Lycium barbarum Polysaccharides and Capsaicin Inhibit Oxidative Stress, Inflammatory Responses, and Pain Signaling in Rats with Dextran Sulfate Sodium-Induced Colitis.

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.

Lactobacillus rhamnosus attenuates Thai chili extracts induced gut inflammation and dysbiosis despite capsaicin bactericidal effect against the probiotics, a possible toxicity of high dose capsaicin.

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 (1→3)-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.

Interest of a standardized hypnotic message for the reduction of pain and anxiety in cancer patients treated by capsaicin patch for neuropathic pain: a randomized controlled trial.

BACKGROUND: Neuropathic pain is characterized by spontaneous painful symptoms. Medical therapies include the use of a capsaicin 8% patch (Qutenza®, Grünenthal Gmbh, Germany), and patients may experience a sharp burning sensation at application and removal of the patch. This study aimed to evaluate the impact of playing a standardized hypnosis recording during application, on the pain and anxiety induced by capsaicin treatment. METHODS: In a randomized, controlled trial, we assessed the benefits of the intervention firstly on pain and secondly on anxiety, as measured using numerical rating scales. All patients had application of the capsaicin patch, including the possibility for the patient to apply a cold patch. Participants were randomly assigned to one of 3 groups, namely the "Standard group" (no intervention), "Hypnosis group", in which a standardized hypnotic message was played during application, or the "Music group" in which relaxing music was played during application of the patch. RESULTS: Sixty-nine patients were included. Overall, there was no significant difference in pain scores between groups (p = 0.355). Compared to standard application, anxiety was significantly lower in the hypnosis group after application (p = 0.007), with no significant difference between the standard and music arms (p = 0.271), or between the hypnosis and music arms (p = 0.423). CONCLUSIONS: Listening to a standardized hypnotic message during application of a capsaicin patch was found to significantly lower anxiety. These findings indicate that the use of a hypnotic message can reduce discomfort and warrant its evaluation in other indications of pain or anxiety during treatment procedures. TRIAL REGISTRATION: NCT02822625 .

Evaluation of In Vitro Capsaicin Release and Antimicrobial Properties of Topical Pharmaceutical Formulation.

(1) Background: Capsaicin is the main capsaicinoid of the Capsicum genus and it is responsible for the pungent taste. Medical uses of the fruits of chili peppers date from the ancient time until nowadays. Most of all, they are used topically as analgesic in anti-inflammatory diseases as rheumatism, arthritis and in diabetic neuropathy. Reports state that the Capsicum genus, among other plant genera, is a good source of antimicrobial and antifungal compounds. The aim of this study was the preparation of a pharmaceutical Carbopol-based formulation containing capsaicin and the evaluation of its in vitro release and antimicrobial and antifungal properties. (2) Methods: It was first stabilized with an extraction method from the Capsicum annuum fruits with 98% ethanol and then the identification and determination of Capsaicin in this extract was realized by HPLC. (3) Results and Conclusions: Rheological analyses revealed that the selected formulation exhibited a pseudo-plastic behavior. In vitro release studies of capsaicin from a Carbopol-based formulation reported that approximately 50% of capsaicin was release within 52 h. Additionally, the Carbopol-based formulation significantly increased the antimicrobial effects of capsaicin towards all tested bacteria and fungi strains.

Efficacy of topical capsaicin for the treatment of cannabinoid hyperemesis syndrome: A retrospective cohort study.

BACKGROUND: Cannabis Hyperemesis Syndrome (CHS) is a clinical disorder characterized by abdominal pain and intractable vomiting among patients with chronic marijuana use. We sought to assess the efficacy of capsaicin to determine whether it could reduce ED length of stay in patients with CHS. METHODS: his retrospective observational study was conducted among patients with CHS. Patients were classified based on whether they received capsaicin, which was pseudorandomized and dependent on the pharmacist available. Outcomes included time to discharge, number of medications given, bounceback rate, and admission rate. Statistical analyses included t-tests, survival analyses, and cox regressions. RESULTS: 55 patients (35 capsaicin, 20 no capsaicin) met inclusion criteria. There was no difference in time to discharge between the experimental and control groups (4.46 h vs 3.52 h, p = 0.10), rounds of medications given (2.60 vs 3.54, p = 0.09), bounceback rate within 24 h (0.11 vs 0.10, p = 0.43), or admission rate to the hospital (0.19 vs 0.05, p = 0.07). A survival analysis and cox regression showed no difference in time to discharge. A subgroup analysis between patients who received capsaicin within their first two rounds of treatment had statistically significantly shorter length of stays than patients who received capsaicin afterwards, (4.83 h vs 7.09 h, p = 0.01). CONCLUSION: Topical capsaicin was not associated with shorter length of stays than no capsaicin. When given earlier during an ED visit, it is associated with a shorter length of stay than when given later.

