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Capsaicin
Kinds of Capsaicin Terms modified by Capsaicin Selected AbstractsCardio-respiratory reflexes evoked by phenylbiguanide in rats involve vagal afferents which are not sensitive to capsaicinACTA PHYSIOLOGICA, Issue 1 2010A. Dutta Abstract Aim:, Stimulation of pulmonary C fibre receptors by phenylbiguanide (PBG, 5-HT3 agonist) produces hypotension, bradycardia and tachypnoea or apnoea. However, tachypnoeic or apnoeic responses are not consistent. Therefore, this study was undertaken to delineate the actions of PBG on respiration and compared with those evoked by capsaicin (TRPV1 agonist). Methods:, Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. The effect of PBG or capsaicin was evaluated before and after ondansetron (5-HT3 antagonist), capsazepine (TRPV1 antagonist) or bilateral vagotomy. In addition, their effect on vagal afferent activity was also evaluated. Results:, Bolus injection of PBG produced concentration-dependent (0.1,100 ,g kg,1) hypotensive and bradycardiac responses, while there was tachypnoea at lower concentrations (0.1,3 ,g kg,1) and apnoea at higher concentrations (10,100 ,g kg,1). After vagotomy or after exposure to ondansetron both tachypnoeic and apnoeic responses were abolished along with cardiovascular responses. However, capsazepine (3 mg kg,1) did not block the PBG-induced reflex responses. Capsaicin (0.1,10 ,g kg,1), on the other hand, produced a concentration-dependent apnoea, hypotension and bradycardia but tachypnoea was not observed. Ondansetron failed to block the capsaicin-induced reflex response while bilateral vagotomy abolished bradycardiac and hypotensive responses and attenuated the apnoeic response. In another series, vagal afferent activity and cardio-respiratory changes evoked by PBG were blocked by ondansetron. However, capsaicin failed to activate the PBG-sensitive vagal afferents even though cardio-respiratory alterations were observed. Conclusions:, The present observations indicate that PBG produced tachypnoea at a lower concentration and apnoea at a higher concentration involving vagal afferents which are different from those excited by capsaicin. [source] Effect of capsaicin on Ca2+ fluxes in Madin-Darby canine renal tubular cellsDRUG DEVELOPMENT RESEARCH, Issue 2 2010Jeng-Hsien Yeh Abstract The effect of capsaicin, a transient receptor potential vanniloid-1 (TRPV1) receptor agonist, on cytosolic free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells is unclear. This study explored whether capsaicin changed basal [Ca2+]i levels in suspended MDCK cells by using fura-2 as a Ca2+ -sensitive fluorescent dye. Capsaicin at concentrations between 10,100,µM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 80% by removing extracellular Ca2+. Capsacin induced Mn2+ influx, leading to quench of fura-2 fluorescence suggesting Ca2+ influx. This Ca2+ influx was inhibited by phospholipase A2 inhibitor aristolochic acid and the non-selective Ca2+ entry blocker La3+, but not by store-operated Ca2+ channel blockers nifedipine, econazole, and SK&F96365, and protein kinase C/A modulators. In Ca2+ -free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished capsaicin-induced Ca2+ release. Conversely, pretreatment with capsaicin partly reduced thapsigargin-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter capsaicin-induced [Ca2+]i rise. The TRPV1 receptor antagonist capsazepine also induced significant Ca2+ entry and Ca2+ release. Collectively, in MDCK cells, capsaicin induced [Ca2+]i rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A2-regulated, La3+ -sensitive Ca2+ channels in a manner dissociated from stimulation of TRPV1 receptors. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] Synthesis and elucidation of deuterated vanillylamine hydrochloride and capsaicinJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 13 2009Sang Wook Kim Abstract Capsaicin is the major pungent component of hot peppers, which belong to the plant genus Capsicum. Although the biosynthesis of capsaicin is known to involve the condensation of vanillylamine and 8-methylnonenoic acid by capsaicin synthase, the mechanism of biosynthesis is still not fully understood. In this study, deuterium labelled versions of capsaicin and the precursor vanillylamine were synthesized in order to investigate the biosynthesis of capsaicin in hot peppers. Copyright © 2009 John Wiley & Sons, Ltd. [source] The glutamatergic nature of TRPV1-expressing neurons in the spinal dorsal hornJOURNAL OF NEUROCHEMISTRY, Issue 1 2009Hong-Yi Zhou Abstract The transient receptor potential vanilloid receptor 1 (TRPV1) is expressed on primary afferent terminals and spinal dorsal horn neurons. However, the neurochemical phenotypes and functions of TRPV1-expressing post-synaptic neurons in the spinal cord are not clear. In this study, we tested the hypothesis that TRPV1-expressing dorsal horn neurons are glutamatergic. Immunocytochemical labeling revealed that TRPV1 and vesicular glutamate transporter-2 were colocalized in dorsal horn neurons and their terminals in the rat spinal cord. Resiniferatoxin (RTX) treatment or dorsal rhizotomy ablated TRPV1-expressing primary afferents but did not affect TRPV1- and vesicular glutamate transporter-2-expressing dorsal horn neurons. Capsaicin significantly increased the frequency of glutamatergic spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in almost all the lamina II neurons tested in control rats. In RTX-treated or dorsal rhizotomized rats, capsaicin still increased the frequency of spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in the majority of neurons examined, and this effect was abolished by a TRPV1 blocker or by non-NMDA receptor antagonist. In RTX-treated or in dorsal rhizotomized rats, capsaicin also produced an inward current in a subpopulation of lamina II neurons. However, capsaicin had no effect on GABAergic and glycinergic spontaneous inhibitory post-synaptic currents of lamina II neurons in RTX-treated or dorsal rhizotomized rats. Collectively, our study provides new histological and functional evidence that TRPV1-expressing dorsal horn neurons in the spinal cord are glutamatergic and that they mediate excitatory synaptic transmission. This finding is important to our understanding of the circuitry and phenotypes of intrinsic dorsal horn neurons in the spinal cord. [source] Influence of topical capsaicin on facial sensitivity in response to experimental painJOURNAL OF ORAL REHABILITATION, Issue 1 2007Y.