Dihydrocapsiate does not increase energy expenditure nor fat oxidation during aerobic exercise in men with overweight/obesity: a randomized, triple-blinded, placebo-controlled, crossover trial.

Background: Prior evidence suggests that capsinoids ingestion may increase resting energy expenditure (EE) and fat oxidation (FATox), yet whether they can modulate those parameters during exercise conditions remains poorly understood. We hypothesized that dihydrocapsiate (DHC) ingestion would increase EE and specifically FATox during an acute bout of aerobic exercise at FATmax intensity (the intensity that elicits maximal fat oxidation during exercise [MFO]) in men with overweight/obesity. Since FATmax and MFO during aerobic exercise appear to be indicators of metabolic flexibility, whether DHC has an impact on FATox in this type of population is of clinical interest. Methods: A total of 24 sedentary men (age = 40.2 ± 9.2 years-old; body mass index = 31.6 ± 4.5 kg/m2 [n = 11 overweight, n = 13 obese]) participated in this randomized, triple-blinded, placebo-controlled, crossover trial (registered under ClinicalTrials.gov Identifier no. NCT05156697). On the first day, participants underwent a submaximal exercise test on a cycle ergometer to determine their MFO and FATmax intensity during exercise. After 72 hours had elapsed, the participants returned on 2 further days (≥ 72 hours apart) and performed a 60 min steady-state exercise bout (i.e. cycling at their FATmax, constant intensity) after ingesting either 12 mg of DHC or placebo; these conditions were randomized. Respiratory gas exchange was monitored by indirect calorimetry. Serum marker concentrations (i.e. glucose, triglycerides, non-esterified fatty acids (NEFAs), skin temperature, thermal perception, heart rate, and perceived fatigue) were assessed. Results: There were no significant differences (P > 0.05) between DHC and placebo conditions in the EE and FATox during exercise. Similarly, no significant changes were observed in glucose, triglycerides, or NEFAs serum levels, neither in the skin temperature nor thermal perception across conditions. Heart rate and perceived fatigue did not differ between conditions. Conclusions: DHC supplementation does not affect energy metabolism during exercise in men with overweight/obesity.

[Real-world clinical efficacy assessment of Kapsikam a combined topical medication based on nonivamide synthetic capsaicin analog in patients with acute nonspecific musculoskeletal back pain: LOCUS observational study outcomes]. / Otsenka klinicheskoi effektivnosti Kapsikama u patsientov s ostroi nespetsificheskoi skeletno-myshechnoi bol'yu v spine v real'noi praktike: rezul'taty nablyudatel'nogo issledovaniya LOKUS.

OBJECTIVE: Evaluation of the effect of local therapy with Kapsikam on the dynamics of clinical symptoms and indices of the disability scale, as well as on reducing the doses of systemic non-steroidal anti-inflammatory drugs (NSAIDs) used in patients with acute back pain (LOCUS study). MATERIALS AND METHODS: An observational study included 120 patients with nonspecific pain in the lower back and a verified diagnosis of Lumbodynia M54.5; «Lumbodynia with sciatica¼ M54.4, of which 78 received in addition to the basic treatment with systemic NSAIDs topical drug Kapsikam and 42 - only basic treatment.Results and conclusion. The addition of Kapsikam ointment to systemic NSAIDs accelerated the onset of the analgesic effect, which made it possible to discontinue NSAIDs in 50% of patients after 5 days of use. Local therapy was accompanied by easily tolerated adverse events that did not affect the use of the drug. 97.4% of patients used the study drug as prescribed until the end of the study.

Effects of Capsinoid Intake on Brown Adipose Tissue Vascular Density and Resting Energy Expenditure in Healthy, Middle-Aged Adults: A Randomized, Double-Blind, Placebo-Controlled Study.

