Role Of TRPV1 Research Articles

Capsaicin Improves Systemic Inflammation, Atherosclerosis, and Macrophage-Derived Foam Cells by Stimulating PPAR Gamma and TRPV1 Receptors.

Capsaicin, a bioactive compound found in peppers, is recognized for its anti-inflammatory, antioxidant, and anti-lipidemic properties. This study aimed to evaluate the effects of capsaicin on atherosclerosis progression. Apolipoprotein E knockout mice and their C57BL/6 controls were utilized to assess blood lipid profile, inflammatory status, and atherosclerotic lesions. We also examined the influence of capsaicin on cholesterol influx and efflux, and the role of TRPV1 and PPARγ signaling pathways in bone marrow-derived macrophages. Capsaicin treatment reduced weight gain, visceral adiposity, blood triglycerides, and total and non-HDL cholesterol. These improvements were associated with a reduction in atherosclerotic lesions in the aorta and carotid. Capsaicin also improved hepatic oxidative and inflammatory status. Systemic inflammation was also reduced, as indicated by reduced leukocyte rolling and adhesion on the mesenteric plexus. Capsaicin decreased foam cell formation by reducing cholesterol influx through scavenger receptor A and increasing cholesterol efflux via ATP-binding cassette transporter A1, an effect primarily linked to TRPV1 activation. These findings underscore the potential of capsaicin as a promising agent for atherosclerosis prevention, highlighting its comprehensive role in modulating lipid metabolism, foam cell formation, and inflammatory responses.

TRPV4-driven Regulation of miR-146a Expression in Macrophages and in a Mouse Model of Atherosclerosis

MicroRNAs (miRs) are small, non-coding RNAs that have emerged as powerful regulators of gene expression. Emerging evidence suggests that miR-146a orchestrates anti-inflammatory/fibrotic processes in numerous cell types. Trpv4 (Transient Receptor Potential subfamily V member 4), a mechanosensitive, calcium-permeant channel/receptor, is expressed in numerous cell types including macrophages. Published work by our group and others show that Trpv4 is activated by a range of soluble and physical stimuli including matrix stiffness and cytokines. In mice, Trpv4 deficiency is associated with altered pressure responses, foreign body response, fibrosis, and inflammation. Previous work by our group and others suggest a pro-inflammatory/atherogenic role for Trpv4. Herein, we tested the hypothesis that Trpv4 regulates the expression of microRNA-146a in macrophages and in a mouse model of atherosclerosis. Our research found a 38% drop in miR-146a expression in macrophages treated with lipopolysaccharide (LPS) on a stiffer polyacrylamide hydrogel compared to a softer one as determined by RNAseq analysis, signifying miR-146a's sensitivity to mechanical factors. Trpv4's presence suppresses the LPS-induced increase of miR-146a in macrophages based on time and dosage. Trpv4 also plays a role in the suppression of miR-146a due to matrix stiffness. Notably, in mice, Trpv4 reduces the increase of macrophage miR-146a caused by a high-fat diet in aortic root regions. Given that matrix stiffening is common in atherosclerosis, this indicates a link between stiffness, Trpv4, and miR-146a. On the mechanism side, Trpv4 affects miR-146a expression not through its promoter methylation or activation of MAPKs, Stat1, AKT, and NFκB. Trpv4 residues 100 to 130 are required for suppression of LPS-induced upregulation of miR-146a. To sum up, Trpv4 appears to inhibit macrophage miR-146a expression through pathways that are distinct from those involving MAKPs/Stat1/AKT or NFκB. Understanding this mechanism could pave the way for new treatments targeting miR-146a to counter inflammatory diseases. Source of research support: NIH (R01 AI172086) grant to Shaik O. Rahaman. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Role of TRPV1 and TRPA1 in TSLP production in nasal epithelial cells