-S. LEE summary, Capsaicin, the pungent component of the red pepper, has been used as an analgesic in a variety of pain conditions, but sensory impairment after long-term treatment has been concerned. This study investigated the influence of topical capsaicin on various types of sensations including pain in the facial areas innervated by the mental nerve, and also evaluated whether the measurement of cutaneous current perception threshold (CPT) is reliable for the quantification of sensory change following capsaicin application. Twenty healthy subjects were given topical capsaicin cream (0·075%), which was applied to the mental area unilaterally, four times daily for 2 weeks. Burning sensation after capsaicin application gradually decreased with repeated applications. Repeated topical capsaicin resulted in reduced sensation to mechanical, heat and cold pain without changing non-painful tactile sensation. It also resulted in increased CPTs at 5 Hz and 250 Hz stimuli but no change in the CPTs at 2000 Hz from the first evaluation after capsaicin treatment and throughout the treatment period. This study demonstrated that topical capsaicin treatment for the management of chronic localized pain can be safely applied to the face without affecting non-painful normal sensations, and that CPT testing is a clinically useful tool for the quantification of sensory changes following capsaicin application. [source] Determination of capsaicinoid profile of different chilli peppers grown in TurkeyJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 9 2005Ender Sinan Poyrazo Abstract In this research the major pungent components of chilli peppers, namely capsaicin, dihydrocapsaicin and nordihydrocapsaicin, were determined by high-performance liquid chromatography. Chilli pepper varieties Mara,, Süs, Cin and Isot were collected from different regions (Mara, and Urfa) of Turkey. Capsaicin, dihydrocapsaicin and nordihydrocapsaicin contents of Mara, peppers were 0.81,1.42, 0.38,0.70 and 0.01,0.04 mg g,1 respectively. Total capsaicinoid contents of Süs, Cin and Isot peppers were 2.11, 4.70 and 0.55 mg g,1 respectively, while total capsaicinoid contents of their seeds were 0.63, 1.70 and 1.60 mg g,1 respectively. All the peppers in this study belong to the family Solanaceae, genus Capsicum and species annuum or frutescens. Copyright © 2005 Society of Chemical Industry [source] The effects of capsaicin on reflux, gastric emptying and dyspepsiaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2000Rodriguez-Stanley Aims: To evaluate capsaicin's effects on heartburn, dyspepsia, gastric acidity and emptying, and gastro-oesophageal reflux, and to test the hypothesis that capsaicin induces heartburn and exacerbates symptoms by sensitizing the oesophagus. Methods: Eleven heartburn sufferers underwent two separate pH monitoring sessions and assessments of gastric emptying (13C-octanoic acid breath test), heartburn and dyspepsia (100 mm VAS) after a non-irritant meal. The meal consisted of a sausage biscuit with egg, cheese and 30 g raw onion, 8 oz chocolate milk and a peppermint patty. Thirty minutes prior to meal consumption, subjects were administered a placebo capsule. On visit 1, subjects consumed the meal containing 100 ,l 13C-octanoic acid cooked in the egg, over 15 min. On visit 2, subjects consumed the meal plus 5 mg capsaicin in gelatin capsules. Results: Oesophageal and gastric pH profiles and gastric emptying were not different between meals. Capsaicin did not alter mean heartburn and dyspepsia scores (P > 0.05), but significantly decreased time to peak heartburn (120 min vs. 247 min; P < 0.003). Time to peak dyspepsia was not altered by capsaicin (P > 0.05). Conclusion: Capsaicin enhances noxious postprandial heartburn, presumably by direct effects on sensory neurons. [source] Capsaicin modulates pulmonary antioxidant defense system during benzo(a)pyrene-induced lung cancer in swiss albino micePHYTOTHERAPY RESEARCH, Issue 4 2008P. Anandakumar Abstract The effect of a pungent ingredient of red pepper, capsaicin, on oxidative stress induced changes in the antioxidant defense system by benzo(a)pyrene in the lungs of mice was studied. Oral gavage administration of benzo(a)pyrene (50 mg/kg body weight) to mice led to a marked increase in oxidative stress indicated by alterations in pulmonary lipid peroxidation, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione- S -transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Pre-co-treatment with capsaicin (10 mg/kg body weight i.p.) restored cellular normalcy, highlighting the antioxidant potential of capsaicin in mitigating the oxidative stress mediated damage produced during benzo(a)pyrene-induced lung cancer. Copyright © 2008 John Wiley & Sons, Ltd. [source] The effect of capsaicin on blood glucose, plasma insulin levels and insulin binding in dog modelsPHYTOTHERAPY RESEARCH, Issue 5 2001I. Tolan Abstract Capsicum frutescens has been used to treat diabetes mellitus by traditional healers in Jamaica. This study was designed to identify any hypoglycaemic principle(s) and to determine the mechanism of action. Purification experiments employing thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) led to the extraction of the active principle, capsaicin. Capsaicin caused a decrease in blood glucose levels of 4.91,±,0.52 (n,=,6),mmol/dL versus 6.40,±,0.13,mmol/dL (n,=,6) for the control (p,<,0.05) at the 2.5,h time interval when the oral glucose tolerance test (OGTT) was performed on dogs treated with capsaicin and compared with the control. Plasma insulin levels measured at the 2.5,h time interval showed that there was an increase in plasma insulin levels of 5.78,±,0.76,µIU/mL (n,=,6) for the capsaicin treated dogs versus 3.70,±,0.43,µIU/mL (n,=,10) for the control (p,<,0.05). Insulin receptor studies, using a modification of the method of Gambhir et al. done on monocytes obtained from blood at the 2.5,h time interval showed that there was a decrease in the percentage receptor binding for the capsaicin treated dogs when compared with the control. Insulin affinity results