The effects of capsaicin upon electrogenic ion transport in rat descending colon

Summary Preparations of rat descending colon mucosa have been used to record changes in short circuit current (SCC) under voltage clamp conditions. When added to the basolateral compartment capsaicin (8-methyl-N-vanillyl-6-nonenamide, 0.1-3 M) caused an initial transient increase in SCC, followed by a more prolonged reduction in SCC, that lasted for 20–30 min.Repeated applications of 3 M capsaicin caused desensitisation of the initial secretory response. The antisecretory effects (i. e. reduction in SCC from the original baseline) remained, although they were significantly reduced. In some preparations described as non-responders, 3 M capsaicin did not elicit a secretory response. No desensitisation of the remaining antisecretory responses was observed in these tissues; in fact these reductions in SCC were consistently larger than those from tissues which responded with a secretory response.Tetrodotoxin (100 nM), hexamethonium (10 M), and yohimbine (50 M) had no significant effect upon either secretory or antisecretory responses. Ruthenium red (10 M) abolished the secretory response to 3 M capsaicin, but had no effect upon the antisecretory responses. Pretreatment of the tissues with 1 M substance P(SP) resulted in significant desensitisation to the peptide and abolished the secretory response to 3 M capsaicin. The antisecretory responses remained, and were significantly larger compared with responses from control tissues. Send offprint requests to H. M. Cox at present address     

Altered neural control of micturition in the aged F344 rat

The purpose of this study was to determine whether micturition reflexes are altered in aged rats. Voiding frequencies and awake cystometrograms (CMGs) were measured in young (3–5 months old) and aged (24 months) F344 male rats. Bladder contractions induced by subcutaneous apomorphine and intravesical capsaicin stimulation were measured using awake CMGs. Urodynamic parameters were compared. Aged rats voided less frequently (4.1 vs 6.9 times/18 h, P=0.006), with a higher volume per void (1.1 vs 0.7 ml, P=0.02) and had a higher micturitional threshold pressure (8.7 vs 4.6 mmHg, P=0.0001) than the young rats. Apomorphine induced a higher frequency of bladder contractions in aged animals compared to young animals (5.5 vs 3.1 contractions/min, P=0.03). Intravesical capsaicin caused a lower pressure bladder response in the aged rats (38.5 vs 70.6 mmHg, P=0.01) compared to the young rats. Bladder afferents and central micturition pathways may be altered in aged rats. Impaired bladder contractility in the elderly may be exacerbated by reduced sensory input, whereas the propensity for detrusor instability could result from altered central processing. This study demonstrated the utility of the F344 animal model to study micturitional changes resulting from aging. Received: 14 April 2000 / Accepted: 4 July 2000     

The effect of neonatal capsaicin on the c-Fos-like immunoreactivity induced in subnucleus oralis neurons by noxious intraoral stimulation

The noxious stimulus-dependent induction of c-Fos-like immunoreactivity (Fos-LI) in neurons in the subnucleus oralis and the medullary dorsal horn (MDH) was significantly suppressed by the selective destruction of unmyelinated primary neurons. The induction of Fos-LI by topical capsaicin application to the lingual mucosal stimulation was almost completely suppressed by neonatal capsaicin treatment. Fos-LI induction by the tooth pulp stimulation and by formalin injection to the lingual mucosa were only partially reduced. These results provide an evidence that the noxious signals from the intraoral structures are transmitted by both unmyelinated and myelinated nociceptors to the subnucleus oralis as well as the MDH.     

HPLC法测定辣椒风湿膏中辣椒素的含量

目的:建立辣椒风湿膏中辣椒素的含量测定方法.方法:选用C18柱,稀磷酸(PH=3.1～3.5)溶液-乙腈(50:50)为流动相,检测波长207nm.结果:此方法线性关系良好,平均加样回收率为98.1%,RSD为0.84%(n=5).结论:方法简便,结果准确,灵敏度高,重复性好,可用于辣椒风湿膏的质量控制.     

辣椒素对胃动力的影响及其机制

辣椒素(capsaicin,CAP)药理作用广泛,其对胃动力的影响已引起消化学者的关注.多数研究认为小剂量的CAP可促进胃动力,一定剂量范围的CAP可调节胃动力,而大剂量CAP对胃动力可能有抑制作用.CAP对胃动力的作用机制可能与CAP受体(vanilloid receptor subtype l,VRl)、P物质(SP)、乙酰胆碱、神经激肽A、生长激素释放肽和钙离子等有关.CAP可能成为一种有前景的胃动力新药.     

Reflux-related symptoms reflect poor asthma control and the presence of airway neuronal dysfunction

BackgroundGastroesophageal reflux may be associated with the worsening of asthma by increasing cough reflex sensitivity. Hull Airway Reflux Questionnaire (HARQ) consists of 14 prevalent reflux-related symptoms. It may be useful in predicting the presence of cough reflex hypersensitivity in asthma.MethodsFrom August 2018 to July 2020, 266 asthmatic patients completed the HARQ. They underwent blood analysis, spirometry, fraction of exhaled nitric oxide (FeNO) measurement, and the capsaicin cough challenge test. Patients were considered to have reflux-related symptoms if their HARQ scores were 13 points or higher. We evaluated the association between reflux-related symptoms and clinical asthma outcomes. Finally, we performed a multivariate analysis to determine the clinical significance of the HARQ for asthma. This study was registered in the University Hospital Medical Information Network (UMIN000040732).ResultsThe mean HARQ scores were 13.1 (standard deviation 12.0). Patients in the high HARQ scores group (HARQ ≥13, n = 105) showed a lower prevalence of atopic predisposition, lower levels of FeNO, heightened capsaicin cough reflex sensitivity, poorer asthma control, and more frequent admissions due to asthma than those in the low HARQ groups (all p values < 0.05). The HARQ was useful in selecting patients with poor controlled asthma and those with severe cough when the cut-off value was set at 13. Multivariate analysis revealed that heightened capsaicin cough reflex sensitivity affected reflux-related symptoms, as well as lower levels of FeNO and younger age.ConclusionsHigher HARQ scores (≥13) may be useful in predicting not only poor asthma condition but also the presence of airway neuronal dysfunction in patients with asthma to some extent.     

