Capsaicin

Psychophysical methods were used to assess changes in the intensity of irritant sensations elicited by repeated application of capsaicin and nicotine delivered unilaterally to the tongue of human subjects. Whereas capsaicin (0.5 or 3 p.p.m.; repeated at 1 min intervals over 10 min) evoked progressively stronger ratings of irritation (sensitization), there was a significant decrement in irritation ratings (desensitization) to repeated application of nicotine (0.1%). A two-alternative forced-choice (2-AFC) procedure was additionally used to test for self-and cross-desensitization. After the subjects had received either repeated capsaicin or nicotine, a rest period ensued followed by the 2-AFC procedure. Either capsaicin or nicotine was delivered bilaterally to the tongue and subjects were asked to choose which side yielded a stronger sensation. Following capsaicin pretreatment, subjects reported that capsaicin evoked a stronger sensation on the previously untreated side (capsaicin self-desensitization). Similar self-desensitization was observed with nicotine. Furthermore, nicotine evoked a significantly weaker sensation on the side of the tongue pretreated with capsaicin (cross-desensitization). In contrast, capsaicin did not consistently evoke a weaker sensation on the nicotine-pretreated side, indicating an absence of cross-desensitization. These results are discussed in terms of physiological mechanisms that might underlie the contrasting sensory effects of nicotine versus capsaicin. Chem.

Pungency in Capsicum fruits is due to the accumulation of the alkaloid capsaicin and its analogs. The biosynthesis of capsaicin is restricted to the genus Capsicum and results from the acylation of an aromatic moiety, vanillylamine, by a branched-chain fatty acid. Many of the enzymes involved in capsaicin biosynthesis are not well characterized and the regulation of the pathway is not fully understood. Based on the current pathway model, candidate genes were identified in public databases and the literature, and genetically mapped. A published EST co-localized with the Pun1 locus which is required for the presence of capsaicinoids. This gene, AT3, has been isolated and its nucleotide sequence has been determined in an array of genotypes within the genus. AT3 showed significant similarity to acyltransferases in the BAHD superfamily. The recessive allele at this locus contains a deletion spanning the promoter and first exon of the predicted coding region in every non-pungent accession tested. Transcript and protein expression of AT3 was tissue-specific and developmentally regulated. Virus-induced gene silencing of AT3 resulted in a decrease in the accumulation of capsaicinoids, a phenotype consistent with pun1. In conclusion, gene mapping, allele sequence data, expression profile and silencing analysis collectively indicate that the Pun1 locus in pepper encodes a putative acyltransferase, and the pun1 allele, used in pepper breeding for nearly 50 000 years, results from a large deletion at this locus.

Spice bioactive compounds, capsaicin and curcumin, were both individually and in combination examined for antilithogenic potential during experimental induction of cholesterol gallstones in mice. Cholesterol gallstones were induced by feeding mice a high-cholesterol (0.5%) diet for 10 weeks. Groups of mice were maintained on a lithogenic diet that was supplemented with 0.015% capsaicin/0.2% curcumin/0.015% capsaicin + 0.2% curcumin. The lithogenic diet that contained capsaicin, curcumin, or their combination reduced the incidence of cholesterol gallstones by 50%, 66%, and 56%, respectively, compared with lithogenic control. This was accompanied by reduced biliary cholesterol and a marginal increase in phospholipid in these spice-fed groups. Increased cholesterol saturation index and cholesterol : phospholipid ratio in the bile caused by the lithogenic diet was countered by the dietary spice compounds. The antilithogenic influence of spice compounds was attributable to the cholesterol-lowering effect of these dietary spices in blood and liver, as well as a moderate increase in phospholipids. Decreased activities of hepatic glutathione reductase and glutathione-S-transferase caused by the lithogenic diet were countered by the combination of capsaicin and curcumin. The increased lipid peroxidation and the decreased concentration of ascorbic acid in the liver that was caused by the lithogenic diet was countered by the dietary spice compounds, individually or in combination. Thus, while the capsaicin and curcumin combination did not have an additive influence in reducing the incidence of cholesterol gallstones in mice, their combination nevertheless was more beneficial in enhancing the activity of hepatic antioxidant enzyme ─ glutathione reductase in the lithogenic situation. The antioxidant effects of dietary spice compounds are consistent with the observed reduction in cholesterol gallstones formed under lithogenic condition.

Isolation of carrot fruit (Daucus carrota L., cultivar ''Chanteney") essential oil by supercritical carbon dioxide was investigated from the pretreatment of herbaceous matrix and extraction conditions to the chemical composition of obtained extract and its antimicrobial activity. The qualitative and quantitative analyses of the supercritical extract, as well as of the essential oil obtained by hydrodistillation, were done by GC/FID and GC/MS methods. Antimicrobial properties of both samples were investigated against ten species of microorganisms. Experimental results showed that the particle size had no influence on the extraction process. The highest yield was obtained at 40°C and 10 MPa. The main component of the supercritical extract, as well as of the essential oil was carotol. The supercritical extract was characterized by the presence of heavier molecular weight compounds, while some lighter compounds, e.g. pinenes, were not detected. The supercritical extract and the essential oil were the most effective against Gram-positive bacteria.