Capsinoids are some of the most promising ingredients to increase energy expenditure (EE) due to brown adipose tissue (BAT) activation. However, there is limited information regarding the effect of prolonged capsinoid ingestion (CI) on BAT activity and resting EE (REE) in healthy, middle-aged, normal to overweight subjects (Subhealthy) with distinct BAT characteristics. We examined the changes in BAT density (BAT-d), using near-infrared time-resolved spectroscopy, and REE/kg induced by daily CI. Forty Subhealthy [age, 43.8 (mean) years; BMI, 25.4 kg/m2] received either capsinoid (9 mg/day) or a placebo daily for 6 weeks in a double-blind design. Total hemoglobin concentration in the supraclavicular region ([total-Hb]sup), an indicator of BAT-d, and REE/kg were measured. The changes in post-intervention [total-Hb]sup were greater in the capsinoid group (CA-G) than in the placebo group (PL-G) [5.8 µM (+12.4%) versus 1.0 µM (+2.1%); p = 0.017]. There was a significant relationship between BAT-d and REE/kg; however, post-supplementation REE/kg was not significantly different between the two groups (p = 0.228). In the overweight subgroup, changes in REE/kg were greater in the CA-G than in the PL-G [0.6 cal/kg/min (+4.3%) versus -0.3 cal/kg/min (-2.1%); p = 0.021]. CI enhanced [total-Hb]sup, a reflection of BAT-d, showing a good correlation with REE in Subhealthy.

Amelioration from the ocular irritant Capsaicin: development and assessment of a Capsazepine in situ gel system for ocular delivery.

BACKGROUND: Defense personnel utilize capsaicin-based ocular sprays as non-lethal agents for law implementation during instances of mob violence. This study involves the capsaicin antagonist Capsazepine and the investigation of whether Capsazepine's antagonistic approach can be favorably utilized for defense utilization to block capsaicin-initiated pain and inflammation via the ocular pathway. RESEARCH DESIGN AND METHODS: Ocular capsazepine in situ gels were prepared with polymers Pluronic F-127 and Chitosan; optimized formulation was quantified in ocular tissues chromatographically and by in vivo live ocular imaging; anti-inflammatory efficacy was determined by eye irritation testing, corneal and retinal imaging, ocular prostaglandin estimation, and by viability and proliferation testing using human ocular cell lines, etc. RESULTS: A physicochemically stable Capsazepine in situ gel was formulated which showed little ocular irritation, considerable transcorneal permeation; was precisely quantified in ocular tissues by gas chromatography and in vivo live ocular imaging; showed anti-inflammatory properties against capsaicin by eye imaging experiments, prostaglandin declination and showed acceptable cytocompatibility when studied using human ocular cell lines. CONCLUSIONS: The fabricated in situ Capsazepine gel system might be promising for ocular delivery as it appears a pharmacologically potent and safe development, suitable for utilization in the ocular clinical therapy, provided there is additional research to substantiate it.

Assessment of Capsaicinoid and Capsinoid Accumulation Patterns during Fruit Development in Three Chili Pepper Genotypes (Capsicum spp.) Carrying Pun1 and pAMT Alleles Related to Pungency.

Quantification, using an accurate analytical approach, of capsinoids and capsaicinoids was performed on three chili pepper (Capsicum spp.) genotypes: "Chiltepín", "Tampiqueño 74", and "Bhut Jolokia" at various stages of fruit development. The accumulation of capsinoids, in all these peppers started between 10 to 20 days post-anthesis (dpa), increased and reached the highest capsinoid amount at 40 dpa, and then decreased until 60 dpa. Conversely, capsaicinoids could already be determined at 10 dpa in "Bhut Jolokia" and their accumulation pattern was different from that of the capsinoids in this genotype. The capsiate/dihydrocapsiate ratio presented a higher variation between genotypes and developmental stages than the capsaicin/dihydrocapsaicin ratio. Capsinoid ratios (4-24%) and Pun1/pAMT genotyping were determined. These results provide information on the progress of the accumulation of capsinoids in the aforementioned pungent and superhot cultivars and could support future breeding studies toward the understanding of the factors affecting their accumulation.

Do TRPV1 antagonists increase the risk for skin tumourigenesis? A collaborative in vitro and in vivo assessment.