BackgroundTRP protein is sensitive to external temperature changes, but its pathogenic mechanism in the upper airway mucosa is still unclear. ObjectiveTo investigate the mechanism of TRPV1and TRPA1 in regulating the secretion of inflammatory factors in nasal epithelial cells. MethodsThe expression of TRPV1 and TRPA1 in nasal mucosal epithelial cells was investigated using immunofluorescence assays. Epithelial cells were stimulated with TRPV1 and TRPA1 agonists and antagonists, and changes in Ca2+ release and inflammatory factor secretion in epithelial cells were detected. TSLP secretion stimulated with the calcium chelating agent EGTA was evaluated. The transcription factor NFAT was observed by immunofluorescence staining. ResultsTRPV1 and TRPA1 expression was detected in nasal epithelial cells, and Ca2+ influx was increased after stimulation with agonists. After the activation of TRPV1 and TRPA1, the gene expression of TSLP, IL-25, and IL-33 and the protein expression levels of TSLP and IL-33 were increased, and only TSLP could be inhibited by antagonists and siRNAs. After administration of EGTA, the secretion of TSLP was inhibited significantly, and the expression of the transcription factor NFAT in the nucleus was observed after activation of the TRPV1 and TRPA1 proteins in epithelial cells. ConclusionActivation of TRPV1 and TRPA1 on nasal epithelial cells stimulates the generation of TSLP through the Ca2+/NFAT pathway. It also induces upregulation of IL-25 and IL-33 gene expression levels and increased levels of IL-33 protein, leading to the development of airway inflammation.

Role of TRPV4 in wet Cupping (Hijama Bi’l Shurt) in knee osteoarthritis (Waja ur Rukba): Clinical research

Role of TRPV4 in wet Cupping (Hijama Bi’l Shurt) in knee osteoarthritis (Waja ur Rukba): Clinical research

Garlic prevents the oxidizing and inflammatory effects of sepsis induced by bacterial lipopolysaccharide at the systemic and aortic level in the rat. Role of trpv1

Garlic (Allium sativum) possesses healing properties for diseases like systemic arterial hypertension, cancer and diabetes, among others. Its main component, allicin, binds to the Transient Receptor Potential Vanilloid Type 1 (TRPV1). In this study, we investigated TRPV1′s involvement in the regulation of various molecules at the systemic and aortic levels in Wistar rats treated with bacterial lipopolysaccharide (LPS) and garlic to activate the receptor. The experimental groups were as follows: 1) Control, 2) LPS, 3) Garlic, and 4) LPS + Garlic.Using Uv–visible spectrophotometry and capillary zone electrophoresis, we measured the levels of nitric oxide (NO), biopterins BH2 and BH4, total antioxidant capacity (TAC) and oxidizing capacity (OXCA). We also analyzed molecules related to vascular homeostasis such as angiotensin Ang 1–7 and Ang II, as well as endothelin ET-1. In addition, we assessed the inflammatory response by determining the levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and galectin-3 (GTN-3). For cell damage assessment, we measured levels of malondialdehyde (MDA), malonate (MTO) and 8-hydroxy-2-deoxyguanosine (8HO2dG).The results showed that LPS influenced the NO pathway at both systemic and aortic levels by increasing OXCA and reducing TAC. It also disrupted vascular homeostasis by increasing Ang-II and ET-1, while decreasing Ang1-7 levels. IL-6, TNFα, GTN-3, as well as MDA, MTO, and 8HO2dG were significantly elevated compared to the control group. The expression of iNOS was increased, but TRPV1 remained unaffected by LPS. However, garlic treatment effectively mitigated the effects of LPS and significantly increased TRPV1 expression.Furthermore, LPS caused a significant decrease in calcitonin gene-related peptide (CGRP) in the aorta, which was counteracted by garlic treatment. Overall, TRPV1 appears to play a crucial role in regulating oxidative stress and the molecules involved in damage and inflammation induced by LPS. Thus, studying TRPV1, CGRP, and allicin may offer a potential strategy for mitigating inflammatory and oxidative stress in sepsis.

Activation of TRPV1 Channels Inhibits the Release of Acetylcholine and Improves Muscle Contractility in Mice.