Substance P and its receptor (NK1) are thought to play an important role in pain and hyperalgesia. Here we have further examined this role by comparing the behavioural responses to intradermal capsaicin of mutant mice with a disruption of the NK1 receptor (NK1 KO) and wildtype (WT) mice. We have also evaluated the contribution of peripheral NK1 receptors to capsaicin-evoked behaviour by selective blockade of peripheral NK1 receptors in WT mice using a non-brain penetrant NK1 receptor antagonist. Injection of 6 mg capsaicin into the heel evoked paw licking with the same latency in WT and KO mice, but a signi®cantly longer duration in WT mice. A higher dose (30 mg) evoked a similar duration of licking in both groups. There were no differences in mechanical sensitivity tested with von Frey hairs between WT and KO mice before capsaicin. Both capsaicin doses resulted in pronounced increases in responses to von Frey hairs (hyperalgesia) and novel responses to cotton wisps (allodynia) applied to the digits of the injected paw in WT mice, but no signi®cant changes from baseline in KO mice. Selective blockade of peripheral NK1 receptors in WT mice resulted in a complete inhibition of capsaicin-evoked plasma extravasation, but the mechanical hyperalgesia induced by 30 mg capsaicin intraplantar was still signi®cantly greater than that seen in KO mice. We conclude that the response to intradermal capsaicin is still present but abbreviated in mice lacking NK1 receptors, such that secondary hyperalgesia is not observed even after a high dose. Further, the lack of secondary hyperalgesia in NK1 KO mice is largely due to the loss of central rather than peripheral NK1 receptors. The phenotype of the NK1 KO mice is consistent with a loss of function of mechanicallyinsensitive nociceptors, and thus we propose that substance P may be expressed by this group of primary sensory neurones and required for their function.

Itch sensation can be inhibited by simultaneously applied cutaneous pain at the same skin site via a central mechanism. Deep muscle pain is often associated with sensory changes in the corresponding dermatome. We investigated whether experimentally induced muscle pain has any influence on histamine-induced itch and vice versa in a double blind placebo-controlled study. Experiments were performed in 18 healthy subjects. In nine individuals control iontophoresis of histamine into the forearm produced a distinct itch sensation. Another nine individuals participated in an additional experiment in which histamine and saline were iontophoresed on the forearm in a randomized double-blinded two-way crossover design after intramuscular injection of capsaicin into the ipsilateral brachioradial muscle. Capsaicin-induced muscle pain reduced itch sensation significantly. In contrast, capsaicininduced muscle pain increased significantly after cutaneous histamine application compared to muscle pain after iontophoresis of saline (placebo). These novel data indicate that muscle pain inhibits itch and histamine increases muscle pain. A bi-directional interaction between cutaneous histamine-sensitive afferents and nociceptive muscle afferents via central mechanisms is suggested.

AbstractÐA series of N-(3-acyloxy-2-benzylpropyl)-N H -(4-hydroxy-3-methoxybenzyl)thiourea derivatives were investigated as vanilloid receptor ligands in an eort to discover a novel class of analgesics. The proposed pharmacophore model of resiniferatoxin, which includes the C 20 -homovanillic moiety, the C 3 -carbonyl and the orthoester phenyl ring as key pharmacophoric groups, was utilized as a guide for drug design. The compounds were synthesized after several steps from diethylmalonate and evaluated in vitro in a receptor binding assay and in a capsaicin-activated channel assay. Additional evaluation of analgesic activity, anti-in¯ammatory activity and pungency was conducted in animal models by the writhing test, the ear edema assay, and the eye-wiping test, respectively. Among the new compounds, 23 and 28 were found to be the most potent receptor agonists of the series with K i values of 19 nM and 11 nM, respectively. Their strong in vitro potencies were also re¯ected by an excellent analgesic pro®le in animal tests with ED 50 values of 0.5 mg/kg for 23 and 1.0 mg/kg for 28. Relative to capsaicin these compounds appear to be ca. 600 and 300 times more potent. Both 23 and 28 were found to be less pungent than capsaicin based on the eye-wiping test. However, the compounds did not show sig-ni®cant anti-in¯ammatory activity. A molecular modeling study comparing the energy-minimized structures of resiniferatoxin and 35 demonstrated a good correlation in the spatial disposition of the corresponding key pharmacophores. The thioureas described in this investigation, which were designed as simpli®ed resiniferatoxin surrogates, represent a novel class of potent vanilloid receptor agonists endowed with potent analgesic activity and reduced pungency. #

Capsaicin is the active ingredient of chili peppers and gives them the characteristic pungent flavor. Understanding the actions of capsaicin led to the discovery of its receptor, transient receptor potential vanilloid subfamily member 1 (TRPV1). This receptor is found on key sensory afferents, and so the use of capsaicin to selectively activate pain afferents has been studied in animal and human models for various indications. Capsaicin is unique among naturally occurring irritant compounds because the initial neuronal excitation evoked by it is followed by a long-lasting refractory period, during which the previously excited neurons are no longer responsive to a broad range of stimuli. This process known as defunctionalisation has been exploited for therapeutic use of capsaicin in various painful conditions. We reviewed different studies on mechanisms of action of capsaicin and its utility in different clinical conditions. A beneficial role of capsaicin has been reported in obesity, cardiovascular and gastrointestinal conditions, various cancers, neurogenic bladder, and dermatologic conditions. Various theories have been put forth to explain these effects. Interestingly many of these pharmacological actions are TRPV1 independent. This review is aimed at providing an overview of these mechanisms and to also present literature which contradicts the proposed beneficial effects of capsaicin. Most of the literature comes from animal studies and since many of these mechanisms are poorly understood, more investigation is required in human subjects.

