Capsaicin Exposure Research Articles

The effects of simulated gastroesophageal reflux on infant pig oropharyngeal feeding physiology.

The neural connectivity among the oral cavity, pharynx, and esophagus is a critical component of infant feeding physiology. Central integration of oral and pharyngeal afferents alters motor outputs to structures that power swallowing, but the potential effects of esophageal afferents on preesophageal feeding physiology are unclear. These effects may explain the prevalence of oropharyngeal dysphagia in infants suffering from gastroesophageal reflux (GER), though the mechanism underlying this relationship remains unknown. Here we use the validated infant pig model to assess the impacts of simulated GER on preesophageal feeding parameters. We used high-speed videofluoroscopy and electromyography to record bottle-feeding before and following the infusion of a capsaicin-containing solution into the lower esophagus. Sucking parameters were minimally affected by capsaicin exposure, such that genioglossus activity was unchanged and tongue kinematics were largely unaffected. Aspects of the pharyngeal swallow were altered with simulated GER, including increased thyrohyoid muscle activity, increased excursions of the hyoid and thyroid per swallow, decreased swallow frequency, and increased bolus sizes. These results suggest that esophageal afferents can elicit changes in pharyngeal swallowing. In addition, decreased swallowing frequency may be the mechanism by which esophageal pathologies induce oropharyngeal dysphagia. Although recent work indicates that oral or pharyngeal capsaicin may improve dysphagia symptoms, the decreased performance following esophageal capsaicin exposure highlights the importance of designing sensory interventions based upon neurophysiology and the mechanisms underlying disordered feeding. This mechanistic approach requires comprehensive data collection across the entirety of the feeding process, which can be achieved using models such as the infant pig.NEW & NOTEWORTHY Simulated gastroesophageal reflux (GER) in an infant pig model resulted in significant changes in pharyngeal swallowing, which suggests that esophageal afferents are centrally integrated to alter motor outputs to the pharynx. In addition, decreased swallow frequency and increased bolus sizes may be underlying mechanisms by which esophageal pathologies induce oropharyngeal dysphagia. The infant pig model used here allows for a mechanistic approach, which can facilitate the design of intervention strategies based on neurophysiology.

Inducible desensitization to capsaicin with repeated low-dose exposure in human volunteers

Responses to capsaicin are reduced following repeated exposure, a phenomenon known as capsaicin desensitization. Heavy consumers of chilies consistently report reduced oral burn relative to infrequent consumers, presumably due to chronic desensitization. However, the mechanism(s) underlying capsaicin desensitization remain poorly understood. We hypothesized that reduced response to capsaicin due to repeated oral exposure may result from a change in the expression of the capsaicin receptor (TRPV1) gene. To test this, we conducted two longitudinal desensitization studies in healthy human volunteers. In Study 1, 51 adults completed a 17-day capsaicin desensitization protocol. The study consisted of three in-person visits where they were asked to sample stimuli, including 3, 6, and 9 ppm capsaicin, and rate intensity on a general labeled magnitude scale (gLMS). Between days 3 & 17, participants rinsed at home with 6 ppm capsaicin (n = 31) or a control (n = 20) solution (20 uM sucrose octaccetate; SOA) twice a day. Before and after the oral exposure protocol, a clinician collected fungiform papillae. Participants randomized to the capsaicin rinse showed a statistically significant reduction in oral burn ratings that was not observed in controls, indicating repeated low-dose exposure can systematically induce desensitization. TRPV1 expression was not associated with reported capsaicin burn, and there was no evidence of a decrease in TRPV1 expression following capsaicin exposure. In Study 2, participants (n = 45) rinsed with 6 ppm capsaicin in a similar protocol, rating capsaicin, vanillyl butyl ether (VBE), cinnamaldehyde, ethanol, menthol, and sucrose on days 1, 3, & 17. Burn from capsaicin, VBE, cinnamaldehyde, and ethanol all showed a statistically significant change – capsaicin, VBE and cinnamaldehyde burn all dropped ∼20 %, and a larger reduction was seen for ethanol – while menthol cooling and sucrose sweetness did not change. Collectively, this suggests reductions in oral burn following chronic capsaicin exposure generalizes to other stimuli (i.e., cross desensitization) and this cannot be explained by a change in TRPV1 mRNA expression. More work is needed to elucidate the underlying mechanism for capsaicin desensitization in the oral cavity.