A recent hypothesis suggesting that the pharmacological target TRPV1 (transient receptor potential vanilloid subfamily, member 1) may function as a tumour suppressor, which potentially impacts the development of TRPV1 antagonist therapeutics for a range of conditions. However, little is known about the long-term physiologic effects of TRPV1 blockade in the skin. In vitro and in vivo studies suggested that the potent TRPV1 competitive antagonist AMG-9810 promoted proliferation in N/TERT1 cells (telomerase-immortalised primary human keratinocytes 1) and tumour development in mouse skin that was mediated through EGFR/Akt/mTOR signalling. We attempted to reproduce the reported in vitro and in vivo findings to further explore this hypothesis to understand the underlying mechanism and the risk associated with TRPV1 antagonism in the skin. In vitro proliferation studies using multiple methods and topical application with AMG-9810 and structurally similar TRPV1 antagonists such as SB-705498 and PAC-14028 were performed. Although we confirmed expression of TRPV1 in primary human epidermal keratinocytes (HEKn) and spontaneously immortalised human keratinocytes (HaCaT), we were unable to demonstrate cell proliferation in either cell type or any clear evidence of increased expression of proteins in the EGFR/Akt/mTOR signalling pathway with these molecules. We were also unable to demonstrate skin tumour promotion or underlying molecular mechanisms involved in the EGFR/Akt/mTOR signalling pathway in a single-dose and two-stage carcinogenesis mouse study treated with TRPV1 antagonists. In conclusion, our data suggest that inhibiting the pharmacological function of TRPV1 in skin by specific antagonists has not been considered to be indicative of skin tumour development.

Dihydrocapsiate improved age-associated impairments in mice by increasing energy expenditure.

Metabolic dysfunction is associated with aging and results in age-associated chronic diseases, including type 2 diabetes mellitus, cardiovascular disease, and stroke. Hence, there has been a focus on increasing energy expenditure in aged populations to protect them from age-associated diseases. Dihydrocapsiate (DCT) is a compound that belongs to the capsinoid family. Capsinoids are capsaicin analogs that are found in nonpungent peppers and increase whole body energy expenditure. However, their effect on energy expenditure has been reported only in young populations, and to date the effectiveness of DCT in increasing energy expenditure in aged populations has not been investigated. In this study, we investigated whether DCT supplementation in aged mice improves age-associated impairments. We obtained 5-wk-old and 1-yr-old male C57BL/6J mice and randomly assigned the aged mice to two groups, resulting in a total of three groups: 1) young mice, 2) old mice, and 3) old mice supplemented with 0.3% DCT. After 12 wk of supplementation, blood and tissue samples were collected and analyzed. DCT significantly suppressed age-associated fat accumulation, adipocyte hypertrophy, and liver steatosis. In addition, the DCT treatment dramatically suppressed age-associated increases in hepatic inflammation, immune cell infiltration, and oxidative stress. DCT exerted these suppression effects by increasing energy expenditure linked to upregulation of both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that DCT efficiently improves age-associated impairments, including liver steatosis and inflammation, in part by increasing energy expenditure via activation of the fat oxidation pathway in skeletal muscle.

Correlation between different markers for the assessment of red chilli pepper powders stability during shelf-life.

Pungency and red colour of Capsicum powders deteriorate during processing and storage, resulting in a decrease in market value. Two varieties of pepper with different pungencies were monitored for capsaicinoids, colour and furosine. Aliquots were stored at room and at low temperature during one year. At low temperature all indicators were stable in both varieties, while at room temperature, redness and capsacinoids decreased significantly, while furosine increased. High correlation was found between those markers. The more pungent variety exhibited higher stability in terms of all parameters. Differences observed suggest a potential protective effect exerted by capsaicinoids on powder stability. The decrease in capsaicinoids and redness accompanied by furosine increase showed a linkage between those markers never reported before. Considering that capsaicinoids and furosine occurrence have strong impact on the nutritional profile, the findings of this work show relevant changes in the nutritional value of chilli pepper powder after storage.

Capsiate supplementation reduces oxidative cost of contraction in exercising mouse skeletal muscle in vivo.

Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight) on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the Km of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz), both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.

A combination of exercise and capsinoid supplementation additively suppresses diet-induced obesity by increasing energy expenditure in mice.