Capsaicin is a selective transient receptor potential vanilloid 1 (TRPV1) ion channel agonist and has been demonstrated to reduce nerve conduction of nociceptive C fibers in the trigeminal nerve without affecting conduction in Aδ fibers. This chapter reviews the classification of chronic rhinitis subtypes, the prevalence and epidemiology of nonallergic rhinitis (NAR), postulated pathophysiology and mechanisms of NAR including the role of transient receptor potential (TRP) ion channels and discusses the potential therapeutic benefits of capsaicin in the treatment of chronic rhinitis subtypes, specifically NAR. Evidence supports that hypersensitivity of TRP ion channels on sensory afferent neurons innervating nasal mucosa is responsible for inducing NAR symptoms. These symptoms, characterized as excessive nasal glandular secretion, nasal congestion, and headache, are mediated through neuropeptide release during axonal and parasympathetic reflexes which are initiated by a spectrum of nonspecific irritants that activate TRP channels. Rational approaches to treat the pathophysiology of NAR would be to develop therapies with selective TRPV1 agonist activity like capsaicin that target desensitization of TRP ion channels on sensory afferent nerves.

Objectives. To critically evaluate the evidence regarding complementary and alternative medicine (CAM) taken orally or applied topically (excluding glucosamine and chondroitin) in the treatment of OA. Methods. Randomized clinical trials of OA using CAMs, in comparison with other treatments or placebo, published in English up to January 2009, were eligible for inclusion. They were identified using systematic searches of bibliographic databases and manual searching of reference lists. Information was extracted on outcomes, and statistical significance, in comparison with alternative treatment of placebo, and side effects were reported. The methodological quality of the primary studies was determined. Results. The present review found consistent evidence that capsaicin gel and S-adenosyl methionine were effective in the management of OA. There was also some consistency to the evidence that Indian Frankincense, methylsulphonylmethane and rose hip may be effective. For other substances with promising evidence, the evidence base was either insufficiently large or the evidence base was inconsistent. Most of the CAM compounds studied were free of major adverse effects. Conclusion. The major limitation in reviewing the evidence is the paucity of randomized controlled trials in the area: widening the evidence base, particularly for those compounds for which there is promising evidence, should be a priority for both researchers and funders.

Cashew nut-shell liquid and the contained anacardic acids (AAs) have been shown to possess antioxidant, lipoxygenase inhibitory, anti-Helicobacter pylori and antitumor properties. Despite these known effects, hitherto there were no published reports on their likely gastroprotective effects. The present study was designed to verify whether AAs afford gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2 mL of ethanol (96%). Mice in groups were pretreated orally with AAs (10, 30 and 100 mg/kg), misoprostol (50 g/kg), or vehicle (2% Tween 80 in saline, 10 mL/kg), 45 min before ethanol administration. They were sacrificed 30 min later, the stomachs excised, and the mucosal lesion area (mm 2 ) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide and ATP-sensitive potassium channels were analysed. Treatments effects on ethanol-associated oxidative stress markers GSH, MDA, catalase, SOD, and total nitrate/nitrite levels as an index of NO were measured in gastric tissue. Besides, the effects of AAs on gastric secretory volume and total acidity were analysed in 4-h pylorus-ligated rat. AAs afforded a dose-related gastroprotection against the ethanol damage and further prevented the ethanol-induced changes in the levels of GSH, MDA, catalase, SOD and nitrate/nitrite. However, they failed to modify the gastric secretion or the total acidity. It was observed that the gastroprotection by AAs was greatly reduced in animals pretreated with capsazepine, indomethacin, l-NAME or glibenclamide. These results suggest that AAs afford gastroprotection principally through an antioxidant mechanism. Other complementary mechanisms include the activation of capsaicin-sensitive gastric afferents, stimulation of endogenous prostaglandins and nitric oxide, and opening of K + ATP channels. These combined effects are likely to be accompanied by an increase in gastric microcirculation.

