptor was discovered on nociceptive fibers in the peripheral nervous system. TRPV1 was recently found to be expressed by non-neuronal cells, such as epithelial cells. ...

  15. Human Keratinocytes Are Vanilloid Resistant

    OpenAIRE

    Pecze, László; Szabó, Kornélia; Széll, Márta; Jósvay, Katalin; Kaszás, Krisztián; Kúsz, Erzsébet; Letoha, Tamás; Prorok, János; Koncz, István; Tóth, András; Kemény, Lajos; Vizler, Csaba; Oláh, Zoltán

    2008-01-01

    Background Use of capsaicin or resiniferatoxin (RTX) as analgesics is an attractive therapeutic option. RTX opens the cation channel inflammatory pain/vanilloid receptor type 1 (TRPV1) permanently and selectively removes nociceptive neurons by Ca2+-cytotoxicity. Paradoxically, not only nociceptors, but non-neuronal cells, including keratinocytes express full length TRPV1 mRNA, while patient dogs and experimental animals that underwent topical treatment or anatomically targeted molecular surge...

  16. Resiniferatoxin (RTX) Causes a Uniquely Protracted Musculoskeletal Hyperalgesia in Mice by Activation of TRPV1 Receptors

    OpenAIRE

    Abdelhamid, Ramy E.; Kovács, Katalin J.; Honda, Christopher N.; Nunez, Myra G.; Larson, Alice A.

    2013-01-01

    Inactivation of TRPV1 receptors is one approach to analgesic drug development. However, TRPV1 receptors exert different effects on each modality of pain. Because muscle pain is clinically important, we compared the effect of TRPV1 ligands on musculoskeletal nociception to that on thermal and tactile nociception. Injected parenterally, capsaicin had no effect on von Frey fiber responses (tactile) but induced a transient hypothermia and hyperalgesia in both the tail flick (thermal) and grip for...

  17. Vanilloid receptor-1 (TRPV1) expression and function in the vasculature of the rat

    OpenAIRE

    Tóth Attila (1971-) (molekuláris biológus); Czikora Ágnes (1982-) (molekuláris biológus); Pásztorné Tóth Enikő (1966-) (laboratóriumi analitikus); Dienes Beatrix (1972-) (élettanász, molekuláris biológus); Bai Péter (1976-) (biokémikus); Csernoch László (1961-) (élettanász); Rutkai Ibolya (1985-) (molekuláris biológus); Csató Viktória (1986-) (molekuláris biológus); Mányiné Siket Ivetta (1962-) (laborasszisztens); Pórszász Róbert (1965-) (farmakológus, klinikai farmakológus); Édes István (1952-) (kardiológus); Papp Zoltán (1959-) (fizikus); Boczán Judit (1972-) (neurológus)

    2014-01-01

    Transient receptor potential (TRP) cation channels are emerging in vascular biology. In particular, the expression of the capsaicin receptor (TRPV1) was reported in vascular smooth muscle cells. This study characterized the arteriolar TRPV1 function and expression in the rat. TRPV1 mRNA was expressed in various vascular beds. Six commercially available antibodies were tested for TRPV1 specificity. Two of them were specific (immunostaining was abolished by blocking peptides) for neuronal TRPV1...

  18. TRPV1 senses both acidic and basic pH

    OpenAIRE

    Dhaka, Ajay; Uzzell, Valerie; Dubin, Adrienne; Mathur, Jayanti; Petrus, Matt; Bandell, Michael; Patapoutian, Ardem

    2009-01-01

    Maintaining physiological pH is required for survival, and exposure to alkaline chemicals such as ammonia (smelling salts) elicits severe pain and inflammation through unknown mechanisms. TRPV1, the capsaicin receptor, is an integrator of noxious stimuli including heat and extracellular acidic pH. Here we report that ammonia activates TRPV1, TRPA1 (another polymodal nocisensor), and other unknown receptor(s) expressed in sensory neurons. Ammonia and intracellular alkalization activate TRPV1 t...

  19. Calcitonin gene-related peptide stimulates stromal cell osteogenic differentiation and inhibits RANKL induced NF-κB activation, osteoclastogenesis and bone resorption

    OpenAIRE

    Wang, Liping; Shi, Xiaoyou; Zhao, Rong; Halloran, Bernard P.; Clark, David J; Jacobs, Christopher R; Kingery, Wade S.

    2009-01-01

    Previously we observed that capsaicin treatment in rats inhibited sensory neuropeptide signaling, with a concurrent reduction in trabecular bone formation and bone volume, and an increase in osteoclast numbers and bone resorption. Calcitonin gene-related peptide (CGRP) is a neuropeptide richly distributed in sensory neurons innervating the skeleton and we postulated that CGRP signaling regulates bone integrity. In this study we examined CGRP effects on stromal and bone cell differentiation an...

  20. Pharmacotherapy for pain: what to measure, how to measure?

    OpenAIRE

    Martini, Christian Hubert

    2015-01-01

    In this thesis novel techniques are described which are developed to analyze or predict the efficacy of pharmacotherapy for pain. In Chapter 2 an overview is presented on recent pharmacokinetic pharmacodynamic (PKPD) modeling in acute and chronic pain. Chapter 3 describes the analgesic effect of a capsaicin patch in diabetic painful neuropathy (DPN) pain patients. A longitudinal population PD analysis is performed. In Chapter 4 a subgroup analysis is performed on pooled data from 4 multicente...

  1. Characteristics of dorsal root ganglia neurons sensitive to Substance P

    OpenAIRE

    Moraes, Eder Ricardo; Kushmerick, Christopher; Naves, Ligia Araujo

    2014-01-01

    Background Substance P modulates ion channels and the excitability of sensory neurons in pain pathways. Within the heterogeneous population of Dorsal Root Ganglia (DRG) primary sensory neurons, the properties of cells that are sensitive to Substance P are poorly characterized. To define this population better, dissociated rat DRG neurons were tested for their responsiveness to capsaicin, ATP and acid. Responses to ATP were classified according to the kinetics of current activation and desensi...

  2. Modulatory effect of neuropeptide Y on acetylcholine-induced oedema and vasoconstriction in isolated perfused lungs of rabbit.

    OpenAIRE

    Delaunois, A; Gustin, P; Dessy-Doize, C; Ansay, M

    1994-01-01

    1. The modulatory role of neuropeptide Y (NPY) on pulmonary oedema induced by acetylcholine and capsaicin was investigated. The effects of NPY on the haemodynamic response to acetylcholine, phenylephrine and substance P were also investigated. 2. Isolated, ventilated, exsanguinated lungs of the rabbit were perfused with a constant flow of recirculating blood-free perfusate. The double/arterial/venous occlusion method was used to partition the total pressure gradient (delta Pt) into four compo...

  3. Paradoxic effects of propofol on visceral pain induced by various TRPV1 agonists

    OpenAIRE

    Ji, Wenjin; Cui, Can; Zhang, Zhiwei; Liang, Jiexian

    2013-01-01

    Intraperitoneal injection of propofol inhibits subsequent acetic acid-induced writhing response in mice. Propofol increases the sensitivity of dorsal root ganglion neurons to capsaicin through transient receptor potential ankyrin subtype-1 (TRPA1) and protein kinase Cε (PKCε)-mediated phosphorylation of transient receptor potential vanilloid subtype-1 (TRPV1). Intraperitoneal co-injection of propofol may increase visceral nociception induced by TRPV1 agonists via sensitization of TRPV1. There...

  4. トウガラシにおける新規カプサイシン類似物質・カプシコニノイドの含量

    OpenAIRE

    田中, 義行

    2014-01-01

     In the course of analyses of nonpungent capsaicinoidanalogs named capsinoids, two unknown compounds werediscovered in pepper fruits. These compounds were isolatedfrom the fruit of ‘CCB’(Capsicum baccatum var.praetermissum). Their structures were determined to beconiferyl (E)‒8‒methyl‒6‒nonenoate and coniferyl8‒methylnonanoate. These novel capsaicin analogs werenamed capsiconiate and dihydrocapsiconiate, respectively,and the coniferyl ester group was named capsiconinoid.Capsiconinoids have ag...

  5. Exogenous Asymmetric Dimethylarginine (ADMA in Pathogenesis of Ischemia-Reperfusion-Induced Gastric Lesions: Interaction with Protective Nitric Oxide (NO and Calcitonin Gene-Related Peptide (CGRP

    Directory of Open Access Journals (Sweden)

    Marcin Magierowski

    2014-03-01

    Full Text Available Asymmetric dimethylarginine (ADMA is an endogenous nitric oxide (NO synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I and 3 h of reperfusion (R. These I/R animals were pretreated with ADMA with or without the combination of l-arginine, calcitonin gene-related peptide (CGRP or a small dose of capsaicin, all of which are known to afford protection against gastric lesions, or with a farnesoid X receptor (FXR agonist, GW 4064, to increase the metabolism of ADMA. In the second series, ADMA was administered to capsaicin-denervated rats. The area of gastric damage was measured with planimetry, gastric blood flow (GBF was determined by H2-gas clearance, and plasma ADMA and CGRP levels were determined using ELISA and RIA. ADMA significantly increased I/R-induced gastric injury while significantly decreasing GBF, the luminal NO content, and the plasma level of CGRP. This effect of ADMA was significantly attenuated by pretreatment with CGRP, l-arginine, capsaicin, or a PGE2 analogue. In GW4064 pretreated animals, the I/R injury was significantly reduced and this effect was abolished by co-treatment with ADMA. I/R damage potentiated by ADMA was exacerbated in capsaicin-denervated animals with a further reduction of CGRP. Plasma levels of IL-10 were significantly decreased while malonylodialdehyde (MDA and plasma TNF-α contents were significantly increased by ADMA. In conclusion, ADMA aggravates I/R-induced gastric lesions due to a decrease of GBF, which is mediated by a fall in NO and CGRP release, and the enhancement of lipid peroxidation and its pro-inflammatory properties.

  6. Exogenous asymmetric dimethylarginine (ADMA) in pathogenesis of ischemia-reperfusion-induced gastric lesions: interaction with protective nitric oxide (NO) and calcitonin gene-related peptide (CGRP).

    Science.gov (United States)

    Magierowski, Marcin; Jasnos, Katarzyna; Sliwowski, Zbigniew; Surmiak, Marcin; Krzysiek-Maczka, Gracjana; Ptak-Belowska, Agata; Kwiecien, Slawomir; Brzozowski, Tomasz

    2014-01-01

    Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I) and 3 h of reperfusion (R). These I/R animals were pretreated with ADMA with or without the combination of L-arginine, calcitonin gene-related peptide (CGRP) or a small dose of capsaicin, all of which are known to afford protection against gastric lesions, or with a farnesoid X receptor (FXR) agonist, GW 4064, to increase the metabolism of ADMA. In the second series, ADMA was administered to capsaicin-denervated rats. The area of gastric damage was measured with planimetry, gastric blood flow (GBF) was determined by H2-gas clearance, and plasma ADMA and CGRP levels were determined using ELISA and RIA. ADMA significantly increased I/R-induced gastric injury while significantly decreasing GBF, the luminal NO content, and the plasma level of CGRP. This effect of ADMA was significantly attenuated by pretreatment with CGRP, L-arginine, capsaicin, or a PGE2 analogue. In GW4064 pretreated animals, the I/R injury was significantly reduced and this effect was abolished by co-treatment with ADMA. I/R damage potentiated by ADMA was exacerbated in capsaicin-denervated animals with a further reduction of CGRP. Plasma levels of IL-10 were significantly decreased while malonylodialdehyde (MDA) and plasma TNF-α contents were significantly increased by ADMA. In conclusion, ADMA aggravates I/R-induced gastric lesions due to a decrease of GBF, which is mediated by a fall in NO and CGRP release, and the enhancement of lipid peroxidation and its pro-inflammatory properties. PMID:24658439

  7. TRPV1: A Potential Drug Target for Treating Various Diseases

    OpenAIRE

    Rafael Brito; Sandeep Sheth; Debashree Mukherjea; Rybak, Leonard P; Vickram Ramkumar

    2014-01-01

    Transient receptor potential vanilloid 1 (TRPV1) is an ion channel present on sensory neurons which is activated by heat, protons, capsaicin and a variety of endogenous lipids termed endovanilloids. As such, TRPV1 serves as a multimodal sensor of noxious stimuli which could trigger counteractive measures to avoid pain and injury. Activation of TRPV1 has been linked to chronic inflammatory pain conditions and peripheral neuropathy, as observed in diabetes. Expression of TRPV1 is also observed ...

