No abstract available.
Administration, Topical ; Anesthesia, Epidural ; Capsaicin/*administration & dosage ; Diabetic Nephropathies/*drug therapy/etiology ; Humans ; Male ; Middle Aged ; *Nerve Block ; Sensory System Agents/*administration & dosage ; Skin Cream

DCs, like the sensory neurons, express vanilloid receptor 1 (VR1). Here we demonstrate that the VR1 agonists, capsaicin (CP) and resiniferatoxin (RTX), enhance antiviral CTL responses by increasing MHC class I-restricted viral antigen presentation in dendritic cells (DCs). Bone marrow-derived DCs (BM-DCs) were infected with a recombinant vaccinia virus (VV) expressing OVA (VV-OVA), and then treated with CP or RTX. Both CP and RTX increased MHC class I-restricted presentation of virus-encoded endogenous OVA in BM-DCs. Oral administration of CP or RTX significantly increased MHC class I-restricted OVA presentation by splenic and lymph node DCs in VV-OVA-infected mice, as assessed by directly measuring OVA peptide SIINFEKL-Kb complexes on the cell surface and by performing functional assays using OVA-specific CD8 T cells. Accordingly, oral administration of CP or RTX elicited potent OVA-specific CTL activity in VV-OVA-infected mice. The results from this study demonstrate that VR1 agonists enhance anti-viral CTL responses, as well as a neuro-immune connection in anti-viral immune responses.
Administration, Oral ; Animals ; Antigen Presentation* ; Capsaicin* ; Dendritic Cells* ; Lymph Nodes ; Mice ; Ovum ; Sensory Receptor Cells ; T-Lymphocytes ; Vaccinia virus

This study was to investigate the permeability and absorbability of capsaicin cubosome across abdominal skin of the SD rats in vitro. Diffusion of capsaicin cubosome and cream was performed with the modified Franz diffusion cell technique. The capsaicin cubosome showed no enhancement of skin permeation within 24 hours. However, the deposition amounts of capsaicin in the rat skin in the cubosome group was markedly higher than those in the commercial cream group (P < 0.01). Cubosome showed excellent characetristic of skin-targed which could be a good carrier for the local transdermal drug delivery system.
Administration, Cutaneous ; Animals ; Capsaicin ; administration & dosage ; chemistry ; Kinetics ; Male ; Particle Size ; Permeability ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; metabolism ; Skin Absorption

OBJECTIVECapsaicin transfersomes were prepared and its quality specifications were evaluated.

METHODCapsaicin transfersomes were prepared by high shear dispersing machine and evaluated on the entrapment efficiency, drugs release rate and in vitro skin permeation.

RESULTCapsaicin transfersomes is composed of single unilamellar vesicles, with average size of 150.6 nm. Capsaicin entrapment efficiency achieved 96.7% while concentration of lecithin used was 8%. cumulative release amount of capsaicin was in direct proportion to the ethanol concentration in the medium. The in vitro rate cumulative penetration rate of capsaicin was higher in transfersomes than in cream and suspension in rats. Adomen skin cumulative penetration rate in vitro of capsaicin transfersomes in mouse was significantly higher than that from rat and men. In the same way,cumulative penetration rate in vitro of capsaicin transfersomes through abdomen skin epidermal membrance was significantly higher than that with derma and full skin in men.

CONCLUSIONEntrapment efficiency of capsaicin transfersomes reached 96.7%, meeting the criterion of China pharmacopia( > 80%), skin penetration of capsaicin was enhanced by a capsaicin transfersomes preparation and was affected by diverse characters and levels of skin.

Administration, Cutaneous ; Analgesics, Non-Narcotic ; administration & dosage ; pharmacokinetics ; Animals ; Capsaicin ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; methods ; Humans ; In Vitro Techniques ; Male ; Mice ; Particle Size ; Phosphatidylcholines ; administration & dosage ; chemistry ; pharmacology ; Rats ; Skin ; drug effects ; metabolism ; Skin Absorption ; drug effects

PURPOSE: The clinical and urodynamic effects of intravesical capsaicin, a neurotoxic substance causing a reversible suppression of unmyelinated C fiber afferent neuronal activity, were investigated for treatment of detrusor hyperreflexia in patients with spinal cord injury. MATERIALS AND METHODS: Capsaicin solution (2mM) dissolved in 30% alcohol was instilled intravesically in 7 men with detrusor hyperreflexia due to spinal cord injury. Effects on bladder function and subjective symptoms were evaluated before and after intravesical instillation of capsaicin. RESULTS: Bladder function was improved in all but 1 patient. The improvement was expressed as an increase from 108ml to 270ml in maximal bladder capacity and a decrease from 75cmH2O to 44cmH2O in maximal detrusor pressure. Four patients had subjective improvement following treatment and the effects lasted for 4 to 6 weeks. Immediately after capsaicin instillation the ice water test was negative in 2 patients. Autonomic dysreflexia was observed in 4 patients, suprapubic discomfort in 3 patients and gross hematuria in 1 patient. CONCLUSION: Intravesical capsaicin seems to be a promising method for treatment of detrusor hyperreflexia, but the general use of intravesical capsaicin was limited due to side effects.
Administration, Intravesical ; Autonomic Dysreflexia ; Capsaicin* ; Hematuria ; Humans ; Ice ; Male ; Nerve Fibers, Unmyelinated ; Neurons, Afferent ; Reflex, Abnormal* ; Spinal Cord Injuries* ; Urinary Bladder ; Urodynamics ; Water

