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Thomas Viereckel, Sylvie Dumas, Casey J A Smith-Anttila, Bianca Vlcek, Zisis Bimpisidis, Malin C Lagerström, Åsa Konradsson-Geuken, Åsa Wallén-Mackenzie
The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) of the midbrain are associated with Parkinson's disease (PD), schizophrenia, mood disorders and addiction. Based on the recently unraveled heterogeneity within the VTA and SNc, where glutamate, GABA and co-releasing neurons have been found to co-exist with the classical dopamine neurons, there is a compelling need for identification of gene expression patterns that represent this heterogeneity and that are of value for development of human therapies...
October 20, 2016: Scientific Reports
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
Cassandra E Deering-Rice, Chris Stockmann, Erin G Romero, Zhenyu Lu, Darien Shapiro, Brian L Stone, Bernhard Fassl, Flory Nkoy, Derek A Uchida, Robert M Ward, John M Veranth, Christopher A Reilly
Transient receptor potential (TRP) channels are activated by environmental particulate materials. We hypothesized that polymorphic variants of TRPV1 would be uniquely responsive to insoluble coal fly ash compared to the prototypical soluble agonist capsaicin. Furthermore, these changes would manifest as differences in lung cell responses to these agonists and perhaps correlate with changes in asthma symptom control. The TRPV1 I315M and T469I variants were more responsive to capsaicin and coal fly ash. The I585V variant was less responsive to coal fly ash particles, due to reduced translation of protein and an apparent role for I585 in activation by particles...
October 7, 2016: Journal of Biological Chemistry
Lovish Marwaha, Yashika Bansal, Raghunath Singh, Priyanka Saroj, Rupinder Kaur Sodhi, Anurag Kuhad
TRP channels have been discovered as a specialized group of somatosensory neurons involved in the detection of noxious stimuli. Desensitization of TRPV1 located on dorsal root and trigeminal ganglia exhibits analgesic effect and makes it potential therapeutic target for treatment of neuropathic pain. With this background, the present study was aimed to investigate the protective effect of niflumic acid, a TRPV1 modulator, on stavudine (STV)-induced neuropathic pain in rats. Stavudine (50 mg/kg) was administered intravenously via tail vein in rats to induce neuropathic pain...
October 18, 2016: Inflammopharmacology
Lovish Marwaha, Yashika Bansal, Raghunath Singh, Priyanka Saroj, Ranjana Bhandari, Anurag Kuhad
Neuropathic pain is a debilitating disease which affects central as well as peripheral nervous system. Transient receptor potential (TRP) channels are ligand-gated ion channels that detect physical and chemical stimuli and promote painful sensations via nociceptor activation. TRP channels have physiological role in the mechanisms controlling several physiological responses like temperature and mechanical sensations, response to painful stimuli, taste, and pheromones. TRP channel family involves six different TRPs (TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPA1) which are expressed in pain sensing neurons and primary afferent nociceptors...
October 18, 2016: Inflammopharmacology
Petra Mrozkova, Diana Spicarova, Jiri Palecek
Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) receptors in the peripheral nerve endings are implicated in the development of increased sensitivity to mechanical and thermal stimuli, especially during inflammatory states. Both PAR2 and TRPV1 receptors are co-expressed in nociceptive dorsal root ganglion (DRG) neurons on their peripheral endings and also on presynaptic endings in the spinal cord dorsal horn. However, the modulation of nociceptive synaptic transmission in the superficial dorsal horn after activation of PAR2 and their functional coupling with TRPV1 is not clear...
2016: PloS One
Yuanting Cui, Li Li, Peng Gao, Liqun Ma, Daoyan Liu, Zhiming Zhu
OBJECTIVE: Obesity is global healthy problem. Uncoupling protein 1 (UCP1) mainly expresses on brown adipose tissue (BAT), uncouples energy substrate oxidation from mitochondrial ATP production and results in the loss of potential energy as heat. Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is the heat-gated cation ion channel. The aim of this study was to investigate the in vivo role of TRPV1 and UCP1 co-action in obesity. DESIGN AND METHOD: We generated and characterized UCP1 mice lacking TRPV1 activity (TRPV1/UCP1 mice)...
