RESUMEN
The objective of this work was to determine whether the addition of phytogenic compounds based on essential oils (carvacrol, eugenol, cinnamaldehyde) and resinous pepper oil (capsaicin) to the diet of Jersey cows at the beginning of lactation affects anti-inflammatory, antioxidant and immunomodulatory responses, as well as whether there are effects of EO on blood metabolites, ruminal fermentation, digestibility and milk production and composition. Six primiparous cows (370.00 ± 17 kg body weight (BW); 13.02 kg dry matter intake (DMI); 21 days of lactation and average milk production of 20 ± 2 L per day) were allocated to crossed experimental design (2 × 2) with two experimental periods of 28 days and two treatments. Blood, milk and rumen fluid were collected and, at the end of each period, feed and feces samples were collected to evaluate the apparent digestibility of nutrients. The groups were control (CLT) without supplementation and treated (BEO) with the addition of 150 mg/kg of dry matter of the phytogenic to the concentrated portion of the diet. Cows in the BEO group had lower numbers of leukocytes (P ≤ 0.05) and lymphocytes (P ≤ 0.02), but total protein and globulin levels were higher on days 21 and 28 (P ≤ 0.01). In the BEO group, the levels of immunoglobulin A, immunoglobulin heavy chain and transferrin were higher (P ≤ 0.05). The levels of ceruloplasmin, haptoglobin and C-reactive protein were lower in the BEO group (P ≤ 0.05). Lipid peroxidation levels and protein carbonyl content were lower in the BEO group. The total antioxidant capacity (P ≤ 0.09) and the activity of glutathione S-transferase (P ≤ 0.03) and glutathione peroxidase (P ≤ 0.05) were higher in the BEO group. Cows in the BEO group had lower pH (P ≤ 0.05), acetic acid concentrations (P ≤ 0.01) and higher protozoa counts (P ≤ 0.01). Our results suggest that phytogenic supplementation has positive effects on the health of Jersey cows in early lactation, characterized by immunostimulant, antioxidant and anti-inflammatory effects.
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Alimentación Animal , Antioxidantes , Capsaicina , Dieta , Lactancia , Aceites Volátiles , Animales , Bovinos , Femenino , Lactancia/efectos de los fármacos , Dieta/veterinaria , Aceites Volátiles/administración & dosificación , Aceites Volátiles/farmacología , Alimentación Animal/análisis , Capsaicina/administración & dosificación , Capsaicina/farmacología , Leche/química , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Suplementos Dietéticos/análisis , Rumen/metabolismoRESUMEN
Background and Objectives: This study aimed to evaluate the histological and biochemical effects of capsaicin on implant osseointegration and oxidative stress. Materials and Methods: Male Wistar albino rats weighing between 250 and 300 g were used in this study. Twenty-four rats were randomly divided into three equal groups: implant + control (n = 8), implant + capsaicin-1 (n = 8), and implant + capsaicin-2 (n = 8). Additionally, 2.5 mm diameter and 4 mm length titanium implants were surgically integrated into the corticocancellous bone parts of the femurs. In the treatment groups, rats were injected intraperitoneally with 25 mg/kg (implant + capsaicin-1) and 50 mg/kg (implant + capsaicin-2) of capsaicin. No additional applications were made in the control group. Three rats in total died during and after the experiment as a result of the analyses performed on 21 animals. Results: The highest total antioxidant status value was found in capsaicin dose 2, according to the analysis. The control group had the highest total oxidant status and oxidative stress index values, while group 2 of capsaicin had the lowest. After analysis, we found that there was no observed positive effect on osteointegration in this study (p > 0.05), although the bone implant connection was higher in the groups treated with capsaicin. Conclusions: A positive effect on osteointegration was not observed in this study. This may be due to osteoclast activation. However, it was found that it has a positive effect on oxidative stress. Osteoclast activation may be the cause of this phenomenon. Capsaicin was found to have a positive effect on oxidative stress (p < 0.05). It was also observed to have a positive effect on oxidative stress.