  8. Natural products and body weight control

    OpenAIRE

    Jay Lee; Yanmei Li; Chunhua Li; Duo Li

    2011-01-01

    The purpose of the review was to summarise the effect of some commonly available natural products used for body weight management. We collected data from PubMed and scientific journals. There are numerous publications on this topic, however we have summarized the most commonly available and potent natural products from recent 53 publications. The natural products analyzed in this paper include catechins, capsaicin, conjugated linoleic acid, fucoxanthin, soy isoflavone, glabridin, astaxanthin ...

  9. Inhibition of guinea-pig and human sensory nerve activity and the cough reflex in guinea-pigs by cannabinoid (CB2) receptor activation

    OpenAIRE

    Patel, Hema J; Birrell, Mark A; Crispino, Natascia; Hele, David J.; Venkatesan, Priya; Barnes, Peter J; Yacoub, Magdi H.; Belvisi, Maria G.

    2003-01-01

    There is considerable interest in novel therapies for cough, since currently used agents such as codeine have limited beneficial value due to the associated side effects. Sensory nerves in the airways mediate the cough reflex via activation of C-fibres and RARs. Evidence suggests that cannabinoids may inhibit sensory nerve-mediated responses.We have investigated the inhibitory actions of cannabinoids on sensory nerve depolarisation mediated by capsaicin, hypertonic saline and PGE2 on isolated...

  10. Effects of capsinoid ingestion on energy expenditure and lipid oxidation at rest and during exercise

    OpenAIRE

    Staples Aaron W; Andrews Richard; Holwerda Andrew M; Sherriffs Scott S; Josse Andrea R; Phillips Stuart M

    2010-01-01

    Abstract Background The thermogenic and metabolic properties of capsinoids appear to mimic those of the more pungent sister compound capsaicin. However, few data exist on how capsinoid ingestion affects energy expenditure in humans and no data exist on its interaction with exercise. We aimed to determine how ingestion of capsinoids affected energy expenditure, lipid oxidation and blood metabolites at rest and during moderate intensity exercise. Methods Twelve healthy young men (age = 24.3 ± 3...

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

    OpenAIRE

    Jürgens, Tim P; Reetz, Romy; May, Arne

    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 ...

  12. Respiratory actions of vanilloid receptor agonists in the nucleus of the solitary tract: comparison of resiniferatoxin with non-pungent agents and anandamide

    OpenAIRE

    Geraghty, Dominic P; Mazzone, Stuart B.

    2002-01-01

    Activation of vanilloid receptors on sensory nerve terminals in the commissural nucleus of the solitary tract (cNTS) of rats with capsaicin, produces respiratory slowing. In this study, we used microinjection techniques employing pungent and non-pungent vanilloids to further characterize vanilloid receptors in the cNTS.Microinjection of the pungent vanilloid, resiniferatoxin (RTX), into the cNTS of urethane-anaesthetized rats, dose-dependently reduced respiratory rate without affecting tidal ...

  13. Excitation by irritant chemical substances of sensory afferent units in the cat's cornea.

    Science.gov (United States)

    Belmonte, C; Gallar, J; Pozo, M A; Rebollo, I

    1991-01-01

    1. Single-unit electrical activity was recorded from thin myelinated sensory nerve fibres innervating the cornea of deeply anaesthetized cats. 2. Based on their responses to mechanical (calibrated von Frey hairs), chemical (10 mM-acetic acid and/or 616 mM-NaCl) and thermal (ice-cold or heat up to 51 degrees C) stimuli, corneal A delta fibres were classified as polymodal nociceptors (63%), high-threshold mechanoceptors (22%) and mechano-heat nociceptors (15%). Thin myelinated fibres responding only to cold were found in the limbus of the eye. 3. Application of 10 mM-acetic acid on the corneal surface for 30 s evoked in polymodal fibres a brisk discharge of impulses often followed by a low-frequency impulse activity. NaCl (616 mM) produced a more gradual and sustained firing response. 4. The responses of polymodal fibres to acid were proportional to extracellular pH values (pH range: 4.5-6.0). After sensitization to repeated heating, most mechano-heat units developed a sensitivity to acidic stimulation. 5. Topical 0.33 mM-capsaicin excited polymodal nociceptors of the cornea; 5 min after capsaicin about 15% of these fibres were inactivated to all subsequent stimuli. In the rest of the fibres, chemical and thermal sensitivity disappeared after 0.33-3.3 mM-capsaicin, but mechanosensitivity was preserved. 6. Corneal mechanoceptors and limbal cold receptors were not affected by capsaicin (up to 33 mM). 7. These experiments demonstrate that the cornea of the cat is innervated by polymodal as well as mechanoceptive A delta nociceptors. In polymodal nociceptive fibres, mechanical and chemical sensitivities appear to be subserved by separate transduction mechanisms. PMID:1890657

  14. Impaired diffuse noxious inhibitory controls in specific alternation of rhythm in temperature-stressed rats.

    Science.gov (United States)

    Itomi, Yasuo; Tsukimi, Yasuhiro; Kawamura, Toru

    2016-08-01

    Fibromyalgia is characterized by chronic widespread musculoskeletal pain. A hypofunction in descending pain inhibitory systems is considered to be involved in the chronic pain of fibromyalgia. We examined functional changes in descending pain inhibitory systems in rats with specific alternation of rhythm in temperature (SART) stress, by measuring the strength of diffuse noxious inhibitory controls (DNIC). Hindpaw withdrawal thresholds to mechanical von Frey filament or fiber-specific electrical stimuli by the Neurometer system were used to measure the pain response. To induce DNIC, capsaicin was injected into the intraplantar of the forepaw. SART-stressed rats were established by exposure to repeated cold stress for 4 days. In the control rats, heterotopic intraplantar capsaicin injection increased withdrawal threshold, indicative of analgesia by DNIC. The strength of DNIC was reduced by naloxone (μ-opioid receptor antagonist, intraperitoneally and intracerebroventricularly), yohimbine (α2-adrenoceptor antagonist, intrathecally), and WAY-100635 (5-HT1A receptor antagonist, intrathecally) in the von Frey test. In SART-stressed rats, capsaicin injection did not increase withdrawal threshold in the von Frey test, indicating deficits in DNIC. In the Neurometer test, deficient DNIC in SART-stressed rats were observed only for Aδ- and C-fibers, but not Aβ-fibers stimulation. Analgesic effect of intracerebroventricular morphine was markedly reduced in SART-stressed rats compared with the control rats. Taken together, in SART-stressed rats, capsaicin-induced DNIC were deficient, and a hypofunction of opioid-mediated central pain modulation system may cause the DNIC deficit. PMID:27178898

  15. Involvement of multiple µ-opioid receptor subtypes on the presynaptic or postsynaptic inhibition of spinal pain transmission.

    Science.gov (United States)

    Mizoguchi, Hirokazu; Takagi, Hirokazu; Watanabe, Chizuko; Yonezawa, Akihiko; Sato, Takumi; Sakurada, Tsukasa; Sakurada, Shinobu

    2014-01-01

    The involvement of the μ-opioid receptor subtypes on the presynaptic or postsynaptic inhibition of spinal pain transmission was characterized in ddY mice using endomorphins. Intrathecal treatment with capsaicin, N-methyl-d-aspartate (NMDA) or substance P elicited characteristic nociceptive behaviors that consisted primarily of vigorous biting and/or licking with some scratching. Intrathecal co-administration of endogenous μ-opioid peptide endomorphin-1 or endomorphin-2 resulted in a potent antinociceptive effect against the nociceptive behaviors induced by capsaicin, NMDA or substance P, which was eliminated by i.t. co-administration of the μ-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP). The antinociceptive effect of endomorphin-1 was significantly suppressed by i.t.-co-administration of the μ2-opioid receptor antagonist Tyr-D-Pro-Trp-Phe-NH2 (D-Pro2-endomorphin-1) but not the μ1-opioid receptor antagonist Tyr-D-Pro-Phe-Phe-NH2 (D-Pro2-endomorphin-2) on capsaicin- or NMDA-elicited nociceptive behaviors. In contrast, the antinociceptive effect of endomorphin-2 was significantly suppressed by i.t.-co-administration of D-Pro2-endomorphin-2 but not D-Pro2-endomorphin-1 on capsaicin-, NMDA- or substance P-elicited nociceptive behaviors. Interestingly, regarding substance P-elicited nociceptive behaviors, the antinociceptive effect of endomorphin-1 was significantly suppressed by i.t.-co-administration of another μ2-opioid receptor antagonist, Tyr-D-Pro-Trp-Gly-NH2 (D-Pro2-Tyr-W-MIF-1), but not D-Pro2-endomorphin-1 or D-Pro2-endomorphin-2. The present results suggest that the multiple μ-opioid receptor subtypes are involved in the presynaptic or postsynaptic inhibition of spinal pain transmission. PMID:24512946

  16. Autonomic skin responses in females with Fabry disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Bach, Flemming W.; Feldt-Rasmussen, Ulla;

    2009-01-01

    Fabry disease is a genetic lysosomal disorder with dysfunction of the lysosomal enzyme alpha-galactosidase A causing accumulation of glycolipids in multiple organs including the nervous system and with neuropathy as a prominent manifestation. Neurological symptoms include pain and autonomic...... response to iontophoresis of acetylcholine (p = 0.04) and a smaller capsaicin-induced flare compared to controls. These findings suggest that female patients both have an impaired C-fiber function and local abnormalities in blood vessels and sweat glands....

  17. Nerve fibers that were not stained with the non-specific acetylcholinesterase (NsAchE) method, and TRPV1- and IB4-positive nerve fibers in the rat cornea.

    Science.gov (United States)

    Nakagawa, Hiroshi; Hiura, Akio; Mitome, Masato; Ishimura, Kazunori

    2009-08-01

    Previously, we noticed the presence of nerve fiber-like structures in a whole mount preparation of the rat cornea that had not been stained with the non-specific acetylcholinesterase (NsAchE) method. These nerve-like fibers were projected into the central area of the cornea, forming a mesh-like pattern. The aim of this study is to examine the properties of these mesh-like fibers using the following two methods: their sensitivity to capsaicin and the detection of isolectin B4 (IB4)- and capsaicin receptor TRPV1 (transient receptor potential vanilloid 1)-reactivities. The mean disappeared area of non-stained fibers after NsAchE treatment was 26% of the total areas in the neonatally capsaicin-treated cornea. Bunches composed of fine IB4-positive nerve fibers were seen in a whole mount preparation. There were connections between the bunches, producing a mesh-like pattern similar to that of the fibers that were not stained with NsAchE. Fine TRPV1-immunoreactive (ir) nerve fibers were also shown to form bunches, with connections between each bunch observed in whole mount preparations. Thus, TRPV1-ir nerve fibers seem to densely innervate the rat corneal subepithelial stroma and are distinct from the NsAchE-positive nerve fibers. The TRPV1-ir fine nerve fibers overlapped with the IB4-positive nerve fibers, suggesting that the mesh-like fibers that were not stained with NsAchE are fine nociceptive sensory nerve fibers because of their sensitivity to capsaicin and similar distribution pattern to IB4- and TRPV1-positive nerve fibers. PMID:19763029

  18. Cough responsiveness in neurogenic dysphagia

    OpenAIRE

    SMITH, P.; Wiles, C

    1998-01-01

    OBJECTIVES—In neurogenic dysphagia a good cough is important for airway protection. If triggering of cough, or its effectiveness, is impaired this might result in an increased aspiration risk. Capsaicin, an agent which induces cough through sensory nerve stimulation, was used to test cough sensitivity in groups of patients with and without neurogenic dysphagia.
METHODS—On the basis of swallowing speed (ml/s) in a validated water test 28 alert neurological inpatients (16 wome...