Low-irritative oral preparation Poly(ε-caprolactone) Weight-loss strategy Capsaicinoids show several pharmacological effects including weight loss. However, their pungency limits the long-term use through the gastrointestinal tract. In that sense, the goal of this study was to prepare capsaicinoids-loaded poly(ε-caprolactone) microparticles as an oral carrier in order to improve their gastric tolerability and to make feasible the long-term treatment of obesity. Formulations containing 3, 5 and 10% capsaicinoids were successfully obtained by simple emulsion/solvent evaporation method. Values of encapsulation efficiency above 90% were achieved. Microparticles showed spherical shape and smooth surface. The particle size was suitable for oral use in order to provide an extended release through the gastrointestinal tract. No chemical bond was observed between drug and polymer. Microencapsulation led to drug amorphization. Formulations prolonged the release of capsaicinoids without changing the release kinetic (biexponential model). Microencapsulation increased the gastric tolerability of capsaicinoids because it prevented inflammatory processes in the stomach of rats. Microparticles containing 5% capsaicinoids demonstrated a statistically significant reduction of Lee index, mesenteric and retroperitoneal fat pads of rats with obesity induced by hypothalamic lesion using monosodium L-glutamate. In summary, capsaicinoids-loaded poly(ε-caprolactone) microparticles are lowirritative oral controlled-release carriers for a long-term use in obesity.

Isolation of carrot fruit (Daucus carrota L., cultivar ''Chanteney") essential oil by supercritical carbon dioxide was investigated from the pretreatment of herbaceous matrix and extraction conditions to the chemical composition of obtained extract and its antimicrobial activity. The qualitative and quantitative analyses of the supercritical extract, as well as of the essential oil obtained by hydrodistillation, were done by GC/FID and GC/MS methods. Antimicrobial properties of both samples were investigated against ten species of microorganisms. Experimental results showed that the particle size had no influence on the extraction process. The highest yield was obtained at 40°C and 10 MPa. The main component of the supercritical extract, as well as of the essential oil was carotol. The supercritical extract was characterized by the presence of heavier molecular weight compounds, while some lighter compounds, e.g. pinenes, were not detected. The supercritical extract and the essential oil were the most effective against Gram-positive bacteria.

In the eye of rats the long-lasting specific desensitization induced by local or systemic capsaicin treatment is characterized by three phases: 1. complete insensitivity, 2. decreased sensitivity and a tendency to rapid adaptation, 3. normal initial sensitivity with a tendency to rapid adaptation to chemical pain stimuli. A low density of microvesicles and swollen mitochondria were found after local capsaicin treatment in certain nerve endings of the cornea of rats, but no signs of axonal degeneration or alteration in fine structure of non-neural elements were seen. Systemic capsaicin desensitization induced selective mitochondrial swelling in B type of neurons of the trigeminal ganglion which was demonstrable even 60 days after the pretreatment. Actinomycin-D, 8-azaguanine, 6-azauracil, aminopterin, mannomustin or cycloheximide in high doses did not alter the desensitizing effect of systemic capsaicin treatment. However, pretreatment of rats with colchicine or vinblastine prolonged the desensitizing effect of local capsaicin application, probably by inhibiting the axonal flow. It is concluded that capsaicin is a specific sensory neuron blocking agent having a practically irreversible effect in rats and guineapigs.

The generation of transgenic mice that lack or overexpress genes relevant to pain is becoming increasing common. However, only one visceral pain model, the writhing test, is widely used in mice. Here we describe a novel model, chemical stimulation of the colon, which we have developed in mice. Mice of either sex were injected i.v. with 30 mg/kg Evan's Blue for subsequent determination of plasma extravasation. For behavioural testing, they were placed on a raised grid and 50 ml of saline, mustard oil (0.25±2.5%) or capsaicin (0.03±0.3%) was administered by inserting a ®ne cannula into the colon via the anus. Visceral pain-related behaviours (licking abdomen, stretching, contractions of abdomen etc) were counted for 20 min. Before intracolonic administration, and 20 min after, the frequency of withdrawal responses to the application of von Frey probes to the abdomen was tested. The colon was removed post-mortem and the Evan's Blue content measured. Mustard oil and capsaicin administration evoked dose-dependent visceral pain behaviours, referred hyperalgesia (signi®cant increase in responses to von Frey hairs) and colon plasma extravasation. The peak behavioural responses were evoked by 0.1% capsaicin and by 1% mustard oil respectively. The nociceptive behavioural responses were dose-dependently reversed by morphine (ED50 1.9^1 mg/ kg s.c.). We conclude that this model represents a useful tool both for phenotyping mutant mice and for classical pharmacology since information on visceral pain, referred hyperalgesia and colon in¯ammation can all obtained from the same animal. q (J.M.A. Laird).

A simple method for the analysis of capsaicin and dihydrocapsaicin in peppers and pepper sauces by solid phase microextraction–gas chromatography–mass spectrometry has been developed. A novel device was designed for direct extraction solid phase microextraction in order to avoid damage to the fiber. The analysis was performed without derivatization for the gas chromatography–mass spectrometry analysis. Selection fiber, extraction temperature, extraction time and pH, were optimized. The method was linear in the range 0.109–1.323 μg/mL for capsaicin and 0.107–1.713 μg/mL for dihydrocapsaicin with correlation coefficient up to r = 0.9970 for both capsaicinoids. The precision of the method was less than 10%. The method was applied to the analysis of 11 varieties of peppers and four pepper sauces. A broad range of capsaicin (55.0–25 459 μg/g) and dihydrocapsaicin (93–1 130 μg/g) was found in the pepper and pepper sauces samples (4.3–717.3 and 1.0–134.8 μg/g), respectively.