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Capsaicina , Oseointegración , Estrés Oxidativo , Ratas Wistar , Titanio , Animales , Capsaicina/farmacología , Capsaicina/administración & dosificación , Oseointegración/efectos de los fármacos , Masculino , Ratas , Estrés Oxidativo/efectos de los fármacos , Fémur/efectos de los fármacos , Fémur/cirugía , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/administración & dosificación , Distribución AleatoriaRESUMEN
PURPOSE: We examined the efficacy of topical capsaicin in reducing delayed chemotherapy-induced nausea and vomiting (CINV). METHODS: Adults on highly emetogenic chemotherapy regimens applied 2 g of capsaicin ointment (0.075%) or matching placebo four times a day to the abdomen for 5 days in addition to standard antiemetic regimen in this blinded randomized controlled trial. Patients were monitored for nausea and vomiting in the immediate (day 1), delayed (days 2-5), and extended phases (days 2-15). Self-reported incidence and daily episodes of CINV were compared between the groups. Onset, severity, need for rescue antiemetics, cumulative vomiting episodes, and safety were also compared. RESULTS: In total, 160 patients were enrolled. The final modified intention-to-treat population included 75 patients each in the capsaicin and placebo groups. Fewer patients experienced nausea (36.0% [n = 27] v 53.3% [n = 40]; P = .033) and vomiting (28.0% [n = 21] v 42.7% [n = 32]; P = .060) in the capsaicin arm during the delayed phase. During the extended phase, there was a significantly lower incidence of nausea (44% v 64.0%; P = .014) in the capsaicin arm. No difference in nausea (26.7% v 25.3%) or vomiting (22.7% v 18.7%) was evident in the immediate phase. The average daily episodes of nausea and vomiting were significantly fewer in the capsaicin arm during the delayed and extended phases. With capsaicin, no grade 3 nausea (9.3% v 0.0%; P = .007) was observed, and the time to first nausea and vomiting was significantly prolonged. There were no differences between the groups with respect to rescue antiemetics, unscheduled hospital visits, and adverse events. CONCLUSION: Topical capsaicin reduced the incidence of nausea and the average number of vomiting episodes during delayed and extended phases without increasing adverse effects.
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Capsaicina , Náusea , Vómitos , Humanos , Capsaicina/administración & dosificación , Capsaicina/efectos adversos , Vómitos/inducido químicamente , Vómitos/prevención & control , Vómitos/epidemiología , Náusea/inducido químicamente , Náusea/prevención & control , Náusea/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Administración Tópica , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Antieméticos/administración & dosificación , Antieméticos/uso terapéutico , Neoplasias/tratamiento farmacológicoRESUMEN
There is an urgent clinical need to develop nerve-blocking agents capable of inducing long duration sensory block without muscle weakness or paralysis to treat post-operative and chronic pain conditions. Here, we report a galacturonic acid-capsaicin (GalA-CAP) prodrug as an effective nociceptive-selective axon blocking agent. Capsaicin selectively acts on nociceptive signaling without motor nerve blockade or disruption of proprioception and touch sensation, and the galacturonic acid moiety enhance prodrug permeability across the restrictive peripheral nerve barriers (PNBs) via carrier-mediated transport by the facilitative glucose transporters (GLUTs). In addition, following prodrug transport across PNBs, the inactive prodrug is converted to active capsaicin through linker hydrolysis, leading to sustained drug release. A single injection of GalA-CAP prodrug at the sciatic nerves of rats led to nociceptive-selective nerve blockade lasting for 234 ± 37 h, which is a sufficient duration to address the most intense period of postsurgical pain. Furthermore, the prodrug markedly mitigated capsaicin-associated side effects, leading to a notable decrease in systemic toxicity, benign local tissue reactions, and diminished burning and irritant effects.
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Capsaicina , Bloqueo Nervioso , Profármacos , Ratas Sprague-Dawley , Nervio Ciático , Profármacos/administración & dosificación , Animales , Capsaicina/administración & dosificación , Capsaicina/análogos & derivados , Masculino , Nervio Ciático/efectos de los fármacos , Bloqueo Nervioso/métodos , Ratas , Analgésicos/administración & dosificación , Analgésicos/farmacologíaRESUMEN
While treatment side effects may adversely impact patients, they could also potentially function as indicators for effective treatment. In this study, we investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes. In this pre-registered trial (DRKS00026648), 77 healthy participants were made to believe that they will receive fentanyl nasal sprays before receiving thermal pain in a controlled experimental setting. However, nasal sprays did not contain fentanyl, rather they either contained capsaicin to induce a side effect (mild burning sensation) or saline (inert). After the first session, participants were randomized to two groups and underwent functional MRI. One group continued to believe that the nasal sprays could contain fentanyl while the other group was explicitly informed that no fentanyl was included. This allowed for the independent manipulation of the side effects and the expectation of pain relief. Our results revealed that nasal sprays with a side effect lead to lower pain than inert nasal sprays without side effects. The influence of side effects on pain was dependent on individual beliefs about how side effects are related to treatment outcome, as well as on expectations about received treatment. Functional MRI data indicated an involvement of the descending pain modulatory system including the anterior cingulate cortex and the periaqueductal gray during pain after experiencing a nasal spray with side effects. In summary, our data show that mild side effects can serve as a signal for effective treatment thereby influencing treatment expectations and outcomes, which is mediated by the descending pain modulatory system. Using these mechanisms in clinical practice could provide an efficient way to optimize treatment outcome. In addition, our results indicate an important confound in clinical trials, where a treatment (with potential side effects) is compared to placebo.