  19. The Effects of Chili Pepper on Reaction to Ostracism

    OpenAIRE

    Choi, Mun Sun

    2013-01-01

    Functional magnetic resonance imaging research has shown that ostracism and physical pain share a common neurological basis in the anterior cingulate cortex. This evidence supports the idea that the sensations of social and physical pain overlap and interact [1]. We evaluated this relationship in human subjects by having 90 psychology students consume spicy tomato soup (the spice used is Capsaicin) to trigger physical pain, and by having them play Cyberball immediately after (Cyberball is an ...

  20. Possible role of the CA2+/calmodulin dependent kinase II phosphorylation site T704 in acute desensitization of the vanilloid receptor TRPV1

    Czech Academy of Sciences Publication Activity Database

    Benedikt, Jan; Toušová, Karolina; Sušánková, Klára; Samad, Abdul; Vyklický st., Ladislav; Teisinger, Jan; Vlachová, Viktorie

    Praha : The Czech Neuroscience Society, 2007. s. 36-36. [Conference of the Czech Neuroscience Society /6./. 19.11.2007-20.11.2007, Praha] R&D Projects: GA ČR(CZ) GA305/06/0319; GA MŠk(CZ) LC554; GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z50110509 Keywords : spo2 * TRPV 1 * capsaicin Subject RIV: ED - Physiology

  1. Improved superfusion technique for rapid cooling or heating of cultured cells under patch-clamp conditions

    Czech Academy of Sciences Publication Activity Database

    Dittert, Ivan; Benedikt, Jan; Vyklický st., Ladislav; Zimmermann, K.; Reeh, P. W.; Vlachová, Viktorie

    2006-01-01

    Roč. 151, č. 2 (2006), s. 178-185. ISSN 0165-0270 R&D Projects: GA ČR(CZ) GA305/03/0802; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554 Grant ostatní: DFG(DE) SFB 353 Institutional research plan: CEZ:AV0Z50110509 Keywords : capsaicin * TRPV1 * TRPM8 Subject RIV: FH - Neurology Impact factor: 2.243, year: 2006

  2. Analgetické účinky kapsaicinu: tisíce let nepoznaný mechanismus

    Czech Academy of Sciences Publication Activity Database

    Toušová, Karolina; Benedikt, Jan; Samad, Abdul; Vyklický st., Ladislav; Vlachová, Viktorie

    2007-01-01

    Roč. 10, č. 2 (2007), s. 76-81. ISSN 1212-0634 R&D Projects: GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GA305/06/0319 Institutional research plan: CEZ:AV0Z60870520; CEZ:AV0Z50110509 Keywords : nociception * capsaicin * vanilloid receptor Subject RIV: ED - Physiology

  3. Ethanol inhibits cold-menthol receptor TRPM8 by modulating its interactio with membrane phosphatidylinositol 4,5-bisphosphate

    Czech Academy of Sciences Publication Activity Database

    Benedikt, Jan; Teisinger, Jan; Vyklický st., Ladislav; Vlachová, Viktorie

    ISBN 0-916110-40-0. [Neuroscince 2006. Annual meeting /36./. 14.10.2006-18.10.2006, Atlanta] R&D Projects: GA ČR(CZ) 305/06/0319; GA AV ČR(CZ) 309/04/0496; GA MŠk(CZ) 1M0517; GA MŠk LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : TRPV1, receptor, capsaicin Subject RIV: ED - Physiology

  4. Reducing and oxidizing agents sensitize heat-activated vanilloid receptor (TRPV1) current

    Czech Academy of Sciences Publication Activity Database

    Sušánková, Klára; Toušová, Karolina; Vyklický st., Ladislav; Teisinger, Jan; Vlachová, Viktorie

    2006-01-01

    Roč. 70, č. 1 (2006), s. 383-394. ISSN 0026-895X R&D Projects: GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GA309/04/0496; GA ČR(CZ) GA305/06/0319 Institutional research plan: CEZ:AV0Z5011922 Keywords : capsaicin * TRPV1 * receptor Subject RIV: ED - Physiology Impact factor: 4.469, year: 2006

  5. Possible role of the ca2+/calmodulin dependent kinase II phosphorylation site T704 in acute desensitization of the vanilloid receptor TRPV1

    Czech Academy of Sciences Publication Activity Database

    Benedikt, Jan; Toušová, Karolina; Sušánková, Klára; Samad, Abdul; Vyklický st., Ladislav; Teisinger, Jan; Vlachová, Viktorie

    Breckenridge : Keystone Symposia, 2007. s. 49-49. [Keystone Symposia on Molecular and Cellular Biology. 18.09.2007-23.09.2007, Breckenridge] R&D Projects: GA ČR(CZ) GA305/06/0319; GA ČR(CZ) GA303/07/0915; GA MŠk(CZ) LC554; GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z50110509 Keywords : spo2 * capsaicin * TRPV1 Subject RIV: ED - Physiology

  6. Central nervous system mast cells in peripheral inflammatory nociception

    Directory of Open Access Journals (Sweden)

    Ellmeier Wilfried

    2011-06-01

    Full Text Available Abstract Background Functional aspects of mast cell-neuronal interactions remain poorly understood. Mast cell activation and degranulation can result in the release of powerful pro-inflammatory mediators such as histamine and cytokines. Cerebral dural mast cells have been proposed to modulate meningeal nociceptor activity and be involved in migraine pathophysiology. Little is known about the functional role of spinal cord dural mast cells. In this study, we examine their potential involvement in nociception and synaptic plasticity in superficial spinal dorsal horn. Changes of lower spinal cord dura mast cells and their contribution to hyperalgesia are examined in animal models of peripheral neurogenic and non-neurogenic inflammation. Results Spinal application of supernatant from activated cultured mast cells induces significant mechanical hyperalgesia and long-term potentiation (LTP at spinal synapses of C-fibers. Lumbar, thoracic and thalamic preparations are then examined for mast cell number and degranulation status after intraplantar capsaicin and carrageenan. Intradermal capsaicin induces a significant percent increase of lumbar dural mast cells at 3 hours post-administration. Peripheral carrageenan in female rats significantly increases mast cell density in the lumbar dura, but not in thoracic dura or thalamus. Intrathecal administration of the mast cell stabilizer sodium cromoglycate or the spleen tyrosine kinase (Syk inhibitor BAY-613606 reduce the increased percent degranulation and degranulated cell density of lumbar dural mast cells after capsaicin and carrageenan respectively, without affecting hyperalgesia. Conclusion The results suggest that lumbar dural mast cells may be sufficient but are not necessary for capsaicin or carrageenan-induced hyperalgesia.

  7. Molekulární mechanismy modulace vaniloidního receptoru TRPV1

    Czech Academy of Sciences Publication Activity Database

    Sušánková, Klára; Vlachová, Viktorie

    9, č. 4 (2006), s. 230-234. ISSN 1212-0634 R&D Projects: GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GA305/06/0319; GA ČR(CZ) GA309/04/0496 Institutional research plan: CEZ:AV0Z50110509 Keywords : nociception * vanilloid receptor * capsaicin Subject RIV: ED - Physiology

  8. Vanilloid receptor TRPV1 is not activated by vanilloids applied intracellularly

    Czech Academy of Sciences Publication Activity Database

    Vyklický st., Ladislav; Lyfenko, Alla; Kuffler, D. P.; Vlachová, Viktorie

    2003-01-01

    Roč. 14, č. 7 (2003), s. 1061-1065. ISSN 0959-4965 R&D Projects: GA ČR GA305/03/0802; GA MŠk LN00B122 Grant ostatní: NATO(XX) 977062 Institutional research plan: CEZ:AV0Z5011922 Keywords : binding domain * capsaicin receptor * nociception Subject RIV: FH - Neurology Impact factor: 2.503, year: 2003

  9. Oxidizing reagent copper-o-phenanthroline is an open channel blocker of the vanilloid receptor TRPV1

    Czech Academy of Sciences Publication Activity Database

    Toušová, Karolina; Sušánková, Klára; Teisinger, Jan; Vyklický st., Ladislav; Vlachová, Viktorie

    2004-01-01

    Roč. 47, č. 2 (2004), s. 273-285. ISSN 0028-3908 R&D Projects: GA ČR GA305/03/0802; GA ČR GA309/02/1479; GA MŠk LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : vanilloid receptor * TRP channels * capsaicin Subject RIV: ED - Physiology Impact factor: 3.734, year: 2004

  10. Plant-derived health: the effects of turmeric and curcuminoids Efectos saludables de la cúrcuma y de los curcuminoides

    OpenAIRE

    S. Bengmark; M.ª D. Mesa; Gil, A.

    2009-01-01

    Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies su...

  11. Selective killing of K-ras-transformed pancreatic cancer cells by targeting NAD(P)H oxidase

    Institute of Scientific and Technical Information of China (English)

    Peng Wang; Yi-Chen Sun; Wen-Hua Lu; Peng Huang; and Yumin Hu

    2015-01-01

    Introduction:Oncogenic activation of the K-ras gene occurs in>90%of pancreatic ductal carcinoma and plays a critical role in the pathogenesis of this malignancy. Increase of reactive oxygen species (ROS) has also been observed in a wide spectrum of cancers. This study aimed to investigate the mechanistic association between K-ras–induced transformation and increased ROS stress and its therapeutic implications in pancreatic cancer. Methods:ROS level, NADPH oxidase (NOX) activity and expression, and cel invasion were examined in human pancreatic duct epithelial E6E7 cel s transfected with K-rasG12V compared with parental E6E7 cel s. The cytotoxic effect and antitumor effect of capsaicin, a NOX inhibitor, were also tested in vitro and in vivo. Results:K-ras transfection caused activation of the membrane-associated redox enzyme NOX and elevated ROS generation through the phosphatidylinositol 3′-kinase (PI3K) pathway. Importantly, capsaicin preferential y inhibited the enzyme activity of NOX and induced severe ROS accumulation in K-ras–transformed cel s compared with parental E6E7 cel s. Furthermore, capsaicin effectively inhibited cel proliferation, prevented invasiveness of K-ras–transformed pancreatic cancer cel s, and caused minimum toxicity to parental E6E7 cel s. In vivo, capsaicin exhibited antitumor activity against pancreatic cancer and showed oxidative damage to the xenograft tumor cel s. Conclusions:K-ras oncogenic signaling causes increased ROS stress through NOX, and abnormal ROS stress can selectively kil tumor cel s by using NOX inhibitors. Our study provides a basis for developing a novel therapeutic strategy to effectively kil K-ras–transformed cel s through a redox-mediated mechanism.