Treatment and Management of Loin Pain Hematuria Syndrome.

PURPOSE OF REVIEW: Loin pain hematuria syndrome (LPHS) is rare and seldom diagnosed, yet it has a particularly significant impact on those affected. This is a review of the latest and seminal evidence of the pathophysiology and diagnosis of LPHS and presents the typical clinical presentation and treatment options available. RECENT FINDINGS: LPHS is typically found in young women with characteristic symptoms, including severe recurrent flank pain and gross or microscopic hematuria. The majority of patients will experience crippling pain for many years without effective therapy, often requiring frequent use of narcotic medication. However, the lack of conclusive pathophysiology, in conjunction with the rarity of LPHS, has prohibited the development and trial of definitive treatment options. Nevertheless, in order to combat this rare but severe disease, management strategies have continued to evolve, ranging from conservative measures to invasive procedures. This review presents an overview of the current hypotheses on the pathophysiology of LPHS in addition to summarizing the management strategies that have been utilized. Only 30% of LPHS patients will experience spontaneous resolution, whereas the majority will continue to face chronic, crippling pain. Several methods of treatment, including invasive and non-invasive, may provide an improved outcome to these patients. Treatment should be individually tailored and multi-disciplinary in nature. Further research is required to further elucidate the pathophysiology and develop new, specific, treatment options.

Topical capsaicin for the treatment of cannabinoid hyperemesis syndrome, a systematic review and meta-analysis.

INTRODUCTION: Cannabinoid hyperemesis syndrome (CHS) is a condition that is being recognized and treated more frequently in emergency departments (EDs) across the United States. Currently, ED providers rely on antiemetics, antipsychotics and benzodiazepines to alleviate the symptoms. Topical capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, has been proposed in recent years as a low-cost and effective alternative to the traditional antiemetic regimen when treating CHS. The aim of this systematic review and meta-analysis is to demonstrate the reliability and the gaps of what is known about this treatment modality. METHODS: Articles were extracted from PubMed, SCOPUS, and Google Scholar databases. Publication dates ranged from the inception of the databases to October 2020. Initial searches found 328 studies. After careful review and screening by two investigators, 7 studies met the inclusion criteria and were included for our meta-analysis. Variables that were evaluated included the prevalence of hospital admissions for patients treated with capsaicin, time to relief of symptoms after capsaicin administration, and ED length of stay (LOS). I-square and Q-statistic values were used to assess heterogeneity. RESULTS: Among the 7 studies, there was a total of 106 patients. Two studies reported time to resolution of symptoms following capsaicin administration and ED LOS. Means for these outcomes were 325 (95% CI 234-787) and 379 (95% CI 10-747) minutes respectively. I-square was 44%, and Q-statistic was 11 with 6 degrees of freedom, with a p-value of 0.1. DISCUSSION: With acceptable time to resolution of symptoms after topical administration and ED LOS, capsaicin appears to be an effective treatment option for symptomatic relief of CHS. Further randomized controlled trials should be conducted to examine if it is the more efficacious and efficient treatment for CHS across various care settings.

Ethnic Differences in Experimental Pain Responses Following a Paired Verbal Suggestion With Saline Infusion: A Quasiexperimental Study.