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Capsaicina , Fentanilo , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Adulto , Fentanilo/efectos adversos , Fentanilo/uso terapéutico , Capsaicina/efectos adversos , Capsaicina/administración & dosificación , Resultado del Tratamiento , Adulto Joven , Rociadores Nasales , Dolor/tratamiento farmacológico , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Administración Intranasal , Dimensión del Dolor/métodos , Manejo del Dolor/métodosRESUMEN
Osteoarthritis (OA) affects hundreds of millions of people worldwide. The objective was to critically appraise the efficacy and safety of topical capsaicin in reducing pain in OA. MEDLINE (PubMed) and Embase (Ebsco) were searched from inceptions until February 2023. The eligibility criteria included randomized controlled trials (RCTs), evaluating topical capsaicin in OA patients. Standard Cochrane methods were used to extract data and to appraise eligible studies. Eight double-blind RCTs involving 498 patients were included. Five trials (62.5%) were at an overall low risk of bias, and three (37.5%) were at a high risk of bias. Meta-analysis showed that, in various OA patients, compared with placebo, topical capsaicin (0.0125%-5%) may reduce pain severity measured with visual analog scale (standardized mean difference = -0.84, 95% confidence intervals [CIs] = -1.48 to -0.19, p = 0.01; eight studies). However, topical capsaicin may increase burning sensation at the application site (risk ratio = 5.56, 95% CI = 1.75-17.69, p = 0.004, numbers needed to harm = 3; five studies) when compared with placebo. Limitations include short study durations, small sample sizes, high heterogeneity, and overall low-to-very-low certainty of the evidence. Topical capsaicin may reduce OA pain at follow-ups of up to 3 months. Larger trials, potentially evaluating capsaicin in combination with phytopharmaceuticals having anti-inflammatory effects, with longer follow-ups might be needed to reduce the existing uncertainties. Topical capsaicin might be recommended for short-term management of pain in OA patients intolerant to nonsteroidal anti-inflammatory drugs.
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Administración Tópica , Capsaicina , Osteoartritis , Capsaicina/administración & dosificación , Capsaicina/uso terapéutico , Humanos , Osteoartritis/tratamiento farmacológico , Dolor/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: gustatory ability is a marker of health not routinely tested in the medical practice. The current study wants to assess whether taste strips can be useful to monitor taste function from home. METHODS: we performed simple sensory tests in lab setting vs. unassisted testing at home, and compared the results with self-reports ability to taste and smell. Using paper strips impregnated with sweet, bitter, salty, or sour tastants, and with two trigeminal stimuli (capsaicin, tannins) in high and low concentrations, we assessed gustatory and trigeminal function in 74 participants (47 women) in the lab, where paper strips were administered by an experimenter, and in 77 participants (59 women) at home, where they self-administered the test. RESULTS: we found that high (but not low) concentration taste strips are correctly identified by vast majority of participants. On average, taste identification, intensity and pleasantness scores did not differ for the 8 taste strips, while identification of capsaicin was significantly better in the lab. Taste identification scores correlated with intensity ratings in both settings (r = 0.56, in the lab, r = 0.48, at home, p < 0.005). Self-rated taste ability correlated with self-rated smell ability (r = 0.68, and r = 0.39, p ≤ 0.005), but not with scores in the strips test. CONCLUSION: home testing with impregnated taste strips is feasible, and can be used for telemedical purposes.
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Estudios de Factibilidad , Gusto , Nervio Trigémino , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Gusto/fisiología , Nervio Trigémino/fisiología , Adulto Joven , Anciano , Olfato/fisiología , Capsaicina/administración & dosificaciónRESUMEN
BACKGROUND: Nonopioid management of postsurgical pain remains a major unmet need. Few studies have evaluated transient receptor potential vanilloid subfamily member 1 agonists for analgesia after surgery. This study examines intraoperative vocacapsaicin, a novel prodrug of the transient receptor potential vanilloid subfamily member 1 agonist capsaicin, in a validated model of postsurgical pain. METHODS: This was a triple-blinded, randomized, placebo-controlled, dose-ranging trial in patients undergoing bunionectomy. Patients were randomized 1:1:1:1 to surgical site administration of 14 ml of placebo or one of three vocacapsaicin concentrations: 0.30, 0.15, or 0.05 mg/ml. The prespecified primary endpoint was the area-under-the-curve of the numerical rating scale pain score at rest through 96 h for the 0.30 mg/ml group. Prespecified ordered, secondary endpoints for the 0.30 mg/ml group included the percentage of patients who did not require opioids from 0 to 96 h, total opioid consumption through 96 h, and the area-under-the-curve of the numerical rating scale pain score for the first week. RESULTS: The 147 patients were randomized. During the first 96 h, vocacapsaicin (0.30 mg/ml) reduced pain at rest by 33% versus placebo (primary endpoint, 95% CI [10%, 52%], effect size [Cohen's d] = 0.61, P = 0.005). Of patients receiving vocacapsaicin (0.30 mg/ml), 26% did not require postoperative opioids for analgesia (P = 0.025) versus 5% of patients receiving placebo. Vocacapsaicin (0.30 mg/ml) reduced opioid consumption over the first 96 h by 50% versus placebo (95% CI [26%, 67%], effect size = 0.76, P = 0.002). Vocacapsaicin (0.30 mg/ml) reduced pain over the first week by 37% versus placebo (95% CI [12%, 57%], effect size = 0.62, P = 0.004). The treatment effect persisted for at least 2 weeks. All study endpoints showed an administered concentration-versus-response relationship. Vocacapsaicin was well tolerated with no differences between groups in any safety parameter. CONCLUSIONS: A single, local administration of vocacapsaicin during surgery reduced pain and opioid consumption for at least 96 h after surgery compared to control.