  12. Food Ingredients as Anti-Obesity Agents.

    Science.gov (United States)

    Saito, Masayuki; Yoneshiro, Takeshi; Matsushita, Mami

    2015-11-01

    Brown adipose tissue (BAT) is a site of adaptive non-shivering thermogenesis after cold exposure, and is involved in the regulation of energy expenditure and body fatness. BAT can be activated and recruited by not only cold exposure but also by various food ingredients including capsaicin in chili pepper and catechins in green tea, which would be easily and safely applicable to our daily life for preventing obesity. PMID:26421678

  13. Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Lan Chen

    Full Text Available OBJECTIVES: Transient receptor potential vanilloid 1 (TRPV1 -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R-induced acute kidney injury (AKI. However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist, capsazepine (TRPV1 antagonist and using Trpv1-/- mice. METHODS AND RESULTS: Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight or capsazepine (50 mg/kg body weight. Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE or epoxyeicosatrienoic acids (EETs are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. CONCLUSIONS: Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.

  14. Afferent nerves regulating the cough reflex: Mechanisms and Mediators of Cough in Disease

    OpenAIRE

    Canning, Brendan J.

    2010-01-01

    Bronchopulmonary C-fibers and acid-sensitive, capsaicin-insensitive mechanoreceptors innervating the larynx, trachea and large bronchi regulate the cough reflex. These vagal afferent nerves may interact centrally with sensory input arising from afferent nerves innervating the intrapulmonary airways or even extrapulmonary afferents such as those innervating the nasal mucosa and esophagus to produce chronic cough or enhanced cough responsiveness. The mechanisms of cough initiation in health and...

  15. Quality Characteristics of Stirred Yoghurt Added with Fermented Red Pepper

    OpenAIRE

    Yu, Mi-Sang; Kim, Jeong-Mee; Lee, Chi-Ho; Son, Yoon-Jeong; Kim, Soo-Ki

    2014-01-01

    Pungency of hot pepper has limited its usage even though it shows various health beneficial effects. This study was conducted to develop the novel yoghurt containing hot pepper with diminishing pungency and aimed to examine the quality characteristics of yoghurt prepared with fermented red pepper. Hot pepper was first fermented with Bacillus licheniformis SK1230 to reduce the pungency of capsaicin. We then examined the quality, sensory characteristics, and antioxidant activity of yoghurt cont...

  16. Fruit specific variability in capsaicinoid accumulation and transcription of structural and regulatory genes in Capsicum fruit

    OpenAIRE

    Keyhaninejad, Neda; Curry, Jeanne; Romero, Joslynn; O’Connell, Mary A.

    2013-01-01

    Accumulation of capsaicinoids in the placental tissue of ripening chile (Capsicum spp.) fruit follows the coordinated expression of multiple biosynthetic enzymes producing the substrates for capsaicin synthase. Transcription factors are likely agents to regulate expression of these biosynthetic genes. Placental RNAs from habanero fruit (C. chinense) were screened for expression of candidate transcription factors; with two candidate genes identified, both in the ERF family of transcription fac...

  17. The influence of different growth regulators to Capsicum annuum Jalapeno vitroplantlets

    OpenAIRE

    Liviu POP; Cristian Felix BLIDAR; Simona Ana GABOR-POTOR; Violeta TURCUS

    2007-01-01

    Capsicum annuum is an important vegetable for human alimentation, because of its content in vitamins, minerals and, especially, the capsaicine. In this experiment we have studied the development of Capsicum annuum vitroplantlets, the Mexican variety (Jalapeño), obtained by aseptic germination of this plant’s seeds. The seeds were inoculated on Murashige and Skoog medium (BM), with and without growth regulators, resulting 4 experimental variants: V0–control variant = BM without growth regulato...

  18. Tachykinins Stimulate a Subset of Mouse Taste Cells

    OpenAIRE

    Jeff Grant

    2012-01-01

    The tachykinins substance P (SP) and neurokinin A (NKA) are present in nociceptive sensory fibers expressing transient receptor potential cation channel, subfamily V, member 1 (TRPV1). These fibers are found extensively in and around the taste buds of several species. Tachykinins are released from nociceptive fibers by irritants such as capsaicin, the active compound found in chili peppers commonly associated with the sensation of spiciness. Using real-time Ca(2+)-imaging on isolated taste ce...

  19. Capsazepine, a synthetic vanilloid that converts the Na,K-ATPase to Na-ATPase

    OpenAIRE

    Mahmmoud, Yasser A.

    2008-01-01

    Capsazepine (CPZ), a synthetic capsaicin analogue, inhibits ATP hydrolysis by Na,K-ATPase in the presence but not in the absence of K+. Studies with purified membranes revealed that CPZ reduced Na+-dependent phosphorylation by interference with Na+ binding from the intracellular side of the membrane. Kinetic analyses showed that CPZ stabilized an enzyme species that constitutively occluded K+. Low-affinity ATP interaction with the enzyme was strongly reduced after CPZ treatment; in contrast, ...

  20. The sythetic endomorphin-1 analog, CYT-1010, inhibits sensory neuropeptide release, acute neurogenic inflammation and heat injury-induced thermal hyperalgesia in rodent models

    OpenAIRE

    Z. Helyes; J. Szolcsanyi; T. Maione

    2011-01-01

    Calcitonin gene-related peptide (CGRP) and substance P released from capsaicin-sensitive afferents induce neurogenic inflammatory and nociceptive actions. Since we have shown that the m opioid receptor agonist endomorphin-1 inhibits sensory neuropeptide outflow, the effects of its synthetic, peptidase-resistant analog, CYT-1010, was studied on CGRP release, acute neurogenic inflammation and thermal hyperalgesia. CGRP release from sensory fibres of isolated rat tracheae was evoked by electrica...

  1. Effects of the neurotrophic factor artemin on sensory afferent development and sensitivity

    Institute of Scientific and Technical Information of China (English)

    Shuying WANG; Christopher M. Elitt; Sacha A. Malin; Kathryn M. Albers

    2008-01-01

    Artemin is a neuronal survival and differentiation factor in the glial cell line-derived neurotrophic factor family. Its receptor GFRα3 is expressed by a subpopulation of nociceptor type sensory neurons in the dorsal root and trigeminal ganglia (DRG and TG). These neurons co-express the heat, capsaicin and proton-sensitive channel TRPV 1 and the cold and chemical-sensitive channel TRPA1. To further investigate the effects of artemin on sensory neurons, we isolated transgenic mice (ARTN-OE mice) that overexpress artemin in keratinocytes of the skin and tongue. Enhanced levels of artemin led to a 20% increase in the total number of DRG neurons and increases in the level of mRNA encoding TRPV1 and TRPAI. Calcium imaging showed that isolated sensory neurons from ARTN-OE mice were hypersensitive to the TRPV 1 agonist capsaicin and the TRPA1 agonist mustard oil. Behavioral testing of ARTN-OE mice also showed an increased sensitivity to heat, cold, capsaicin and mustard oil stimuli applied either to the skin or in the drinking water. Sensory neurons from wildtype mice also exhibited potentiated capsaicin responses following artemin addition to the media. In addition, injection of artemin into hindpaw skin produced transient thermal hyperalgesia. These findings indicate that artemin can modulate sensory function and that this regulation may occur through changes in channel gene expression. Because artemin mRNA expression is up-regulated in inflamed tissue and following nerve injury, it may have a significant role in cellular changes that underlie pain associated with pathological conditions. Manipulation of artemin expression may therefore offer a new pain treatment strategy.

  2. No effect of omeprazole on pH of exhaled breath condensate in cough associated with gastro-oesophageal reflux

    OpenAIRE

    Torrego, Alfonso; Cimbollek, Stefan; Hew, Mark; Chung, Kian Fan

    2005-01-01

    Background Endogenous airway acidification evaluated as pH in exhaled breath condensate (EBC) has been described in patients with chronic cough. Proton pump inhibitors improve gastro-oesophageal reflux (GOR)-associated cough. Methods We examined pH levels in EBC and capsaicin cough response in 13 patients with chronic cough (mean age 41 years, SD 9) associated with GOR before and after omeprazole treatment (40 mg/day for 14 days) and its relationship with clinical response. Results Omeprazole...

  3. Selective nociceptor activation in volunteers by infrared diode laser

    Directory of Open Access Journals (Sweden)

    Nemenov Mikhail I

    2011-03-01

    Full Text Available Abstract Background Two main classes of peripheral sensory neurons contribute to thermal pain sensitivity: the unmyelinated C fibers and thinly myelinated Aδ fibers. These two fiber types may differentially underlie different clinical pain states and distinctions in the efficacy of analgesic treatments. Methods of differentially testing C and Aδ thermal pain are widely used in animal experimentation, but these methods are not optimal for human volunteer and patient use. Thus, this project aimed to provide psychophysical and electrophysiological evidence that whether different protocols of infrared diode laser stimulation, which allows for direct activation of nociceptive terminals deep in the skin, could differentially activate Aδ or C fiber thermonociceptors in volunteers. Results Short (60 ms, high intensity laser pulses (SP evoked monomodal "pricking" pain which was not enhanced by topical capsaicin, whereas longer, lower power pulses (LP evoked monomodal "burning" pain which was enhanced by topical capsaicin. SP also produced cortical evoked EEG potentials consistent with Aδ mediation, the amplitude of which was directly correlated with pain intensity but was not affected by topical capsaicin. LP also produced a distinct evoked potential pattern the amplitude of which was also correlated with pain intensity, which was enhanced by topical capsaicin, and the latency of which could be used to estimate the conduction velocity of the mediating nociceptive fibers. Conclusions Psychophysical and electrophysiological data were consistent with the ability of short high intensity infrared laser pulses to selectively produce Aδ mediated pain and of longer pulses to selectively produce C fiber mediated thermal pain. Thus, the use of these or similar protocols may be useful in developing and testing novel therapeutics based on the differential molecular mechanisms underlying activation of the two fiber types (e.g., TRPV1, TRPV2, etc. In addition

  4. Histamine is released from skin by substance P but does not act as the final vasodilator in the axon reflex.

    OpenAIRE

    Barnes, P J; Brown, M. J.; Dollery, C. T.; Fuller, R W; Heavey, D. J.; Ind, P. W.

    1986-01-01

    We have explored in man the hypothesis that histamine released from dermal mast cells by neurotransmitters from afferent nerves contributes to vasodilatation of the axon reflex. The ability of substance P to release histamine from human skin in vivo, and the effects of a histamine H1-receptor antagonist on capsaicin-induced axon reflex flares were studied. Intradermal injections of substance P (50 pmol) produced a weal and flare response which was associated with increased histamine concentra...

  5. Nanomiemgel - A Novel Drug Delivery System for Topical Application - In Vitro and In Vivo Evaluation

    OpenAIRE

    Somagoni, Jaganmohan; Boakye, Cedar H. A.; Godugu, Chandraiah; Patel, Apurva R.; Mendonca Faria, Henrique Antonio; Zucolotto, Valtencir; Singh, Mandip

    2014-01-01

    Aim The objective of this study was to formulate and evaluate a unique matrix mixture (nanomiemgel) of nanomicelle and nanoemulsion containing aceclofenac and capsaicin using in vitro and in vivo analyses and to compare it to a marketed formulation (Aceproxyvon). Methods Nanomicelles were prepared using Vitamin E TPGS by solvent evaporation method and nanoemulsion was prepared by high-pressure homogenization method. In vitro drug release and human skin permeation studies were performed and an...

  6. Diaphragm Motor Unit Recruitment in Rats

    OpenAIRE

    Mantilla, Carlos B.; Seven, Yasin B.; Zhan, Wen-Zhi; Sieck, Gary C.