Exercise effectively prevents the development of obesity and obesity-related diseases such as type 2 diabetes. Capsinoids (CSNs) are capsaicin analogs found in a nonpungent pepper that increase whole body energy expenditure. Although both exercise and CSNs have antiobesity functions, the effectiveness of exercise with CSN supplementation has not yet been investigated. Here, we examined whether the beneficial effects of exercise could be further enhanced by CSN supplementation in mice. Mice were randomly assigned to four groups: 1) high-fat diet (HFD, Control), 2) HFD containing 0.3% CSNs, 3) HFD with voluntary running wheel exercise (Exercise), and 4) HFD containing 0.3% CSNs with voluntary running wheel exercise (Exercise + CSN). After 8 wk of ingestion, blood and tissues were collected and analyzed. Although CSNs significantly suppressed body weight gain under the HFD, CSN supplementation with exercise additively decreased body weight gain and fat accumulation and increased whole body energy expenditure compared with exercise alone. Exercise together with CSN supplementation robustly improved metabolic profiles, including the plasma cholesterol level. Furthermore, this combination significantly prevented diet-induced liver steatosis and decreased the size of adipocyte cells in white adipose tissue. Exercise and CSNs significantly increased cAMP levels and PKA activity in brown adipose tissue (BAT), indicating an increase of lipolysis. Moreover, they significantly activated both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that CSNs efficiently promote the antiobesity effect of exercise, in part by increasing energy expenditure via the activation of fat oxidation in skeletal muscle and lipolysis in BAT.

Aroma quality assessment of Korean fermented red pepper paste (gochujang) by aroma extract dilution analysis and headspace solid-phase microextraction-gas chromatography-olfactometry.

The objective of this study was to assess aroma quality of gochujang using purge and trap, simultaneous steam distillation and solvent extraction (SDE), and headspace solid-phase microextraction (HS-SPME), followed by gas chromatography-olfactometry (GC-O). Nineteen and 28 aroma-active compounds were detected by aroma extract dilution analysis of purge and trap and SDE, respectively. Diallyl disulfide and 3-isobutyl-2-methoxypyrazine played a significant role in the aroma quality of gochujang. Twelve aroma-active compounds were detected by HS-SPME-GC-O based on sample dilution analysis. Methional, diallyl disulfide, and 3-isobutyl-2-methoxypyrazine were the most intense aroma-active compounds. 3-Isobutyl-2-methoxypyrazine was identified for the first time in gochujang.

Acute effect on satiety, resting energy expenditure, respiratory quotient, glucagon-like peptide-1, free fatty acids, and glycerol following consumption of a combination of bioactive food ingredients in overweight subjects.

OBJECTIVE: A combination of bioactive food ingredients (capsaicinoids, epigallocatechin gallate, piperin, and l-carnitine, CBFI) may promote satiety and thermogenesis. The study was conducted in order to assess whether there is any effect on satiety, resting energy expenditure (REE), respiratory quotient, glucagon-like peptide-1 (GLP-1), free fatty acids (FFA) and glycerol release, following a standardized mixed meal with or without single consumption of a CBFI. DESIGN: An 8-week randomized double-blind placebo-controlled trial. SETTING: Dietetic and Metabolic Unit, Azienda di Servizi alla Persona, University of Pavia and "Villa delle Querce" Clinical Rehabilitation Institute, Rome, Italy. PARTICIPANTS: Thirty-seven overweight adults (body mass index [BMI]: 25-35). INTERVENTION: Nineteen overweight subjects were included in the supplemented group (14 women, 5 men; age 46.4 ± 6.4; BMI: 30.5 ± 3.3) and 18 in the placebo group (13 women, 5 men; age 40.8 ± 11.5; BMI: 30.1 ± 2.6). Satiety was assessed using 100-mm visual analogue scales (VAS) and the area under the curve was calculated. RESULTS: All measured parameters increased significantly in comparison with baseline in response to meal, both with CBFI and with placebo. However, throughout the study day, the supplemented group experienced a significantly greater increase than the placebo group in their sensation of satiety following acute administration of the supplement. CONCLUSION: CBFI may therefore be of great value in the treatment of overweight patients by increasing satiety and stimulating thermogenesis.

Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans.