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Capsaicina , Dimensión del Dolor , Dolor Postoperatorio , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Capsaicina/administración & dosificación , Capsaicina/uso terapéutico , Dimensión del Dolor/métodos , Dimensión del Dolor/efectos de los fármacos , Resultado del Tratamiento , Método Doble Ciego , Relación Dosis-Respuesta a Droga , Adulto , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Hallux Valgus/cirugía , Profármacos/administración & dosificación , Canales Catiónicos TRPVRESUMEN
Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.
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Enfermedades Metabólicas , Obesidad , Animales , Obesidad/metabolismo , Obesidad/terapia , Ratones , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/terapia , Enfermedades Metabólicas/tratamiento farmacológico , Eje Cerebro-Intestino , Titanio/química , Capsaicina/farmacología , Capsaicina/administración & dosificación , Administración Oral , Terapia por Estimulación Eléctrica/métodos , Ratones Endogámicos C57BL , Masculino , Compuestos de BarioRESUMEN
OBJECTIVE: The aim of this study was to evaluate patient characteristics, concomitant analgesic medication, and pain intensity in a real-world setting in Germany, focusing on the repeated application of high-concentration capsaicin patch (HCCP) for neuropathic pain. DESIGN: Data were collected from electronic medical records of patients who received at least two HCCP treatments between January 2011 and July 2022. Subgroup analyses were performed based on the number of HCCP treatments, age groups, and specific neuropathic pain conditions. SETTING: The study was conducted at an outpatient pain center in Wiesbaden, Germany. SUBJECTS: The study included 97 patients, primarily diagnosed with neuropathic back pain, postoperative or post-traumatic neuropathic pain, and postherpetic neuralgia. METHODS: The daily dose of concomitant medications (eg, opioids and anticonvulsants) at the start of capsaicin therapy was compared with the average within 2 years of capsaicin therapy. The last observation carried forward method was used if HCCP treatment was discontinued before the end of the 2-year period. RESULTS: The majority of patients received concomitant medications, with opioids, anticonvulsants, and antidepressants being the most common. The average daily morphine equivalent dose decreased significantly during HCCP treatment. Pain intensity at baseline was generally high, but substantial improvements were observed in patients who received at least three HCCP applications. CONCLUSIONS: This study provides evidence for the effectiveness of HCCP treatment in reducing pain intensity and concomitant opioid use in patients with neuropathic pain. Further research is needed to explore the long-term outcomes and optimal treatment regimens for different patient populations.
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Capsaicina , Neuralgia , Parche Transdérmico , Humanos , Capsaicina/administración & dosificación , Femenino , Masculino , Neuralgia/tratamiento farmacológico , Neuralgia/etiología , Estudios Retrospectivos , Persona de Mediana Edad , Alemania/epidemiología , Anciano , Adulto , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Resultado del Tratamiento , Fármacos del Sistema Sensorial/administración & dosificación , Dimensión del Dolor/métodos , Analgésicos/administración & dosificación , Analgésicos/uso terapéutico , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Capsaicin is a highly selective agonist of the transient receptor potential vanilloid 1. The adhesive capsaicin patch provides a high capsaicin concentration (8%) directly in the painful area - its efficacy in benign peripheral neuropathic pain (diabetic neuropathy or postherpetic neuralgia) has recently been described in the literature. However, there is scant evidence of its efficacy in chemotherapy-induced peripheral neuropathy (CIPN). This is a concern for patients with multiple myeloma, who suffer from peripheral neuropathic pain induced by first-line treatments (bortezomib or thalidomide). AIM: To describe improved control of CIPN in patients with multiple myeloma using adhesive capsaicin 8% patch. METHODS: We opted for a retrospective observational case series. Between October 2017 and October 2020, we collected clinical data from adult multiple myeloma patients affected by CIPN who were administered the capsaicin 8% patch in our palliative care outpatient clinic. We compiled Numerical Pain Rating Scale (NPRS) scores, patients' medication needs and performance status before and after patch application. RESULTS: Two women and five men with an average age of 62.85 years received bortezomib. Two patients (28.57% of the sample) also received thalidomide. The average NPRS score before patch application was 6.42/10. Five of the seven patients (71.42%) received a mean daily oral morphine dose of 52.85â mg/day, five (71.42%) received gabapentinoids and one (14.28%) received antidepressants. The average NPRS score decreased to 4/10 seven days after patch application, while the mean daily oral morphine dose remained stable. Performance status improved slightly in two patients (28.57%) and remained stable in the rest. One patient (14.28%) required an extra analgesic dose during patch application. CONCLUSIONS: Capsaicin 8% patch application appears to reduce pain intensity in patients with multiple myeloma suffering from CIPN.