BACKGROUND: Ethnic differences in placebo and nocebo responses are an important, yet underresearched, patient factor that might contribute to treatment disparities. PURPOSE: The purpose of this study was to examine ethnic differences in pain trajectories following a verbal suggestion paired with a masked, inert substance (i.e., saline). METHODS: Using a quasiexperimental design, we examined differences between 21 non-Hispanic Black (NHB) participants and 20 non-Hispanic White (NHW) participants in capsaicin-related pain rating trajectories following a nondirectional verbal suggestion + saline infusion. All participants were told that the substance would "either increase pain sensation, decrease it, or leave it unchanged." A spline mixed model was used to quantify the interaction of ethnicity and time on ratings. RESULTS: There was a significant Ethnicity × Time interaction effect (ß = -0.28, p = .002); NHB individuals reported significantly greater increases in pain following, but not before, the verbal suggestion + saline infusion. Sensitivity analyses showed no change in primary results based on differences in education level, general pain sensitivity, or condition order. CONCLUSIONS: The present results showed ethnic differences in pain response trajectories following a verbal suggestion + saline infusion and suggest that future research rigorously examining possible ethnic differences in placebo/nocebo responses is warranted.

Individual responses to topical ibuprofen gel or capsaicin cream for painful knee osteoarthritis: a series of n-of-1 trials.

OBJECTIVES: To determine individual responses to ibuprofen gel or capsaicin cream for painful, radiographic knee OA using a series of n-of-1 trials. METHODS: Twenty-two participants were allocated 5% ibuprofen gel (A) and 0.025% capsaicin cream (B) in random sequence (AB or BA). Patients underwent up to 3 treatment cycles, each comprising one treatment for 4 weeks, an individualized washout period (maximum 4 weeks), then the other treatment for 4 weeks. Differential (ibuprofen or capsaicin) response was defined when change-from-baseline pain intensity scores (0-10 NRS) differed by ≥1 between treatments in ≥2 cycles within a participant. RESULTS: A total of 104 treatment periods were aggregated. Mean pain reduction was 1.2 (95% CI: 0.5, 1.8) on ibuprofen and 1.6 (95% CI: 0.9, 2.4) on capsaicin (P = 0.221). Of 22 participants, 4 (18%) had a greater response to ibuprofen, 9 (41%) to capsaicin, 4 (18%) had similar responses, and 5 (23%) were undetermined. CONCLUSION: Irrespective of equal efficacy overall, 59% of people displayed a greater response to one treatment over the other. Patients who do not benefit from one type of topical treatment should be offered to try another, which may be more effective. N-of-1 trials are useful to identify individual response to treatment. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, NCT03146689.

Topical Capsaicin for the Treatment of Neuropathic Pain.

BACKGROUND: Neuropathic pain (NP) is an egregious problem worldwide. Due to the side-effects of oral drugs, drugs delivered directly to the affected area of pain are preferred. OBJECTIVE: Capsaicin, a chemical compound isolated from chili peppers, is used as an analgesic in topical ointments and dermal patches to alleviate pain. Objective of the study is to review the application and functionality of topical capsaicin in treatment of neuropathic pain. DATA SOURCES: To systematically review capsaicin's functions on NP, we retrieved articles from the PubMed database published in the last ten years. STUDY ELIGIBILITY CRITERIA: The inclusion criteria were capsaicin and the use of capsaicin for the treatment of NP; on the other hand, articles were excluded according to the mentioned criteria such as abstracts, articles written in any language other than English, incomplete articles, and conference papers. PARTICIPANTS AND INTERVENTIONS: Out of 265 articles, 108 articles were selected after filtering through the inclusion and exclusion criteria. The data and knowledge currently existing for capsaicin treatment in NP are summarized. RESULTS: This review indicates that capsaicin effectively improves NP treatment without affecting the motor and large nerve fibres involved in sensory function. Transient receptor potential channel vanilloid type 1 (TRPV1) is the capsaicin receptor expressed in central and peripheral terminals of a sensitive primary nerve cell. Conclusions and implications of key findings: Topical capsaicin has a sensible safety profile and is effective in reducing NP. Therefore, studies over the last decade suggest that capsaicin might be a potential drug for NP treatment.

Capsaicin Analogue Supplementation Does Not Improve 10 km Running Time-Trial Performance in Male Amateur Athletes: A Randomized, Crossover, Double-Blind and Placebo-Controlled Study.