TRPV1 represents a non-selective transient receptor potential cation channel found not only in sensory neurons, but also in motor nerve endings and in skeletal muscle fibers. However, the role of TRPV1 in the functioning of the neuromuscular junction has not yet been fully established. In this study, the Levator Auris Longus muscle preparations were used to assess the effect of pharmacological activation of TRPV1 channels on neuromuscular transmission. The presence of TRPV1 channels in the nerve terminal and in the muscle fiber was confirmed by immunohistochemistry. It was verified by electrophysiology that the TRPV1 channel agonist capsaicin inhibits the acetylcholine release, and this effect was completely absent after preliminary application of the TRPV1 channel blocker SB 366791. Nerve stimulation revealed an increase of amplitude of isometric tetanic contractions upon application of capsaicin which was also eliminated after preliminary application of SB 366791. Similar data were obtained during direct muscle stimulation. Thus, pharmacological activation of TRPV1 channels affects the functioning of both the pre- and postsynaptic compartment of the neuromuscular junction. A moderate decrease in the amount of acetylcholine released from the motor nerve allows to maintain a reserve pool of the mediator to ensure a longer signal transmission process, and an increase in the force of muscle contraction, in its turn, also implies more effective physiological muscle activity in response to prolonged stimulation. This assumption is supported by the fact that when muscle was indirect stimulated with a fatigue protocol, muscle fatigue was attenuated in the presence of capsaicin.

Role of TRPV4 in superficial cervical lymphatic vessel contractile function

Collecting cervical lymphatic vessels pump lymph and macromolecules drained by brain meningeal lymphatics to the cervical lymph nodes. Collecting lymphatics vessels rely on spontaneous contractions to propel lymph against a pressure gradient to re-enter the venous circulation. The calcium permeable transient receptor potential vanilloid 4 channel (TRPV4) has been shown to mediate intraluminal pressure-induced vasodilatory responses in small arteries. However, whether TRPV4 participates in pressure-dependent contractile responses in lymphatic vessels remains unclear. We hypothesized that increases in intraluminal pressure leads to TRPV4-dependent increases in lymphatic pump function. TRPV4 expression was assessed by PCR assay in isolated superficial cervical lymphatic vessels (sCLV). Using pressure myography, contractile function of isolated sCLV was assessed in the presence of TRPV4 antagonist (1μM HC-067047) or vehicle (DMSO). To quantify lymphatic pump function (FPF), the product of contractile frequency (FREQ) and ejection fraction (EF) was analyzed using repeated end-diastolic and end-systolic diameter measurements. We detected TRPV4 mRNA expression following PCR amplification from isolated sCLV tissue of young C57Bl/6J mice (4-6 months). In pressurized sCLV, TRPV4 activation with GSK 1016790A (10 nM) abolished spontaneous rhythm contractions by causing a sustained constriction, consequently leading to a significant decrease in lymphatic pump function (FPF: 4.67±0.58 vs 1.17±0.86, Vehicle vs GSK 1016790A, n=8, p<0.05) at baseline intraluminal pressure (3 cm H2O). TRPV4 antagonism (HC-067047, 1 μM) did not affect basal sCLV contractility (FPF: 5.15±0.6 vs 3.44±0.43, Vehicle vs HC 067047, n=5, p>0.05). Further, when HC-067047 was applied to the bath and intraluminal pressure was maintained at 2 cm H2O, no changes were observed in FREQ (9.3±1.4 vs 11.7±1.3 Hz, Vehicle vs. HC-067047, n=7 / 9, p>0.05), EF (0.253±0.040 vs 0.268±0.037, Vehicle vs. HC-067047, n=7 / 9, p>0.05), or contractile amplitude (22.54±6.769 vs 26.76±3.028 μm, Vehicle vs HC-067047, n=7 / 9, p>0.05). Similarly, TRPV4 blockade did not alter FREQ (12.4±1.3 vs 14.3±1.4 Hz, Vehicle vs. HC-067047, n=7 / 9, p>0.05), EF (0.090±0.024 vs 0.092±0.019, Vehicle vs HC-067047) or contractile amplitude (7.98±2.814 vehicle vs 9.27±1.88 μm, Vehicle vs HC-067047) at the higher intraluminal pressure of 7 cm H2O. Collectively, these data suggest that TRPV4 channels are not involved in pressure-dependent contractile responses of sCLV in mice, despite inducing a robust constriction upon pharmacological activation. National Institutes of Health (R01 AG073230) and the Alzheimer's Association (AARGD-21-850835) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

TRPV1: A promising therapeutic target for skin aging and inflammatory skin diseases.