showed that there was a decrease of 2.4,×,10,4 in monocytes for the capsaicin treated dogs versus 8.77,×,10,4 for the control (p,<,0.05). Also, insulin receptor calculations showed a decrease in number, 2.63,×,108,±,5.73,×,107, compared with 8.77,×,108,±,1.47,×,108 for the control. In conclusion it can be stated that capsaicin is responsible for the hypoglycaemic episodes seen in the dogs and that it also causes an increase in insulin secretion which leads to a reduction of insulin binding on the insulin receptors. Copyright © 2001 John Wiley & Sons, Ltd. [source] Chemopreventive Task of Capsaicin against Benzo(a)pyrene-induced Lung Cancer in Swiss Albino MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2009Pandi Anandakumar The present study is an effort to identify the chemopreventive role of alkaloid capsaicin against benzo(a)pyrene-induced lung cancer in Swiss albino mice. Benzo(a)pyrene-induced lung cancer-bearing animals showed abnormal changes in body weight, lung weight, tumour incidence and alterations in the activities of marker enzymes adenosine deaminase, aryl hydrocarbon hydroxylase, ,-glutamyl transpeptidase, 5,-nucleotidase and lactate dehydrogenase. On capsaicin pre-co-treatment, all the above alterations were returned to near normal. Immunohistochemical analysis of proliferating cell nuclear antigen together with lung histological examination further supported our biochemical findings that demonstrated the chemoprotective role of capsaicin against benzo(a)pyrene-induced experimental lung cancer. [source] 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 stabilityBIOMEDICAL CHROMATOGRAPHY, Issue 2 2009Francis Beaudry Abstract 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 × 2 mm C18 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 µL/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 T1/2 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. Copyright © 2008 John Wiley & Sons, Ltd. [source] Nociceptin/orphanin FQ inhibits capsaicin-induced guinea-pig airway contraction through an inward-rectifier potassium channelBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2002Yanlin Jia Nociceptin/orphanin FQ (N/OFQ), an endogenous opioid-like orphan receptor (NOP receptor, previously termed ORL1 receptor) agonist, has been found to inhibit capsaicin-induced bronchoconstriction in isolated guinea-pig lungs and in vivo. The underlying mechanisms are not clear. In the present studies, we tested the effect of N/OFQ on VR1 channel function in isolated guinea-pig nodose ganglia cells. Capsaicin increased intracellular Ca2+ concentration in these cells through activation of vanilloid receptors. Capsaicin-induced Ca2+ responses were attenuated by pretreatment of nodose neurons with N/OFQ (1 ,M). N/OFQ inhibitory effect on the Ca2+ response in nodose ganglia cells was antagonized by tertiapin (0.5 ,M), an inhibitor of inward-rectifier K+ channels, but not by verapamil, a voltage gated Ca2+ channel blocker, indicating that an inward-rectifier K+ channel is involved in N/OFQ inhibitory effect. In isolated guinea-pig bronchus, N/OFQ (1 ,M) inhibited capsaicin-induced airway contraction. Tertiapin (0.5 ,M) abolished the N/OFQ inhibition of capsaicin-induced bronchial contraction. Capsaicin (10 ,g) increased pulmonary inflation pressure in the isolated perfused guinea-pig lungs. This response was significantly attenuated by pretreatment with N/OFQ (1 ,M). Tertiapin also abolished the N/OFQ inhibitory effect on capsaicin-induced bronchoconstriction in perfused lungs. Capsaicin increased the release of substance P and neurokinin A from isolated lungs. N/OFQ (1 ,M) blocked the capsaicin-induced tachykinin release. These results indicate that N/OFQ-induced hyperpolarization of tachykinin containing airway sensory nerves, through an inward-rectifier K+ channel activation, accounts for the inhibition of capsaicin-evoked broncoconstriction. British Journal of Pharmacology (2002) 135, 764,770; doi:10.1038/sj.bjp.0704515 [source] Frequent association between MEN 2A and cutaneous lichen amyloidosisCLINICAL ENDOCRINOLOGY, Issue 2 2003Uberta Verga Summary objective Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are genetic diseases due to activating mutations of the RET proto-oncogene. Affected patients develop medullary thyroid carcinoma (100%), in an isolated form (FMTC) or in association with phaeochromocytoma (30,50%), and primary hyperparathyroidism (10,20%) (MEN 2A). The presence of cutaneous lichen amyloidosis (CLA) has been anecdotally described in few families harbouring RET proto-oncogene mutation in codon 634. The aim of the study was to evaluate the incidence of CLA in MEN 2A/FMTC families. patients and design Ten MEN 2A/FMTC families were studied and RET gene mutations identified in all. Complete dermatological assessment was carried out in each family member. Skin biopsy for histological studies was performed in patients with CLA. results Among 10 MEN 2A/FMTC families, the presence of CLA was found only in patients belonging to the three families with MEN 2A and RET mutation in codon 634. Nine of 25 patients (36%) with codon 634 mutation presented CLA, though two of them did not show CLA skin lesions but the typical neurological pruritus in the upper back. In all patients, neurological pruritus was present since infancy as a precocious marker of the disorder. The dermatological study of patients with CLA skin lesions added further evidence that pruritus has a pivotal role in the development of CLA, the amyloid deposition being the consequence of repeated scratching. Light microscopy revealed orthokeratotic hyperkeratosis, with elongation of the rete ridges, rare intramalpighian apoptic keratinocytes and deposits of amorphous material in the superficial dermis. Examination under ultraviolet light showed thioflavin T-positive staining, confirming the presence of amyloid in the papillary dermis. The use of Capsaicin at the dilution of 0·025% had a mild efficacy on the cutaneous symptoms. conclusions Among the members of the three families with MEN 2A and RET 634 mutation, the incidence of CLA was 36%, a figure similar to that reported in the literature for phaeochromocytoma (30,50%) and even higher than that for hyperparathyroidism (10,20%). The present data confirm that CLA is linked to codon 