Constipation is a major source of distress for patients with cancer, significantly affecting quality of life. It can be secondary to disease sequelae, side effects of treatment, or preexisting conditions. It often is unrecognized, underassessed, and ineffectively managed. Nurses play a key role in the prevention and management of constipation and need evidence-based interventions. This article summarizes the existing research evidence for constipation interventions and identifies gaps. Many of the strategies have been evaluated in nononcology populations; researchers should evaluate their effectiveness in oncology populations. F Many expert opinions are available on the prevention and management of constipation in patients with cancer, but no high-level evidence supports the recommendations.

Capsaicinoids, salicylic acid, methyl and ethyl salicylate, glycol monosalicylate, camphor and l-menthol are widely used in topical formulations to relieve local pain. For each separate compound or simple mixtures, quantitative analysis methods are reported. However, for a mixture containing all above mentioned active compounds, no assay methods were found. Due to the differing physicochemical characteristics, two methods were developed and optimized simultaneously. The non-volatile capsaicinoids, salicylic acid and glycol monosalicylate were analyzed with liquid chromatography following liquid-liquid extraction, whereas the volatile compounds were analyzed with static headspace-gas chromatography. For the latter method, liquid paraffin was selected as compatible dilution solvent. The optimized methods were validated in terms of specificity, linearity, accuracy and precision in a range of 80% to 120% of the expected concentrations. For both methods, peaks were well separated without interference of other compounds. Linear relationships were demonstrated with R 2 values higher than 0.996 for all compounds. Accuracy was assessed by performing replicate recovery experiments with spiked blank samples. Mean recovery values were all between 98% and 102%. Precision was checked at three levels: system repeatability, method precision and intermediate precision. Both methods were found to be acceptably precise at all three levels. Finally, the method was successfully applied to the analysis of some real samples (cutaneous sticks).

T his chapter is a comprehensive review of the health promoting phytochemicals commonly found in our daily food. These include carotenoids, phenolics, phytoestrogenes, polyunsaturated fatty acids, conjugated linoleic acids, tocols, allicin, glucosinolates, limonene and capsaicinoids. The review encompasses the main food sources of these chemicals in the diet, the possible mechanisms of their activity, evidence for potential health promoting activity and possible harmful effects. The newly emerged interest in these phytochemicals in animal nutrition as substitutes for synthetic antibiotic growth promoters has also been addressed.

. When the psychosis-- nonpsychosis grouping was considered, patients with psychosis responded dramatically better to ECT in all assessments, whereas those without psychosis responded similarly to both treatments. Conclusions: Overall ECT was a more potent treatment for patients with MDD, this being particularly evident in patients with MDD and psychosis; however, in patients with MDD without psychosis the effects of rTMS were similar to those of ECT. The results we report are encouraging and support an important role for rTMS in the treatment of severe MDD; however, additional blinded studies are needed to precisely define this role. Biol Psychiatry 2000;47:314--324 2000 Society of Biological Psychiatry Key Words: TMS, ECT, MDD, transcranial magnetic stimulation, electroconvulsive therapy Introduction T ranscranial magnetic stimulation (TMS) was introduced by Barker et al in 1985 as a new method for noninvas

Pancreatic cancer is fourth leading cause of cancer-related deaths in the United States of America. In spite of recent advances in the current therapeutic modalities such as surgery, radiation and chemotherapy patients, the average five year survival rate remains still less than 5%. Recently, compounds from natural sources receive ample of attention as anti-cancer agents. Many epidemiological studies published over the past few decades provide a strong correlation between consumption of vegetables, fruits or plant derived products and reduced incidence of cancer. The present review focuses on the potential antitumor effects of various natural products.

Liquid chromatography-mass spectrometry was used to identify and quantify the predominant capsaicinoid analogues in extracts of fresh peppers, in oleoresin capsicum, and pepper sprays. The concentration of capsaicinoids in fresh peppers was variable. Variability was dependent upon the relative pungency of the pepper type and geographical origin of the pepper. Nonivamide was conclusively identified in the extracts of fresh peppers, despite numerous reports that nonivamide was not a natural product. In the oleoresin capsicum samples, the pungency was proportional to the total concentration of capsaicinoids and was related by a factor of approximately 15,000 Scoville Heat Units (SHU)/microg of total capsaicinoids. The principle analogues detected in oleoresin capsicum were capsaicin and dihydrocapsaicin and appeared to be the analogues primarily responsible for the pungency of the sample. The analysis of selected samples of commercially available pepper spray products also demonstrated...