The role of CGRP and afferent nerves in the modulation of pancreatic enzyme secretion in the rat

Summary Conclusion Stimulation of pancreatic sensory nerves by capsaicin produced secretory effects probably caused, at least in part, by the release of CGRP. Background In the pancreas calcitonin gene-related peptide (CGRP) has been localized in the sensory nerves, but its physiological role is unknown. This study was undertaken to compare the changes of pancreatic enzyme secretion produced by CGRP and by stimulation or destruction of sensory nerves. Methods To stimulate sensory nerves, low doses of capsaicin (0.25–0.5 mg/kg) were given intraduodenally to the conscious rats with chronic pancreatic fistula. To inactivate sensory nerves high doses of capsaicin (100 mg/kg) were given subcutaneously 10 d before tests. For the in vitro experiments pancreatic slices and isolated pancreatic acini were prepared from intact and capsaicin-denervated rats. Results In conscious rats, CGRP given subcutaneously (5–10 μg/kg) and low doses of capsaicin given intraduodenally reduced basal pancreatic secretion. In isolated pancreatic acini, CGRP (10⁻¹⁰–10⁻⁶ M), but not capsaicin, increased basal or secretagog-stimulated amylase release. In pancreatic slices (containing nerve fibers) capsaicin (10⁻¹⁰–10⁻⁶ M) increased enzyme secretion, and this secretion was abolished by previous inactivation of sensory nerves by this neurotoxin. Capsaicin deactivation did not affect the secretory response of pancreatic acini to CGRP, cerulein, or urecholine. Sensory denervation by capsaicin did not change basal protein secretion, but reduced that produced by feeding or diversion of pancreatic juice to the exterior during first 2 h of the tests.     

辣椒素对脂多糖诱导血管内皮细胞活化的影响及机制

 目的:探讨辣椒素对脂多糖（LPS）刺激后小鼠主动脉内皮细胞活化的影响,并探讨其可能机制。方法:（1）体外分离培养小鼠主动脉内皮细胞,免疫荧光鉴定内皮细胞特异性标志。（2）以100 μg/L LPS作用于血管内皮细胞后,以不同浓度的辣椒素（50 μmol/L、100 μmol/L和200 μmol/L）进行干预,分别于12、24和48 h收集主动脉血管内皮细胞及细胞上清液。采用ELISA法检测各组细胞上清液中的可溶性细胞间黏附分子 1（sICAM-1）、可溶性血管细胞黏附分子 1（sVCAM-1）和可溶性P-选择素(sP-selectin)水平,Western blotting法检测各组主动脉血管内皮细胞核内NF-κB p65水平和胞浆p-IκBα、IκBα水平。结果:与对照组相比,LPS组细胞上清液中sP-selectin、sICAM-1和sVCAM-1含量显著升高（P<0.05）, LPS能够时间依赖性上调sICAM-1和sVCAM-1的含量。与同时点的LPS组相比,辣椒素能够剂量依赖性下调sP-selectin、sICAM-1和sVCAM-1水平。与对照组相比,LPS作用24 h后, 细胞核内NF-κB p65和胞浆p-IκBα蛋白水平显著升高（P<0.05）,胞浆IκBα蛋白水平显著降低（P<0.05）。与同时点LPS组相比,辣椒素能够剂量依赖性下调细胞核内NF-κB p65和胞浆p-IκBα蛋白的水平（P<0.05）,剂量依赖性上调胞浆IκBα蛋白水平（P<0.05）。结论: 辣椒素能够显著抑制LPS作用后血管内皮细胞活化水平,该效应可能是通过下调IκBα降解和NF-κB p65胞核内转位而实现的。     

Laser Doppler imaging in the detection of peripheral neuropathy

Small fiber neuropathy is common in a number of systemic diseases and is often challenging to diagnose. Laser Doppler imaging (LDI) is a test of small fiber neurovascular function that can quantify the integrity of the vasomotor C-fiber mediated axon-reflex, but no standardized method of analysis exists. We developed a novel LDI analysis technique and tested it in a human model of small fiber neuropathy. Eighteen healthy subjects (age 24 ± 3 years) underwent LDI testing to assess the axon-mediated flare area in response to 10% acetylcholine iontophoresis. LDI measurements were taken before and longitudinally after a 48-hour application of 0.1% capsaicin (to cause a transient small fiber neuropathy) on the skin of the thigh; placebo cream was placed on the contralateral thigh as a control. We compared our new LDI image analysis technique to two previously published methods. The new LDI analysis technique was the only method to show a consistent difference in axon-reflex area between capsaicin treated and placebo treated skin on all testing days (p < 0.05) with maximum attenuation of the flare area immediately post-application (438 ± 298 mm² vs. 824 ± 375 mm², p < 0.05). In conclusion, this study demonstrates that our novel flare area method for LDI analysis can detect neurovascular dysfunction in a model of small fiber neuropathy, is an improvement over existing methods, and may supplement clinical assessment of small fiber neuropathy.