634 RET mutations and is a precocious marker of the disorder. [source] Cardio-respiratory reflexes evoked by phenylbiguanide in rats involve vagal afferents which are not sensitive to capsaicinACTA PHYSIOLOGICA, Issue 1 2010A. Dutta Abstract Aim:, Stimulation of pulmonary C fibre receptors by phenylbiguanide (PBG, 5-HT3 agonist) produces hypotension, bradycardia and tachypnoea or apnoea. However, tachypnoeic or apnoeic responses are not consistent. Therefore, this study was undertaken to delineate the actions of PBG on respiration and compared with those evoked by capsaicin (TRPV1 agonist). Methods:, Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. The effect of PBG or capsaicin was evaluated before and after ondansetron (5-HT3 antagonist), capsazepine (TRPV1 antagonist) or bilateral vagotomy. In addition, their effect on vagal afferent activity was also evaluated. Results:, Bolus injection of PBG produced concentration-dependent (0.1,100 ,g kg,1) hypotensive and bradycardiac responses, while there was tachypnoea at lower concentrations (0.1,3 ,g kg,1) and apnoea at higher concentrations (10,100 ,g kg,1). After vagotomy or after exposure to ondansetron both tachypnoeic and apnoeic responses were abolished along with cardiovascular responses. However, capsazepine (3 mg kg,1) did not block the PBG-induced reflex responses. Capsaicin (0.1,10 ,g kg,1), on the other hand, produced a concentration-dependent apnoea, hypotension and bradycardia but tachypnoea was not observed. Ondansetron failed to block the capsaicin-induced reflex response while bilateral vagotomy abolished bradycardiac and hypotensive responses and attenuated the apnoeic response. In another series, vagal afferent activity and cardio-respiratory changes evoked by PBG were blocked by ondansetron. However, capsaicin failed to activate the PBG-sensitive vagal afferents even though cardio-respiratory alterations were observed. Conclusions:, The present observations indicate that PBG produced tachypnoea at a lower concentration and apnoea at a higher concentration involving vagal afferents which are different from those excited by capsaicin. [source] Prostaglandin I2 sensory input into the enteric nervous system during distension-induced colonic chloride secretion in rat colonACTA PHYSIOLOGICA, Issue 3 2010J. D. Schulzke Abstract Aim:, Intestinal pressure differences or experimental distension induce ion secretion via the enteric nervous system, the sensorial origin of which is only poorly understood. This study aimed to investigate sensorial inputs and the role of afferent and interneurones in mechanically activated submucosal secretory reflex circuits. Methods:, Distension-induced rheogenic chloride secretion was measured as increase in short-circuit current 10 min after distension (,ISC10; distension parameters ± 100 ,L, 2 Hz, 20 s) in partially stripped rat distal colon in the Ussing-chamber in vitro. PGE2 and PGI2 were measured by radioimmunoassay. Results:, ,ISC10 was 2.0 ± 0.2 ,mol h,1 cm,2 and could be attenuated by lobeline, mecamylamine and dimethylphenylpiperazine, indicating an influence of nicotinergic interneurones. Additionally, a contribution of afferent neurones was indicated from the short-term potentiation of ,ISC10 by capsaicin (1 ,m). As evidence for its initial event, indomethacin (1 ,m) inhibited distension-induced secretion and the release of PGI2 was directly detected after distension. Furthermore, serotoninergic mediation was confirmed by granisetron (100 ,m) which was functionally localized distally to PGI2 in this reflex circuit, as granisetron inhibited an iloprost-induced ISC, while indomethacin did not affect serotonin-activated ion secretion. Conclusions:, Distension-induced active electrogenic chloride secretion in rat colon is mediated by a neuronal reflex circuit which includes afferent neurones and nicotinergic interneurones. It is initiated by distension-induced PGI2 release from subepithelial cells triggering this reflex via serotoninergic 5-HT3 receptor transmission. Functionally, this mechanism may help to protect against intestinal stasis but could also contribute to luminal fluid loss, e.g. during intestinal obstruction. [source] Ethnic variations in facial skin neurosensitivity assessed by capsaicin detection thresholdsCONTACT DERMATITIS, Issue 6 2009Roland Jourdain Background: Ethnic variations in sensitive skin have not been thoroughly explored and remain controversial. Objective: To objectively assess ethnic variations in facial skin neurosensitivity through individual detection thresholds of topically applied capsaicin. Patients/Methods: The single-blind, controlled study was performed in 144 women from three ethnicities: Asian, African, and Caucasian. Five solutions with increasing capsaicin concentration were successively applied to one side of nasolabial folds, while the other side simultaneously received the vehicle as control. The test was discontinued when the volunteer reported on the capsaicin side a sensation whatever its nature. Otherwise the experimenter continued the test, using the next solution with higher capsaicin content and so on, until the subject experienced a sensation on the capsaicin side. Results: Each ethnic group was divided into six sub-groups according to the level of sensitivity to capsaicin, i.e. from detection of the lowest concentration up to no detection of the highest concentration, 100-fold higher. Asian women tended to have higher capsaicin detection thresholds than Caucasians, but lower thresholds than Africans. Nevertheless, the distribution did not greatly differ between the three ethnicities. Conclusions: The capsaicin skin neurosensitivity test is painless and the changes across individuals of different ethnic backgrounds appear minimal. [source] Reactive oxygen species in rostral ventrolateral medulla modulate cardiac sympathetic afferent reflex in ratsACTA PHYSIOLOGICA, Issue 4 2009M.-K. Zhong Abstract Aim:, The aim of the present study was to investigate whether reactive oxygen species (ROS) in rostral ventrolateral medulla (RVLM) modulate cardiac sympathetic afferent reflex (CSAR) and the enhanced CSAR response caused by microinjection of angiotensin II (Ang II) into the paraventricular nucleus (PVN). Methods:, Under urethane and ,-chloralose anaesthesia, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic-denervated and cervical-vagotomized rats. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin (1.0 nmol). Results:, Bilateral RVLM microinjection of tempol (a superoxide anion scavenger) or polyethylene glycol-superoxide dismutase (PEG-SOD, an analogue of endogenous superoxide dismutase) attenuated the CSAR, but did not cause significant change in baseline RSNA and MAP. NAD(P)H oxidase inhibitors apocynin or phenylarsine oxide (PAO) also showed similar effects, but SOD inhibitor diethyldithio-carbamic acid (DETC) enhanced the CSAR and baseline RSNA, and increased the baseline MAP. Bilateral PVN microinjection of Ang II (0.3 nmol) enhanced the CSAR and increased RSNA and MAP, which was inhibited by the pre-treatment with RVLM administration of tempol, PEG-SOD, apocynin or PAO. The pre-treatment with DETC in the RVLM only showed a tendency in potentiating the CSAR response of Ang II in the PVN, but significantly potentiated the RSNA and MAP responses of Ang II. Conclusion:, These results suggest that the NAD(P)H oxidase-derived ROS in the RVLM modulate the CSAR. The ROS in the RVLM is necessary for the enhanced CSAR response caused by Ang II in the PVN. [source] Effect of capsaicin on Ca2+ fluxes in Madin-Darby canine renal tubular cellsDRUG DEVELOPMENT RESEARCH, Issue 2 2010Jeng-Hsien Yeh Abstract The effect of capsaicin, a transient receptor potential vanniloid-1 (TRPV1) receptor agonist, on cytosolic free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells is unclear. This study explored whether capsaicin changed basal [Ca2+]i levels in suspended MDCK cells by using fura-2 as a Ca2+ -sensitive fluorescent dye. Capsaicin at concentrations between 10,100,µM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 80% by removing extracellular Ca2+. Capsacin induced Mn2+ influx, leading to quench of fura-2 fluorescence suggesting Ca2+ influx. This Ca2+ influx was inhibited by phospholipase A2 inhibitor aristolochic acid and the non-selective Ca2+ entry blocker La3+, but not by store-operated Ca2+ channel blockers nifedipine, econazole, and SK&F96365, and protein kinase C/A modulators. In Ca2+ -free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished capsaicin-induced Ca2+ release. Conversely, pretreatment with capsaicin partly reduced thapsigargin-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter capsaicin-induced [Ca2+]i rise. The TRPV1 receptor antagonist capsazepine also induced significant Ca2+ entry and Ca2+ release. Collectively, in MDCK cells, capsaicin induced [Ca2+]i rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A2-regulated, La3+ -sensitive Ca2+ channels in a manner dissociated from stimulation of TRPV1 receptors. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] Using Capsaicin Modified Multiwalled Carbon Nanotube Based Electrodes and p -Chloranil Modified Carbon Paste Electrodes for the Determination of Amines: Application to Benzocaine and LidocaineELECTROANALYSIS, Issue 23 2008Roohollah Abstract The utilization of the capsaicin modified carbon nanotube modified basal-plane pyrolytic graphite electrode or p -chloranil modified carbon paste electrodes are presented for the determination of pharmaceutical compounds containing amine functionality, such as benzocaine and lidocaine. In detection of benzocaine at a capsaicin modified electrode, the guaiacol functional group is irreversibly electrochemically oxidized to form the o -quinone derivative which then undergoes nucleophilic attack by the aromatic amine group in benzocaine via a 1,4-Michael addition mechanism forming a catechol-amine adduct. The electrochemically initiated formation of the capsaicin-benzocaine adduct causes a linear decrease in the voltammetric signal corresponding to capsaicin which correlates to the added concentration of benzocaine. [source] Inhibitory Effect of Lamotrigine on A-type Potassium Current in Hippocampal Neuron,Derived H19-7 CellsEPILEPSIA, Issue 7 2004Chin-Wei Huang Summary:,Purpose: We investigated the effects of lamotrigine (LTG) on the rapidly inactivating A-type K+ current (IA) in embryonal hippocampal neurons. Methods: The whole-cell configuration of the patch-clamp technique was applied to investigate the ion currents in cultured hippocampal neuron,derived H19-7 cells in the presence of LTG. Effects of various related compounds on IA in H19-7 cells were compared. Results: LTG (30 ,M,3 mM) caused a reversible reduction in the amplitude of IA. The median inhibitory concentration (IC50) value required for the inhibition of IA by LTG was 160 ,M. 4-Aminopyridine (1 mM), quinidine (30 ,M), and capsaicin (30 ,M) were effective in suppressing the amplitude of IA, whereas tetraethylammonium chloride (1 mM) and gabapentin (100 ,M) had no effect on it. The time course for the inactivation of IA was changed to the biexponential process during cell exposure to LTG (100 ,M). LTG (300 ,M) could shift the steady-state inactivation of IA to a more negative membrane potential by approximately ,10 mV, although it had no effect on the slope of the inactivation curve. Moreover, LTG (100 ,M) produced a significant prolongation in the recovery of IA inactivation. Therefore in addition to the inhibition of voltage-dependent Na+ channels, LTG could interact with the A-type K+ channels to suppress the amplitude of IA. The blockade of IA by LTG does not simply reduce current magnitude, but alters current kinetics, suggesting a state-dependent blockade. LTG might have a higher affinity to the inactivated state than to the resting state of the IA channel. Conclusions: This study suggests that in hippocampal neurons, during exposure to LTG, the LTG-mediated inhibition of these K+ channels could be one of the ionic mechanisms underlying the increased neuronal excitability. [source] Dissociable neural activity to self- vs. externally administered thermal hyperalgesia: a parametric fMRI studyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2008C. Mohr Abstract Little is known regarding how cognitive strategies help to modulate neural responses of the human brain in ongoing pain syndromes to alleviate pain. Under pathological pain conditions, any self-elicited contact with usually non-painful stimuli may become painful. We examined whether the human brain is capable of dissociating