OBJECTIVE: The aim of this study was to investigate the efficacy of capsaicin, a neurotoxin for C-fiber afferents, applied intravesically in the treatment of neurogenic bladder with detrusor hyperreflexia (DH). METHOD: Six subjects, three women and three men with traumatic spinal cord injury who had neurogenic bladder manifested with DH and urinary incontinence resistant to oral and intravesical anticholinergic instillation treatment were tried with intravesical administration of capsaicin (1 mmol/l 100 ml) for 30 minutes. Single instillation was given in five subjects and two instillations in one. Maximal detrusor pressure and maximal bladder volume were monitored by the portable cystometer. Follow-up monitor of pressure and volume was recorded after 1 week and every 3 weeks afterwards for 21 weeks, with one exception (31 weeks). RESULTS: Average maximal detrusor pressure decreased by 50.8% and average bladder capacity at maximal detrusor pressure increased by 68% in five subjects after single instillation of capsaicin. Clinical benefit from single instillation lasted over 21 weeks and same as the subject with two instillations. Maximal effect on detrusor pressure appears during 6~9 weeks period and bladder capacity during 9~15 weeks period. Although autonomic dysreflexia in 5 of 6 subjects during instillation and macroscopic hematuria in 2 subjects during the 1st two days were noted, they were resolved spontaneously. CONCLUSION: Single and repeated intravesical instillation of capsaicin were safe and effective in the management of neurogenic bladder with DH in traumatic spinal cord injured patients.
Administration, Intravesical ; Autonomic Dysreflexia ; Capsaicin* ; Female ; Follow-Up Studies ; Hematuria ; Humans ; Male ; Reflex, Abnormal ; Spinal Cord ; Spinal Cord Injuries ; Urinary Bladder ; Urinary Bladder, Neurogenic* ; Urinary Incontinence

Visceral afferent nerve fibers containing substance P or calcitonin gene-related peptide (CGRP) are distributed in the bladder wall, and are known to be stimulated by and then desensitized by capsaicin. Recently, there have been some reports on the effectiveness of intravesical capsaicin administration for the treatment of hypersensitive lower urinary tract disorder or neurogenic bladder. In this study, the effects of intravesical capsaicin on the substance P or CGRP immunoreactivities in the spinal dorsal horn were investigated and the mechanism of capsaicin treatment for bladder disorders was revealed. After intravesical administration of capsaicin, the substance P and CGRP immunoreactive areas were measured at the dorsal horn of L4 and S1 spinal cord. Before capsaicin treatment, the substance P immuno- reactive area was 2.61+/-0.78 x 105 mm2 in L4 and 1.66+/-0.49 x 105 mm2 in S1. The substance P immunoreactivity was markedly reduced 1~2 weeks after capsaicin treatment in both L4 and S1 spinal cord. The CGRP immunoreactive area was 1.74+/-0.52 x 105 mm2 in L4 and 1.14+/-0.69 x 105 mm2 in S1, but was not reduced after capsaicin treatment. Therefore, capsaicin administered intravesically desensitizes nerve fibers containing substance P and consequently suppresses pain and voiding reflex.
Administration, Intravesical ; Animals ; Calcitonin Gene-Related Peptide ; Capsaicin* ; Horns* ; Nerve Fibers ; Rats* ; Reflex ; Spinal Cord ; Substance P ; Urinary Bladder ; Urinary Bladder, Neurogenic ; Urinary Tract ; Visceral Afferents

AIMTo prepare capsaicin transfersomes and evaluate them in vitro and in vivo.

METHODSCapsaicin transfersomes were prepared by high shear dispersing machine and evaluated by entrapment efficiency, release rate, in vitro skin permeation and distribution in different tissues in vivo.