TRPV1 is a non-selective channel receptor widely expressed in skin tissues, including keratinocytes, peripheral sensory nerve fibers and immune cells. It is activated by a variety of exogenous or endogenous inflammatory mediators, triggering neuropeptide release and neurogenic inflammatory response. Previous studies have shown that TRPV1 is closely related to the occurrence and/or development of skin aging and various chronic inflammatory skin diseases, such as psoriasis, atopic dermatitis, rosacea, herpes zoster, allergic contact dermatitis and prurigo nodularis. This review summarizes the structure of the TRPV1 channel and discusses the expression of TRPV1 in the skin as well as its role of TRPV1 in skin aging and inflammatory skin diseases.

Cultured rat aortic vascular smooth muscle cells do not express a functional TRPV1.

We showed previously that capsaicin, an active compound of chili peppers, can inhibit platelet-derived growth factor-induced proliferation in primary rat vascular smooth muscle cells (VSMCs). The inhibition of BrdU incorporation by capsaicin in these cells was revoked by BCTC, which might be explained by a role of TRPV1 in VSMCs proliferation. To further pursue the hypothesis of a TRPV1-dependent effect of capsaicin, we investigated TRPV1 expression and function. Commercially available antibodies against two different TRPV1 epitopes (N-terminus and C-terminus) were rendered invalid in detecting TRPV1, as shown: i) in western blot experiments using control lysates of TRPV1-expressing (PC-12 and hTRPV1 transfected HEK293T) and TRPV1-downregulated (CRISPR/Cas gene edited A10) cells, and ii) by substantial differences in staining patterns between the applied antibodies using fluorescence confocal microscopy. The TRPV1 agonists capsaicin, resiniferatoxin, piperine and evodiamine did not increase intracellular calcium levels in primary VSMCs and in A10 cells. Using RT qPCR, we could detect a rather low TRPV1 expression in VSMCs at the mRNA level (Cp value around 30), after validating the primer pair in NGF-stimulated PC-12 cells. We conclude that rat vascular smooth muscle cells do not possess canonical TRPV1 channel activity, which could explain the observed antiproliferative effect of capsaicin.

Roles of TRPV4 in Regulating Circulating Angiogenic Cells to Promote Coronary Microvascular Regeneration.

To clarify the mechanisms underlying TRPV4 regulating angiogenesis by enhancing the activity of CACs, we detected the angiogenesis ability of HUVEC co-cultured with CACs, the effects of ILK on TRPV4 expression and CACs activity, and the impacts of TRPV4 agonist or inhibitor on cardio-protection of AMI rats with or without CAC transplantation. ILK overexpression or TRPV4 agonist promoted the angiogenesis in HUVEC co-cultured with CACs. ILK overexpression or activation upregulated TRPV4 expression in CACs, while TRPV4 agonist stimulation also regulated ILK expression. TRPV4 agonist effectively improved the myocardial function of AMI rats. Moreover, this effect could be strengthened when combined with CAC transplantation, as CAC transplantation dramatically upregulated the expression of ILK and TRPV4 in heart tissues of AMI rats. Thus, the application of TRPV4 agonist may maintain the activity of CACs to promote angiogenesis and microcirculation reconstruction in the area of myocardial infarction and substantially improve the therapeutic effect.

Vasopressin regulation of maternal body fluid balance in pregnancy and lactation: A role for TRPV channels?