self-controlled from externally administered thermal hyperalgesia in the experimental capsaicin model. Using functional magnetic resonance imaging, 17 male subjects were investigated in a parametric design with heat stimuli at topically capsaicin-sensitized skin. In contrast to external stimulation, self-administered pain was controllable. For both conditions application trials without noticeable thermal stimulation were introduced and used as high-level baseline (HLB) to account for the capsaicin-induced ongoing pain and other covariables. Following subtraction of the HLB, the anterior insula and the anterior cingulate cortex (ACC) but not the somatosensory cortices maintained parametric neural responses to thermal hyperalgesia. A stronger pain-related activity increase during self-administered stimuli was observed in the posterior insula. In contrast, prefrontal cortex showed stronger increases to uncontrollable external heat stimuli. In the state of ongoing pain (capsaicin), pain-intensity-encoding regions (anterior insula, ACC) but not those with sensory discriminative functions (SI, SII) showed graded, pain-intensity-related neural responses in thermal hyperalgesia. Some areas were able to dissociate between self- and externally administered stimuli in thermal hyperalgesia, which might be related to differences in perceived controllability. Thus, neural mechanisms maintain the ability to dissociate external from self-generated states of injury in thermal hyperalgesia. This may help to understand how cognitive strategies potentially alleviate chronic pain syndromes. [source] Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2007Dorte X. Gram Abstract The system that regulates insulin secretion from ,-cells in the islet of Langerhans has a capsaicin-sensitive inhibitory component. As calcitonin gene-related peptide (CGRP)-expressing primary sensory fibers innervate the islets, and a major proportion of the CGRP-containing primary sensory neurons is sensitive to capsaicin, the islet-innervating sensory fibers may represent the capsaicin-sensitive inhibitory component. Here, we examined the expression of the capsaicin receptor, vanilloid type 1 transient receptor potential receptor (TRPV1) in CGRP-expressing fibers in the pancreatic islets, and the effect of selective elimination of capsaicin-sensitive primary afferents on the decline of glucose homeostasis and insulin secretion in Zucker diabetic fatty (ZDF) rats, which are used to study various aspects of human type 2 diabetes mellitus. We found that CGRP-expressing fibers in the pancreatic islets also express TRPV1. Furthermore, we also found that systemic capsaicin application before the development of hyperglycemia prevents the increase of fasting, non-fasting, and mean 24-h plasma glucose levels, and the deterioration of glucose tolerance assessed on the fifth week following the injection. These effects were accompanied by enhanced insulin secretion and a virtually complete loss of CGRP- and TRPV1-coexpressing islet-innervating fibers. These data indicate that CGRP-containing fibers in the islets are capsaicin sensitive, and that elimination of these fibers contributes to the prevention of the deterioration of glucose homeostasis through increased insulin secretion in ZDF rats. Based on these data we propose that the activity of islet-innervating capsaicin-sensitive fibers may have a role in the development of reduced insulin secretion in human type 2 diabetes mellitus. [source] Background potassium channel block and TRPV1 activation contribute to proton depolarization of sensory neurons from humans with neuropathic painEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2004Thomas K. Baumann Abstract Protons cause a sustained depolarization of human dorsal root ganglion (DRG) neurons [Baumann et al. (1996) Pain, 65, 31,38]. In the present study we sought to determine which ion channels are expressed in human DRG neurons that could mediate the sustained responses observed in the patch-clamp recordings. RT-PCR of material from the DRG tissue revealed the presence of mRNAs for a nonselective cation channel that is activated by protons (TRPV1) and background potassium channels that are blocked by protons (TASK-1, TASK-3 and Kir2.3). Highly acidic solution (pH 5.4) applied to cultured DRG neurons evoked prolonged currents that were associated with a net increase in membrane conductance. Consistent with the involvement of TRPV1, these proton-evoked currents were blocked by capsazepine and were only found in neurons that responded to capsaicin with an increase in membrane conductance. Less acidic extracellular solution (pH 6.0) evoked such currents only rarely, but was able to strongly enhance the currents evoked by capsaicin. Capsazepine (1 µm) blocked the currents evoked by capsaicin at pH 7.35, as well as the potentiated responses to capsaicin at pH 6.0. In neurons that were not excited by capsaicin, moderate extracellular acidification (pH 6.0) caused a sustained decrease in resting membrane conductance. The decrease in membrane conductance by protons was associated with inhibition of background potassium channels. This excitatory effect of protons was not blocked by capsazepine. We conclude that in most neurons the sustained depolarization in response to moderately acidic solutions is the result of blocked background potassium channels. In a subset of neurons, TRPV1 also contributes. [source] Anandamide regulates neuropeptide release from capsaicin-sensitive primary sensory neurons by activating both the cannabinoid 1 receptor and the vanilloid receptor 1 in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2003Jatinder Ahluwalia Abstract The effect of anandamide, which activates both the cannabinoid 1 (CB1) receptor and the vanilloid receptor 1 (VR1), was studied on calcitonin gene-related peptide (CGRP) release from cultured primary sensory neurons, the majority of which coexpress the CB1 receptor and VR1. Concentrations of anandamide <,1 µm produced a small but significant CB1 receptor-mediated inhibition of basal CGRP release while higher concentrations induced VR1-mediated CGRP release. The excitatory effect of anandamide was potentiated by the CB1 receptor antagonist SR141716A. In the presence of SR141716A at concentrations <,100 nm, anandamide was