, VR-339, AKC-89/38, DC-16 and Punjab Lal) of chilli were crossed to derive 25 F 1 hybrids. The 35 genotypes (10 parents and 25 F 1 hybrids) were evaluated for yield and quality (capsaicin and oleoresin) traits. Highly significant correlation was observed between fruit yield per plant and average fruit weight (g). The direct and indirect effect on yield revealed that the maximum direct effect was exhibited by average fruit weight followed by number of fruits per plant via yield per plant. The crosses Pusa Jwala × VR-339, Pusa Jwala × DC-16 and Pant C-1 × VR-339 exhibited higher level of heterobeltiosis for most of the traits. The higher specific combing ability (SCA) for yield was obtained in crosses Kashi Sinduri × Punjab Lal followed by Pant C-1 × VR-339 and Pusa Jwala × VR-339. Among the hybrids, Pusa Jwala × VR-339 had higher yield as well as capsaicin content, moreover, Kashi Sinduri × AKC-89/38 exhibited highest oleoresin content. These best hybrids (Pusa Jwala × VR-339, Kashi Sinduri × Punjab Lal and Pant C-1 × VR-339) might be utilized for further chilli improvement programme.

Capsaicin is a selective transient receptor potential vanilloid 1 (TRPV1) ion channel agonist and has been demonstrated to reduce nerve conduction of nociceptive C fibers in the trigeminal nerve without affecting conduction in Aδ fibers. This chapter reviews the classification of chronic rhinitis subtypes, the prevalence and epidemiology of nonallergic rhinitis (NAR), postulated pathophysiology and mechanisms of NAR including the role of transient receptor potential (TRP) ion channels and discusses the potential therapeutic benefits of capsaicin in the treatment of chronic rhinitis subtypes, specifically NAR. Evidence supports that hypersensitivity of TRP ion channels on sensory afferent neurons innervating nasal mucosa is responsible for inducing NAR symptoms. These symptoms, characterized as excessive nasal glandular secretion, nasal congestion, and headache, are mediated through neuropeptide release during axonal and parasympathetic reflexes which are initiated by a spectrum of nonspecific irritants that activate TRP channels. Rational approaches to treat the pathophysiology of NAR would be to develop therapies with selective TRPV1 agonist activity like capsaicin that target desensitization of TRP ion channels on sensory afferent nerves.

A reversed-phase liquid chromatography (LC) method has been developed, optimised and validated for the separation and quantitation of capsaicin (CP) and dihydrocapsaicin (DHCP) in a topical cream formulation. Sample preparation involves liquid Á/liquid extraction prior to LC analysis. The method uses a Hypersil C 18 BDS, 5 mm, 250)/ 4.6 mm I.D. column maintained at 35 8C. The mobile phase comprises methanol, water, acetonitrile (ACN) and acetic acid (47:42:10:1, v/v/v/v) at a flow rate of 1.0 ml/min. Robustness was evaluated by performing a central composite facecentred design (CCF) experiment. The method shows good selectivity, linearity, sensitivity and repeatability. The conditions allow the separation and quantitation of CP and DHCP without interference from the other substances contained in the cream. #

A reverse-phase high-performance liquid chromatography method was developed to quantify capsaicin (trans-8-methyl-N-vanillyl-6nonenamid), dihydrocapsaicin (8-methyl-N-vanillylnonanamide) and the main capsaicinoid contents of Capsicum extracts. The chromatographic separation was carried out on a C8 column using isocratic mobile phase consisting of 40% (v/v) acetonitrile and 60% (v/v) orthophosphoric acid solution with flow rate of 1.5 mL/min. The concentration of the eluting compounds was monitored by a diode-array detector at wavelength of 281 nm. The method was evaluated for number of validation characteristics (selectivity, accuracy (confidence intervals <1%), repeatability and intermediate precision (RSD% < 2.5%), limit of detection (LOD), limit of quantification (LOQ) and calibration range). The LOD was 0.25 mg/mL and the LOQ was 0.5 mg/mL. Using methanolic solutions of United States Pharmacopoeia (USP) Capsaicin and Dihydrocapsaicin Reference Standards, the method was linear over the concentration range 0.0005 -0.5000 mg/mL for both capsaicinoids. The method was applied to qualify capsaicinoid content of two industrial capsicum extracts according to the USP 29.

El chile piquín, como componente del matorral submontano del noreste de México, es una planta anual que también crece y se desarrolla de manera continua en zonas tropicales. Además de los usos culinarios
se ha reportado su actividad en problemas cardiovasculares, enfermedades crónicas degenerativas, estimulante, digestiva
y colerético, así como su capacidad de reducir los riesgos de contraer cáncer y como bactericida. Ante esta diversidad de aplicaciones y en busca de alternativas que contribuyan a mejorar la calidad de la producción agrícola, se plantea la evaluación de la actividad biológica de extractos etanólicos de frutos de chile piquín (Capsicum annuum L. var aviculare) y de capsaicina, sobre el crecimiento de Aspergillus fl avus, mediante dos técnicas: 1) técnica del pozo en agar-papa-dextrosa (PDA) con la adición 20μL de cada uno de los tratamientos en
concentraciones de 200, 400, 600, 800 y 1000 ppm., 2) la técnica de dilución en agar (PDA) que consiste en realizar una mezcla homogénea entre las soluciones de los tratamientos y el agar (PDA) antes de su solidificación. La actividad de los tratamientos se reflejó por la formación de un halo deinhibición y por el crecimiento radial del
hongo, en cada técnica respectivamente. Los resultados obtenidos mostraron que tanto la capsaicina como los extractos de chile piquín inhibieron significativamente el crecimiento radial de A. flavus, siendo estos resultados estadísticamente comparables a los que se obtienen al aplicar el fungicida comercial captán.