BACKGROUND: Capsinoids-nonpungent capsaicin analogs-are known to activate brown adipose tissue (BAT) thermogenesis and whole-body energy expenditure (EE) in small rodents. BAT activity can be assessed by [¹8F]fluorodeoxyglucose-positron emission tomography (FDG-PET) in humans. OBJECTIVES: The aims of the current study were to examine the acute effects of capsinoid ingestion on EE and to analyze its relation to BAT activity in humans. DESIGN: Eighteen healthy men aged 20-32 y underwent FDG-PET after 2 h of cold exposure (19°C) while wearing light clothing. Whole-body EE and skin temperature, after oral ingestion of capsinoids (9 mg), were measured for 2 h under warm conditions (27°C) in a single-blind, randomized, placebo-controlled, crossover design. RESULTS: When exposed to cold, 10 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining 8 subjects (BAT-negative group) showed no detectable uptake. Under warm conditions (27°C), the mean (±SEM) resting EE was 6114 ± 226 kJ/d in the BAT-positive group and 6307 ± 156 kJ/d in the BAT-negative group (NS). EE increased by 15.2 ± 2.6 kJ/h in 1 h in the BAT-positive group and by 1.7 ± 3.8 kJ/h in the BAT-negative group after oral ingestion of capsinoids (P < 0.01). Placebo ingestion produced no significant change in either group. Neither capsinoids nor placebo changed the skin temperature in various regions, including regions close to BAT deposits. CONCLUSION: Capsinoid ingestion increases EE through the activation of BAT in humans. This trial was registered at http://www.umin.ac.jp/ctr/ as UMIN 000006073.

Assessment of the biological similarity of three capsaicin analogs (Capsinoids) found in non-pungent chili pepper (CH-19 Sweet) fruits.

CH-19 Sweet is a newly found chili pepper breed bearing much less pungent fruits. Because CH-19 Sweet fruits were found to contain three analogs (capsinoids) of capsaicin, a major component of pungency of hot peppers (the analogs are capsiate or CST, dihydrocapsiate or DCT, and nordihydrocapsiate or NDCT), we assessed in this study the bio-potencies of these three capsinoids by comparing them with capsaicin. The three capsinoids bound to transient potential vanilloid 1 (TRPV1) receptors expressed in cultured cells and activated Ca(2+) influx in a concentration-dependent manner with similar magnitudes. In contrast to capsaicin, capsinoids at the same concentration induced virtually no nociceptive responses when applied to the eyes or the oral cavities of mice. Intravenous administration of capsaicin or 20-fold increased doses of each capsinoid to rats induced significant increases in plasma catecholamine levels. Orally administered, each capsinoid enhanced oxygen consumption in mice. Based on the present results, capsaicin and these three capsinoids should have similar bio-potency, though capsinoids do not generate pungency or sensory irritation.

Behavioral assessment and identification of a molecular marker in a salicylate-induced tinnitus in rats.

Tinnitus is a non-observable phantom sensation. As such, it is a difficult condition to investigate and, to date, no effective treatment has been developed. To approach this phantom sensation, we aimed to develop a rat behavioral model of tinnitus using salicylate, an active component of aspirin known to induce tinnitus. We also aimed to establish a molecular marker of tinnitus by assessing the expression of transient receptor potential cation channel superfamily V-1 (TRPV1) in the rat auditory pathway during salicylate-induced tinnitus. Animals were trained to perform "an active avoidance task": animals were conditioned by electrical footshock to move to the other side of the conditioning box when hearing a sound. Animals received a single injection of saline or salicylate (400 mg/kg i.p.) and false positive responses were measured 2 h after injection as the number of movements during a silent period. The number of responses in salicylate-treated animals was highest when the conditioned stimulus was 60 dB sound pressure level (SPL) and 16 kHz. This indicates that animals could feel tinnitus 2 h after salicylate injection, equivalent to that induced by 60 dB SPL and 16 kHz. By means of real-time PCR and western blot analysis, TRPV1 expression was significantly upregulated in spiral ganglion cells 2 h after salicylate injection and this upregulation together with the increase in the number of false positive responses was significantly suppressed by capsazepine (10 mg/kg i.p.), a specific antagonist of TRPV1. This suggests that salicylate could induce tinnitus through activation of TRPV1 in the rat auditory pathway.

Assessment of capsiconinoid composition, nonpungent capsaicinoid analogues, in capsicum cultivars.

Capsiconinoid is a group of nonpungent capsaicinoid analogues produced in Capsicum fruits, which we recently identified. Capsiconinoids have agonist activity for transient receptor potential vanilloid type 1 (TRPV1), which is reported to be a receptor for capsaicin. It is, therefore, important to screen cultivars containing high levels of capsiconinoid for their use as a vegetable or dietary supplement. This study describes the quantitative analysis of capsiconinoid content in fruits of 35 Capsicum cultivars: 18 cultivars of C. annuum, 7 of C. baccatum, 5 of C. chinense, 4 of C. frutescens, and 1 of C. pubescens. Using high-performance liquid chromatography (HPLC), we found that 10 cultivars contained capsiconinoids. Capsiconinoid Baccatum (CCB) (C. baccatum var. praetermissum) showed the highest capsiconinoid content (3314 microg/g DW) and Charapita (C. chinense) had the second highest content. The other 8 cultivars had much lower capsiconinoid content than these two cultivars (<300 microg/g DW). Time-course analysis during fruit development clarified that capsiconinoid content in CCB fruits increased until 30 days after flowering (DAF) and then decreased rapidly until 40 DAF.