BACKGROUND: To investigate the acute effects of a capsaicin analogue supplement on 10 km time-trial performance and physiological responses in amateur athletes. METHODS: Twenty-one participants (age = 29.3 ± 5.5 years, weight 74.2 ± 11.3 kg, height 176.0 ± 0.0 cm, fat mass 12.7 ± 3.8%, V˙O2max 62.7 ± 8.4 mL·k-1·min-1), completed two randomized, double-blind trials: capsaicin analogue condition (Capsiate (CAP) = 24 mg) or a placebo (PLA) condition. The participants consumed two doses of 12 mg of CAP or PLA capsule 45 min before and immediately at the start of each trial. The time required to complete 10 km, lactate concentration, maximum heart rate (HRpeak), and rating of perceived exertion (RPE) were recorded. RESULTS: The 10 km time-trial performance (CAP = 45.07 ± 6.41 min vs. PLA = 45.13 ± 6.73, p = 0.828) was not statistically significantly different between conditions. No statistically significant differences between conditions were detected for lactate concentration (p = 0.507), HRpeak (p = 0.897) and RPE (p = 0.517). CONCLUSION: Two doses of a 12 mg Capsaicin analogue supplement did not improve performance and physiological responses in a 10 km running time-trial in amateur athletes.

The Treatment of Topical Drugs for Postherpetic Neuralgia: A Network Meta-Analysis.

BACKGROUND: Postherpetic neuralgia (PHN) is a neuropathic pain that causes a reduction in patients' quality of life. There are many topical drugs for PHN, including topical lidocaine patch, topical application of capsaicin, and others. OBJECTIVES: This study aims to compare the efficacy and safety of topical drugs for PHN. STUDY DESIGN: Relevant studies were found by systemically searching for terms including "topical" and "Postherpetic neuralgia" in PubMed, Cochrane library, MEDLINE, and EMBASE databases (inception through June 12, 2019). The primary outcome was the percentage of change in the Numeric Rating Scale or the Visual Analog Scale scores from baseline. The secondary outcome was the number of adverse events. METHODS: The efficacy and safety of topical drugs for PHN was investigated by the pairwise meta-analysis and Bayesian network meta-analysis, applying Revman 5.3, the Stata 14.0 software, and GeMTC 0.14.3. RESULTS: Twelve studies met the inclusion criteria, and eligible studies were selected for the ultimate meta-analysis. Our meta-analysis displayed 6 topical drugs for PHN. Lidocaine, high-concentration capsaicin, and aspirin/diethyl ether (ADE) had a higher possibility of bringing pain relief than placebo. Among them, lidocaine had the highest possibility of being the most effective drug for PHN and had the statistical significances compared with diclofenac, high-concentration capsaicin, indomethacin, low-concentration capsaicin, and placebo, and lidocaine was significantly preferable than other effective drugs in the aspect of safety. LIMITATIONS: (1) The small number of included studies; (2) a small number of patients and short-term trials in progress, including lidocaine and ADE; (3) both randomized controlled trial and crossover randomized trial were included in our network meta-analysis; (4) only studies published in English were evaluated; (5) lack of head-to-head comparisons of some treatments; (6) different measurement methods were used in different trial, which may cause deviation; and (7) with the lack of cycles in the included trials, the inconsistency factors cannot be calculated, and node-splitting method cannot be performed in our network meta-analysis to check the inconsistency. CONCLUSIONS: Compared with other topical drugs, lidocaine was the most effective and most tolerable drug to be recommended for PHN.

8% Capsaicin Patch in Treatment of Peripheral Neuropathic Pain.