Renal water reabsorption increases in pregnancy and lactation to expand maternal blood volume to cope with the cardiovascular demands of the developing fetus and new-born baby. Vasopressin (antidiuretic hormone) promotes renal water reabsorption and its secretion is principally stimulated by body fluid osmolality. Hence, lowered osmolality normally decreases vasopressin secretion. However, despite water retention profoundly reducing osmolality in pregnancy and lactation, vasopressin levels are maintained to drive blood volume expansion. Despite its importance for successful reproduction, the cellular mechanisms that maintain vasopressin secretion in the face of decreased osmolality during pregnancy and lactation are unknown. Vasopressin is secreted by neurons that are intrinsically osmosensitive through expression of N-terminal truncated-transient receptor potential vanilloid-1 channel, ΔN-TRPV1, which is mechanically activated by osmotically-induced cell shrinkage to increase vasopressin neuron activity. Vasopressin neurons also express TRPV4 but the role of TRPV4 in vasopressin neuron function is not well characterised. Here, we summarise our novel evidence showing that TRPV4 forms functional channels with ΔN-TRPV1 that have a greater single-channel conductance compared to channels with ΔN-TRPV1 alone. We propose that upregulation of TRPV4 heteromerisation with ΔN-TRPV1 might maintain vasopressin secretion in pregnancy and lactation to expand blood volume for successful reproduction.

TRPV1+ sensory nerves modulate corneal inflammation after epithelial abrasion via RAMP1 and SSTR5 signaling.

Timely initiation and termination of inflammatory response after corneal epithelial abrasion is critical for the recovery of vision. The cornea is innervated with rich sensory nerves with highly dense TRPV1 nociceptors. However, the roles of TRPV1+ sensory neurons in corneal inflammation after epithelial abrasion are not completely understood. Here, we found that depletion of TRPV1+ sensory nerves using resiniferatoxin (RTX) and blockade of TRPV1 using AMG-517 delayed corneal wound closure and enhanced the infiltration of neutrophils and γδ T cells to the wounded cornea after epithelial abrasion. Furthermore, depletion of TRPV1+ sensory nerves increased the number and TNF-α production of corneal CCR2+ macrophages and decreased the number of corneal CCR2- macrophages and IL-10 production. In addition, the TRPV1+ sensory nerves inhibited the recruitment of neutrophils and γδ T cells to the cornea via RAMP1 and SSTR5 signaling, decreased the responses of CCR2+ macrophages via RAMP1 signaling, and increased the responses of CCR2- macrophages via SSTR5 signaling. Collectively, our results suggest that the TRPV1+ sensory nerves suppress inflammation to support corneal wound healing via RAMP1 and SSTR5 signaling, revealing potential approaches for improving defective corneal wound healing in patients with sensory neuropathy.

Transient Receptor Potential-Vanilloid (TRPV1-TRPV4) Channels in the Atlantic Salmon, Salmo salar. A Focus on the Pineal Gland and Melatonin Production.

Fish are ectotherm, which rely on the external temperature to regulate their internal body temperature, although some may perform partial endothermy. Together with photoperiod, temperature oscillations, contribute to synchronizing the daily and seasonal variations of fish metabolism, physiology and behavior. Recent studies are shedding light on the mechanisms of temperature sensing and behavioral thermoregulation in fish. In particular, the role of some members of the transient receptor potential channels (TRP) is being gradually unraveled. The present study in the migratory Atlantic salmon, Salmo salar, aims at identifying the tissue distribution and abundance in mRNA corresponding to the TRP of the vanilloid subfamilies, TRPV1 and TRPV4, and at characterizing their putative role in the control of the temperature-dependent modulation of melatonin production—the time-keeping hormone—by the pineal gland. In Salmo salar, TRPV1 and TRPV4 mRNA tissue distribution appeared ubiquitous; mRNA abundance varied as a function of the month investigated. In situ hybridization and immunohistochemistry indicated specific labeling located in the photoreceptor cells of the pineal gland and the retina. Additionally, TRPV analogs modulated the production of melatonin by isolated pineal glands in culture. The TRPV1 agonist induced an inhibitory response at high concentrations, while evoking a bell-shaped response (stimulatory at low, and inhibitory at high, concentrations) when added with an antagonist. The TRPV4 agonist was stimulatory at the highest concentration used. Altogether, the present results agree with the known widespread distribution and role of TRPV1 and TRPV4 channels, and with published data on trout (Oncorhynchus mykiss), leading to suggest these channels mediate the effects of temperature on S. salar pineal melatonin production. We discuss their involvement in controlling the timing of daily and seasonal events in this migratory species, in the context of an increasing warming of water temperatures.