RESULTSCapsaicin transfersomes were composed of single unilamellar vesicles with an average diameter of 150.6 nm. Capsaicin entrapment efficiency increased distinctly with increasing of concentration of lecithin and entrapment efficiency is 96.7% while concentration of lecithin to 8%. Cumulative release amount of capsaicin is in direct proportion to the ethanol concentration in the receptor medium. In vitro capsaicin cumulative penetration amount showed higher levels in transfersomes than cream and suspension in rat abdominal skin. Abdominal skin cumulative penetration amount in vitro of capsaicin transfersomes in mouse was significantly higher than that from rat and men. In the same way, abdominal skin epidermal membrane cumulative penetration amount in vitro of capsaicin transfersomes was significantly higher than that from derma and full skin in human abdominal skin. The capsaicin tissue distribution of capsaicin injection by multiple celiac injections in rats is different: bone > plasma > skin > muscle. There is a similar result by multiple thigh topical application of capsaicin transfersomes: bone > skin > plasma > muscle.

CONCLUSIONEntrapment efficiency of capsaicin transfersomes reached the criterion of China Pharmacopoeia (> 80%) and capsaicin skin penetration can be increased by capsaicin transfersomes. It should be noted that the diverse characters and levels of skin may probably affect the permeating capability of capsaicin. Capsaicin tissue distribution in bone and muscle is similar and is different in plasma and skin by multiple injections and topical skin apply.

Administration, Cutaneous ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacokinetics ; Capsaicin ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Humans ; Lecithins ; chemistry ; Male ; Mice ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Skin Absorption ; Sodium Cholate ; chemistry ; Tissue Distribution

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 controls, underwent methacholine bronchial provocation test and capsaicin cough provocation test. Elicited cough number and flow-volume curve was examined after inhalation of capsaicin to evaluate cough sensitivity and EAHR. Thirty-three patients, with postnasal drip, showed normal extrathoracic airway responsiveness, and 27 of them showed normal cough sensitivity to capsaicin. Cough sensitivity was enhanced in 14 patients with cough variant asthma (CVA) who showed bronchial hyperresponsiveness; EAHR to inhaled capsaicin was present in 12 of them. The remaining 30 patients were tentatively diagnosed as idiopathic chronic cough (ICC). Eleven ICC patients showed enhanced cough sensitivity and EAHR to inhaled capsaicin while 19 patients showed normal values. These results indicate that cough sensitivity is closely related with extrathoracic airway responsiveness during capsaicin provocation in some chronic cough patients. EAHR and enhanced cough sensitivity to inhaled capsaicin may be a part of mechanism developing chronic cough.
Administration, Inhalation ; Adult ; Bronchial Hyperreactivity/*etiology/physiopathology ; Bronchial Provocation Tests ; Capsaicin/*administration & dosage ; Case-Control Studies ; Chronic Disease ; Cough/*etiology/physiopathology ; Female ; Humans ; Male ; Methacholine Chloride/diagnostic use ; Middle Aged

OBJECTIVETo assess the inhibitory modulation of blood pressure by stimulation of the deep peroneal nerve (DPN) and to determine the involvement of nociceptive fibers in the modulation.

METHODSAll the animals were divided into six groups (A-F). The rats in groups A and B received no pretreatment. The rats in groups C and D received subcutaneous injection of capsaicin or control vehicle, respectively, near the DPN for 2 days. Those in groups E and F had the DPN exposed to capsaicin or control vehicle, respectively, for 20 min. Subsequently, pressor responses were induced by stimulation of paraventricular nucleus (PVN) either electrically (groups A and C C-F) or chemically via injection of glutamate (group B). After two stable pressor responses (baseline), all groups were subject to 5-min DPN stimulation followed by PVN stimulation for 10 s. Arterial blood pressure, heart rate, and electrocardiogram were recorded. The pressor response was calculated as the difference in the mean arterial pressure (MAP) before and after PVN stimulation, and changes from baseline in pressor response after DPN stimulation were compared between the groups.

RESULTSIncreases of MAP of 22.88±2.18 mm Hg and 20.32±5.25 mm Hg were induced by electrical (group A) or chemical (group B) stimulation of the PVN, respectively. These pressor responses were inhibited by stimulation of the DPN, and the MAP was reduced to 12.00±2.10 mm Hg in group A (n=6, P<0.01) and 7.00±2.85 mm Hg in group B (n=6, P<0.01). Subcutaneous injection of capsaicin (125 mg/kg) near the DPN in group C (n=7) had no effect on the inhibitory effect of DPN stimulation compared with the group D (n=9), and neither did blockade of nociceptive fibers with capsaicin in group E (n=6) compared with group F (n=8).

CONCLUSIONStimulation of the DPN mimicking acupuncture has an inhibitory effect on the pressor response, and the effect is mediated by capsaicin-insensitive afferent fibers in the DPN.

Acupuncture Therapy ; Anesthesia ; Animals ; Blood Pressure ; drug effects ; Capsaicin ; administration & dosage ; pharmacology ; Electric Stimulation ; Injections, Subcutaneous ; Male ; Paraventricular Hypothalamic Nucleus ; cytology ; drug effects ; Peroneal Nerve ; drug effects ; physiology ; Pressoreceptors ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley