Asperuloside Enhances Taste Perception and Prevents Weight Gain in High-Fat Fed Mice.

Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.

A new screening method for identifying chemosensory receptors responding to agonist.

Humans sense taste and smell of various chemical substances through approximately 430 chemosensory receptors. The overall picture of ligand-chemosensory receptor interactions has been partially clarified because of numerous interactions. This study presents a new method that enables a rapid and simple screening of chemosensory receptors. It would be useful for identifying chemosensory receptors activated by taste and odor substances.

Suppression of Oral Sweet Sensations during Consumption of Sweet Food in Humans: Effects on Gastric Emptying Rate, Glycemic Response, Appetite, Food Satisfaction and Desire for Basic Tastes.

Suppression of oral sweet sensation (OSS) acutely reduces intake of sweet-tasting food due to lower liking. However, little is known about other physiological responses during both the prandial and postprandial phase. Here, we explored the effects of Gymnema sylvestre (GS)-based suppression of OSS of several types of sweet-tasting food (muffin, sweet yogurt, banana) on gastric emptying, blood glucose (BG), plasma insulin (PI), appetite indices (hunger, fullness and prospective consumption), satisfaction and desire for tastes. Fifteen healthy subjects (22 ± 3 years, 9 women) took part in the study. Subjects rinsed their mouth with either GS solution or distilled water before eating the sweet-tasting food. Subjects felt decreased sweet taste intensity and reduced taste liking associated with GS rinsing after consuming each food, compared with rinsing with distilled water (p < 0.05). Gastric emptying, BG, PI and appetite indices during and after the prandial phase did not significantly change with GS rinsing compared to rinsing with distilled water (p > 0.05). Higher desire for sweet taste as well as lower satisfaction (p < 0.05) in the postprandial phase were observed with GS rinsing. These results suggest that the suppression of OSS does not affect gastric emptying, glycemic response and appetite during and after consumption of sweet-tasting food.

Activation of the bitter taste sensor TRPM5 prevents high salt-induced cardiovascular dysfunction.

High salt intake is a known risk factor of cardiovascular diseases. Our recent study demonstrated that long-term high salt intake impairs transient receptor potential channel M5 (TRPM5)-mediated aversion to high salt concentrations, consequently promoting high salt intake and hypertension; however, it remains unknown whether TRPM5 activation ameliorates cardiovascular dysfunction. Herein we found that bitter melon extract (BME) and cucurbitacin E (CuE), a major compound in BME, lowered high salt-induced hypertension. Long-term BME intake significantly enhanced the aversion to high salt concentrations by upregulating TRPM5 expression and function, eventually decreasing excessive salt consumption in mice. Moreover, dietary BME ameliorated high salt-induced cardiovascular dysfunction and angiotensin II-induced hypertension in vivo. The mechanistic evidence demonstrated that dietary BME inhibited high salt-induced RhoA/Rho kinase pathway overactivation, leading to reduced phosphorylation levels of myosin light chain kinase and myosin phosphatase targeting subunit 1. Furthermore, CuE inhibited vasoconstriction by attenuating L-type Ca2+ channel-induced Ca2+ influx in vascular smooth muscle cells. To summarize, our findings indicate that dietary BME has a beneficial role in antagonizing excessive salt consumption and thus appears promising for the prevention of high salt-induced cardiovascular dysfunction.

Effect of chemical interaction between oleic acid and L-Arginine on oral perception, as a function of polymorphisms of CD36 and OBPIIa and genetic ability to taste 6-n-propylthiouracil.

Oral sensitivity to fats varies in individuals influencing nutritional status and health. Variations in oleic acid perception are associated with CD36 and odorant binding protein (OBPIIa) polymorphisms, and 6-n-propylthiouracil (PROP) sensitivity, which is mediated by TAS2R38 receptor. L-Arginine (L-Arg) supplementation was shown to modify the perception of the five taste qualities. Here we analyzed the effect of three concentrations (5, 10, 15 mmol/L) of L-Arg on oral perception of oleic acid in forty-six subjects classified for PROP taster status and genotyped for TAS2R38, CD36 and OBPIIa polymorphisms. L-Arg supplementation was effective in increasing the perceived intensity of oleic acid in most subjects. The lowest concentration was the most effective, especially in PROP non-tasters or medium tasters, and in subjects with at least an allele A in CD36 and OBPIIa loci. Density Functional Theory (DFT) calculations were exploited to characterize the chemical interaction between L-Arg and oleic acid, showing that a stable 1:1 oleate·ArgH+ adduct can be formed, stabilized by a pair of hydrogen bonds. Results indicate that L-Arg, acting as a 'carrier' of fatty acids in saliva, can selectively modify taste response, and suggest that it may to be used in personalized dietetic strategies to optimize eating behaviors and health.

Enjoyment of Spicy Flavor Enhances Central Salty-Taste Perception and Reduces Salt Intake and Blood Pressure.

High salt intake is a major risk factor for hypertension and is associated with cardiovascular events. Most countries exhibit a traditionally high salt intake; thus, identification of an optimal strategy for salt reduction at the population level may have a major impact on public health. In this multicenter, random-order, double-blind observational and interventional study, subjects with a high spice preference had a lower salt intake and blood pressure than subjects who disliked spicy food. The enjoyment of spicy flavor enhanced salt sensitivity and reduced salt preference. Salt intake and salt preference were related to the regional metabolic activity in the insula and orbitofrontal cortex (OFC) of participants. Administration of capsaicin-the major spicy component of chili pepper-enhanced the insula and OFC metabolic activity in response to high-salt stimuli, which reversed the salt intensity-dependent differences in the metabolism of the insula and OFC. In animal study, OFC activity was closely associated with salt preference, and salty-taste information processed in the OFC was affected in the presence of capsaicin. Thus, interventions related to this region may alter the salt preference in mice through fiber fluorometry and optogenetic techniques. In conclusion, enjoyment of spicy foods may significantly reduce individual salt preference, daily salt intake, and blood pressure by modifying the neural processing of salty taste in the brain. Application of spicy flavor may be a promising behavioral intervention for reducing high salt intake and blood pressure.

Development and evaluation of an oral fast disintegrating anti-allergic film using hot-melt extrusion technology.

The main objective of this novel study was to develop chlorpheniramine maleate orally disintegrating films (ODF) using hot-melt extrusion technology and evaluate the characteristics of the formulation using in vitro and in vivo methods. Modified starch with glycerol was used as a polymer matrix for melt extrusion. Sweetening and saliva-simulating agents were incorporated to improve palatability and lower the disintegration time of film formulations. A standard screw configuration was applied, and the last zone of the barrel was opened to discharge water vapors, which helped to manufacture non-sticky, clear, and uniform films. The film formulations demonstrated rapid disintegration times (6-11s) and more than 95% dissolution in 5min. In addition, the films had characteristic mechanical properties that were helpful in handling and storage. An animal model was employed to determine the taste masking of melt-extruded films. The lead film formulation was subjected to a human panel for evaluation of extent of taste masking and disintegration.

Zizyphin modulates calcium signalling in human taste bud cells and fat taste perception in the mouse.

Zizyphin, isolated from Zizyphus sps. leaf extracts, has been shown to modulate sugar taste perception, and the palatability of a sweet solution is increased by the addition of fatty acids. We, therefore, studied whether zizyphin also modulates fat taste perception. Zizyphin was purified from edible fruit of Zizyphus lotus L. Zizyphin-induced increases in [Ca2+ ]i in human taste bud cells (hTBC). Zizyphin shared the endoplasmic reticulum Ca2+ pool and also recruited, in part, Ca2+ from extracellular environment via the opening of store-operated Ca2+ channels. Zizyphin exerted additive actions on linoleic acid (LA)-induced increases in [Ca2+ ]i in these cells, indicating that zizyphin does not exert its action via fatty acid receptors. However, zizyphin seemed to exert, at least in part, its action via bile acid receptor Takeda-G-protein-receptor-5 in hTBC. In behavioural tests, mice exhibited preference for both LA and zizyphin. Interestingly, zizyphin increased the preference for a solution containing-LA. This study is the first evidence of the modulation of fat taste perception by zizyphin at the cellular level in hTBC. Our study might be helpful for considering the synthesis of zizyphin analogues as 'taste modifiers' with a potential in the management of obesity and lipid-mediated disorders.

Activation of mu-opioid receptors in the ventral pallidum decreases the negative hedonic evaluation of a conditioned aversive taste in rats.

Conditioned taste aversion (CTA) causes a shift in the hedonic evaluation of a conditioned stimulus (CS) from positive to negative, and reduces the CS intake. Mu-opioid receptors (MORs) in the ventral pallidum (VP) are known to be involved in the hedonic evaluation of positive rewarding stimuli; however, their involvement in evaluation of a negative aversive stimulus is still unclear. To explore the neural mechanisms of the negative hedonic evaluation of the CS in CTA, we examined the effects of the activation of VP MORs on the behavioral responses of rats to a CS. Rats implanted with guide cannulae into the bilateral VP received a pairing of 5mM saccharin solution as a CS with an intraperitoneal injection of 0.15M lithium chloride as an unconditioned stimulus. On the test day, after microinjections of MOR agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) into the VP, we observed the behavioral responses to the intraorally infused CS solution. The DAMGO injections caused a larger number of ingestive taste reactivity responses to the CS solution. We also measured the consumption of the CS solution in a separate group of rats, using a single-bottle test. The DAMGO injected rats drank a higher volume of the CS solution than the saline injected rats. These results indicate that the activation of MORs in the VP results in the attenuation of aversion to the CS solution, thereby inducing the larger CS intake. Therefore, it is likely that VP MORs are involved in not only positive but also negative hedonic evaluation.

A High-Throughput Automated Microfluidic Platform for Calcium Imaging of Taste Sensing.

The human enteroendocrine L cell line NCI-H716, expressing taste receptors and taste signaling elements, constitutes a unique model for the studies of cellular responses to glucose, appetite regulation, gastrointestinal motility, and insulin secretion. Targeting these gut taste receptors may provide novel treatments for diabetes and obesity. However, NCI-H716 cells are cultured in suspension and tend to form multicellular aggregates, preventing high-throughput calcium imaging due to interferences caused by laborious immobilization and stimulus delivery procedures. Here, we have developed an automated microfluidic platform that is capable of trapping more than 500 single cells into microwells with a loading efficiency of 77% within two minutes, delivering multiple chemical stimuli and performing calcium imaging with enhanced spatial and temporal resolutions when compared to bath perfusion systems. Results revealed the presence of heterogeneity in cellular responses to the type, concentration, and order of applied sweet and bitter stimuli. Sucralose and denatonium benzoate elicited robust increases in the intracellular Ca(2+) concentration. However, glucose evoked a rapid elevation of intracellular Ca(2+) followed by reduced responses to subsequent glucose stimulation. Using Gymnema sylvestre as a blocking agent for the sweet taste receptor confirmed that different taste receptors were utilized for sweet and bitter tastes. This automated microfluidic platform is cost-effective, easy to fabricate and operate, and may be generally applicable for high-throughput and high-content single-cell analysis and drug screening.

Taste intensity modulates effective connectivity from the insular cortex to the thalamus in humans.

Evaluation of taste intensity is one of the most important perceptual abilities in our daily life. In contrast with extensive research findings regarding the spatial representation of taste in the insula and thalamus, little is known about how the thalamus and insula communicate and reciprocally influence their activities for processing taste intensity. To examine this neurophysiological relationship, we investigated the modulatory effect of intensity of saltiness on connections in the network processing taste signals in the human brain. These "effective connectivity" relationships refer to the neurophysiological influence (including direction and strength of influence) of one brain region on another. Healthy adults (N=34), including 17 males and 17 females (mean age=21.3years, SD=2.4; mean body mass index (BMI)=20.2kg/m(2), SD=2.1) underwent functional magnetic resonance imaging as they tasted three concentrations of sodium chloride solutions. By effective connectivity analysis with dynamic causal modeling, we show that taste intensity enhances top-down signal transmission from the insular cortex to the thalamus. These results are the first to demonstrate the modulatory effect of taste intensity on the taste network in the human brain.

An Interesting Tour of New Research Results on Umami and Umami Compounds.

Knowledge about the fifth basic taste, the umami taste, has been investigated by many scientists in the last years and continues to gain importance. Therefore, a lot of scientific studies were conducted to explore several effects influencing the mechanism of umami, which is elicited and enhanced by defined concentrations of MSG (monosodium glutamate) and umami compounds. This paper covers the most relevant scientific literature regarding umami, its use as a flavor enhancer, and the latest umami compounds, which have been released in the last ten years. The main goal of this overview was to summarize the most important results which were related to umami as one of the five basic tastes, the umami taste receptor, the essential role of umami in a great number of physiological mechanisms, and the MSG symptom complex. Furthermore, the function of umami in the interaction of taste, aftertaste and olfactory pathways has been discussed.

Drug-motivated behavior in rats with lesions of the thalamic orosensory area.

Rats suppress intake of a palatable taste cue when paired with a rewarding or an aversive stimulus in appetitive or aversive conditioning, respectively. A similar phenomenon occurs with drugs of abuse, but the nature of this conditioning has been subject for debate. While relatively little is known about the underlying neural circuitry, we recently reported bilateral lesions of the thalamic trigeminal orosensory area isolate drug-induced suppression of intake of a taste cue. The lesion blocks avoidance of the taste cue when paired with experimenter delivered drugs of abuse, yet has no effect on avoidance of the same cue when paired with an aversive agent or when it predicts access to a highly palatable sucrose solution. We hypothesize the lesion may blunt the rewarding properties of the drug. To test this, we used a runway apparatus, as running speed has been shown to increase with increasing reward value. Our hypothesis was supported by failure of the lesioned rats to increase running speed for morphine. Interestingly, lesioned rats did avoid intake of the drug-paired cue when presented in the runway apparatus and displayed naloxone-precipitated withdrawal. Using a partial crossover design, the lesion prevented avoidance of a cocaine-paired cue when presented in the home cage. We conclude that the lesion disrupts avoidance of a taste cue in anticipation of the rewarding properties of a drug but, at least in the presence of contextual cues, allows for avoidance of a taste cue as it elicits the onset of an aversive conditioned state of withdrawal.

Dose-Dependent Effects of L-Arginine on PROP Bitterness Intensity and Latency and Characteristics of the Chemical Interaction between PROP and L-Arginine.

Genetic variation in the ability to taste the bitterness of 6-n-propylthiouracil (PROP) is a complex trait that has been used to predict food preferences and eating habits. PROP tasting is primarily controlled by polymorphisms in the TAS2R38 gene. However, a variety of factors are known to modify the phenotype. Principle among them is the salivary protein Ps-1 belonging to the basic proline-rich protein family (bPRP). Recently, we showed that oral supplementation with Ps-1 as well as its related free amino acids (L-Arg and L-Lys) enhances PROP bitterness perception, especially for PROP non-tasters who have low salivary levels of Ps-1. Here, we show that salivary L-Arg levels are higher in PROP super-tasters compared to medium tasters and non-tasters, and that oral supplementation with free L-Arg enhances PROP bitterness intensity as well as reduces bitterness latency in a dose-dependent manner, particularly in individuals with low salivary levels of both free L-Arg and Ps-1 protein. Supplementation with L-Arg also enhanced the bitterness of caffeine. We also used 1H-NMR spectroscopy and quantum-mechanical calculations carried out by Density Functional Theory (DFT) to characterize the chemical interaction between free L-Arg and the PROP molecule. Results showed that the -NH2 terminal group of the L-ArgH+ side chain interacts with the carbonyl or thiocarbonyl groups of PROP by forming two hydrogen bonds with the resulting charged adduct. The formation of this PROP•ArgH+ hydrogen-bonded adduct could enhance bitterness intensity by increasing the solubility of PROP in saliva and its availability to receptor sites. Our data suggest that L-Arg could act as a 'carrier' of various bitter molecules in saliva.

Tasting calories differentially affects brain activation during hunger and satiety.

An important function of eating is ingesting energy. Our objectives were to assess whether oral exposure to caloric and non-caloric stimuli elicits discriminable responses in the brain and to determine in how far these responses are modulated by hunger state and sweetness. Thirty women tasted three stimuli in two motivational states (hunger and satiety) while their brain responses were measured using functional magnetic resonance imaging in a randomized crossover design. Stimuli were solutions of sucralose (sweet, no energy), maltodextrin (non-sweet, energy) and sucralose+maltodextrin (sweet, energy). We found no main effect of energy content and no interaction between energy content and sweetness. However, there was an interaction between hunger state and energy content in the median cingulate (bilaterally), ventrolateral prefrontal cortex, anterior insula and thalamus. This indicates that the anterior insula and thalamus, areas in which hunger state and taste of a stimulus are integrated, also integrate hunger state with caloric content of a taste stimulus. Furthermore, in the median cingulate and ventrolateral prefrontal cortex, tasting energy resulted in more activation during satiety compared to hunger. This finding indicates that these areas, which are known to be involved in processes that require approach and avoidance, are also involved in guiding ingestive behavior. In conclusion, our results suggest that energy sensing is a hunger state dependent process, in which the median cingulate, ventrolateral prefrontal cortex, anterior insula and thalamus play a central role by integrating hunger state with stimulus relevance.

Zinc deficiency and taste perception in the elderly.

Taste, one of the major senses in humans, is the ability to detect the flavor of substances such as food, certain minerals, and poisons. Taste distortions in human beings have been attributed to various physiological and environmental factors including aging and disease conditions. Given the fact that taste is one of the most important factors in food preference, selection, and consumption, the decreased appetite in the elderly, probably due to disease conditions, may lead to dietary restrictions that could negatively impact nutritional and health status. The role of zinc on taste distortion in the elderly population and taste impairment are described. Although several studies demonstrate the associative nature of taste degeneration with age, additional investigations are required to clarify the mechanisms by which taste perception is altered with age.

MC4-R signaling within the nucleus accumbens shell, but not the lateral hypothalamus, modulates ethanol palatability in rats.

The Melanocortin (MC) system is one of the crucial neuropeptidergic systems that modulate energy balance. The roles of endogenous MC and MC-4 receptor (MC4-R) signaling within the hypothalamus in the control of homeostatic aspects of feeding are well established. Additional evidence points to a key role for the central MC system in ethanol consumption. Recently, we have shown that nucleus accumbens (NAc), but not lateral hypothalamic (LH), infusion of a selective MC4-R agonist decreases ethanol consumption. Given that MC signaling might contribute to non-homeostatic aspects of feeding within limbic circuits, we assessed here whether MC4-R signaling within the NAc and the lateral hypothalamus (LH) alters normal ingestive hedonic and/or aversive responses to ethanol in rats as measured by a taste reactivity test. Adult male Sprague-Dawley rats were given NAc- or LH- bilateral infusion of the selective MC4-R agonist cyclo (NH-CH(2)-CH(2)-CO-His-D-Phe-Arg-Trp-Glu)-NH(2) (0, 0.75 or 1.5µg/0.5µl/site) and following 30 min, the animals received 1 ml of ethanol solution (6% w/v) intraoral for 1 minute and aversive and hedonic behaviors were recorded. We found that NAc-, but not LH-administration, of a selective MC4-R agonist decreased total duration of hedonic reactions and significantly increased aversive reactions relative to saline-infused animals which support the hypothesis that MC signaling within the NAc may contribute to ethanol consumption by modulating non-homeostatic aspects (palatability) of intake.

The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction.