Case Report: Ocular Capsaicin Exposure with Chemosis from Jalapeño Peppers

Case Report: Ocular Capsaicin Exposure with Chemosis from Jalapeño Peppers

Role of dairy proteins in the reduction of capsaicin-induced oral burning pain

Capsaicin-induced burning sensation in the oral mucosa can be relieved by skimmed and whole milk. The mechanism behind this effect, however, is unknown. This study aimed to asses the role of milk proteins in reducing capsaicin-induced oral burning sensation. 24 healthy participants were included in this single-blinded cross-over study consisting of four sessions. In each sessions, mucosal burning sensation was evoked by having the participants dip their tongues in a cup containing 0.1% capsaicin gel for a total of 8 min. The perceived levels of unpleasantness and burning intensity were scored on two different numerical rating scales. After capsaicin exposure, the participants rinsed their mouth for 10 s with a different solution in each session (3.5% casein, 3.5% whey, 3.5% lactose (non-protein control) and skimmed milk (active/positive control)). Mechanical (64, 128 and 256 mN pinprick) and thermal (5, 40, 45 and 50 ̊C) sensitivity of the tongue was measured using semi-quantative sensory testing at baseline, immediately after capsaicin exposure and when the scores for unpleasantness and burning intensity reached the minimum value of 0. Thermographic images of the tongue were taken at the same time-points. Overall, no statistically significant difference in unpleasantness and burning intensity was found between the four sessions (P ≥ 0.070). Explorative pair-wise comparisons, however, showed slight short-term reduction in unpleasantness and burning intensity when comparing the casein solution with the lactose solution (P ≤ 0.020). Scores for burning intensity and unpleasantness varied over time (P ≤ 0.001). Statistically significant changes in heat and mechanical sensitivity was observed between time-points (P < 0.001) but not sessions (P ≥ 0.410). An increased sensitivity towards heat and a decreased sensitivity towards mechanical stimuli was observed after capsaicin exposure compared with baseline (P < 0.001). Similarly, changes in thermographic temperature of the tongue was observed between time-points (P < 0.001), but not sessions (P ≥ 0.827). An increased maximum, minimum and average temperature of the tongue was observed immediately after capsaicin exposure compared with baseline (P < 0.001). In conclusion, short-term rinsing with room temperature milk proteins did not robustly alter capsaicin-induced oral burning sensation, unpleasantness, somatosensory changes or tongue temperature compared with control. Further studies exploring the effects of increased rinsing time and concentrations are needed in the future.

Targeting TRPV1 activity via high-dose capsaicin in patients with sickle cell disease.

Evidence suggests neuropathic pain (NP) develops over time in sickle cell disease (SCD), contributing to a complex, difficult‐to‐treat phenotype, with management based on scant evidence. One characteristic of NP found is hyperalgesia caused by nervous system sensitization, but risk factors for this have not been identified within the SCD population, as exact mechanisms leading to its development are not well defined. The SPICE (Sickle cell Pain: Intervention with Capsaicin Exposure) trial was a pilot safety and feasibility trial of high‐dose (8%) topical capsaicin for patients with SCD and recurrent/chronic pain with neuropathic features, aimed at exploring capsaicin's utility as a mechanistic probe and adjunctive pain treatment for this population. Ten participants identifying “target” sites of pain with NP‐type qualities consented to treatment. The primary endpoint was safety/tolerability. The novel Localized Peripheral Hypersensitivity Relief score (LPHR) was developed to determine improvement in sensitivity attributable to TRPV1 neutralization. There were no severe treatment‐related adverse events. Higher baseline pain sensitivity at a given body site was associated with self‐reported history of more frequent localized vaso‐occlusive pain episodes at that site. There was a statistically significant improvement in the mean LPHR, evidencing TRPV1's importance to the development of hypersensitivity and a potential therapeutic benefit of capsaicin for SCD.