    2010-01-01

    We hypothesized that considerable force reserve exists for the diaphragm muscle (DIAm) to generate transdiaphragmatic pressures (Pdi) necessary to sustain ventilation. In rats, we measured Pdi and DIAm EMG activity during different ventilatory (eupnea and hypoxia (10% O2) – hypercapnia (5% CO2)) and non-ventilatory (airway occlusion and sneezing induced by intranasal capsaicin) behaviors. Compared to maximum Pdi (Pdimax - generated by bilateral phrenic nerve stimulation), the Pdi generated du...

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

    OpenAIRE

    CJ Saunders; Winston Y Li; Patel, Tulsi D; Muday, Jeffrey A; Silver, Wayne L.

    2013-01-01

    Polymodal neurons of the trigeminal nerve innervate the nasal cavity, nasopharynx, oral cavity and cornea. Trigeminal nociceptive fibers express a diverse collection of receptors and are stimulated by a wide variety of chemicals. However, the mechanism of stimulation is known only for relatively few of these compounds. Capsaicin, for example, activates transient receptor potential vanilloid 1 (TRPV1) channels. In the present study, wildtype (C57Bl/6J) and TRPV1 knockout mice were tested in th...

  8. Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control.

    Science.gov (United States)

    Bessac, Bret F; Jordt, Sven-Eric

    2008-12-01

    New studies have revealed an essential role for TRPA1, a sensory neuronal TRP ion channel, in airway chemosensation and inflammation. TRPA1 is activated by chlorine, reactive oxygen species, and noxious constituents of smoke and smog, initiating irritation and airway reflex responses. Together with TRPV1, the capsaicin receptor, TRPA1 may contribute to chemical hypersensitivity, chronic cough, and airway inflammation in asthma, COPD, and reactive airway dysfunction syndrome. PMID:19074743

  9. Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control

    OpenAIRE

    Bessac, Bret F.; Jordt, Sven-Eric

    2008-01-01

    New studies have revealed an essential role for TRPA1, a sensory neuronal TRP ion channel, in airway chemosensation and inflammation. TRPA1 is activated by chlorine, reactive oxygen species and noxious constituents of smoke and smog, initiating irritation and airway reflex responses. Together with TRPV1, the capsaicin receptor, TRPA1 may contribute to chemical hypersensitivity, chronic cough and airway inflammation in asthma, COPD and reactive airway dysfunction syndrome.

  10. Resiniferatoxin exhibits anti-inflammatory property by inhibits pro-inflammatory mediators in endotoxin-challenged mice

    OpenAIRE

    Oscar Gutierrez-Coronado; Juan Manuel Viveros Paredes

    2013-01-01

    Different chemical structural types of natural products exhibit anti-inflammatory activity and are considered to be potential drug candidates against the inflammation-related pathological processes. Vanilloids bind to the transient receptor potential type V1 (TRPV1) channels, nonselective cation ionophores that play an important role in integration of afferent noxious signals generated by inflammatory mediators. Resiniferatoxin (RTX) is an ultrapotent capsaicin analog showed pharmacological e...

  11. Caged vanilloid ligands for activation of TRPV1 receptors by 1- and 2-photon excitation†

    OpenAIRE

    Zhao, Jun; Gover, Tony D; Muralidharan, Sukumaran; Auston, Darryl A.; Weinreich, Daniel; Kao, Joseph P.Y.

    2006-01-01

    Nociceptive neurons in the peripheral nervous system detect noxious stimuli and report the information to the central nervous system. Most nociceptive neurons express the vanilloid receptor, TRPV1, a non-selective cation channel gated by vanilloid ligands such as capsaicin, the pungent essence of chili peppers. Here, we report the synthesis and biological application of two caged vanilloids—biologically inert precursors that, when photolyzed, release bioactive vanilloid ligands. The two caged...

  12. Female sex and obesity increase photophobic behavior in mice.

    Science.gov (United States)

    Rossi, Heather L; Lara, Orlando; Recober, Ana

    2016-09-01

    Migraine affects predominantly women. Furthermore, epidemiological studies suggest that obesity is a risk factor for migraine and this association is influenced by sex. However, the biological basis for this bias is unclear. To address this issue, we assessed light avoidant behavior, a surrogate of photophobia, in female C57BL/6J mice fed regular diet (RD) or high-fat diet (HFD, 60% kcal from fat). We first assessed sex differences in basal photophobia in 20-25-week-old mice and found that both obese and lean females spent significantly less time in light than their male counterparts. Next, we assessed photophobia evoked by trigeminal stimulation with intradermal capsaicin. Females at 20-25weeks of age did not display capsaicin-evoked photophobic behavior unless they had diet-induced obesity. When we tested 8-11-week-old females to determine if the diet alone could be responsible for this effect, we found that both HFD and RD 8-11-week-old females exhibit capsaicin-evoked photophobic behavior. This is in contrast to what we have previously shown in males and indicates a sex difference in the photophobic behavior of mice. Comparison of 20-25-week-old RD mice with 8-11-week-old RD mice suggests that age or age-related weight gain may contribute to capsaicin-evoked photophobic behavior in males, but not in females. These findings suggest that obesity exacerbates photophobia in both sexes, but additional work is needed to understand the sex- and age-specific mechanisms that may contribute to photophobia and trigeminal pain. PMID:27328418

  13. AT3 (Acyltransferase Gene Isolated From Capsicum frutescens cv. Cakra Hijau

    Directory of Open Access Journals (Sweden)

    Mohamad Habibi

    2013-05-01

    Full Text Available Chili pepper is widely used and cultivated by Indonesian people. There are three species of chili pepper, i.e.: Capsicum annuum L., Capsicum frutescens L., and Capsicum violaceum HBK. Capsicum frutescens L. has a higher economic value due to its pungency and carotenoid content. C. frutescens has several cultivars, one of those is Capsicum frutescens cv. Cakra Hijau. This cultivar is resistant against pest and disease and has very high pungency. This special character of chili pepper is born by its secondary metabolic, Capsaicin. Moreover, capsaicin also serves as defense mechanism, antiarthritis, analgesic, and anticancer. This study aimed to isolate Acyltransferase (AT3 gene which encoding Capsaicin Synthase (CS enzyme. AT3 gene was isolated through PCR using forward primer 5’-ATG GCT TTT GCA TTA CCA TCA-3’ and reverse primer 5’-CCT TCA CAA TTA TTC GCC CA-3’. Data were analyzed using DNA Baser, BLAST, and ClustalX. This study has successfully isolated 404 bp fragments of AT3 gene. This fragments located at 1918-1434 bp referred to AT3 gene from Capsicum frutescens cv. Shuanla. Isolation of upstream and downstream fragments of AT3 gene from Capsicum frutescens cv. Cakra Hijau is undergoing.

  14. TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry-dependent ROS production and mitochondrial depolarization

    International Nuclear Information System (INIS)

    Synoviocyte hyperplasia is critical for rheumatoid arthritis, therefore, potentially an important target for therapeutics. It was found in this work that a TRPV1 agonist capsaicin, and acidic solution (pH 5.5) induced increases in cytosolic calcium concentration ([Ca2+]c) and reactive oxygen species (ROS) production in synoviocytes isolated from a rat model of collagen-induced arthritis. The increases in both [Ca2+]c and ROS production were completely abolished in calcium-free buffer or by a TRPV1 antagonist capsazepine. Further experiments revealed that capsaicin and pH 5.5 solution caused mitochondrial membrane depolarization and reduction in cell viability; such effects were inhibited by capsazepine, or the NAD(P)H oxidase inhibitor diphenylene iodonium. Both capsaicin and pH 5.5 buffer induced apoptosis as shown by nuclear condensation and fragmentation. Furthermore, RT-PCR readily detected TRPV1 mRNA expression in the isolated synoviocytes. Taken together, these data indicated that TRPV1 activation triggered synoviocyte death by [Ca2+]c elevation, ROS production, and mitochondrial membrane depolarization

  15. Inhibition of platelet aggregation by vanilloid-like agents is not mediated by transient receptor potential vanilloid-1 channels or cannabinoid receptors.

    Science.gov (United States)

    Almaghrabi, Safa; Geraghty, Dominic; Ahuja, Kiran; Adams, Murray

    2016-06-01

    Vanilloid-like agents, including capsaicin, N-arachidonoyl-dopamine and N-oleoyldopamine inhibit platelet aggregation, however little is known about the precise mechanism(s) of action. The authors have previously shown that blocking of the capsaicin receptor, transient receptor potential vanilloid-1 (TRPV1), does not interfere with capsaicin action during adenosine diphosphate (ADP)-induced aggregation. This research is extended to investigate the effect of these vanilloid-like-agents on platelet count, and to test whether the effect of these agents is mediated through TRPV1 and/or cannabinoid (CB1 and CB2) receptors in the presence of other agonists, including collagen and arachidonic acid. Incubation of platelets with each of the individual vanilloids, or with receptor antagonists of TRPV1 (SB452533), CB1 (AM251) and CB2 (AM630), for up to 2 h did not significantly affect the platelet count. Similarly, the effect of individual vanilloids on the inhibition of platelet aggregation was not significantly different in the presence of receptor agonists compared to control, irrespective of the agonist used, suggesting that the inhibitory effect of vanilloids on platelet aggregation is independent of TRPV1, CB1 and CB2 receptors. Further research on the antiplatelet activity of vanilloids should focus on mechanisms other than those associated with vanilloid receptors. PMID:26991025

  16. Characterization of functional TRPV1 channels in the sarcoplasmic reticulum of mouse skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Sabine Lotteau

    Full Text Available TRPV1 represents a non-selective cation channel activated by capsaicin, acidosis and high temperature. In the central nervous system where TRPV1 is highly expressed, its physiological role in nociception is clearly identified. In skeletal muscle, TRPV1 appears implicated in energy metabolism and exercise endurance. However, how as a Ca(2+ channel, it contributes to intracellular calcium concentration ([Ca(2+]i maintenance and muscle contraction remains unknown. Here, as in rats, we report that TRPV1 is functionally expressed in mouse skeletal muscle. In contrast to earlier reports, our analysis show TRPV1 presence only at the sarcoplasmic reticulum (SR membrane (preferably at the longitudinal part in the proximity of SERCA1 pumps. Using intracellular Ca(2+ imaging, we directly accessed to the channel functionality in intact FDB mouse fibers. Capsaicin and resiniferatoxin, both agonists as well as high temperature (45°C elicited an increase in [Ca(2+]i. TRPV1-inhibition by capsazepine resulted in a strong inhibition of TRPV1-mediated functional responses and abolished channel activation. Blocking the SR release (with ryanodine or dantrolene led to a reduced capsaicin-induced Ca(2+ elevation suggesting that TRPV1 may participate to a secondary SR Ca(2+ liberation of greater amplitude. In conclusion, our experiments point out that TRPV1 is a functional SR Ca(2+ leak channel and may crosstalk with RyR1 in adult mouse muscle fibers.

  17. Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens.