equipotent with capsaicin in stimulating CGRP release. However, at higher concentrations anandamide produced more CGRP release than equimolar concentrations of capsaicin. Three and ten nanomolar anandamide inhibited the capsaicin-evoked CGRP release. In the presence of SR141716A, treatments which activated protein kinase A, protein kinase C and phospholipase C significantly potentiated the anandamide-evoked CGRP release at all anandamide concentrations. Although this potentiation was reduced when the CB1 receptor antagonist was omitted from the buffer, the CGRP release evoked by 300 nm and 1 µm anandamide was still significantly larger than that seen with nonpotentiated cells. These data indicate that anandamide may regulate CGRP release from capsaicin-sensitive primary sensory neurons in vivo, and that the net effect of anandamide on transmitter release from capsaicin-sensitive primary sensory neurons depends on the concentration of anandamide and the state of the CB1 receptor and VR1. These findings also suggest that anandamide could be one of the molecules responsible for the development of inflammatory heat hyperalgesia. [source] Noxious heat-induced CGRP release from rat sciatic nerve axons in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2001S. K. Sauer Abstract Noxious heat may act as an endogenous activator of the ionotropic capsaicin receptor (VR1) and of its recently found homologue VRL1, expressed in rat dorsal root ganglion cells and present along their nerve fibres. We have previously reported that capsaicin induces receptor-mediated and Ca++ -dependent calcitonin gene-related peptide (CGRP) release from axons of the isolated rat sciatic nerve. Here we extended the investigation to noxious heat stimulation and the transduction mechanisms involved. Heat stimulation augmented the CGRP release from desheathed sciatic nerves in a log,linear manner with a Q10 of ,,15 and a threshold between 40 and 42 °C. The increases were 1.75-fold at 42 °C, 3.8-fold at 45 °C and 29.1-fold at 52 °C; in Ca++ -free solution these heat responses were abolished or reduced by 71 and 92%, respectively. Capsazepine (10 µm) and Ruthenium Red (1 µm) used as capsaicin receptor/channel antagonists did not significantly inhibit the heat-induced release. Pretreatment of the nerves with capsaicin (100 µm for 30 min) caused complete desensitization to 1 µm capsaicin, but a significant heat response remained, indicating that heat sensitivity is not restricted to capsaicin-sensitive fibres. The sciatic nerve axons responded to heat, potassium and capsaicin stimulation with a Ca++ -dependent CGRP release. Blockade of the capsaicin receptor/channels had little effect on the heat-induced neuropeptide release. We conclude therefore that other heat-activated ion channels than VR1 and VRL1 in capsaicin-sensitive and -insensitive nerve fibres may cause excitation, axonal Ca++ influx and subsequent CGRP release. [source] Low-threshold heat response antagonized by capsazepine in chick sensory neurons, which are capsaicin-insensitiveEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2000Antonia Marín-Burgin Abstract The heat-transducing receptor VR1 cloned from rat sensory neurons can be activated by both noxious heat and capsaicin. As the response of sensory neurons to capsaicin is species dependent, it is conceivable that the responses to noxious heat and to capsaicin are transduced by distinct receptors across different species. Therefore, we investigated responses to noxious heat from a capsaicin-insensitive (chick) and a capsaicin-sensitive (rat) species. In chick, whole-cell patch-clamp experiments in isolated dorsal root ganglion neurons revealed two populations of neurons with different thresholds to noxious heat, activated at ,,43 °C and ,,53 °C. In cobalt uptake experiments, the proportion of neurons showing a heat-induced response increased with increasing heat stimuli. Application of capsaicin (1,10 ,m) did not result in inward currents or cobalt uptake. Rat neurons yielded comparable results in heat experiments, but were capsaicin-sensitive. Although chick neurons are insensitive to capsaicin, the competitive capsaicin antagonist capsazepine (1,10 ,m) was effective in blocking heat-induced responses, verified by patch-clamp and cobalt uptake methods. The noncompetitive capsaicin antagonist ruthenium red (10 ,m) reduced to almost nil the proportion of heat-responsive neurons identified with the cobalt uptake method. These findings suggest that chick DRG neurons express a low-threshold heat-transducing receptor with a pharmacological profile distinct from the low-threshold heat receptor VR1 cloned from rat DRG neurons. The data support the idea that there might be heat receptor subtypes with differences in the capsaicin binding site. [source] Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structuresEXPERIMENTAL DERMATOLOGY, Issue 3 2004Sonja Ständer Abstract:, The vanilloid receptor subtype 1 (VR1)/(TRPV1), binding capsaicin, is a non-selective cation channel that recently has been shown in human keratinocytes in vitro and in vivo. However, a description of VR1 localization in other cutaneous compartments in particular cutaneous nerve fibers is still lacking. We therefore investigated VR1 immunoreactivity as well as mRNA and protein expression in a series (n = 26) of normal (n = 7), diseased (n = 13) [prurigo nodularis (PN) (n = 10), generalized pruritus (n = 1), and mastocytosis (n = 2)], and capsaicin-treated human skin (n = 6). VR1 immunoreactivity could be observed in cutaneous sensory nerve fibers, mast cells, epidermal keratinocytes, dermal blood vessels, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands. Upon reverse transcriptase-polymerase chain reaction and Western blot analysis, VR1 was detected in mast cells and keratinocytes from human skin. In pruritic skin of PN, VR1 expression was highly increased in epidermal keratinocytes and nerve fibers, which was normalized after capsaicin application. During capsaicin therapy, a reduction of neuropeptides (substance P, calcitonin gene-related peptide) was observed. After cessation of capsaicin therapy, neuropeptides re-accumulated in skin nerves. In conclusion, VR1 is widely distributed in the skin, suggesting a major role for this receptor, e.g. in nociception and