Oropharyngeal capsaicin exposure improves infant feeding performance in an animal model of superior laryngeal nerve damage.

Sensorimotor feedback is critical to safe and effective swallowing. Because of this, sensory interventions have the potential to treat dysphagia. One such treatment may be found in capsaicin, which activates the internal branch of the superior laryngeal nerve (iSLN). The iSLN initiates the pharyngeal swallow, and a more sensitive iSLN should more readily elicit swallowing and improve swallow safety. We explored the neurophysiological mechanism by which capsaicin improves swallow performance using an infant pig model with a unilateral iSLN lesion. Using high-speed videofluoroscopy, we collected oropharyngeal kinematic data while pigs suckled on bottles, before and after applying capsaicin to the posterior tongue and valleculae. We found that capsaicin application decreased maximal bolus sizes, which improved swallow safety. Furthermore, capsaicin improved performance when infant pigs swallowed more moderately sized boluses. However, capsaicin did not change swallow frequency, the number of sucks prior to each swallow, nor total pharyngeal transit time (TPT). Similarly, excursions of the hyoid, thyroid, and posterior tongue were unchanged. TPT and hyoid and thyroid excursions maintained relationships with bolus size post-capsaicin, suggesting that these variables are less sensitive to sensory intervention. The timing and extent of posterior tongue movement were only correlated with bolus size pre-capsaicin, which could imply that capsaicin fundamentally changes in relationships between tongue movements and bolus size. Our results provide insight into the neural control of swallowing and capsaicin's mechanism of action, and suggest that capsaicin may be beneficial in treating acute infant dysphagia.NEW & NOTEWORTHY Chemical sensory interventions alter swallow physiology, which is well-documented in adults but relatively unexplored in infants. Using videofluoroscopy, we found that capsaicin exposure limited infant pigs' bolus sizes to improve swallow performance without changing swallow frequency. Capsaicin increased the likelihood of safe swallowing with more moderately sized boluses and changed relationships between bolus size and tongue movements, which may impact performance. This work highlights the potential role of capsaicin in treating acute infant dysphagia.

The aflatoxin inhibitors capsaicin and piperine from Capsicum chinense and Piper nigrum fruits modulate the antioxidant system in Aspergillus parasiticus

Several aflatoxin inhibitors can modulate the antioxidant system in fungi. In this work, the effect of the ethanolic extract of Capsicum chinense and Piper nigrum fruits, capsaicin, and piperine on the expression of the aflE, aflG, aflH, aflI, aflK, aflL, aflO, aflP, and aflQ genes involved in the aflatoxin biosynthetic pathway in Aspergillus parasiticus were studied by qRT-PCR analysis. As well as, the effect on the expression of fungal antioxidant genes (sod1, catA, and cat2) and enzymatic activity of catalase (CAT) and superoxide dismutase (SOD). Results reveal that the highest (p < 0.05) radial growth inhibition (68 and 86%) and aflatoxins production inhibition (73 and 80%) was observed with capsaicin and piperine respectively, at 300 µg/mL, instead of the ethanolic extract at the same concentration. The qRT-PCR analysis showed that compounds and extracts at 300 µg/mL induced a down-regulation of aflatoxin genes and an up-regulation on the fungal antioxidant genes. CAT activity increased by 23.15, 36.65, 51.40, and 65.50%, in the presence of C. chinense and P. nigrum extract, capsaicin, and piperine exposure, respectively. While SOD activity was not significantly impacted (p > 0.05). In conclusion, the capsaicin and piperine, two antifungal and anti-aflatoxigenic compounds produce an up-regulation of antioxidant defense genes accompanied by an enhancement of catalase enzymatic activity in A. parasiticus.