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Bortezomib , Capsaicina , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Capsaicina/administración & dosificación , Anciano , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Bortezomib/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Parche Transdérmico , Talidomida/administración & dosificación , Talidomida/efectos adversos , Talidomida/uso terapéutico , Dimensión del Dolor , Neuralgia/tratamiento farmacológico , Neuralgia/inducido químicamenteRESUMEN
ABSTRACT: Growing evidence has suggested that time-varying functional connectivity between different brain regions might underlie the dynamic experience of pain. This study used a novel, data-driven framework to characterize the dynamic interactions of large-scale brain networks during sustained pain by estimating recurrent patterns of phase-synchronization. Resting-state functional magnetic resonance imaging signals were collected from 50 healthy participants before (once) and after (twice) the onset of sustained pain that was induced by topical application of capsaicin cream. We first decoded the instantaneous phase of neural activity and then applied leading eigenvector dynamic analysis on the time-varying phase-synchronization. We identified 3 recurrent brain states that show distinctive phase-synchronization. The presence of state 1, characterized by phase-synchronization between the default mode network and auditory, visual, and sensorimotor networks, together with transitions towards this brain state, increased during sustained pain. These changes can account for the perceived pain intensity and reported unpleasantness induced by capsaicin application. In contrast, state 3, characterized by phase-synchronization between the cognitive control network and sensory networks, decreased after the onset of sustained pain. These results are indicative of a shift toward internally directed self-referential processes (state 1) and away from externally directed cognitive control processes (state 3) during sustained pain.
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Encéfalo , Capsaicina , Imagen por Resonancia Magnética , Dolor , Humanos , Masculino , Femenino , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Dolor/fisiopatología , Dolor/diagnóstico por imagen , Dolor/psicología , Adulto Joven , Capsaicina/administración & dosificación , Descanso/fisiología , Mapeo Encefálico , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Dimensión del Dolor/métodosRESUMEN
Ulcerative colitis (UC) is an inflammatory disease with chronic relapsing symptoms. This study investigated the effects of Lycium barbarum polysaccharides (LBP) and capsaicin (CAP) in dextran sulfate sodium (DSS)-induced UC rats. Rats were divided into normal, DSS-induced UC, and UC treated with 100 mg LBP/kg bw, 12 mg CAP/kg bw, or 50 mg LBP/kg bw and 6 mg CAP/kg bw. Rats were fed LBP or CAP orally by gavage for 4 weeks, and UC model was established by feeding 5% DSS in drinking water for 6 days during week 3. Oral CAP and mixture significantly reduced disease activity index. Oral LBP significantly decreased serum malondialdehyde, interleukin (IL)-6, colonic tumor necrosis factor (TNF)-α levels, and protein expression of transient receptor potential cation channel V1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1), but increased serum catalase activity. Oral CAP significantly suppressed serum IL-6, colonic TRPV1 and TRPA1 protein expression, but elevated IL-10 levels, serum superoxide dismutase and catalase activities. The mixture of LBP and CAP significantly reduced serum IL-6, colonic TNF-α and TRPA1 protein. In conclusion, administration of LBP and/or CAP attenuate DSS-induced UC symptoms through inhibiting oxidative stress, proinflammatory cytokines, and protein expression of TRPV1 and TRPA1.
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Capsaicina/administración & dosificación , Colitis Ulcerosa/tratamiento farmacológico , Sulfato de Dextran/efectos adversos , Medicamentos Herbarios Chinos/administración & dosificación , Proteínas de Fase Aguda/metabolismo , Animales , Capsaicina/farmacología , Proteínas Portadoras/metabolismo , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/inmunología , Medicamentos Herbarios Chinos/farmacología , Interleucina-10/metabolismo , Interleucina-6/sangre , Masculino , Glicoproteínas de Membrana/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Canal Catiónico TRPA1/metabolismo , Canales Catiónicos TRPV/metabolismoRESUMEN
A reverse-phase high-performance liquid chromatography method was developed to determine and quantify capsaicin (trans-8-methyl-N-vanillyl-6- nonenamid), dihydrocapsaicin (8-methyl-N-vanillylnonanamide), and camphor (trimethylbicyclo[2.2.1]heptan-2-one). It is applicable in analyses of over-the-counter (OTC) medications for topical use and raw materials such as chili pepper oleoresin. Chromatographic separation was carried out on a C18 column using an isocratic flow of the mobile phase containing acetonitrile and ultrapure water in a ratio of 2:3, with pH adjusted to 3.2 using glacial acetic acid, and a flow rate of 1.5 mL/min. The concentration of the eluting compounds was monitored by a diode-array detector at a wavelength of 281 nm. The method was evaluated for several validation parameters, including selectivity, accuracy (confidence intervals < 0.05%), repeatability, and intermediate precision. The limit of detection (LOD) was determined to be 0.070 µg/mL for capsaicin, 0.211 µg/mL for dihydrocapsaicin, and 0.060 µg/mL for camphor. The limit of quantification (LOQ) was determined to be 0.212 µg/mL for capsaicin, 0.640 µg/mL for dihydrocapsaicin, and 0.320 µg/mL for camphor. Linearity was set in the range of 2.5-200 µg/mL for capsaicin and dihydrocapsaicin and 25-2000 µg/mL for camphor. The suggested analytical method can be used for quality control of formulated pharmaceutical products containing capsaicinoids, camphor, and propolis.