BACKGROUND: Neuropathic pain is a complex condition that is difficult to control and has a high impact on quality of life. 8% Capsaicin patch can be a therapeutic strategy in the treatment of peripheral neuropathic pain. OBJECTIVES: This study aims to (1) evaluate clinical efficacy and (2) tolerability of 8% capsaicin patch in a Pain Unit. STUDY DESIGN: Retrospective observational study. SETTING: Portuguese Pain Unit. METHODS: A sample of 120 patients diagnosed with peripheral neuropathic pain, underwent treatment with the 8% capsaicin patch between February 2011 and February 2019 in a Portuguese Pain Unit. Patients were included in one of the following groups according to the etiology of pain: postherpetic neuralgia (PHN), chronic post-surgical pain (CPSP), post traumatic neuropathic pain (PTNP), diabetic neuropathy (DN), regional pain syndrome. complex I and II (CRPS I / II), HIV-associated neuropathy (HIVN), lumbar neuropathic pain (LNP), trigeminal neuralgia (TN) and other neuropathies (O). The evaluated parameters were: pain intensity according to unit protocol (numerical rating scale), pain characteristics, location, size of the painful area. The evolution of pain intensity after treatment (patients were considered as responders to therapy if the decrease in NRS was equal to or greater than 30%; patients with a decrease in NRS of 50% or more were also analyzed), the area of pain and the need for adjuvant analgesic therapy, as well as the tolerability to treatment and the identification of eventual predictors of its efficacy were evaluated, at 15 days, 8 weeks and 12 weeks after 8% capsaicin patch. RESULTS: Of the 120 patients in the sample, 40.8% had a >= 30% decrease in basal pain intensity 15 days after treatment, 43.3% after 8 weeks and 45.0% after 12 weeks. 30.8% of patients had >= 50% decreased basal pain intensity 15 days after treatment, 27.5% after 8 weeks and 30.0% after 12 weeks. Pain area decreased in 36.7% of patients and 18.3% reduced chronic analgesic therapy within 12 weeks after 8% capsaicin patch application. There was only one case of intolerance to the treatment. LIMITATIONS: This study has the limitations inherent to a retrospective study. The study period was only 12 weeks and some diagnostic groups included a small number of patients. CONCLUSION: Treatment of peripheral neuropathic pain with 8% capsaicin patch seem to be effective in the short and medium term, both in decreasing pain intensity and in reducing the painful area. Its application is tolerated by most patients.

[Effect of small dose capsaicin for treatment of pulmonary fibrosis in mice and its mechanism].

Objective: To observe whether the mechanism of small dose capsaicin (Cap) against pulmonary fibrosis in mouse is mediated by agitating transient receptor potential vanilloid 1 (TRPV1). Methods: A total of 60 BALB/c mice were randomly divided into control (CON) group, bleomycin (BLM)group, Cap (0.5, 1,2 mg/kg) groups and Cap (2 mg/kg) plus SB-452533 (2.5 mg/kg) group. C57BL/6 mice were intratracheally injected with 3.5 mg/kg BLM to induce pulmonary fibrosis model. Animals for drugs treatment received daily drug via subcutaneous injection for 21 days. The morphological changes and collagen deposition in lung tissues were analysed by HE staining, Masson staining and immunohistochemistry. The concentration of calcitonin gene-related peptide (CGRP) in plasma was determined by ELISA. The mRNA and (or) proteins levels of α-CGRP, ß-CGRP, collagen I, collagen III, E-Cadherin, zonula occludens-1 (ZO-1), vimentin, alpha smooth muscle actin (α-SMA), TRPV1, p-ERK1/2 and eukaryotic initiation factor 3a (eIF3a) were detected by qPCR and (or) Western blot. Results: Compared with the BLM group, small dose Cap significantly reduced bleomycin-induced pulmonary fibrosis in mice and obviously reversed alveolar epithelial cells epithelial-mesenchymal transition (EMT) (the expression of E-cadherin and ZO-1 were increased(P＜0.05 or P＜0.01)and the expression of α-SMA and Vimentin were decreased (P＜0.05 or P＜0.01) after drugs treatment for 21 day, concomitantly with the increase the expressions of TRPV1 and CGRP (P＜0.05 or P＜0.01), and inhibiting ERK1/2 phosphorylation and eIF3a expression (P＜0.05 or P＜0.01). These effects of small dose Cap were abolished in the presence of TRPV1 receptor antagonist SB-452533. Conclusion: The results suggest that small dose Cap can reverse alveolar epithelial cells EMT and alleviate bleomycin-induced pulmonary fibrosis in mice by inhibiting ERK1/2/eIF3asignaling pathway, which is related to agitating TRPV1 receptor and releasing of CGRP.

Comparison of topical capsaicin and topical piroxicam in the treatment of acute trauma-induced pain: A randomized double-blind trial.