Traumatic Injuries From an Encounter With a North American Grizzly Bear

<h3>Introduction</h3> Estimates of grizzly bear, Ursus arctos horribilis, populations in North America include 25,000 in Canada, 30,000 in Alaska, and 1,918 in the lower-48 states.^1,2 Because of population growth due to wildlife conservation and increased outdoor recreation, bear encounters are more common in recent years, contributing to a greater incidence of human injuries.^3,4,5 Encounters are classified as "sudden," "provoked," or "predatory," with most human injuries being associated with "sudden" encounters in response to a perceived threat by the bear.^3,6,7 These encounters are likely to occur in the remote wilderness leading to a significant delay in treatment and transport to definitive care.⁸ We report a patient with injuries sustained from a "sudden" grizzly bear encounter who was treated and transported via helicopter emergency medical services (HEMS) to a trauma center. <h3>Case Report</h3> After a bear encounter in a remote wilderness area, a 41-year-old male patient sustained a scalp avulsion at the right occiput above the superior nuchal line and an approximately seven-inch laceration running contralaterally from the avulsion to the left occiput. Bleeding at both injury sites was self-limiting and successfully controlled with direct pressure. Substantial bruising and abrasions to the left anterior chest were noted, along with mild abrasions to the right hip and a puncture wound to the right posterior forearm. The patient's eyes also became irritated from capsaicin exposure when a bear spray canister deployed after being punctured during the encounter. The patient was alert and oriented without respiratory distress and displayed no signs of hemodynamic instability throughout the transport. Pain was managed with fentanyl and antibiotic prophylaxis was initiated with cefazolin. The patient was delivered to the trauma team at the receiving facility in a stable condition. <h3>Discussion</h3> Bear encounter injury patterns that predominate in the literature are puncture, avulsion, and crush injuries, notably to the head, face, and scalp.^3,6 These injuries stem from a combination of the bear's jaws, teeth, and claws. Infection risk is considerable due to aerobic and anaerobic species in the oral cavity as well as contamination with foreign material from the environment.^4,9 These injuries require thorough debridement and broad-spectrum antibiotic therapy should be initiated early. Capsaicin spray has been shown to be an effective bear deterrent and its use in this case, though incidental, likely contributed to termination of the encounter.^3,10 <h3>Conclusion</h3> This case underscores the serious and potentially life-threatening injuries that can result from encounters with grizzly bears and is consistent with previously reported encounters. Patients may present with complex soft-tissue and musculoskeletal injuries and risk of infection, requiring acute trauma resuscitation and early antibiotic treatment. Additional research on bear encounter injuries and their management will help improve the care of these patients by HEMS crews that are likely to care for these patients on "scene" flights or hospital transports to higher levels of trauma care.

Sucrose alleviates capsaicin-induced tongue burning: An in vivo study.

BackgroundSpicy foods are flavorful and stimulate salivation, which is beneficial for individuals with poor appetite. They are also ubiquitous in many regional cuisines, but the chemical compounds in such foods, especially capsaicin from chili peppers, can cause tissue inflammation and generate intolerable burning pain in the oral cavity. Material and MethodsTo identify a potential method to reduce capsaicin-induced burning pain without influencing food flavor, we tested the effects of mouth rinsing with various concentrations of sucrose. Inclusion criteria were good general and oral health, while exclusion criteria were poor baseline smell or taste, capsaicin allergy, and current orofacial pain complaints. To define an appropriate capsaicin dose, participants placed filter paper strips impregnated with 0.003%–0.3% capsaicin on the tip of the tongue and rated burning sensation by visual analog scale (VAS) score. ResultsA 0.1% capsaicin solution induced tongue burning in the midrange (VAS = 6.33 ± 0.52) and so was used for subsequent tests. We then examined the efficacy concentration of sucrose for reducing tongue burning by recording VAS scores at multiple time points following a 15-s oral rinse with various aqueous sucrose solutions (5%, 10%, and 20%), milk, or pure water (control) after 0.1% capsaicin application. Scores were compared at each time point by one-way ANOVA with post hoc Dunnett’s tests. A 15-s rinse with 20% sucrose significantly alleviated burning pain compared to water rinse at 45, 60, 120, and 180 s after capsaicin exposure. ConclusionsThus, periodic rinsing with 20% aqueous sucrose may help promote spicy food consumption among individuals with poor appetite. Key words:Capsaicin, sucrose, burning sensation.