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Alcanfor/análisis , Alcanfor/química , Capsaicina/análisis , Capsaicina/química , Cromatografía Líquida de Alta Presión , Medicamentos sin Prescripción/análisis , Medicamentos sin Prescripción/química , Administración Tópica , Alcanfor/administración & dosificación , Capsaicina/administración & dosificación , Capsaicina/análogos & derivados , Fraccionamiento Químico/métodos , Cromatografía Líquida de Alta Presión/métodos , Estructura Molecular , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Capsaicin (CAP) activates the transient receptor potential vanilloid 1 (TRPV1) channel on sensory neurons, improving ATP production, vascular function, fatigue resistance, and thus exercise performance. However, the underlying mechanisms of CAP-induced ergogenic effects and fatigue-resistance, remain elusive. To evaluate the potential anti-fatigue effects of CAP, 10 young healthy males performed constant-load cycling exercise time to exhaustion (TTE) trials (85% maximal work rate) after ingestion of placebo (PL; fiber) or CAP capsules in a blinded, counterbalanced, crossover design, while cardiorespiratory responses were monitored. Fatigue was assessed with the interpolated twitch technique, pre-post exercise, during isometric maximal voluntary contractions (MVC). No significant differences (p > 0.05) were detected in cardiorespiratory responses and self-reported fatigue (RPE scale) during the time trial or in TTE (375 ± 26 and 327 ± 36 s, respectively). CAP attenuated the reduction in potentiated twitch (PL: -52 ± 6 vs. CAP: -42 ± 11%, p = 0.037), and tended to attenuate the decline in maximal relaxation rate (PL: -47 ± 33 vs. CAP: -29 ± 68%, p = 0.057), but not maximal rate of force development, MVC, or voluntary muscle activation. Thus, CAP might attenuate neuromuscular fatigue through alterations in afferent signaling or neuromuscular relaxation kinetics, perhaps mediated via the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps, thereby increasing the rate of Ca2+ reuptake and relaxation.
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Rendimiento Atlético/fisiología , Capsaicina/administración & dosificación , Ejercicio Físico/fisiología , Fatiga Muscular/efectos de los fármacos , Sustancias para Mejorar el Rendimiento/administración & dosificación , Ciclismo/fisiología , Estudios Cruzados , Prueba de Esfuerzo , Voluntarios Sanos , Humanos , Inflamación , Contracción Isométrica/efectos de los fármacos , Masculino , Músculo Esquelético/efectos de los fármacos , Método Simple Ciego , Adulto JovenRESUMEN
BACKGROUND: Bioactive dietary constituents activating Transient receptor potential (TRP) channels have emerged as promising candidates for the prevention of metabolic disorders. OBJECTIVE: The present study is an attempt to evaluate anti-obesity potential of a dietary TRP-based tri-agonist, combination of sub-effective doses of capsaicin (TRPV1 agonist), menthol (TRPM8 agonist), and cinnamaldehyde (TRPA1 agonist) in high-fat diet (HFD)-fed mice. DESIGN: Male C57BL/6 J mice divided into three groups (n = 8), were fed on normal pellet diet (NPD), or high-fat diet (HFD) (60% energy by fat) and HFD + CB (combination of capsaicin 0.4 mg/Kg, menthol 20 mg/Kg, and cinnamaldehyde 2 mg/Kg; p.o) for 12 weeks. Effects on HFD-induced weight gain, biochemical, histological and genomic changes in the WAT, BAT, liver and hypothalamus tissues were studied. RESULTS: Administration of tri-agonist prevented HFD-induced increase in weight gain, improved altered morphometric parameters, glucose homeostasis, and adipose tissue hypertrophy. Tri-agonist supplementation was found to induce browning of white adipose tissue and promote brown adipose tissue activation. Enhanced glucose utilization and prevention of lipid accumulation and insulin resistance in the liver was observed in mice supplemented with a tri-agonist. CONCLUSION: The present work provides evidence that the new approach based on combination of sub-effective doses of TRP channel agonists (TRI-AGONIST) can be employed to develop concept-based functional food for therapeutic and preventive strategies against HFD-associated pathological complications.