    Science.gov (United States)

    Schmelz, M; Schmidt, R; Weidner, C; Hilliges, Marita; Torebjork, H E; Handwerker, H O

    2003-05-01

    Vasoneuroactive substances were applied through intradermal microdialysis membranes and characterized as itch- or pain-inducing in psychophysical experiments. Histamine always provoked itching and rarely pain, capsaicin always pain but never itching. Prostaglandin E(2) (PGE(2)) led preferentially to moderate itching. Serotonin, acetylcholine, and bradykinin induced pain more often than itching. Subsequently the same substances were used in microneurography experiments to characterize the sensitivity profile of human cutaneous C-nociceptors. The responses of 89 mechanoresponsive (CMH, polymodal nociceptors), 52 mechanoinsensitive, histamine-negative (CMi(His-)), and 24 mechanoinsensitive, histamine-positive (CMi(His+)) units were compared. CMi(His+) units were most responsive to histamine and to PGE(2) and less to serotonin, ACh, bradykinin, and capsaicin. CMH units (polymodal nociceptors) and CMi(His-) units showed significantly weaker responses to histamine, PGE(2), and acetylcholine. Capsaicin and bradykinin responses were not significantly different in the two classes of mechano-insensitive units. We conclude that CMi(His+) units are "selective," but not "specific" for pruritogenic substances and that the pruritic potency of a mediator increases with its ability to activate CMi(His+) units but decreases with activation of CMH and CMi(His-) units. PMID:12611975

  18. Measurement of Capsaicinoids in Chiltepin Hot Pepper: A Comparison Study between Spectrophotometric Method and High Performance Liquid Chromatography Analysis

    Directory of Open Access Journals (Sweden)

    Alberto González-Zamora

    2015-01-01

    Full Text Available Direct spectrophotometric determination of capsaicinoids content in Chiltepin pepper was investigated as a possible alternative to HPLC analysis. Capsaicinoids were extracted from Chiltepin in red ripe and green fruit with acetonitrile and evaluated quantitatively using the HPLC method with capsaicin and dihydrocapsaicin standards. Three samples of different treatment were analyzed for their capsaicinoids content successfully by these methods. HPLC-DAD revealed that capsaicin, dihydrocapsaicin, and nordihydrocapsaicin comprised up to 98% of total capsaicinoids detected. The absorbance of the diluted samples was read on a spectrophotometer at 215–300 nm and monitored at 280 nm. We report herein the comparison between traditional UV assays and HPLC-DAD methods for the determination of the molar absorptivity coefficient of capsaicin (ε280=3,410 and ε280=3,720 M−1 cm−1 and dihydrocapsaicin (ε280=4,175 and ε280=4,350 M−1 cm−1, respectively. Statistical comparisons were performed using the regression analyses (ordinary linear regression and Deming regression and Bland-Altman analysis. Comparative data for pungency was determined spectrophotometrically and by HPLC on samples ranging from 29.55 to 129 mg/g with a correlation of 0.91. These results indicate that the two methods significantly agree. The described spectrophotometric method can be routinely used for total capsaicinoids analysis and quality control in agricultural and pharmaceutical analysis.

  19. Antitussive activity of iodo-resiniferatoxin in guinea pigs

    Science.gov (United States)

    Trevisani, M; Milan, A; Gatti, R; Zanasi, A; Harrison, S; Fontana, G; Morice, A; Geppetti, P

    2004-01-01

    Background: Iodo-resiniferatoxin (I-RTX) has recently been described as an ultra potent antagonist of the transient receptor potential vanilloid-1 (TRPV1). Methods: The ability of I-RTX to inhibit cough induced by inhalation of two putative TRPV1 stimulants (capsaicin and citric acid) was tested in non-anaesthetised guinea pigs. Results: Pretreatment with I-RTX either intraperitoneally (0.03–0.3 µmol/kg) or by aerosol (0.1–3 µM) reduced the number of coughs produced by inhalation of citric acid (0.25 M) and capsaicin (30 µM) in a dose dependent manner. Capsazepine (CPZ) also reduced citric acid and capsaicin induced cough, but the activity of I-RTX was 10–100 times more potent than CPZ in all the experimental conditions tested. Conclusions: I-RTX is a novel and potent antitussive drug which inhibits cough mediated by agents possibly acting via TRPV1 activation. PMID:15333853

  20. Use of taste repellants and emetics to prevent accidental poisoning of dogs.

    Science.gov (United States)

    Houpt, K; Zgoda, J C; Stahlbaum, C C

    1984-08-01

    Twelve taste repellents and 3 oral emetics were tested. The taste repellents were capsaicin, capsicum, oleoresin, sucrose octaacetate, quinine tonic, quassia wood extract, vanillamide, horseradish extract, caffeine, pepperoni enhancer, acorn extract, and commercially available bitter and hot flavors. The emetics tested were: antimony potassium tartrate, apomorphine, and copper sulfate. Intake of a 20% sucrose solution by Beagles was significantly depressed by addition of vanillamide at concentrations greater than 0.001%, by capsicum and capsaicin at concentrations greater than 0.01%, and by horseradish extract, pepperoni enhancer, and a commercially available hot flavor at concentrations greater than 0.1%. Antimony potassium tartrate, when added to the 20% sucrose solution at a concentration of 0.1%, produced emesis as did apomorphine at a concentration of 0.005% and copper sulfate at 1%. When the emetic antimony potassium tartrate was combined with vanillamide in a 20% sucrose solution, intake was reduced to less than 20 ml, and vomiting occurred within 15 minutes. Capsaicin (0.02%) inhibited intake of ethylene glycol to less than the lethal dose in 5 dogs tested. Incorporation of such taste repellents and/or emetics into potentially poisonous substances would reduce accidental poisoning of animals and children. PMID:6476561

  1. The pain receptor TRPV1 displays agonist-dependent activation stoichiometry.

    Science.gov (United States)

    Hazan, Adina; Kumar, Rakesh; Matzner, Henry; Priel, Avi

    2015-01-01

    The receptor channel TRPV1 (Transient Receptor Potential Vanilloid 1) is expressed by primary afferent sensory neurons of the pain pathway, where it functions as a sensor of noxious heat and various chemicals, including eicosanoids, capsaicin, protons and peptide toxins. Comprised of four identical subunits that organize into a non-selective cationic permeable channel, this receptor has a variety of binding sites responsible for detecting their respective agonists. Although its physiological role as a chemosensor has been described in detail, the stoichiometry of TRPV1 activation by its different ligands remains unknown. Here, we combined the use of concatemeric constructs harboring mutated binding sites with patch-clamp recordings in order to determine the stoichiometry for TRPV1 activation through the vanilloid binding site and the outer-pore domain by capsaicin and protons, respectively. We show that, while a single capsaicin-bound subunit was sufficient to achieve a maximal open-channel lifetime, all four proton-binding sites were required. Thus, our results demonstrate a distinct stoichiometry of TRPV1 activation through two of its different agonist-binding domains. PMID:26194846

  2. In vitro and in vivo antifungal activity of natural inhibitors against Penicillium expansum

    Directory of Open Access Journals (Sweden)

    Claudia Fieira

    2013-02-01

    Full Text Available Penicillium expansum is the causative agent of apple blue mold. The inhibitory effects of the capsaicin derived from Capsicum spp. fruits and yeast Hansenula wingei against P. expansum were evaluated in an in vitro and in in vivo assay using Fuji apples. The minimum inhibitory concentration of capsaicin determined using the broth micro-dilution method was 122.16 µg mL-1. Capsaicin did not reduce blue mold incidence in apples. However, it was able to delay fungal growth in the first 14 days of the in vivo assay. The in vivo effect of the yeast Hansenula wingei AM2(-2, alone and combined with thiabendazole at low dosage (40 µg mL-1, on the incidence of apple diseases caused by P. expansum was also described. H. wingei AM2(-2 combined with a low fungicide dosage (10% of the dosage recommended by the manufacturer showed the best efficacy (100% up to 7 days of storage at 21 ºC, later showing a non-statistically different decrease (p > 0.05 after 14 (80.45% and 21 days (72.13%, respectively. These results contribute providing new options for using antifungal agents against Penicillium expansum.

  3. RNA interference prevents lipopolysaccharide-induced preprotachykinin gene expression

    International Nuclear Information System (INIS)

    We showed previously that lipopolysaccharide (LPS) induces noncholinergic airway hyperreactivity to capsaicin via an upregulation of tachykinin synthesis. This study was designed to test whether double-stranded preprotachykinin (ds PPT) RNA, RNA interference (RNAi), prevents the LPS-induced alterations. First, cultured primary nodose ganglial cells of newborn Brown-Norway rats were divided into four groups: control; LPS; LPS+RNAi; and LPS+RNAi+liposome. Second, young Brown-Norway rats for the in vivo study were divided into three groups (control; LPS; and LPS+RNAi), and ds PPT RNA was microinjected bilaterally into the nodose ganglia in the LPS+RNAi group. Then, ganglial cells were collected from the culture whereas the nodose ganglia and lungs were sampled from the animals, and PPT mRNA and substance P (SP) levels were analyzed. Also, airway reactivity to capsaicin was performed in vivo. LPS induced significant increases in PPT mRNA and SP levels in vitro and in vivo and an increase in airway reactivity to capsaicin in vivo. However, ds PPT RNA, but not scrambled RNA, prevented all LPS-induced alterations. The effect of ds PPT RNA was not enhanced by liposome in vitro. Therefore, we demonstrated that the local application of RNAi prevents effectively the activation of the noncholinergic system modulating the lungs/airways

  4. Differentiation of autonomic reflex control begins with cellular mechanisms at the first synapse within the nucleus tractus solitarius

    Directory of Open Access Journals (Sweden)

    M.C. Andresen

    2004-04-01

    Full Text Available Visceral afferents send information via cranial nerves to the nucleus tractus solitarius (NTS. The NTS is the initial step of information processing that culminates in homeostatic reflex responses. Recent evidence suggests that strong afferent synaptic responses in the NTS are most often modulated by depression and this forms a basic principle of central integration of these autonomic pathways. The visceral afferent synapse is uncommonly powerful at the NTS with large unitary response amplitudes and depression rather than facilitation at moderate to high frequencies of activation. Substantial signal depression occurs through multiple mechanisms at this very first brainstem synapse onto second order NTS neurons. This review highlights new approaches to the study of these basic processes featuring patch clamp recordings in NTS brain slices and optical techniques with fluorescent tracers. The vanilloid receptor agonist, capsaicin, distinguishes two classes of second order neurons (capsaicin sensitive or capsaicin resistant that appear to reflect unmyelinated and myelinated afferent pathways. The differences in cellular properties of these two classes of NTS neurons indicate clear functional differentiation at both the pre- and postsynaptic portions of these first synapses. By virtue of their position at the earliest stage of these pathways, such mechanistic differences probably impart important differentiation in the performance over the entire reflex pathways.