BACKGROUND: This study aimed to compare the analgesic efficacy of topical capsaicin and topical piroxicam in acute musculoskeletal injuries. METHODS: This is a prospective, randomized, controlled, double-blinded study. The data for the 67 patients in the piroxicam group and the 69 in the capsaicin group were examined. The initial visual analog scale (VAS) scores were compared with the 60th and 120th minute as well as the 24th and 72nd hour values. Differences between the VAS scores, clinical effectiveness of the treatment and side effects were evaluated. RESULTS: In the capsaicin group, the mean difference in the delta VAS scores was significantly higher at each measurement time. The mean of the percentage of reduction in the VAS scores of the topical capsaicin group was significantly higher than that in the topical piroxicam group. The highest difference in terms of both outcomes was determined at the 72nd hour VAS change. Mean differences were 1.53 (95% CI: 0.85-2.221) and 19.7 (95% CI: 12.4-27.2) respectively (p < 0.001). In the capsaicin group, the clinical effect of the treatment was found significantly higher (p < 0.01). The difference between the clinical effectiveness of the groups regarding the treatment outcomes was also statistically significant (p < 0.001). There was no significant difference between the patient groups regarding the presence of side effects. CONCLUSION: Topical capsaicin can be used as an alternative to topical piroxicam initially and at follow-up in patients presenting to the emergency department with acute pain as there were no observable differences in side-effects between the two groups.

Capsaicin Supplementation during High-intensity Continuous Exercise: A Double-blind Study.

To investigate the effect of acute capsaicin (CAP) supplementation on time to exhaustion, physiological responses and energy systems contribution during continuous high-intensity exercise session in runners. Fifteen recreationally-trained runners completed two randomized, double-blind continuous high-intensity exercises at the speed eliciting 90% V̇O2peak (90% s V̇O2peak), 45 minutes after consuming capsaicin or an isocaloric placebo. Time to exhaustion, blood lactate concentration, oxygen consumption during and 20-min post-exercise, energy systems contribution, time to reach V̇O2peak, heart rate and the rate of perceived exertion (RPE) were evaluated. There was no significant difference between conditions for time to reach V̇O2peak (CAP:391.71±221.8 vs. PLA:298.20±174.5 sec, ES:0.58, p=0.872), peak lactate (CAP:7.98±2.11 vs. PLA:8.58±2.15 µmol, ES:-0.28, p=0.257), time to exhaustion (CAP:654.28±195.44 vs. PLA:709.20±208.44 sec, ES:-0.28, p=0.462, end-of-exercise heart rate (CAP:177.6±14.9 vs. PLA:177.5±17.9 bpm, ES:-0.10, p=0.979) and end-of-exercise RPE (CAP: 19±0.8 vs. PLA: 18±2.4, ES: 0.89, p=0.623). In conclusion, acute CAP supplementation did not increase time to exhaustion during high-intensity continuous exercise nor alter physiological responses in runners.

Role of TRPV1/TRPV3 channels in olanzapine-induced metabolic alteration: Possible involvement in hypothalamic energy-sensing, appetite regulation, inflammation and mesolimbic pathway.

Atypical antipsychotics (AAPs) have the tendency of inducing severe metabolic alterations like obesity, diabetes mellitus, insulin resistance, dyslipidemia and cardiovascular complications. These alterations have been attributed to altered hypothalamic appetite regulation, energy sensing, insulin/leptin signaling, inflammatory reactions and active reward anticipation. Line of evidence suggests that transient receptor potential vanilloid type 1 and 3 (TRPV1 and TRPV3) channels are emerging targets in treatment of obesity, diabetes mellitus and could modulate feed intake. The present study was aimed to investigate the putative role TRPV1/TRPV3 in olanzapine-induced metabolic alterations in mice. Female BALB/c mice were treated with olanzapine for six weeks to induce metabolic alterations. Non-selective TRPV1/TRPV3 antagonist (ruthenium red) and selective TRPV1 (capsazepine) and TRPV3 antagonists (2,2-diphenyltetrahydrofuran or DPTHF) were used to investigate the involvement of TRPV1/TRPV3 in chronic olanzapine-induced metabolic alterations. These metabolic alterations were differentially reversed by ruthenium red and capsazepine, while DPTHF didn't show any significant effect. Olanzapine treatment also altered the mRNA expression of hypothalamic appetite-regulating and nutrient-sensing factors, inflammatory genes and TRPV1/TRPV3, which were reversed with ruthenium red and capsazepine treatment. Furthermore, olanzapine treatment also increased expression of TRPV1/TRPV3 in nucleus accumbens (NAc), TRPV3 expression in ventral tegmental area (VTA), which were reversed by the respective antagonists. However, DPTHF treatment showed reduced feed intake in olanzapine treated mice, which might be due to TRPV3 specific antagonism and reduced hedonic feed intake. In conclusion, our results suggested the putative role TRPV1 in hypothalamic dysregulations and TRPV3 in the mesolimbic pathway; both regulate feeding in olanzapine treated mice.