Role of TRPV1 in hyaluronan-induced apoptosis avoidance in MCF-7 cells

Role of TRPV1 in hyaluronan-induced apoptosis avoidance in MCF-7 cells

Role of TRPV4 in skeletal function and its mutant-mediated skeletal disorders.

TRPV4 is a non-selective cation channel that belongs to the TRP super family. This channel can be activated by physiological temperatures and mechanical stimuli. In addition, TRPV4 is modulated by several endogenous mediators including specific lipids, cholesterol and their metabolic products. TRPV4 gene is present in all vertebrates and is widely expressed in tissues originating from ectoderm, endoderm and mesoderm. Although TRPV4 knockout is not lethal, point mutations in TRPV4 cause severe clinical phenotypes with variable penetration in human population. These mutations are mostly "gain-of-function" in nature and primarily affect muscles, bones and peripheral neurons, endorsing TRPV4 as critical regulator of musculoskeletal systems. Here we critically analyze the involvement of TRPV4 in musculoskeletal system. Studies of TRPV4 mutations provide detailed information on musculoskeletal disorders at molecular, cellular and metabolic levels.

TRPV1 mediates itch-associated scratching and skin barrier dysfunction in DNFB-induced atopic dermatitis mice.

In chronic pruritic diseases such as atopic dermatitis (AD), pruritus and skin lesions are exacerbated by scratching in clinical and experimental settings. TRPV1 is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in itch-associated scratching in AD is poorly understood. In this study, we examined the efficacy of cutting off nailsand TRPV1 antagonist, ruthenium red (RR) in a murine model of AD induced by DNFB and further investigated the underlying mechanism. Nail clipping or RR could markedly ameliorate the general AD-like symptoms as manifested by the reduced clinical severity of dermatitis, IgE and Th2-related cytokine levels, and mast cell degranulation. Moreover, scratching behaviour, the levels of pruritogenic mediators, including HIS, TSLP, IL-31 and SP, and skin pH and TEWL were all significantly decreased in nail clipping or RR-treated mice, suggesting a reduction in itch-associated scratching and skin barrier defects. Immunofluorescence staining and Western blot results revealed thatantipruriticeffect ofnail clipping or RR in AD may be explained, at least in part, by the suppression of TRPV1 activation. In summary, these data show that TRPV1mediates itch-associated scratching and subsequent skin barrier defects, suggesting its potential as a therapeutic target in AD.

344 THE ROLE OF TRPV2 IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Transient receptor potential vanilloid 2 (TRPV2) was recently shown to be involved in migrant potentials. Previous studies reported that TRPV2 was involved in cancer progression, migration, and invasion. The present study aimed to investigate its role in esophageal squamous cell carcinoma (ESCC). Methods In human ESCC cell lines, we investigated the role of TPRV2 in ESCC using a cancer function assay with the knockdown of TRPV2 by siRNA, microarray, pathway, and gene ontology analyses. The significance of TRPV2 expression in 62 ESCC samples was then evaluated by immunohistochemical staining. Results TRPV2 was overexpressed in TE15 and KYSE170 cells. TRPV2 depletion suppressed cell proliferation, cell cycle progression, and invasion/migration, and induced apoptosis. A pathway analysis of microarray data revealed that TRPV2 depletion down-regulated WNT/β-catenin signaling-related genes and basal cell carcinoma signaling-related genes. The suppression of cancer functions, such as proliferation, invasion, and angiogenesis, by TRPV2 depletion was predicted in the ontology analysis. Immunohistochemical staining revealed a relationship between strong TRPV2 expression and a poor prognosis in ESCC patients. Conclusion The present results suggest that TRPV2 regulates tumor progression by affecting WNT/β-catenin or basal cell carcinoma signaling, and that its strong expression is associated with a worse prognosis in ESCC patients. These results provide an insight into the role of TRPV2 as a therapeutic target or biomarker for ESCC.

TRPV1: Role in Skin and Skin Diseases and Potential Target for Improving Wound Healing.