Investigating potential TRPV1 positive feedback to explain TRPV1 upregulation in airway disease states

Objective The airway epithelium is a potential source of pathophysiology through activation of transient potential receptor vallinoid type 1 (TRPV1) channel. A positive feedback cycle caused by TRPV1 activity is hypothesized to induce upregulation and production of inflammatory cytokines, leading to exacerbations of chronic airway diseases. These cytokine and protein regulation effects were investigated in this study. Methods Healthy (BEAS-2B) and cancer-derived (Calu-3) airway epithelial cell lines were assessed for changes to TRPV1 protein expression and mRNA expression following exposure to capsaicin (5–50 µM), and TRPV1 modulators including heat (43 °C), and hydrochloric acid (pH 3.4 to pH 6.4). Cytotoxicity was measured to determine the working concentration ranges of treatment. Subsequent bronchoconstriction by TRPV1 activation with capsaicin was measured on guinea pig airway tissue to confirm locally mediated activity without the action of known neuronal inputs. Results TRPV1 protein expression was not different for all capsaicin, acidity, and heat exposures (p > 0.05), and was replicated in mRNA protein expression (p > 0.05). IL-6 and IL-8 expression were lower in BEAS-2B and Calu-3 cell lines exposed with acidity and heat (p < 0.05), but not consistently with capsaicin exposure, with potential cytotoxic effects possible. Conclusions TRPV1 expression was present in airway epithelial cells but its expression was not changed after activation by TRPV1 activators. Thus, it was not apparent the reason for reported TRPV1 upregulation in patients with airway disease states. More complex mechanisms are likely involved and will require further investigation.

Cold exposure and capsaicin promote 1,2-dimethylhyrazine-induced colon carcinogenesis in rats correlates with extracellular matrix remodeling.

BACKGROUNDExtracellular matrix (ECM) remodeling and stiffening, which are correlated with tumor malignancy, drives tumor development. However, the relationship between ECM remodeling and rat experimental model of 1,2-dimethylhyrazine (DMH)-induced colorectal cancer (CRC) imposed by cold and capsaicin exposure remains unclear.AIMTo explore the effects of cold exposure and capsaicin on ECM remodeling and ECM enzymes in DMH-induced CRC.METHODSFor histopathological analysis, the sections of colon tissues were stained with hematoxylin and eosin, Masson’s trichrome, Picrosirius red, and Weigert’s Resorcin-Fuchsin to observe the remodeling of collagen and elastin. Additionally, the protein expression level of type I collagen (COL I), type 3 collagen (COL III0, elastin, matrix metalloproteinase (MMP) 1, MMP2, MMP9, and tissue-specific matrix metalloproteinase 1 (TIMP1) was assessed by immunohistochemistry. The messenger RNA (mRNA) levels of COL I, COL III, elastin, and lysyl oxidase-like-2 (LOXL2) in the colon tissues of rats was measured by reverse-transcriptase quantitative polymerase chain reaction.RESULTSAlthough no differences were observed in the proportion of adenomas, a trend towards the increase of invasive tumors was observed in the cold and capsaicin group. The cold exposure group had a metastasis rate compared with the other groups. Additionally, abnormal accumulation of both collagen and elastin was observed in the cold exposure and capsaicin group. Specifically, collagen quantitative analysis showed increased length, width, angle, and straightness compared with the DMH group. Collagen deposition and straightness were significantly increased in the cold exposure group compared with the capsaicin group. Cold exposure and capsaicin significantly increased the protein levels of COL I, elastin, and LOXL2 along with increases in their mRNA levels in the colon tissues compared with the DMH group, while COL III did not show a significant difference. Furthermore, in immunohistochemical evaluations, MMP1, MMP2, MMP9, and TIMP1 staining increased in the cold exposure and capsaicin group compared with the DMH group.CONCLUSIONThese results suggest that chronic cold and capsaicin exposure further increased the deposition of collagen and elastin in the colonic tissue. Increased COL I and elastin mRNA and protein levels expression may account for the enhanced ECM remodel and stiffness variations of colon tissue. The upregulated expression of the LOXL2 and physiological imbalance between MMP/TIMP activation and deactivation could contribute to the progression of the CRC resulting from cold and capsaicin exposure.

