capsaicin receptor

Methylglyoxal (MG), a reactive metabolic byproduct of glycolysis, is a causative of painful diabetic neuropathy. Patients with diabetes are associated with more frequent severe asthma exacerbation. Stimulation of capsaicin-sensitive lung vagal (CSLV) afferents may contribute to the pathogenesis of hyperreactive airway diseases such as asthma. However, the possibility of the stimulatory effect of MG on CSLV afferents and the underlying mechanisms remain unknown. Our results showed that intravenous injection of MG (25 mg/kg, MG25) in anesthetized, spontaneously breathing rats elicited pulmonary chemoreflexes characterized by apnea, bradycardia, and hypotension...

BACKGROUND AND AIM: Phytoformulation therapy is a pioneering strategy for the treatment of metabolic disorders and related diseases. The aim of the present study was to investigate the protective effect of a phytoformulation consisting of hydroxycitric acid and capsaicin against obesity-related cardiomyopathy. EXPERIMENTAL PROCEDURE: Sprague-Dawley rats were fed HFD for 21 weeks, and phytoformulation (100 mg/kg body weight) was administered orally for 45 days starting at week 16...

Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) are nonselective cation channels expressed in primary sensory neurons and several other non-neuronal structures such as immune cells, keratinocytes, and vascular smooth muscle cells. They play important roles in nociception, pain processing and their chanellopathies are associated with the development of several pathological conditions. They are located in cholesterol- and sphingolipid-rich membrane lipid raft regions serving as platforms to modulate their activations...

BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) cation channels, expressed on nociceptors, are well established as key contributors to abdominal pain in inflammatory bowel disease (IBD). Previous attempts at blocking these channels have been riddled with side effects. Here, we propose a novel treatment strategy, utilizing the large pore of TRPV1 channels as a drug delivery system to selectively inhibit visceral nociceptors. METHODS: We induced colitis in rats using intrarectal dinitrobenzene sulfonic acid...

Several decades of research support the involvement of transient receptor potential (TRP) channels in nociception. Despite the disappointments of early TRPV1 antagonist programs, the TRP family remains a promising therapeutic target in pain disorders. High-dose capsaicin patches are already in clinical use to relieve neuropathic pain. At present, localized injections of the side-directed TRPV1 agonist capsaicin and resiniferatoxin are undergoing clinical trials in patients with osteoarthritis and bone cancer pain...

Chronic nonallergic rhinitis (NAR) syndromes encompasses various conditions, of which vasomotor (VMR) rhinitis is the most common form representing approximately 80% of patients also referred to as nonallergic rhinopathy, nasal hyperreactivity, neurogenic rhinitis or idiopathic rhinitis. Expert panels have recommended replacing VMR terminology as it is more descriptive of this condition that is characterized by symptoms triggered by chemical irritants and weather changes through chemosensors, mechanosensors, thermosensors, and/or osmosensors activated through different Transient Receptor Potential (TRP) calcium ion channels...

Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses...

Bleomycin is an effective antibiotic with a significant anticancer properties, but its use is limited due to its potential to induce dose-dependent pulmonary fibrosis. Therefore, this study aimed to assess the therapeutic potential of Capsaicin as an additional treatment to enhance patient tolerance to Bleomycin compared to the antifibrotic drug Pirfenidone. Pulmonary fibrosis was induced in rats through by a single intratracheal Bleomycin administration in day zero, followed by either Capsaicin or Pirfenidone treatment for 7 days...

Intravenous (systemic) bolus injection of fentanyl (FNT) reportedly induces an immediate vagal-mediated apnea; however, the precise origin of vagal afferents responsible for this apnea remains unknown. We tested whether intralaryngeal (local) application of FNT would also trigger an apnea and whether the apneic response to both local and systemic administration of FNT was laryngeal afferent-mediated. Cardiorespiratory responses to FNT were recorded in anesthetized male adult rats with and without bilateral sectioning of the superior laryngeal nerve (SLNx) or peri-SLN capsaicin treatment (SLNcap) to block local C-fiber signal conduction...

Nicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4β2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into the lower hind leg, spinal nerve injury, chronic constriction injury, or chronic nicotine exposure...

Individuals living with sickle cell disease (SCD) experience severe recurrent acute and chronic pain. Challenges to gaining mechanistic insight into pathogenic SCD pain processes include differential gene expression and function of sensory neurons between humans and mice with SCD, and extremely limited availability of neuronal tissues from SCD patients. Here we used SCD patient-derived induced pluripotent stem cells (iPSCs) differentiated into sensory neurons (SCD iSNs) to begin to overcome these challenges...