Skin is innervated by a multitude of sensory nerves that are important to the function of this barrier tissue in homeostasis and injury. The role of innervation and neuromediators has been previously reviewed so here we focus on the role of the transient receptor potential cation channel, subfamily V member 1 (TRPV1) in wound healing, with the intent of targeting it in treatment of non-healing wounds. TRPV1 structure and function as well as the outcomes of TRPV1-targeted therapies utilized in several diseases and tissues are summarized. In skin, keratinocytes, sebocytes, nociceptors, and several immune cells express TRPV1, making it an attractive focus area for treating wounds. Many intrinsic and extrinsic factors confound the function and targeting of TRPV1 and may lead to adverse or off-target effects. Therefore, a better understanding of what is known about the role of TRPV1 in skin and wound healing will inform future therapies to treat impaired and chronic wounds to improve healing.

Cimifugin relieves pruritus in psoriasis by inhibiting TRPV4

Psoriasis is an immune-mediated chronic inflammatory skin disease characterized by erythema, scales, and infiltration of the skin, which causes deleterious effects on patient quality of life. TRP channel played important roles in the generation and conductance of itch signal . According to our results, psoriasis induced itch was TRPV4 dependent, and TRPV4 expression in both epidermis and DRG were up-regulated in psoriasis. Thus, TRPV4 is an attractive candidate for treating psoriasis induced itch. Cimifugin is a common compound in antipruritic Chinese medicine. In our study, GSK1016790A, a TRPV4 channel specific agonist, induced acute itch was inhibited by cimifugin in a dose-dependent manner. Furthermore, cimifugin treatment reduced the scratching behavior and reversed the TRPV4 up-regulation induced by psoriasis. In particular, cimifugin decreased GSK1016790A induced calcium response both in HaCaT cells and DRG neurons. Importantly, in TRPV4 transfected HEK293 cells, GSK101 induced calcium response was also significantly inhibited by cimifugin pretreatment. Consistent with our calcium imaging result, cimifugin pretreatment also inhibited GSK101 induced inward currents. Our study delineated a new role of TRPV4 in psoriasis and emphasized the antipruritic effect of cimifugin, which opened a new avenue to itch management in psoriasis.

TRPV1 Responses in the Cerebellum Lobules VI, VII, VIII Using Electroacupuncture Treatment for Chronic Pain and Depression Comorbidity in a Murine Model.

Depression is a prominent complex psychiatric disorder, usually complicated through expression of comorbid conditions, with chronic pain being among the most prevalent. This comorbidity is consistently associated with a poor prognosis and has been shown to negatively impact patient outcomes. With a global rise in this condition presenting itself, the importance of discovering long-term, effective, and affordable treatments is crucial. Electroacupuncture has demonstrated renowned success in its use for the treatment of pain and is a widely recognized therapy in clinical practice for the treatment of various psychosomatic disorders, most notably depression. Our study aimed to investigate the effects and mechanisms of Acid-Saline (AS) inducing states of chronic pain and depression comorbidity in the cerebellum, using the ST36 acupoint as the therapeutic intervention. Furthermore, the role of TRPV1 was relatedly explored through the use of TRPV1−/− mice (KO). The results indicated significant differences in the four behavioral tests used to characterize pain and depression states in mice. The AS and AS + SHAM group showed significant differences when compared to the Control and AS + EA groups in the von Frey and Hargreaves’s tests, as well as the Open-Field and Forced Swimming tests. This evidence was further substantiated in the protein levels observed in immunoblotting, with significant differences between the AS and AS + SHAM groups when compared to the AS + EA and AS + KO groups being identified. In addition, immunofluorescence visibly served to corroborate the quantitative outcomes. Conclusively these findings suggest that AS-induced chronic pain and depression comorbidity elicits changes in the cerebellum lobules VI, VII, VIII, which are ameliorated through the use of EA at ST36 via its action on TRPV1 and related molecular pathways. The action of TRPV1 is not singular in CPDC, which would suggest other potential targets such as acid-sensing ion channel subtype 3 (ASIC3) or voltage-gated sodium channels (Navs) that could be explored in future studies.