Heat But Not Mechanical Hypersensitivity Depends on Voltage-Gated CaV2.2 Calcium Channel Activity in Peripheral Axon Terminals Innervating Skin.

Voltage-gated CaV2.2 calcium channels are expressed in nociceptors at presynaptic terminals, soma, and axons. CaV2.2 channel inhibitors applied to the spinal cord relieve pain in humans and rodents, especially during pathologic pain, but a biological function of nociceptor CaV2.2 channels in processing of nociception, outside presynaptic terminals in the spinal cord, is underappreciated. Here, we demonstrate that functional CaV2.2 channels in peripheral axons innervating skin are required for capsaicin-induced heat hypersensitivity in male and female mice. We show that CaV2.2 channels in TRPV1-nociceptor endings are activated by capsaicin-induced depolarization and contribute to increased intracellular calcium. Capsaicin induces hypersensitivity of both thermal nociceptors and mechanoreceptors, but only heat hypersensitivity depends on peripheral CaV2.2 channel activity, and especially a cell-type-specific CaV2.2 splice isoform. CaV2.2 channels at peripheral nerve endings might be important therapeutic targets to mitigate certain forms of chronic pain.SIGNIFICANCE STATEMENT It is generally assumed that nociceptor termini in the spinal cord dorsal horn are the functionally significant sites of CaV2.2 channel in control of transmitter release and the transmission of sensory information from the periphery to central sites. We show that peripheral CaV2.2 channels are essential for the classic heat hypersensitivity response to develop in skin following capsaicin exposure. This function of CaV2.2 is highly selective for heat, but not mechanical hypersensitivity induced by capsaicin exposure, and is not a property of closely related CaV2.1 channels. Our findings suggest that interrupting CaV2.2-dependent calcium entry in skin might reduce heat hypersensitivity that develops after noxious heat exposure and may limit the degree of heat hypersensitivity associated with certain other forms of pain.

Effect of cold exposure and capsaicin on the expression of histone acetylation and Toll-like receptors in 1,2-dimethylhydrazine-induced colon carcinogenesis.

Previous studies have indicated that capsaicin-rich diet and cold weather have shown strong association with tumor incidence. Thus, we investigated the effects of capsaicin and cold exposure in 1,2-dimethylhydrazine (DMH)-induced colorectal cancer as well as the mechanisms underlying capsaicin and cold-induced CRC. Rats were randomly divided into four groups and received cold still water and capsaicin via intragastric gavage until the end of the experiment. The rat's body weight, thymus weight, and food intakes were assessed. Global levels of histone H3K9, H3K18, H3K27, and H4K16 acetylation and histone deacetylase (HDACs) in colon mucosa were assessed by western blot. Expression levels of Toll-like receptors 2 (TLR2) and Toll-like receptors 4 (TLR4) were measured by western blot and reverse-transcriptase quantitative polymerase chain reaction (qPCR). We found that cold and low-dose capsaicin increased tumor numbers and multiplicity, although there were no differences in tumor incidence. Additionally, rat exposure to cold water and capsaicin display further higher levels of histone H3 lysine 9 (H3K9AC), histone H3 lysine 18 (H3K18AC), histone H3 lysine 27 (H3K27AC), and HDACs compared with the DMH and normal rats. In contrast, a considerable decrease of histone H4 lysine 16 (H4K16AC) was detected in the colon mucosa. Cold and low-dose capsaicin exposure groups were also increased TLR2 and TLR4 protein levels and mRNA levels. These results suggest that chronic cold exposure and capsaicin at a low-dose intervention exacerbate ectopic expression of global histone acetylation and TLR level, which are crucial mechanisms responsible for the progression of colorectal cancer in rats.