Our interest in healthy aging and in evolutionarily conserved mechanisms of lifespan extension prompted us to investigate whether features of age-related decline in the honey bee could be attenuated with resveratrol. Resveratrol is regarded as a caloric restriction mimetic known to extend lifespan in some but not all model species. The current, prevailing view is that resveratrol works largely by activating signaling pathways. It has also been suggested that resveratrol may act as an antioxidant and confer protection against nervous system impairment and oxidative stress. To test whether honey bee lifespan, learning performance, and food perception could be altered by resveratrol, we supplemented the diets of honey bees and measured lifespan, olfactory learning, and gustatory responsiveness to sucrose. Furthermore, to test the effects of resveratrol under metabolic challenge, we used hyperoxic environments to generate oxidative stress. Under normal oxygen conditions, two resveratrol treatments-30 and 130 µM-lengthened average lifespan in wild-type honey bees by 38% and 33%, respectively. Both resveratrol treatments also lengthened maximum and median lifespan. In contrast, hyperoxic stress abolished the resveratrol life-extension response. Furthermore, resveratrol did not affect learning performance, but did alter gustation. Honey bees that were not fed resveratrol exhibited greater responsiveness to sugar, while those supplemented with resveratrol were less responsive to sugar. We also discovered that individuals fed a high dose of resveratrol-compared to controls-ingested fewer quantities of food under ad libitum feeding conditions.

Altered processing of sweet taste in the brain of diet soda drinkers.

Artificially sweetened beverage consumption has been linked to obesity, and it has been hypothesized that considerable exposure to nonnutritive sweeteners may be associated with impaired energy regulation. The reward system plays an integral role in modulating energy intake, but little is known about whether habitual use of artificial sweetener (i.e., diet soda consumption) may be related to altered reward processing of sweet taste in the brain. To investigate this, we examined fMRI response after a 12-hour fast to sucrose (a nutritive sweetener) and saccharin (a nonnutritive sweetener) during hedonic evaluation in young adult diet soda drinkers and non-diet soda drinkers. Diet soda drinkers demonstrated greater activation to sweet taste in the dopaminergic midbrain (including ventral tegmental area) and right amygdala. Saccharin elicited a greater response in the right orbitofrontal cortex (Brodmann Area 47) relative to sucrose in non-diet soda drinkers. There was no difference in fMRI response to the nutritive or nonnutritive sweetener for diet soda drinkers. Within the diet soda drinkers, fMRI activation of the right caudate head in response to saccharin was negatively associated with the amount of diet sodas consumed per week; individuals who consumed a greater number of diet sodas had reduced caudate head activation. These findings suggest that there are alterations in reward processing of sweet taste in individuals who regularly consume diet soda, and this is associated with the degree of consumption. These findings may provide some insight into the link between diet soda consumption and obesity.

Differences in the chemesthetic subqualities of capsaicin, ibuprofen, and olive oil.

Chemesthetic sensations elicited by ibuprofen, extra-virgin olive oil, and capsaicin were compared to quantify perceptual differences between known agonists of TRPA1 and TRPV1. Extra virgin olive oil contains a phenolic compound, oleocanthal, which is thought to share unique chemesthetic qualities with the nonsteroidal anti-inflammatory drug, ibuprofen. Pilot work suggested participants had difficulty distinguishing between multiple chemesthetic subqualities (e.g., burn, sting, itch, tickle, etc.) in a multiattribute rating task. Here, we assessed overall irritation via direct scaling, and a check all that apply task was used to collect information about chemesthetic subqualities over time. Replicated ratings were collected at discrete intervals using the generalized labeled magnitude scale to generate time-intensity curves; maximum intensity (Imax) and area under the curve were extracted for each participant. Intensity responses varied substantially across participants, and within a participant, the relationship was strongest between ibuprofen and olive oil. However, there were also positive, albeit weaker, correlations between capsaicin and ibuprofen and capsaicin and olive oil. The correlation found between olive oil and capsaicin may suggest the presence of unknown TRPV1 agonists in olive oil. This view was also supported by the qualitative data: capsaicin was described most often as burning and warm/hot, whereas ibuprofen was numbing and tickling. Olive oil shared characteristics with both capsaicin (warm/hot) and ibuprofen (tickle).