BACKGROUND: Capsaicin is a highly selective agonist of the transient receptor potential vanilloid 1. The adhesive capsaicin patch provides a high capsaicin concentration (8%) directly in the painful area - its efficacy in benign peripheral neuropathic pain (diabetic neuropathy or postherpetic neuralgia) has recently been described in the literature. However, there is scant evidence of its efficacy in chemotherapy-induced peripheral neuropathy (CIPN). This is a concern for patients with multiple myeloma, who suffer from peripheral neuropathic pain induced by first-line treatments (bortezomib or thalidomide)...

Transient receptor potential (TRP) channels are pivotal in modulating vascular functions. In fact, topical application of cinnamaldehyde or capsaicin (TRPA1 and TRPV1 channel agonists, respectively) induces "local" changes in blood flow by releasing vasodilator neuropeptides. We investigated TRP channels' contributions and the pharmacological mechanisms driving vasodilation in human isolated dermal arteries. Ex vivo studies assessed the vascular function of artery segments and analyzed the effects of different compounds...

INTRODUCTION: Capsaicin, a chili pepper extract, can stimulate increased skin blood flow (SkBF) with a perceived warming sensation on application areas. Larger surface area application may exert a more systemic thermoregulatory response. Capsaicin could assist with maintaining heat transport to the distal extremities, minimizing cold weather injury risk. However, the thermoregulatory and perceptual impact of topical capsaicin cream application prior to exercise in the cold is unknown...

BACKGROUND: Vagal afferent neurons represent the key neurosensory branch of the gut-brain axis, which describes the bidirectional communication between the gastrointestinal system and the brain. These neurons are important for detecting and relaying sensory information from the periphery to the central nervous system to modulate feeding behavior, metabolism, and inflammation. Confounding variables complicate the process of isolating the role of the vagal afferents in mediating these physiological processes...

Background : We previously found that cimifugin has a potent antiallergic inflammatory effect in atopic dermatitis (AD). However, whether cimifugin has an antipruritic effect in AD was unknown. Methods : Mouse scratching behavior tests were performed to verify the proposed antipruritic effect of cimifugin on DNFB- or FITC-mediated AD. Chloroquine (CQ)- and compound 48/80-evoked acute itch models were employed to clarify the effect of cimifugin on histamine-dependent or -independent itch. Intracellular calcium changes were assessed in a primary culture of mouse dorsal root ganglia (DRG) in response to pruritogen exposure with or without cimifugin treatment, including CQ, histamine, allyl-isothiocyanate (AITC), and capsaicin...

Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, the clinical application for capsaicin as the TRPV1 agonist is largely limited by its chronic toxicity. To address this issue, we developed a bifunctional controllable magnetothermal switch targeting TRPV1 for the alleviation of OA progression by coupling of magnetic nanoparticles (MNPs) to TRPV1 monoclonal antibodies (MNPs-TRPV1)...

Orexin is a neuropeptide released from hypothalamus regulating feeding, sleeping, arousal, and cardiovascular activity. Past research has demonstrated that orexin receptor 2 (OX2R) agonist infusion in the brain results in sympathoexcitatory responses. Here, we found that epicardial administration of OX2R agonism leads to opposite responses. We proved that OX2R is expressed mainly in DRG neurons and transported to sensory nerve endings innervating the heart. In a capsaicin-induced cardiac sympathetic afferent reflex (CSAR) model, we recorded the calcium influx in DRG neurons, measured heart rate variability, and examined the PVN c-Fos activity to prove that epicardial OX2R agonism administration could attenuate capsaicin-induced CSAR...

To discover mode-selective TRPV1 antagonists as thermoneutral drug candidates, the previous potent antagonist benzopyridone 2 was optimized based on the pharmacophore A- and C-regions. The structure activity relationship was investigated systematically by modifying the A-region by incorporating a polar side chain on the pyridone and then by changing the C-region with a variety of substituted pyridine and pyrazole moieties. The 3-t-butyl and 3-(1-methylcyclopropyl) pyrazole C-region analogs provided high potency as well as mode-selectivity...

Physical stimulation with mild heat possesses the notable ability to induce immunomodulation within the tumor microenvironment (TME). It transforms the immunosuppressive TME into an immune-active state, making tumors more receptive to immune checkpoint inhibitor (ICI) therapy. Transient receptor potential vanilloid 1 (TRPV1), which can be activated by mild heat, holds the potential to induce these alterations in the TME. However, achieving precise temperature control within tumors while protecting neighboring tissues remains a significant challenge when using external heat sources...