The piquin chile as a component of submontane shrubland in northeastern Mexico, is an annual plant that also grows and develops
across the tropics. In addition to its culinary uses the fruit has been reported as having compounds with stimulant, choleretic and
digestive activity, helpful in the treatment of cardiovascular and chronic degenerative diseases and able to reduce the risk of cancer or act as a bactericide. Given this diversity of effects and seeking alternatives
to help improve the quality of agricultural production, the biological activity of ethanol extracts of piquin chile fruits (Capsicum annuum var. aviculare L.) and of capsaicin on Aspergillus fl avus growth was evaluated, using two techniques: 1) In the well in plate diffusion technique, 20 μL of capsaicin or extract at a concentration of 200, 400, 600, 800 and 1000 ppm were poured into wells made in potato dextrose agar (PDA) plates previously inoculated with A. flavus spores. 2) For the dilution technique, 2 mL of capsaicin or fruit extract in the concentrations mentioned were added to PDA making a homogeneous mixture before solidification. The activity of the treatments was reflected by the formation of an inhibition halo and the radial growth of fungus in each technique, respectively. The results showed that both capsaicin and piquin chile extracts signifi cantly inhibited radial growths of A. flavus, these results are statistically equal to those obtained by applying the commercial fungicide captan.

Spices and herbs are traditionally added to olive oil in Mediterranean gastronomy to enhance its aroma and taste. This paper aims to characterize olive oil aromatized by addition of dried chili pepper (Capsicum annum) (DCP) at different concentrations (10% and 20% by weight) up to 30 days of infusion. Capsaicinoids quantification by HPLC-DAD, volatile compounds analysis by SPME-GC–MS and antioxidant activity by ABTS method were performed on chili pepper flavored olive oil (CPOO) in comparison to whole olive oil. At day 7 of infusion, the maximum capsaicinoids content was reached for both the concentrations used and no significant increase was observed for longer infusion times. The volatile headspace composition of CPOOs was influenced by the concentration of DCP added. The addition of DCP caused a significant increase in hexanal, related to oxidation processes. 2-Methylbutanal, 3-methylbutanal and 6-methyl-5-hepten-2-one were also detected in CPOO and derived from chili as degradation products of the drying process. DCP infusion significantly enriched olive oil with antioxidant compounds and also modified its volatile profile. Capsaicinoids and aroma compounds were rapidly released within the first week of chili infusion in CPOOs, thus suggesting reducing infusion time by optimizing DCP concentration in order to improve CPOO quality and shelf life.

The influence of operating parameters (solvent type, powder to solvent ratio and temperature) on the ultrasonically assisted extraction of capsaicinoids from dried Capsicum frutescens (fruit) was studied. From the economic perspective, the suitable condition for capsaicinoid extraction by indirect sonication in an ultrasonic bath with a working frequency of 35 kHz was at a ratio of 1 g of solid material: 5 ml of 95% (v/v) ethanol, 45°C, where 85% of the capsaicinoids were removed from the raw material in 3 h. In an experimental pilot study in 20-l extraction tank at the fixed ultrasonic frequency of 26 kHz and 70 kHz, the recovery of capsaicinoids was 76% and 70%, respectively. It was shown that the ultrasonic extraction produced a significant reduction in extraction time at a lower operational temperature than under a conventional industrial hot maceration process.

Chronic pain is a major clinical problem and opiates are often the only treatment, but they cause significant problems ranging from sedation to deadly respiratory depression. Resiniferatoxin (RTX), a potent agonist of Transient Receptor Potential Vanilloid 1 (TRPV1), causes a slow, sustained and irreversible activation of TRPV1 and increases the frequency of spontaneous excitatory postsynaptic currents, but causes significant depression of evoked EPSCs due to nerve terminal depolarization block. Intrathecal administration of RTX to rats in the short-term inhibits nociceptive synaptic transmission, and in the long-term causes a localized, selective ablation of TRPV1-expressing central sensory nerve terminals leading to long lasting analgesia in behavioral models. Since RTX actions are selective for central sensory nerve terminals, other efferent functions of dorsal root ganglion neurons can be preserved. Preventing nociceptive transmission at the level of the spinal cord can be a useful strategy to treat chronic, debilitating and intractable pain.