Capsaicin 8% dermal patch in clinical practice: an expert opinion.

INTRODUCTION: Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system, which can severely impact patients' quality of life. The current-approved treatments for NP comprise of both centrally acting agents and topical drugs, including capsaicin 8% dermal patches, which is approved for the treatment of peripheral NP. AREAS COVERED: The authors summarize literature data regarding capsaicin use in patients who suffer from NP and discuss the clinical applications of this topical approach. EXPERT OPINION: Overall, the capsaicin 8% dermal patch is as effective in reducing pain intensity as other centrally active agents (i.e. pregabalin). Some studies have also reported fewer systemic side effects, a faster onset of action and superior treatment satisfaction compared with systemic agents. In our opinion, capsaicin 8% dermal patches also present additional advantages, such as a good systemic tolerability, the scarcity of adverse events, the possibility to combine it with other agents, and a good cost-effective profile. It is important to note that, as the mechanism of action of capsaicin 8% is the 'defunctionalization' of small afferent fibers through interaction with TRPV1 receptors, the peripheral expression of this receptor on nociceptor fibers, is crucial to predict patient's response to treatment.

A Pilot Trial of Topical Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome.

OBJECTIVES: Patients with cannabinoid hyperemesis syndrome (CHS) present frequently to the emergency department. Previous case studies suggest dramatic symptomatic improvement with topical capsaicin treatment. This exploratory study examined the potential effectiveness of topical capsaicin in patients with nausea and vomiting due to a suspected CHS exacerbation. METHODS: This was a double-blind, randomized placebo-controlled pilot trial. Adults who presented with vomiting suspected to be from CHS were eligible for enrollment. We excluded pregnant women and those with resolution of symptoms. Following randomization, topical 0.1% capsaicin or placebo cream was applied to the anterior abdomen in a uniform manner. The primary outcome was the severity of nausea on a visual analog scale (VAS) of 0 to 10 cm assessed at 30 minutes. Secondary outcomes were adverse events, occurrence of posttreatment vomiting, nausea by VAS at 60 minutes, and hospital admission. RESULTS: This pilot trial enrolled 30 patients, 17 in the capsaicin arm and 13 in the placebo arm. One patient in the capsaicin arm did not tolerate treatment due to skin irritation. Mean ± SD nausea severity at 30 minutes was 4.1 ± 2.3 cm in the capsaicin arm and 6.1 ± 3.3 cm in the placebo arm (difference = -2.0 cm, 95% confidence interval [CI] = 0.2 to -4.2 cm). At 60 minutes, mean ± SD nausea severity was 3.2 ± 3.2 cm versus 6.4 ± 2.8 cm (difference = -3.2 cm, 95% CI = -0.9 to -5.4 cm). The percent reduction in nausea at 60 minutes from baseline was 46.0% in the capsaicin arm and 24.9% in the placebo arm (difference = 21.1%, 95% CI = -5.6% to 47.9%). A higher proportion of capsaicin group patients (29.4% vs. 0%) had complete resolution of nausea (relative risk = 3.4, 95% CI = 1.6 to 7.1). CONCLUSION: In this pilot trial, the application of topical capsaicin cream was associated with a significant reduction in nausea at 60 minutes but not at 30 minutes and provided more complete relief of nausea.