neurogenic inflammation. [source] Lysosomal abnormalities during benzo(a)pyrene-induced experimental lung carcinogenesis , defensive role of capsaicinFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2009P. Anandakumar Abstract The objective of the present study was to investigate whether lysosome is a target in benzo(a)pyrene-induced, oxidative stress-mediated lung cancer in Swiss albino mice and the plausible role of the phytochemical substance capsaicin in mitigating lysosomal damage. Oxidative stress was assessed based on the level of carbonyl content. The activities of lysosomal proteases like cathepsin-D, cathepsin-B, ,- d -glucosidase, ,- d -galactosidase, ,- d -glucuronidase, ,- d - N -acetylglucosaminidase and acid phosphatase were assessed to evaluate lysosomal function. Administration of benzo(a)pyrene (50 mg/kg body weight) to mice induced a increase in the activities of lysosomal enzymes and oxidative stress was evident by the increase in carbonyl content. Treatment with capsaicin (10 mg/kg body weight) decreased carbonyl content and restored the activities of lysosomal enzymes to near normalcy. Transmission electron microscopic study of lysosomes further showed the defensive action of capsaicin against the lysosomal damage caused in benzo(a)pyrene-induced lung cancer. From the present study, it can be concluded that lysosomal damage is an indispensable event in benzo(a)pyrene-induced lung cancer, and capsaicin was able to effectively prevent it, which proves the chemoprotective effect of capsaicin against benzo(a)pyrene-induced experimental lung carcinogenesis. [source] Neuron,Glia Signaling in Trigeminal Ganglion: Implications for Migraine PathologyHEADACHE, Issue 7 2007Srikanth Thalakoti BS Objective.,The goal of this study was to investigate neuronal,glial cell signaling in trigeminal ganglia under basal and inflammatory conditions using an in vivo model of trigeminal nerve activation. Background.,Activation of trigeminal ganglion nerves and release of calcitonin gene-related peptide (CGRP) are implicated in the pathology of migraine. Cell bodies of trigeminal neurons reside in the ganglion in close association with glial cells. Neuron,glia interactions are involved in all stages of inflammation and pain associated with several central nervous system (CNS) diseases. However, the role of neuron,glia interactions within the trigeminal ganglion under normal and inflammatory conditions is not known. Methods.,Sprague,Dawley rats were utilized to study neuron,glia signaling in the trigeminal ganglion. Initially, True Blue was used as a retrograde tracer to localize neuronal cell bodies in the ganglion by fluorescent microscopy and multiple image alignment. Dye-coupling studies were conducted under basal conditions and in response to capsaicin injection into the TMJ capsule. S100B and p38 expression in neurons and glia were determined by immunohistochemistry following chemical stimulation. CGRP levels in the ganglion were measured by radioimmunoassay in response to capsaicin. In addition, the effect of CGRP on the release of 19 different cytokines from cultured glial cells was investigated by protein microarray analysis. Results.,In unstimulated control animals, True Blue was detected primarily in neuronal cell bodies localized in clusters within the ganglion corresponding to the V3 region (TMJ capsule), V2 region (whisker pad), or V1 region (eyebrow and eye). However, True Blue was detected in both neuronal cell bodies and adjacent glia in the V3 region of the ganglion obtained from animals injected with capsaicin. Dye movement into the surrounding glia correlated with the time after capsaicin injection. Chemical stimulation of V3 trigeminal nerves was found to increase the expression of the inflammatory proteins S100B and p38 in both neurons and glia within the V3 region. Unexpectedly, increased levels of these proteins were also observed in the V2 and V1 regions of the ganglion. CGRP and the vesicle docking protein SNAP-25 were colocalized in many neuronal cell bodies and processes. Decreased CGRP levels in the ganglion were observed 2 hours following capsaicin stimulation. Using protein microarray analysis, CGRP was shown to differentially regulate cytokine secretion from cultured trigeminal ganglion glia. Conclusions.,We demonstrated that activation of trigeminal neurons leads to changes in adjacent glia that involve communication through gap junctions and paracrine signaling. This is the first evidence, to our knowledge, of neuron,glia signaling via gap junctions within the trigeminal ganglion. Based on our findings, it is likely that neuronal,glial communication via gap junctions and paracrine signaling are involved in the development of peripheral sensitization within the trigeminal ganglion and, thus, are likely to play an important role in the initiation of migraine. Furthermore, we propose that propagation of inflammatory signals within the ganglion may help to explain commonly reported symptoms of comorbid conditions associated with migraine. [source] Blockage of the neurokinin 1 receptor and capsaicin-induced ablation of the enteric afferent nerves protect SCID mice against T-cell-induced chronic colitisINFLAMMATORY BOWEL DISEASES, Issue 8 2009Monika Gad PhD Abstract 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 expressing afferent nerves for disease development was studied in recipient SCID mice systemically treated with either high-affinity NK-1 receptor antagonists or neurotoxic doses of capsaicin. In addition, we studied the colitis-inducing effect of NK-1 receptor deleted CD4+CD25, T cells. Results: Treatment with the NK-1 receptor antagonist CAM 4092 reduced the severity of colitis, but colitis was induced by NK-1 receptor-deleted T cells, suggesting that SP in colitis targets the recipient mouse cells and not the colitogenic donor T cells. Capsaicin-induced depletion of nociceptive afferent nerves prior to CD4+CD25, T-cell transfer completely inhibited the development of colitis. Conclusions: Our data demonstrate the importance of an intact enteric afferent nerve system and NK-1 signaling in mucosal inflammation and may suggest new treatment modalities for patients suffering from inflammatory bowel disease. (Inflamm Bowel Dis 2009) [source] | ||||||||||||||||||||||||||||||||||||||||