Several temperature-activated transient receptor potential (thermo-TRP) ion channels are the molecular receptors of natural compounds that evoke thermal and pain sensations. Menthol, popularly known for its cooling effect, activates TRPM8-a cold-activated thermoTRP ion channel. However, human physiological studies demonstrate a paradoxical role of menthol in modulation of warm sensation, and here, we show that menthol also activates heat-activated TRPV3. We further show that menthol inhibits TRPA1, potentially explaining the use of menthol as an analgesic. Similar to menthol, both camphor and cinnamaldehyde (initially reported to be specific activators of TRPV3 and TRPA1, respectively) also modulate other thermoTRPs. Therefore, we find that many ''sensory compounds'' presumed to be specific have a promiscuous relationship with thermoTRPs. D

Capsicum species are not only cultivated as vegetable and condiment crops but are also incorporated into a number of medicinal preparations in the ancient literature around the world. 'Naga chilli' or 'Bhoot Jolokia' (Capsicum chinense Jacq.) is a chilli variety indigenous to the northeast region of India and has been recognized as the hottest chilli in the world. It has also been used conventionally in treating various human ailments since time immemorial by the indigenous people of the northeast India. Despite being an important crop of the northeast India, the information on the biology and cultivation of Naga chilli is very scanty and scattered. The present article reviews the scientific literature on above aspects with particular emphasis on identifying the key regional issues which need to be addressed urgently by the policy makers in order to harness its potential as an important source of capsaicinoids. Further, an attempt has been made to collate the potential of capsaicinoids in various ethnopharmacological applications such as pain therapy, body temperature regulation, anti-obesity treatments, anticancer therapy and as antioxidant and antimicrobial agent. We anticipate that this literature analysis of traditional medicinal uses and experimental trials of Capsicum using modern scientific approaches shall provide a basis for suggesting important areas where sincere research efforts are warranted to bridge the gap between traditional medicinal knowledge and modern biomedical knowledge.

There is a paucity of scientific literature that has reviewed the conservative and surgical treatment efficacy for the management of injuries causing neurapraxia and axonotmesis. This retrospective study evaluates the clinical outcomes of certain treatments for these injuries. Twenty-seven patients fulfilled the inclusion/exclusion criteria for the study, and represented both genders and a wide variety of ages, weights, levels of education, and backgrounds. Surgical intervention resulted in a slightly better clinical outcome when compared to conservative therapies. Patients undergoing surgery for a single nerve problem improved more than those who underwent surgery when three or more nerves were involved. Failure was most often associated with: 1) muttiple nerve injuries, 2) a previous history of psychopathology, and 3) application of conservative therapy without surgical intervention for single nerve injury.

Proteases that are released during inflammation and injury cleave protease-activated receptor 2 (PAR 2 ) on primary afferent neurons to cause neurogenic inflammation and hyperalgesia. PAR 2 -induced thermal hyperalgesia depends on sensitization of transient receptor potential vanilloid receptor 1 (TRPV1), which is gated by capsaicin, protons and noxious heat. However, the signalling mechanisms by which PAR 2 sensitizes TRPV1 are not fully characterized. Using immunofluorescence and confocal microscopy, we observed that PAR 2 was colocalized with protein kinase (PK) Cε and PKA in a subset of dorsal root ganglia neurons in rats, and that PAR 2 agonists promoted translocation of PKCε and PKA catalytic subunits from the cytosol to the plasma membrane of cultured neurons and HEK 293 cells. Subcellular fractionation and Western blotting confirmed this redistribution of kinases, which is indicative of activation. Although PAR 2 couples to phospholipase Cβ, leading to stimulation of PKC, we also observed that PAR 2 agonists increased cAMP generation in neurons and HEK 293 cells, which would activate PKA. PAR 2 agonists enhanced capsaicin-stimulated increases in [Ca 2+ ] i and whole-cell currents in HEK 293 cells, indicating TRPV1 sensitization. The combined intraplantar injection of non-algesic doses of PAR 2 agonist and capsaicin decreased the latency of paw withdrawal to radiant heat in mice, indicative of thermal hyperalgesia. Antagonists of PKCε and PKA prevented sensitization of TRPV1 Ca 2+ signals and currents in HEK 293 cells, and suppressed thermal hyperalgesia in mice. Thus, PAR 2 activates PKCε and PKA in sensory neurons, and thereby sensitizes TRPV1 to cause thermal hyperalgesia. These mechanisms may underlie inflammatory pain, where multiple proteases are generated and released.

Capsaicin, the active ingredient in hot chilli peppers, has selective actions on unmyelinated C-fibres and thinly myelinated A primary sensory neurones . Most capsaicin-sensitive fibres are polymodal nociceptors which respond to a range of sensory stimuli including noxious pressure, heat and chemical irritants , and are the most abundant class of nociceptive fibre. Nociceptive neurones are likely to release glutamate as a rapid central neurotransmitter, and also express neuropeptides such as calcitonin gene-related peptide (CGRP), substance P, neurokinin A and somatostatin which can be released into the spinal cord during intense stimulation . The tachykinins (e.g. substance P and neurokinin A) and excitatory amino acids (EAAs) (e.g. glutamate) cooperate and are thought to increase synaptic activation of dorsal horn neurones via EAA receptors . Noxious stimulation in the peripheral nervous system results in long-term increases in spinal excitability which may contribute to central mechanisms of allodynia and hyperalgesia . Much of the neuropeptide synthesized in the dorsal root ganglion (DRG) cell body is actually exported peripherally rather than centrally. In peripheral nerve peptide release can contribute to neurogenic inflammation.