September 2016: Journal of Hypertension
Puneet Kaur Randhawa, Amteshwar Singh Jaggi
Remote ischemic preconditioning (RIPC) treatment strategy is a breakthrough in the field of cardiovascular pharmacology as it has the potential to attenuate myocardial ischemia-reperfusion injury. However, the underlying intracellular pathways have not been widely explored. The present study intends to explore the possible role of TRPV1 channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 cycles in succession) was delivered by tying the blood pressure cuff at the inguinal level of the rat...
October 17, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Yuguang Wang, Ying-Ying Huang, Yong Wang, Peijun Lyu, Michael R Hamblin
Photobiomodulation (PBM) using red or near-infrared (NIR) light has been used to stimulate the proliferation and differentiation of adipose-derived stem cells. The use of NIR wavelengths such as 810nm is reasonably well accepted to stimulate mitochondrial activity and ATP production via absorption of photons by cytochrome c oxidase. However, the mechanism of action of 980nm is less well understood. Here we study the effects of both wavelengths (810nm and 980nm) on adipose-derived stem cells in vitro. Both wavelengths showed a biphasic dose response, but 810nm had a peak dose response at 3J/cm(2) for stimulation of proliferation at 24h, while the peak dose for 980nm was 10-100 times lower at 0...
October 15, 2016: Biochimica et Biophysica Acta
F Sakakibara, K Takahama, M Nanri, E Sasaki
Patients with spinal cord injury (SCI) usually develop lower urinary tract dysfunctions, including detrusor overactivity which is also known to be a risk factor for upper urinary tract dysfunction. Antimuscarinic agents, such as propiverine, have been used clinically for the treatment of detrusor overactivity. Also, propiverine has been known to possess antagonistic activity against L-type Ca(2+) channels and transient receptor potential vanilloid subtype 1 (TRPV1), in addition to activity against muscarinic receptors...
September 2016: Drug Research
Siyang Yan, Amanda C Kentner
Exposure to painful procedures and/or stressors during the early neonatal period can reprogram the underlying neurocircuitry involved in nociception and neuropathic pain perception. The reprogramming of these systems can result in an enduring elevation in sensitivity towards mechanical and thermal stimuli. Recent evidence suggests that exposure to mild inflammatory mediators during the neonatal period can induce similar pain responses in both adolescent and adult rats. Therefore, we sought to profile changes in the expression of several genes across brain areas involved in the active modulation of nociception and neuropathic pain using a well-recognized model of neonatal inflammation...
October 11, 2016: Brain, Behavior, and Immunity
W Ma, B St-Jacques, U Rudakou, Y N Kim
BACKGROUND: Persistent peripheral sensitization contributes to chronic pain. Plasticity of nociceptive dorsal root ganglion (DRG) neurons (nociceptors) induced by pro-inflammatory mediators contributes to sensitization. Prostaglandin E2 (PGE2) enriched in injured tissues is known not only directly to sensitize DRG neurons, but also to potentiate sensitizing effects of other pain mediators such as capsaicin and its receptor transient receptor potential vanilloid-1 (TRPV1). It remains unknown whether PGE2 potentiates TRPV1 activity by stimulating its synthesis, cell surface and axonal trafficking in DRG neurons...
October 14, 2016: European Journal of Pain: EJP
Youn Yi Jo, Ji Yeon Lee, Chul-Kyu Park
The neuropeptide substance P (SP) is expressed in primary sensory neurons and is commonly regarded as a "pain" neurotransmitter. Upon peripheral inflammation, SP activates the neurokinin-1 (NK-1) receptor and potentiates activity of transient receptor potential vanilloid subtype 1 (TRPV1), which is coexpressed by nociceptive neurons. Therefore, SP functions as an important neurotransmitter involved in the hypersensitization of inflammatory pain. Resolvin E1 (RvE1), derived from omega-3 polyunsaturated fatty acids, inhibits TRPV1 activity via activation of the chemerin 23 receptor (ChemR23)-an RvE1 receptor located in dorsal root ganglion neurons-and therefore exerts an inhibitory effect on inflammatory pain...