  5. Nociceptin/orphanin FQ receptor expression in clinical pain disorders and functional effects in cultured neurons.

    Science.gov (United States)

    Anand, Praveen; Yiangou, Yiangos; Anand, Uma; Mukerji, Gaurav; Sinisi, Marco; Fox, Michael; McQuillan, Anthony; Quick, Tom; Korchev, Yuri E; Hein, Peter

    2016-09-01

    The nociceptin/orphanin FQ peptide receptor (NOP), activated by its endogenous peptide ligand nociceptin/orphanin FQ (N/OFQ), exerts several effects including modulation of pain signalling. We have examined, for the first time, the tissue distribution of the NOP receptor in clinical visceral and somatic pain disorders by immunohistochemistry and assessed functional effects of NOP and μ-opioid receptor activation in cultured human and rat dorsal root ganglion (DRG) neurons. Quantification of NOP-positive nerve fibres within the bladder suburothelium revealed a remarkable several-fold increase in detrusor overactivity (P numbers. NOP immunoreactivity was significantly decreased in injured peripheral nerves (P = 0.0004), and also in painful neuromas (P = 0.025). Calcium-imaging studies in cultured rat DRG neurons demonstrated dose-dependent inhibition of capsaicin responses in the presence of N/OFQ, with an IC50 of 8.6 pM. In cultured human DRG neurons, 32% inhibition of capsaicin responses was observed in the presence of 1 pM N/OFQ (P < 0.001). The maximum inhibition of capsaicin responses was greater with N/OFQ than μ-opioid receptor agonist DAMGO. Our findings highlight the potential of NOP agonists, particularly in urinary bladder overactivity and pain syndromes. The regulation of NOP expression in visceral and somatic sensory neurons by target-derived neurotrophic factors deserves further study, and the efficacy of NOP selective agonists in clinical trials. PMID:27127846

  6. Peripheral site of action of levodropropizine in experimentally-induced cough: role of sensory neuropeptides.

    Science.gov (United States)

    Lavezzo, A; Melillo, G; Clavenna, G; Omini, C

    1992-06-01

    The mechanism of action of levodropropizine has been investigated in different models of experimentally-induced cough in guinea-pigs. In particular it has been demonstrated that the antitussive drug has a peripheral site of action by injecting the drug intracerebroventricularly (i.c.v.). In these experiments levodropropizine (40 micrograms/50 microliters i.c.v.) did not prevent electrically-induced cough. On the other hand, codeine (5 micrograms/50 microliters i.c.v.) markedly prevented coughing. A difference in the potency ratio of levodropropizine and codeine has been demonstrated in capsaicin-induced cough; after oral administration, codeine was about two to three times more potent than levodropropizine. However, after aerosol administration the two compounds were equipotent. These data might suggest a peripheral site of action for levodropropizine which is related to sensory neuropeptides. Further support for the role of sensory neuropeptides in the mechanism of action of levodropropizine comes from the results obtained in capsaicin-desensitized animals. In this experimental model levodropropizine failed to prevent the vagally elicited cough in neuropeptide-depleted animals, whereas codeine did not differentiate between control and capsaicin-treated animals. In conclusion, our results support the suggestion that levodropropizine has a peripheral site of action. In addition, the interference with the sensory neuropeptide system may explain, at least in part, its activity in experimentally-induced cough. PMID:1611233

  7. Evolution of Capsaicinoids in Peter Pepper (Capsicum annuum var. annuum) During Fruit Ripening.

    Science.gov (United States)

    Barbero, Gerardo F; de Aguiar, Ana C; Carrera, Ceferino; Olachea, Ángel; Ferreiro-González, Marta; Martínez, Julian; Palma, Miguel; Barroso, Carmelo G

    2016-08-01

    The evolution of individual and total contents of capsaicinoids present in Peter peppers (Capsicum annuum var. annuum) at different ripening stages has been studied. Plants were grown in a glasshouse and the new peppers were marked in a temporal space of ten days. The extraction of capsaicinoids was performed by ultrasound-assisted extraction with MeOH. The capsaicinoids nordihydrocapsaicin (n-DHC), capsaicin, dihydrocapsaicin, homocapsaicin, and homodihydrocapsaicin were analyzed by ultraperformance liquid chromatography (UHPLC)-fluorescence and identified by UHPLC-Q-ToF-MS. The results indicate that the total capsaicinoids increase in a linear manner from the first point of harvest at ten days (0.283 mg/g FW) up to 90 days, at which point they reach a concentration of 1.301 mg/g FW. The evolution as a percentage of the individual capsaicinoids showed the initial predominance of capsaicin, dihydrocapsaicin, and n-DHC. Dihydrocapsaicin was the major capsaicinoid up to day 50 of maturation. After 50 days, capsaicin became the major capsaicinoid as the concentration of dihydrocapsaicin fell slightly. The time of harvest of Peter pepper based on the total capsaicinoids content should be performed as late as possible. In any case, harvesting should be performed before overripening of the fruit is observed. PMID:27416068

  8. Involvement of mast cells and proteinase-activated receptor 2 in oxaliplatin-induced mechanical allodynia in mice.

    Science.gov (United States)

    Sakamoto, Ayumi; Andoh, Tsugunobu; Kuraishi, Yasushi

    2016-03-01

    The chemotherapeutic agent oxaliplatin induces neuropathic pain, a dose-limiting side effect, but the underlying mechanisms are not fully understood. Here, we show the potential involvement of cutaneous mast cells in oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin induced mechanical allodynia, which peaked on day 10 after injection. Oxaliplatin-induced mechanical allodynia was almost completely prevented by congenital mast cell deficiency. The numbers of total and degranulated mast cells was significantly increased in the skin after oxaliplatin administration. Repetitive topical application of the mast cell stabilizer azelastine hydrochloride inhibited mechanical allodynia and the degranulation of mast cells without affecting the number of mast cells in oxaliplatin-treated mice. The serine protease inhibitor camostat mesilate and the proteinase-activated receptor 2 (PAR2) antagonist FSLLRY-NH2 significantly inhibited oxaliplatin-induced mechanical allodynia. However, it was not inhibited by the H1 histamine receptor antagonist terfenadine. Single oxaliplatin administration increased the activity of cutaneous serine proteases, which was attenuated by camostat and mast cell deficiency. Depletion of the capsaicin-sensitive primary afferents by neonatal capsaicin treatment almost completely prevented oxaliplatin-induced mechanical allodynia, the increase in the number of mast cells, and the activity of cutaneous serine proteases. These results suggest that serine protease(s) released from mast cells and PAR2 are involved in oxaliplatin-induced mechanical allodynia. Therefore, oxaliplatin may indirectly affect the functions of mast cells through its action on capsaicin-sensitive primary afferents. PMID:26804251

  9. Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS.

    Directory of Open Access Journals (Sweden)

    Marco Schlepütz

    Full Text Available The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS respond to electric field stimulation (EFS and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM caused bronchoconstriction in human (4 from 7 and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC. However, this effect was notably smaller in human responder (30 ± 7.1% than in guinea pig (79 ± 5.1% PCLS. The transient receptor potential (TRP channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.

  10. Modulation of TRP channels by resveratrol and other stilbenoids

    Directory of Open Access Journals (Sweden)

    Yu Lina

    2013-02-01

    Full Text Available Abstract Background Resveratrol (3,5,4’ - trihydroxy-trans-stilbene, a widely distributed natural stilbenoid, was proposed to account for the unique effects of red wine on life span and health. It has been reported to possess various biological and pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-carcinogenic effects. Here, using whole-cell patch-clamp techniques and behavioral analyses, we investigated whether resveratrol and other stilbenoids can modulate TRP channels in sensory neurons in vitro, and have analgesic effects in vivo. Results We found that resveratrol dose-dependently suppressed the allyl isothiocyanate (AITC-induced currents (IAITC in HEK293 cells that express TRPA1, as well as in rat dorsal root ganglion (DRG neurons. Instead, pinosylvin methyl ether (PME, another derivate of stilbene which has a similar structure to resveratrol, dose-dependently blocked the capsaicin-induced currents (ICAP in HEK293 cells that express TRPV1 as well as in DRG neurons. Interestingly, resveratrol had no inhibitory effect on the ICAP, and PME had no effect on the IAITC. Otherwise, trans-stilbene showed no any effect on IAITC or ICAP. The concentration response curve of AITC showed that resveratrol inhibited the action of TRPA1 not by changing the EC50, but by suppressing the AITC-induced maximum response. By contrast, the inhibition of TRPV1 by PME did not change the capsaicin-induced maximum response but did cause a right shift of the EC50. Moreover, pre-administration of resveratrol suppressed intraplantar injections of AITC-evoked nocifensive behaviors, as well as that PME suppressed capsaicin-evoked one. Conclusions These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels. In addition, these stilbenoids modulate TRP channel activity in different ways.

  11. Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors

    Directory of Open Access Journals (Sweden)

    Moran Magdalene M

    2009-04-01

    Full Text Available Abstract Background TRPA1 has been implicated in both chemo- and mechanosensation. Recent work demonstrates that inhibiting TRPA1 function reduces mechanical hypersensitivity produced by inflammation. Furthermore, a broad range of chemical irritants require functional TRPA1 to exert their effects. In this study we use the ex-vivo skin-nerve preparation to directly determine the contribution of TRPA1 to mechanical- and chemical-evoked responses at the level of the primary afferent terminal. Results Acute application of HC-030031, a selective TRPA1 antagonist, inhibited all formalin responses in rat C fibers but had no effect on TRPV1 function, assessed by capsaicin responsiveness. Genetic ablation experiments corroborated the pharmacological findings as C fibers from wild type mice responded to both formalin and capsaicin, but fibers from their TRPA1-deficient littermates responded only to capsaicin. HC-030031 markedly reduced the mechanically-evoked action potential firing in rat and wild type mouse C fibers, particularly at high-intensity forces, but had no effect on the mechanical responsiveness of Aδ fiber nociceptors. Furthermore, HC-030031 had no effect on mechanically-evoked firing in C fibers from TRPA1-deficient mice, indicating that HC-030031 inhibits mechanically-evoked firing via a TRPA1-dependent mechanism. Conclusion Our data show that acute pharmacological blockade of TRPA1 at the cutaneous receptive field inhibits formalin-evoked activation and markedly reduces mechanically-evoked action potential firing in C fibers. Thus, functional TRPA1 at sensory afferent terminals in skin is required for their responsiveness to both noxious chemical and mechanical stimuli.

  12. Interaction between paired-pulse facilitation and long-term potentiation during the stimulation of the cannabinoid and vanilloid systems in the dentate gyrus.

    Science.gov (United States)

    Tahmasebi, Lida; Komaki, Alireza; Karamian, Ruhollah; Shahidi, Siamak; Sarihi, Abdolrahman; Komaki, Hamidreza

    2016-07-15

    Synaptic plasticity includes short-term and long-term changes in synaptic strength. Short-term plasticity can be used to assess the site mediating the long-lasting forms of synaptic plasticity such as long-term potentiation (LTP). The endogenous endocannabinoid systems can modulate LTP, and similarly, the activation of the vanilloid system has been shown to mediate synaptic plasticity in the hippocampus. In this study, we examined the interaction between short-term and long-term plasticity during the stimulation of the cannabinoid and vanilloid systems in the hippocampus of rats in vivo. Forty male Wistar rats, divided into four groups, were treated with the following compounds: control (saline+dimethyl sulfoxide), WIN55,212-2, capsaicin, and WIN55,212-2+capsaicin. The animals were anesthetized with urethane and then recording and stimulating electrodes were positioned at the dentate gyrus(DG) and perforant pathway(PP), respectively. Population spike (PS) amplitudes were measured before and after the induction of LTP, which was induced with high-frequency stimulation (HFS). The paired-pulse ratio (PPR) was measured before and after the induction of LTP in all groups. We showed that WIN55,212-2 reduced the PS amplitude after HFS, whereas the vanilloid agonist increased the induction of LTP compared with the control treatment. In the present study, we found that in the presence of WIN55,212-2 and capsaicin, the induction of LTP changed the PPR. Additionally, we showed that the co-administration of cannabinoid and vanilloid agonists modulate the PPR. These findings suggest the presynaptic expression of this LTP form, and therefore, this form of LTP is caused by the increase of neurotransmitter release. PMID:27130895

  13. Naringenin reduces inflammatory pain in mice.

    Science.gov (United States)

    Pinho-Ribeiro, Felipe A; Zarpelon, Ana C; Fattori, Victor; Manchope, Marília F; Mizokami, Sandra S; Casagrande, Rubia; Verri, Waldiceu A

    2016-06-01

    Naringenin is a flavonoid widely consumed by humans that present anti-inflammatory activity and low toxicity. Recently, the analgesic effect of naringenin has been demonstrated in neuropathic pain models. Herein, we tested the analgesic effects of naringenin in several models of inflammatory pain. Mice received treatment with naringenin (16.7-150 mg/kg, per oral), or with the controls anti-inflammatory drugs indomethacin (5 mg/kg, intraperitoneal) or dipyrone (80 mg/kg, intraperitoneal) prior the inflammatory stimuli injection. For acute pain, we used acetic acid- and PBQ-induced visceral pain (abdominal writhings), and formalin-, capsaicin-, and CFA-induced paw flinching and licking. By using an electronic version of von Frey filaments, we also investigated the effects of naringenin in pain intensity to a mechanical stimulus (mechanical hyperalgesia) after carrageenan, capsaicin, CFA, or PGE2 intraplantar injection. Naringenin (50 mg/kg) reduced acute pain behaviors induced by all tested stimuli, including both phases of formalin test, suggesting a direct nociceptor modulatory effect of this compound besides its anti-inflammatory activity. Accordingly, naringenin also inhibited the increased sensitivity to mechanical stimulus induced by carrageenan, capsaicin, and PGE2. Daily treatment with naringenin during 7 days also reduced CFA-induced mechanical hyperalgesia without gastric or hepatic toxicity. The mechanisms of naringenin involve the inhibition of carrageenan-induced oxidative stress, hyperalgesic cytokines (IL-33, TNF-α, and IL-1β) production and NF-κB activation in the paw skin. Naringenin also activated the analgesic NO-cyclic GMP-PKG-ATP sensitive K(+) channel signaling pathway to inhibit carrageenan-induced mechanical hyperalgesia and neutrophil recruitment. These results suggest that naringenin inhibits both inflammatory pain and neurogenic inflammation. PMID:26907804

  14. Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

    Science.gov (United States)

    Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

    2016-05-01

    Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. PMID:26883566

  15. 5-HT7 Receptors Are Not Involved in Neuropeptide Release in Primary Cultured Rat Trigeminal Ganglion Neurons.