Enhanced energy expenditure and fat oxidation in humans with high BMI scores by the ingestion of novel and non-pungent capsaicin analogues (capsinoids).

The biochemical and physiological indices were monitored in 44 subjects after 4-week capsinoids (capsaicin analogues with low pungency) intake. The subjects were randomly assigned to 3 groups: CSNs3 (3 mg/kg of capsinoids), CSNs10 (10 mg/kg of capsinoids) and the control (placebo). Measurements were performed in the morning on overnight-fasted subjects. The oxygen consumption (VO(2)), resting energy expenditure (REE) and fat oxidation increased slightly compared to pre-administration values without any adverse effects, although the increase was not significant. The increase in fat oxidation was positively and significantly correlated with the body mass index (BMI). A meta-analysis was therefore conducted on a subgroup consisting of subjects with BMI >or= 25 (n=28). As a result, not only VO(2) increased significantly (p<0.05) in the CSNs10 group, but also REE in the CSNs10 group and fat oxidation in the CSNs3 and CSNs10 groups tended to increase (p<0.1). Consequently, a capsinoids intake would be able to enhance the energy expenditure and fat burning in humans, particularly those with high BMI.

Assessment of pepper spray product potency in Asian and Caucasian forearm skin using transepidermal water loss, skin temperature and reflectance colorimetry.

Historically, pepper spray product potency has been established using a taste test evaluation. A taste test is subjective and may not be appropriate for assessing pepper potency in skin. The current study evaluated chemically diverse pepper sprays in human forearm skin using three objective, noninvasive parameters: transepidermal water loss, skin surface temperature and erythema, as a means for assessing dermal pharmacology, toxicology and product potency. Five commercial pepper spray products containing various capsaicinoid analogs at various concentrations were evaluated in duplicate on volar forearms of six Caucasians and six Asians using a 10 min exposure. Mean surface skin temperature, transepidermal water loss results were highly variable and therefore did not demonstrate dose responsive behavior to increasing capsaicinoid concentrations. Erythema, as measured by increases in a* (reflected light in the red-to-green color spectrum) of the L*a*b* uniform color scale, was superior among parameters evaluated in discriminating pepper spray potency and correlated well with the relative and total capsaicinoid concentration in the products. Products containing greater than 16 mg ml(-1) capsaicinoid concentration produced greater erythema responses in Caucasians than Asians. Asians responded greater to the synthetic analog, nonivamide, than to mixtures of capsaicinoids, while Caucasians responded equally to both capsaicinoid analogs. Thus, pepper spray product potency in human skin reflects the total capsaicinoid concentration, the specific capsaicin analog(s) present, and the race of the individual exposed. The finding that the reflectance colorimeter a* scale can differentiate these parameters in skin will have a significant impact on evaluating the use and efficacy of pepper spray products in humans.

An assessment of vascular pain using the flexor reflex in anesthetized rats.

This study assessed the flexor reflex induced by intraarterial algogenic drugs in anesthetized rats. The experiments were performed on male Sprague Dawley rats weighing 290-350 g. The animals were anesthetized with urethane (1.3 g/kg i.p.) and an arterial cannula was inserted to the level of the bifurcation of the femoral artery. The magnitude of the flexor reflex was examined by recording the electromyograph from the posterior biceps femoris/semitendinous muscles. Results showed that the flexor reflex evoked by intra-arterial injection of capsaicin (0.05-0.5 microg) was dose-dependent. A similar reflex resulted from pinching the toe of the hindlimb. These responses were inhibited by morphine (5 mg/kg s.c.) and restored with naloxone (1.5 mg/kg s.c.). Intraarterial preinjection of procaine (2%, 200 microl) and capsazepine (20 microg), which is a selective vanilloid receptor antagonist, inhibited the capsaicin-evoked response, but not that of pinching. These results indicate that the flexor reflex is a useful tool for assessing vascular pain in anesthetized animals.