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Metabolismo Energético/efectos de los fármacos , Canales de Potencial de Receptor Transitorio/agonistas , Acroleína/administración & dosificación , Acroleína/análogos & derivados , Acroleína/uso terapéutico , Animales , Capsaicina/administración & dosificación , Capsaicina/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Dieta Alta en Grasa/métodos , Modelos Animales de Enfermedad , Mentol/administración & dosificación , Mentol/uso terapéutico , Ratones , Ratones Endogámicos C57BL/crecimiento & desarrollo , Ratones Endogámicos C57BL/metabolismo , Fenotipo , Canales de Potencial de Receptor Transitorio/farmacologíaRESUMEN
ABSTRACT: Neuroimaging studies have revealed important pathomechanisms related to disorders of brain-gut interactions, such as irritable bowel syndrome and functional dyspepsia. More detailed investigations aimed at neural processing in the brainstem, including the key relay station of the nucleus of the solitary tract (NTS), have hitherto been hampered by technical shortcomings. To ascertain these processes in more detail, we used multiecho multiband 7T functional magnetic resonance imaging and a novel translational experimental model based on a nutrient-derived intestinal chemonociceptive stimulus. In a randomized cross-over fashion, subjects received duodenal infusion of capsaicin (the pungent principle in red peppers) and placebo (saline). During infusion, functional magnetic resonance imaging data and concomitant symptom ratings were acquired. Of 26 healthy female volunteers included, 18 were included in the final analysis. Significantly increased brain activation over time during capsaicin infusion, as compared with placebo, was observed in brain regions implicated in pain processing, in particular the NTS. Brain activation in the thalamus, cingulate cortex, and insula was more pronounced in subjects who reported abdominal pain (visual analogue scale > 10 mm), as compared with subjects who experienced no pain. On the contrary, activations at the level of the NTS were independent of subjective pain ratings. The current experimental paradigm therefore allowed us to demonstrate activation of the principal relay station for visceral afferents in the brainstem, the NTS, which was engaged irrespective of the conscious pain response. These findings contribute to understanding the fundamental mechanism necessary for developing novel therapies aimed at correcting disturbances in visceral afferent pain processing.
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Núcleo Solitario , Dolor Visceral , Encéfalo , Mapeo Encefálico , Capsaicina/administración & dosificación , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Núcleo Solitario/fisiología , Dolor Visceral/diagnóstico por imagen , Dolor Visceral/tratamiento farmacológicoRESUMEN
Because of a possible impact of capsaicin in the high concentrations on enterocyte injury (cytotoxicity) and bactericidal activity on probiotics, Lactobacillus rhamnosus L34 (L34) and Lactobacillus rhamnosus GG (LGG), the probiotics derived from Thai and Caucasian population, respectively, were tested in the chili-extract administered C57BL/6 mice and in vitro experiments. In comparison with placebo, 2 weeks administration of the extract from Thai chili in mice caused loose feces and induced intestinal permeability defect as indicated by FITC-dextran assay and the reduction in tight junction molecules (occludin and zona occludens-1) using fluorescent staining and gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the chili extracts also induced the translocation of gut pathogen molecules; lipopolysaccharide (LPS) and (1â3)-ß-d-glucan (BG) and fecal dysbiosis (microbiome analysis), including reduced Firmicutes, increased Bacteroides, and enhanced total Gram-negative bacteria in feces. Both L34 and LGG attenuated gut barrier defect (FITC-dextran, the fluorescent staining and gene expression of tight junction molecules) but not improved fecal consistency. Additionally, high concentrations of capsaicin (0.02-2 mM) damage enterocytes (Caco-2 and HT-29) as indicated by cell viability test, supernatant cytokine (IL-8), transepithelial electrical resistance (TEER) and transepithelial FITC-dextran (4.4 kDa) but were attenuated by Lactobacillus condition media (LCM) from both probiotic-strains. The 24 h incubation with 2 mM capsaicin (but not the lower concentrations) reduced the abundance of LGG (but not L34) implying a higher capsaicin tolerance of L34. However, Lactobacillus rhamnosus fecal abundance, using qRT-PCR, of L34 or LGG after 3, 7, and 20 days of the administration in the Thai healthy volunteers demonstrated the similarity between both strains. In conclusion, high dose chili extracts impaired gut permeability and induced gut dysbiosis but were attenuated by probiotics. Despite a better capsaicin tolerance of L34 compared with LGG in vitro, L34 abundance in feces was not different to LGG in the healthy volunteers. More studies on probiotics with a higher intake of chili in human are interesting.