    Science.gov (United States)

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

    2016-06-01

    Migraine is a common but complex neurological disorder. Its precise mechanisms are not fully understood. Increasing indirect evidence indicates that 5-HT7 receptors may be involved; however, their role remains unknown. Our previous in vivo study showed that selective blockade of 5-HT7 receptors caused decreased serum levels of calcitonin gene-related peptide (CGRP) in the external jugular vein following electrical stimulation of the trigeminal ganglion (TG) in an animal model of migraine. In the present study, we used an in vitro model of cultured TG cells to further investigate whether 5-HT7 receptors are directly responsible for the release of CGRP and substance P from TG neurons. We stimulated rat primary cultured TG neurons with capsaicin or potassium chloride (KCl) to mimic neurogenic inflammation, resulting in release of CGRP and substance P. 5-HT7 receptors were abundantly expressed in TG neurons. Greater than 93 % of 5-HT7 receptor-positive neurons co-expressed CGRP and 56 % co-expressed substance P. Both the capsaicin- and KCl-induced release of CGRP and substance P were unaffected by pretreatment of cultured TG cells with the selective 5-HT7 receptor agonist AS19 and antagonist SB269970. This study demonstrates for the first time that 5-HT7 receptors are abundantly co-expressed with CGRP and substance P in rat primary TG neurons and suggests that they are not responsible for the release of CGRP and substance P from cultured TG neurons evoked by capsaicin or KCl. PMID:26892478

  16. Anti-inflammatory effects of red pepper (Capsicum baccatum) on carrageenan- and antigen-induced inflammation.

    Science.gov (United States)

    Spiller, Fernando; Alves, Márcia K; Vieira, Sílvio M; Carvalho, Toni A; Leite, Carlos E; Lunardelli, Adroaldo; Poloni, José A; Cunha, Fernando Q; de Oliveira, Jarbas R

    2008-04-01

    Inflammation is a pivotal component of a variety of diseases, such as atherosclerosis and tumour progression. Various naturally occurring phytochemicals exhibit anti-inflammatory activity and are considered to be potential drug candidates against inflammation-related pathological processes. Capsicum baccatum L. var. pendulum (Willd.) Eshbaugh (Solanaceae) is the most consumed species in Brazil, and its compounds, such as capsaicinoids, have been found to inhibit the inflammatory process. However, the anti-inflammatory effects of C. baccatum have not been characterized. Thus, this study was designed to evaluate the effects of C. baccatum juice in animal models of acute inflammation induced by carrageenan and immune inflammation induced by methylated bovine serum albumin. Pretreatment (30 min) of rats with pepper juice (0.25-2.0 g kg(-1)) significantly decreased leucocyte and neutrophil migration, exudate volume and protein and LDH concentration in pleural exudates of a pleurisy model. This juice also inhibited neutrophil migration and reduced the vascular permeability on carrageenan-induced peritonitis in mice. C. baccatum juice also reduced neutrophil recruitment and exudate levels of pro-inflammatory cytokines TNF-alpha and IL-1beta in mouse inflammatory immune peritonitis. Furthermore, we demonstrated that the main constituent of C. baccatum juice, as extracted with chloroform, is capsaicin. In agreement with this, capsaicin was able to inhibit the neutrophil migration towards the inflammatory focus. To our knowledge, this is the first demonstration of the anti-inflammatory effect of C. baccatum juice and our data suggest that this effect may be induced by capsaicin. Moreover, the anti-inflammatory effect induced by red pepper may be by inhibition of pro-inflammatory cytokine production at the inflammatory site. PMID:18380920

  17. Activation of endogenous TRPV1 fails to induce overstimulation-based cytotoxicity in breast and prostate cancer cells but not in pain-sensing neurons.

    Science.gov (United States)

    Pecze, László; Jósvay, Katalin; Blum, Walter; Petrovics, György; Vizler, Csaba; Oláh, Zoltán; Schwaller, Beat

    2016-08-01

    Vanilloids including capsaicin and resiniferatoxin are potent transient receptor potential vanilloid type 1 (TRPV1) agonists. TRPV1 overstimulation selectively ablates capsaicin-sensitive sensory neurons in animal models in vivo. The cytotoxic mechanisms are based on strong Na(+) and Ca(2+) influx via TRPV1 channels, which leads to mitochondrial Ca(2+) accumulation and necrotic cell swelling. Increased TRPV1 expression levels are also observed in breast and prostate cancer and derived cell lines. Here, we examined whether potent agonist-induced overstimulation mediated by TRPV1 might represent a means for the eradication of prostate carcinoma (PC-3, Du 145, LNCaP) and breast cancer (MCF7, MDA-MB-231, BT-474) cells in vitro. While rat sensory neurons were highly vanilloid-sensitive, normal rat prostate epithelial cells were resistant in vivo. We found TRPV1 to be expressed in all cancer cell lines at mRNA and protein levels, yet protein expression levels were significantly lower compared to sensory neurons. Treatment of all human carcinoma cell lines with capsaicin didn't lead to overstimulation cytotoxicity in vitro. We assume that the low vanilloid-sensitivity of prostate and breast cancer cells is associated with low expression levels of TRPV1, since ectopic TRPV1 expression rendered them susceptible to the cytotoxic effect of vanilloids evidenced by plateau-type Ca(2+) signals, mitochondrial Ca(2+) accumulation and Na(+)- and Ca(2+)-dependent membrane disorganization. Moreover, long-term monitoring revealed that merely the ectopic expression of TRPV1 stopped cell proliferation and often induced apoptotic processes via strong activation of caspase-3 activity. Our results indicate that specific targeting of TRPV1 function remains a putative strategy for cancer treatment. PMID:27180305

  18. Neurofibromatosis: The role of guanosine triphosphatase activating proteins in sensory neuron function

    Institute of Scientific and Technical Information of China (English)

    Cynthia M. Hingtgen

    2008-01-01

    Neurofibromatosis type 1 (NF1) is a common autosomal dominant disease characterized by formation of multiple benign and malignant tumors. People with this disorder also experience chronic pain, which can be disabling. Neurofibromin, the protein product of the Nfl gene, is a gnanosine triphosphatase activating protein (GAP) for p21Ras (Ras). Loss of Nfl results in an increase in activity of the Ras transduction cascade. Because of the growing evidence suggesting involvement of downstream components of the Ras transduction cascade in the sensitization of nociceptive sensory neurons, we examined the stimulus-evoked release of the neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP), from primary sensory neurons of mice with a mutation of the Nfl gene (NfI+1-). Measuring the levels of SP and CGRP by radioimmunoassay, we demonstrated that capsaicin-stimulated release of neuropep-tides is 3-5 folds higher in spinal cord slices from Nfl+1-mice than that from wildtype mouse tissue. In addition, the potassium- and capsaicin-stimulated release of CGRP from the culture of sensory neurons isolated from Nfl+1- mice was more than double that from the culture of wildtype neurons. Using patch-clamp electrophysiological techniques, we also examined the excitability of capsaicin-sensitive sensory neurons. It was found that the number of action potentials generated by the neurons from Nfl+1- mice, responsing to a ramp of depolarizing current, was more than three times of that generated by wildtype neurons. Consistent with that observation, neurons from Nfl+1- mice had lower firing thresholds, lower rheobase currents and shorter firing latencies compared with wildtype neurons. These data clearly demonstrate that GAPs, such as neurofihromin, can alter the excitability of nociceptive sensory neurons. The augmented response of sensory neurons with altered Ras signaling may explain the abnormal pain sensations experienced by people with NFI and suggests an important

  19. In vivo potency of different ligands on voltage-gated sodium channels.

    Science.gov (United States)

    Safrany-Fark, Arpad; Petrovszki, Zita; Kekesi, Gabriella; Liszli, Peter; Benedek, Gyorgy; Keresztes, Csilla; Horvath, Gyongyi

    2015-09-01

    The Ranvier nodes of thick myelinated nerve fibers contain almost exclusively voltage-gated sodium channels (Navs), while the unmyelinated fibers have several receptors (e.g., cannabinoid, transient receptor potential vanilloid receptor 1), too. Therefore, a nerve which contains only motor fibers can be an appropriate in vivo model for selective influence of Navs. The goals were to evaluate the potency of local anesthetic drugs on such a nerve in vivo; furthermore, to investigate the effects of ligands with different structures (arachidonic acid, anandamide, capsaicin and nisoxetine) that were proved to inhibit Navs in vitro with antinociceptive properties. The marginal mandibular branch of the facial nerve was explored in anesthetized Wistar rats; after its stimulation, the electrical activity of the vibrissae muscles was registered following the perineural injection of different drugs. Lidocaine, bupivacaine and ropivacaine evoked dose-dependent decrease in electromyographic activity, i.e., lidocaine had lower potency than bupivacaine or ropivacaine. QX-314 did not cause any effect by itself, but its co-application with lidocaine produced a prolonged inhibition. Nisoxetine had a very low potency. While anandamide and capsaicin in high doses caused about 50% decrease in the amplitude of action potential, arachidonic acid did not influence the responses. We proved that the classical local anesthetics have high potency on motor nerves, suggesting that this method might be a reliable model for selective targeting of Navs in vivo circumstances. It is proposed that the effects of these endogenous lipids and capsaicin on sensory fibers are not primarily mediated by Navs. PMID:26033207

  20. An alternative method to screen for pepper spray residue.

    Science.gov (United States)

    Gillis, Trevor D; Kubic, Thomas A; De Forest, Peter R

    2003-01-01

    A method was developed to screen for pepper spray residue using instruments and methods other than those techniques commonly employed to analyze chemical residue (i.e.. gas chromatography mass spectrometry-GCMS or liquid chromatography mass spectrometry-LCMS). The method employed gas chromatography (GC), thin layer chromatography (TLC), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) to screen for dried pepper spray stains. Pepper sprays from nine different manufacturers were investigated. Capsaicin and dihydrocapsaicin were identified and unique IR reflectance spectra are presented. An additional five compounds were presumptively found. Results showed that a particular stain could be characterized as a pepper-based stain. PMID:12570209