trpm8

Objective: To explore the effects between transient receptor potential melastatin 8 (TRPM8) on pain symptom and neuronal proliferation in mice with interstitial cystitis/bladder pain syndrome (IC/BPS). Methods: Female wild-type C57BL/6 mice (8-10 weeks old) were divided into control group, IC/BPS model group, and IC/BPS model+menthol group (6 mice each) by random number table method; TRPM8 knockout mice were randomly divided into TRPM8 knockout group and TRPM8 knockout model group (6 mice each). The IC/BPS model group, the IC/BPS model+menthol group, and the TRPM8 knockout model group were injected subcutaneously with residues 65-84 of murine uroplakin 3A (UPK3A65-84)...

Transient receptor potential melastatin 8 (TRPM8) is a cold sensory receptor in primary sensory neurons that regulates various neuronal functions. Substance P (SP) is a pro-inflammatory neuropeptide secreted by the neurons, and it aggravates colitis. However, the regulatory role of TRPM8 in SP release is still unclear. Our study aimed to investigate TRPM8's role in SP release from primary sensory neurons during colitis and clarify the effect of SP on colonic epithelium. We analyzed inflammatory bowel disease patients' data from the Gene Expression Omnibus dataset...

Streptococcus pneumoniae infection remains a leading cause of pneumonia-related deaths. Transient receptor potential melastatin 8 (TRPM8) exerts crucial roles in lung diseases. We first dissected the role of TRPM8 in pneumococcal pneumonia and the mechanism related to TRPM8 effects. TRPM8 expression and inflammation cytokines level were determined in 15 paired patients and controls. A549 cells were pretreated with si-TRPM8, followed by infection with S. pneumoniae D39 strain (D39). TRPM8 expressions in D39-treated cells were detected and the effect of TRPM8 inhibition on the viability, apoptosis, and inflammation induced by D39 was evaluated...

Cold injury or frostbite is a common medical condition that causes serious clinical complications including sensory abnormalities and chronic pain ultimately affecting overall well-being. Opioids are the first-choice drug for the treatment of frostbite-induced chronic pain; however, their notable side effects, including sedation, motor incoordination, respiratory depression, and drug addiction, present substantial obstacle to their clinical utility. To address this challenge, we have exploited peripheral mu-opioid receptors as potential target for the treatment of frostbite-induced chronic pain...

Amphibians, like the paddy frog ( Fejervarya multistriata ), have played a critical role in the transition from water to land. Hibernation is a vital survival adaptation in cold environments with limited food resources. We decoded the paddy frog genome to reveal the molecular adaptations linked to hibernation in ectotherms. The genome contained 13 chromosomes, with a significant proportion of repetitive sequences. We identified the key genes encoding the proteins of AANAT, TRPM8, EGLN1, and VEGFA essential for circadian rhythms, thermosensation, and hypoxia during hibernation by comparing the hibernator and non-hibernator genomes...

PURPOSE: Sensory nerve terminals are highly distributed in the cornea, and regulate ocular surface sensation and homeostasis in response to various endogenous and exogenous stimuli. However, little is known about mediators regulating the physiological and pathophysiological activities of corneal sensory nerves. The aim of this study was to investigate the presence of cholinergic regulation in sensory nerves in the cornea. METHODS: Localization of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (vAChT) was evaluated using western blotting and immunohistochemical analysis...

Removing water from wet fur or feathers is important for thermoregulation in warm-blooded animals. The "wet dog shake" (WDS) behavior has been largely characterized in mammals but to a much lesser extent in birds. Although it is known that TRPM8 is the main molecular transducer of low temperature in mammals, it is not clear if wetness-induced shaking in furred and feathered animals is dependent on TRPM8. Here, we show that a novel TRPM8 agonist induces WDS in rodents and, importantly, in birds, similar to the shaking behavior evoked by water-spraying...

Neuropathic corneal pain (NCP) is a new and ill-defined disease characterized by pain, discomfort, aching, burning sensation, irritation, dryness, and grittiness. However, the mechanism underlying NCP remain unclear. Here, we reported a novel rat model of primary NCP induced by long ciliary nerve (LCN) ligation. After sustained LCN ligation, the rats developed increased corneal mechanical and chemical sensitivity, spontaneous blinking, and photophobia, which were ameliorated by intraperitoneal injection of morphine or gabapentin...

Frostbite, a debilitating condition, significantly affects the well-being of military veterans and high-altitude residents, causing severe clinical complications such as chronic pain that markedly impacts overall quality of life. There has been a notable increase in the development of pre-clinical models for studying frostbite injury, but their suitability for pain evaluation remains limited. The major hurdle in the development of novel therapeutics for the treatment of frostbite-induced chronic pain is the unavailability of well-established preclinical models...

BACKGROUND: Prurigo nodularis (PN) is an intensively pruritic skin disease that negatively influences quality of life. Cryosim-1 (Intrinsic IB Spot) is a synthetic, selective transient receptor potential melastatin 8 agonist. AIMS: To investigate the efficacy and safety of cryosim-1 in PN patients. PATIENTS/METHODS: A randomized, double-blinded, placebo-controlled clinical trial including 30 patients was conducted. The numerical rating scale (NRS) of pruritus was evaluated before and 2 h after cryosim-1 application at every visit...