2016: Mediators of Inflammation
Luara A Batista, Andrea S Haibara, Luiz C Schenberg, Fabricio A Moreira
Selective stimulation of carotid chemoreceptors by intravenous infusion of low doses of potassium cyanide (KCN) produces short-lasting escape responses that have been proposed as a model of panic attack. In turn, preclinical studies suggest that facilitation of the endocannabinoid system attenuate panic-like responses. Here, we compared the effects of cannabinoid-related compounds to those of alprazolam, a clinically effective panicolytic, on the duration of the escape reaction induced by intravenous infusion of KCN (80μg) in rats...
October 11, 2016: Behavioural Brain Research
L Buntinx, T Voets, B Morlion, L Vangeel, M Janssen, E Cornelissen, J Vriens, J de Hoon, E Levtchenko
Cystinosis is a rare autosomal recessive disorder characterized by lysosomal cystine accumulation due to loss of function of the lysosomal cystine transporter (CTNS). The most common mutation in cystinosis patients of Northern Europe consists of a 57-kb deletion. This deletion not only inactivates the CTNS gene but also extends into the non-coding region upstream of the start codon of the TRPV1 gene, encoding the capsaicin- and heat-sensitive ion channel TRPV1. To evaluate the consequences of the 57-kb deletion on functional TRPV1 expression, we compared thermal, mechanical and chemical sensitivity of cystinosis patients with matched healthy controls...
October 13, 2016: Scientific Reports
Damir Omerbašić, Ewan St J Smith, Mirko Moroni, Johanna Homfeld, Ole Eigenbrod, Nigel C Bennett, Jane Reznick, Chris G Faulkes, Matthias Selbach, Gary R Lewin
The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF), an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1...
October 11, 2016: Cell Reports
Shi-Xun Ma, Seung-Hwan Kwon, Jee-Yeon Seo, Ji-Young Hwang, Sa-Ik Hong, Hyoung-Chun Kim, Seok-Yong Lee, Choon-Gon Jang
Transient receptor potential vanilloid type 1 (TRPV1), the archetypal member of the vanilloid TRP family, was initially identified as the receptor for capsaicin, the pungent ingredient in hot chili peppers. We previously demonstrated that TRPV1 in the dorsal striatum significantly contributes to morphine reward by using the conditioned place preference paradigm in mice; however, it is unknown whether TRPV1 has the same effect in other reward models. In this study, we investigated the role of TRPV1 in morphine reward by using a self-administration paradigm in rats...
October 11, 2016: Addiction Biology
Tao Liu, Gang Wang, Huangheng Tao, Zhonghua Yang, Yongzhi Wang, Zhe Meng, Rui Cao, Yu Xiao, Xinghuan Wang, Jiajie Zhou
BACKGROUND: Renal cell carcinoma (RCC) is one of the tumors most refractory to chemotherapy to date. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin (CPS), a natural active ingredient of green and red peppers, and a ligand of transient receptor potential vanilloid type 1 (TRPV1), has been showed potential in suppression of tumorigenesis of several cancers. Nonetheless, the anti-cancer activity of CPS has never been studied in human RCC. METHODS: CCK8 analysis, LDH release activity and ROS generation analysis, flow cytometry analysis, and nuclear staining test were performed to test the influence of CPS in cultured cells in vitro, meanwhile western blot was done to uncover the precise molecular mechanisms...
October 12, 2016: BMC Cancer
Ji Young Kwon, Hyun Soo Lee, Choun-Ki Joo
PURPOSE: To determine the immunologic functions of TRPA1 or TRPV1 in allergic conjunctivitis (AC). METHODS: Mice were sensitized with ovalbumin (OVA), after which TRPA1 antagonist or TRPV1 antagonist was administered before topical OVA challenge. Expression of TRPV1 or TRPA1 in AC was examined by western blotting and multicolor immunofluorescence. Clinical signs, OVA-specific IgE, infiltration of inflammatory cells into conjunctivae (CJs), and Th2 cytokine in draining lymph nodes (LNs) were evaluated by microscopy, flow cytometry, and ELISA...
October 11, 2016: Ocular Immunology and Inflammation
Frances Corrigan, Kimberley A Mander, Anna V Leonard, Robert Vink
BACKGROUND: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. MAIN BODY: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI...
October 11, 2016: Journal of Neuroinflammation
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