ACUTE AND CHRONICAL BIOLOGICAL EFFECTS OF W BAND MILLIMETRIC WAVES EXPOSURE IN RATS

The biological effects of millimetric waves systems, MMW (e.g. 5G communications, automotive radars, or crowd control systems, ADS) systems are still scarcely investigated. Hairless rats were exposed to 2 94GHz continuous wave (MMW, CW), under acute high power conditions (3sec at10kW/m ) and under 2 environmental/professional lower power exposure (4 hours a day, for 5 days a week, for 6 months at 10mW/cm ). It was found that the 94 GHz acute exposure provoked the disappearance of the epidermis upper corneal layers and the increase of the inammatory gene expression SOCS-3 after 3Hrs. Besides, neither histological nor genetic modication could be observed after chronic 94 GHz exposure and after an acute and a chronic capsaicin exposure. Conclusions :After a powerful acute exposition a thermal effect is observable, associated with a localized inammatory response. After chronic, low power exposition, an hypoalgesia effect was found, possibly related with an increase in brain plasticity. Mechanistically, the hypothesis is based on low noise stimulation of thermal pain receptors at subthreshold level. Conversely, neither inammation nor no direct change in was found.

TRPV1 (Transient Receptor Potential Vanilloid 1) Sensitization of Skeletal Muscle Afferents in Type 2 Diabetic Rats With Hyperglycemia.

[Figure: see text].

Sickle Cell Pain: Intervention with Capsaicin Exposure (SPICE)

Sickle Cell Pain: Intervention with Capsaicin Exposure (SPICE)

Lowered Cyclin E levels increase the efficiency and the specificity of capsaicin against cancerous cells of mesothelium

Capsaicin is one of the most extensively studied phytochemicals and its cytotoxicity on various types of cancer has been demonstrated both in vitro and in vivo. The evaluation of its effect on mesothelioma, however, has remained quite limited. In this study, we investigated the anti-mesothelioma potential of capsaicin by observing its cytotoxicity on healthy, immortalized and cancerous cells of mesothelium in vitro and how this potential be affected by lowered Cyclin E levels, a key regulator of G1/S transition of cell cycle. For this purpose, we determined and compared the IC50 values of capsaicin in both FBS (Fetal Bovine Serum) containing and FBS-deprived medium of each cell population studied. Additionally, we examined the changes in both protein and mRNA levels of caspase-3 upon capsaicin exposure as well as conducted a series of experiments through which the relatively long term effect of capsaicin on the growth rate of the cells was assessed. As a result, the reduced Cyclin E obtained through the absence of FBS in growth medium was found not only to decrease IC50 values for all cell types dramatically (p&lt;0.05) but also to cause a considerable difference between the values determined for cancerous and non-cancerous populations (p&lt;0.05), which had not been observed in regular medium. Moreover, along with the fact that capsaicin exposure did not have an impact on the cell growth in long term in most cases, caspase-3 levels also remained the same when exposed to capsaicin, suggesting a mechanism of cell death independent of caspases.

Assessing regional sensitivity and desensitization to capsaicin among oral cavity mucosae.

This study aimed to determine perceptual response differences and characterize desensitization to capsaicin over time across several oral cavity mucosae- the tongue, cheek, hard palate, and lip. For each region, subjects rated the intensity of capsaicin and a vehicle control over a 10-minute period. Following a rest period, capsaicin was reapplied on each pretreated area and subjects indicated which side felt more irritated then rated each side every 30 seconds, over 3.5 minutes. Results from the initial task indicated significantly greater irritation on the tongue than hard palate, hard palate than cheek and lip, but no significant differences between the cheek and lip. Time to max intensity was delayed on the hard palate compared to the tongue, cheek, and lip. Desensitization, as indicated by a significant proportion of subjects choosing the vehicle-pretreated side over capsaicin-pretreated side as having stronger irritation, was exhibited on the tongue and hard palate, but not the cheek and lip. Given these data, a secondary experiment that utilized a higher capsaicin concentration was conducted on the cheek and lip only. Results showed significantly higher overall irritation on the lip than the cheek. Desensitization was exhibited on both areas, although the extent was greater on the lip. Based on differences in sensitivity and the extent of desensitization among these areas, these results indicate oral cavity mucosae respond to, but are impacted differently by, capsaicin exposure.

Changes in TRPV1-Mediated Physiological Function in Rats Systemically Treated With Capsaicin on the Neonate.