Chemotherapy-induced neuropathic pain (CINP) is one of the most prominent and incapacitating complication associated with chemotherapeutic regimens. The exact mechanisms underlying CINP are not fully understood yet, which hampers the development of effective therapeutics. The current study has been designed to investigate the effect of bergenin on CINP and dissect the underlying cellular and molecular mechanisms. Behavioural responsiveness assays were conducted in rats before and after CINP induction and at different time points post-bergenin treatment...

Itch (pruritus) is a sensation in the skin that provokes the desire to scratch. The sensation of itch is mediated through a subclass of primary afferent sensory neurons, termed pruriceptors, which express molecular receptors that are activated by itch-evoking ligands. Also expressed in pruriceptors are several types of Transient Receptor Potential (TRP) channels. TRP channels are a diverse class of cation channels that are responsive to various somatosensory stimuli like touch, pain, itch, and temperature. In pruriceptors, TRP channels can be activated through intracellular signaling cascades initiated by pruritogen receptors and underly neuronal activation...

"Sulmona Red Garlic" is a well-known Italian traditional product. Bulbs, used for culinary purposes, have been largely investigated for their medicinal properties whereas aerial bulbils are usually removed as waste material. Here, for the first time, chemical composition and biological properties of the hydroalcoholic extract from aerial bulbils were investigated. Complementary information on metabolite composition were obtained using both NMR based untargeted and HPLC-DAD targeted methodologies. The NMR analysis revealed the presence of sugars, organic acids, amino acids, organosulphur compounds (methiin, alliin, allicin and cycloalliin), and other secondary metabolites...

Headaches, including migraines, can have a causal relationship to exposure to cold, and this relationship may be both positive and negative, as cold can both provoke and alleviate cephalgia. The role of thermoreceptors responsible for transduction of low temperatures belongs to the transient receptor potential cation channel subfamily melastatin member 8 (TRPM8). These channels mediate normal cooling sensation and have a role in both cold pain and cooling-mediated analgesia; they are seen as a potential target for principally new anti-migraine pharmaceuticals...

Intraneuronal inclusions of alpha-synuclein (α-synuclein, α-syn) are commonly found in the brain of patients with Parkinson's disease (PD). The pathogenesis of the abundant α-syn protein in the blood has been extensively studied to understand its properties better. In recent years, peptidome analysis has received increasing attention. In this study, we identified and analyzed serum peptides from wild-type (WT) and the (Thy-1)-h[A30P] alpha-synuclein transgenic mice (SNCA-A30P mice) using liquid chromatography-tandem mass spectrometry (LC-MS/MS)...

PURPOSE: To reveal the role of transient receptor potential cation subfamily M member 8 (TRPM8) channels in herpes simplex keratitis (HSK). METHODS: HSK models were established using TRPM8 knockout (TRPM8-/-) mice and their wild-type (WT) littermates. The infected corneas were graded and harvested to evaluate the mRNA levels of inflammatory factors through quantitative real-time polymerase chain reaction (RT-PCR), as well as the infiltration of inflammatory cells through immunofluorescence staining and flow cytometry...

ETHNOPHARMACOLOGICAL RELEVANCE: Borneol is a long-established traditional Chinese medicine that has been found to be effective in treating pain and itchy skin. However, whether borneol has a therapeutic effect on chronic itch and its related mechanisms remain unclear. AIM OF THE STUDY: To investigate the antipruritic effect of borneol and its molecular mechanism. MATERIALS AND METHODS: DrugBAN framework and molecular docking were applied to predict the targets of borneol, and the calcium imaging or patch-clamp recording analysis were used to detect the effects of borneol on TRPA1, TRPM8 or TRPV3 channels in HEK293T cells...

TRPM8 agonist has been reported to promote osteogenic differentiation of mesenchymal stem cells (MSCs), therefore we evaluated whether cooling-induced activation of TRPM8 promotes myogenic differentiation of MSCs. We used 5-azacytidine as a myogenic differentiation inducer in murine bone marrow-derived MSCs. Addition of menthol, a TRPM8 agonist, to the differentiation induction medium significantly, increased the percentage of MyoD-positive cells, a specific marker of myogenic differentiation. We performed intracellular Ca2+ imaging experiments using fura-2 to confirm TRPM8 activation by cooling stimulation...

Bromelain, the main protease enzyme found in the pineapple plant ( Ananas comosus ), has had its antinociceptive effect previously demonstrated. This investigation aimed to appraise the role of TRP (Transient Receptor Potential) channels in the nociception-relieving effects of bromelain in the orofacial region of adult zebrafish. The animals were pretreated with bromelain (3.0, 10.0 or 30.0 mg/mL; gavage) and submitted to open field and acute orofacial (capsaicin - TRPV1 agonist, cinnamaldehyde - TRPA1 agonist or menthol - TRPM8 agonist) nociception tests...

Transient receptor potential vanilloid 3 (TRPV3) channel is a temperature-sensitive and Ca2+ -permeable nonselective cation channel, which is abundantly expressed in skin keratinocyte and plays an important role in skin homeostasis and repair. However, only a few TRPV3 inhibitors were reported. Few selective and potent modulators of the TRPV3 channel have hindered the progress of the investigation and clinical application. TRPV3 channel research still faces challenges and requires the new inhibitors. Flavonoids are a kind of natural compounds with various biological and pharmacological activities including anti-inflammatory and anti allergic effects, which is associated with some physiological effects mediated by TRPV3 channel...