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Capsaicina/efectos adversos , Disbiosis/prevención & control , Tracto Gastrointestinal/efectos de los fármacos , Inflamación/prevención & control , Lacticaseibacillus rhamnosus/química , Probióticos/administración & dosificación , Adolescente , Adulto , Anciano , Animales , Antibacterianos/administración & dosificación , Antipruriginosos/administración & dosificación , Antipruriginosos/efectos adversos , Capsaicina/administración & dosificación , Citocinas/metabolismo , Disbiosis/inducido químicamente , Disbiosis/microbiología , Disbiosis/patología , Heces/microbiología , Femenino , Tracto Gastrointestinal/microbiología , Humanos , Inflamación/inducido químicamente , Inflamación/microbiología , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Extractos Vegetales/administración & dosificación , Extractos Vegetales/efectos adversos , Probióticos/efectos adversos , Uniones Estrechas , Adulto JovenRESUMEN
The present study examined contribution of the transient receptor potential vanilloid 1 channel (TRPV1) to the chronic orofacial pain. Bilateral partial nerve ligation (PNL) of the mental nerve, a branch of trigeminal nerve, was performed to induce neuropathic pain. The withdrawal threshold in response to mechanical stimulation of the lower lip skin was substantially reduced after the surgery in the PNL rats while it remained unchanged in the sham rats. This reduction in the PNL rats was alleviated by pregabalin injected intraperitoneally (10 mg/kg) and intracisternally (10, 30, 100 µg). Furthermore, an intracisternal injection of AMG9810, an antagonist of TRPV1, (1.5, 5.0 µg) attenuated the reduction of withdrawal threshold. Spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) were recorded from the spinal trigeminal subnucleus caudalis (Vc) neurons in the brainstem slice, which receive the orofacial nociceptive signals. In the PNL rats, superfusion of capsaicin (0.03, 0.1 µM) enhanced their frequency without effect on the amplitude and the highest concentration (0.3 µM) increased both the frequency and amplitude. In the sham rats, only 0.3 µM capsaicin increased their frequency. Thus, capsaicin-induced facilitation of sEPSCs and mEPSCs in the PNL rats was significantly stronger than that in the sham rats. AMG9810 (0.1 µM) attenuated the capsaicin's effect. Capsaicin was ineffective on the trigeminal tract-evoked EPSCs in the PNL and sham rats. These results suggest that the chronic orofacial pain in the PNL model results from facilitation of the spontaneous excitatory synaptic transmission in the Vc region through TRPV1 at least partly.
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Dolor Crónico/patología , Dolor Facial/patología , Neuralgia/patología , Canales Catiónicos TRPV/metabolismo , Núcleo Caudal del Trigémino/metabolismo , Animales , Capsaicina/administración & dosificación , Capsaicina/toxicidad , Dolor Crónico/inducido químicamente , Dolor Crónico/tratamiento farmacológico , Modelos Animales de Enfermedad , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Dolor Facial/inducido químicamente , Dolor Facial/tratamiento farmacológico , Humanos , Masculino , Neuralgia/inducido químicamente , Neuralgia/tratamiento farmacológico , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratas , Transmisión Sináptica/efectos de los fármacos , Canales Catiónicos TRPV/antagonistas & inhibidores , Núcleo Caudal del Trigémino/citología , Núcleo Caudal del Trigémino/efectos de los fármacosRESUMEN
Dry cough has been reported in patients receiving statin therapy. However, the underlying mechanism or other possible alterations in the airways induced by statins remain unknown. Thus, the aim of this study was to evaluate whether simvastatin promotes alterations in airways, such as bronchoconstriction and plasma extravasation, as well as the mechanism involved in these events. Using methods to detect alterations in airway resistance and plasma extravasation, we demonstrated that simvastatin [20 mg/kg, intravenous (i.v.)] caused plasma extravasation in the trachea (79.8 + 14.8 µg/g/tissue) and bronchi (73.3 + 8.8 µg/g/tissue) of rats, compared to the vehicle (34.2 + 3.6 µg/g/tissue and 29.3 + 5.3 µg/g/tissue, respectively). NG-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg, intraperitoneal), a nitric oxide (NO) synthase inhibitor, Icatibant [HOE 140, 10 nmol/50 µl, intratracheal (i.t.)], a bradykinin B2 antagonist, and capsazepine (100 nmol/50 µl, i.t.), a TRPV1 antagonist, attenuated simvastatin-induced plasma extravasation. Simvastatin (5, 10 and 20 mg/kg) did not cause bronchoconstriction per se, but exacerbated the bronchoconstrictive response to bradykinin (30 nmol/kg, i.v.), a B2 agonist (0.7 + 0.1 ml/H2O), or capsaicin (30 nmol/kg, i.v.), a TRPV1 agonist (0.8 + 0.1 ml/H2O), compared to the vehicle (0.1 + 0.04 ml/H2O and 0.04 + 0.01 ml/H2O, respectively). The bronchoconstriction elicited by bradykinin (100 nmol/kg, i.v.) in simvastatin non-treated rats was inhibited by L-NAME. The exacerbation of bronchoconstriction induced by bradykinin or capsaicin in simvastatin-treated rats was inhibited by L-NAME, HOE 140 or capsazepine. These results suggest that treatment with simvastatin promotes the release of bradykinin, which, via B2 receptors, releases NO that can then activate the TRPV1 to promote plasma extravasation and bronchoconstriction.