Capsaicin is the active component of chili peppers and is a hydrophobic, colorless, odorless, and crystalline to waxy compound. The transient receptor potential vanilloid 1 (TRPV1) is the capsaicin receptor channels that are involved in a variety of functions like transduction and transmission of the physiological stimulus. Subcutaneous injection of capsaicin to a newborn rat leads to involuntary lifelong TRPV1 desensitization. Various physiological changes including sensory and homeostatic actions in the body associated with neonatal capsaicin treatment are induced by direct TRPV1 channel targeting. Interesting changes include unique phenomena such as the reduction in pain perception, abnormal body temperature, increase in infection, infectious or neuropathological itching, and irregular circadian core body temperature rhythm. These symptoms are associated with relatively higher fever or loss of sensory c-fiber related to TRPV1 desensitization. The aforementioned outcomes not only provide a warning about the risk of capsaicin exposure in newborns but also indicate the possible occurrence of relatively rare diseases that are difficult to diagnose. Therefore, Therefore, the present review aims to summarize the unique phenomena caused by systemic capsaicin administration in neonatal rats.

Sensitization of group lV skeletal muscle afferents in type 1 diabetic rats

The blood pressure (BP) response to exercise is abnormally exaggerated in type 1 diabetes mellitus (T1DM). However, the mechanisms underlying the potentiated BP response remain largely unclear. Sensory information from working muscle, generated by activation of mechanically and metabolically sensitive muscle afferents, is known to contribute importantly to this exercise‐induced exaggeration in BP. Moreover, receptors for advanced glycation end products (RAGE) and protein kinase C (PKC) interact to modulate neuronal function, including muscle afferents. It is possible that the interactive relationship between RAGE and PKC is altered in T1DM. Therefore, it was hypothesized that the potentiated exercise‐induced BP response in T1DM is mediated by sensitization of skeletal muscle afferent fibers via an overactive RAGE/PKC signaling pathway.PURPOSETo investigate 1) action potential responses to mechanical and chemical stimulation in muscle afferents of healthy and T1DM rats in vitro, 2) the impact of T1DM on plasma levels of high‐mobility group box‐protein 1 (HMGB‐1), a RAGE ligand, and 3) the impact of T1DM on PKC activation in dorsal root ganglion (DRG) subserving skeletal muscle afferent neurons.METHODST1DM was induced in Sprague‐Dawley rats by intraperitoneally injecting a single dose of 50 mg/kg streptozotocin. In healthy control animals, only saline was injected. At 1–3 weeks after the injection, the function of mechanically (application of a 0–196 mN ramped stimulus) or chemically (administration of 1 μM capsaicin) activated group IV fibers were assessed by obtaining single‐fiber recordings using the extensor digitorum longus muscle‐nerve preparation. Plasma HMGB1 was determined using ELISA. Phosphorylated PKC protein levels were quantified in DRG (L3‐L5) by western blotting.RESULTST1DM rats exhibited hyperglycemia after overnight fasting (P&lt;0.05). Plasma insulin in T1DM tended to be lower as compared to control animals (P=0.09). Spontaneous activity in group IV fibers was significantly larger in diabetic rats than in control animals (P&lt;0.05). Compared to control, response magnitudes to mechanical stimulation (P&lt;0.01) and capsaicin exposure (P=0.01) in group IV afferents were significantly greater in T1DM. Plasma HMGB1 levels were significantly higher in T1DM as compared with control (P&lt;0.01). T1DM showed markedly increased phosphorylated PKC levels in DRGs compared with control (P&lt;0.05).CONCLUSIONSIn T1DM, the sensitivity of group IV skeletal muscle afferent fibers to mechanical and chemical stimuli is abnormally increased. The data likewise suggest this enhanced afferent sensitivity may be due to augmented activation of the RAGE/PKC pathway. Importantly, these changes likely contribute significantly to the exaggerated pressor response to exercise characteristic of T1DM.Support or Funding InformationSupported by Lawson &amp; Rogers Lacy Research Fund and SHP Interdisciplinary Research Grant Program.