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https://www.readbyqxmd.com/read/29425797/antinociceptive-effects-of-the-endogenous-cannabinoid-peptide-agonist-vd-hemopressin-%C3%AE-in-mice
#1
Pei Wang, Ting Zheng, Mengna Zhang, Biao Xu, Run Zhang, Ting Zhang, Weidong Zhao, Xuerui Shi, Qinqin Zhang, Quan Fang
Cannabinoids (CBs) play important roles in pain modulation. Recently, VD-hemopressin(β) [VD-Hpβ], a 12-residue β-hemoglobin-derived peptide, was reported to activate both CB1 and CB2 receptors in vitro. To further characterize in vivo actions of VD-Hpβ, its antinociceptive activity and site(s) were evaluated in the mouse tail-flick test, and supraspinal antinociception of VD-Hpβ was further assessed in the writhing test. Our results demonstrated that supraspinal, intrathecal, subcutaneous and intraperitoneal administrations of VD-Hpβ produced analgesia in the tail-flick test...
February 6, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29424035/involvement-of-spinal-cannabinoid-receptors-in-the-antipruritic-effects-of-win-55-212-2-a-cannabinoid-receptor-agonist
#2
K A Bilir, G Anli, E Ozkan, O Gunduz, A Ulugol
BACKGROUND: Cannabinoids have been used for their analgesic and euphoric effects for millennia, but recently the antipruritic effects of cannabis have been discovered. Considering the similarities between pain and itch sensations, we hypothesized that cannabinoid receptors may play a role in the antipruritic effects of cannabinoids. AIM: To analyse the role of the spinal cannabinoid receptors, CB1 and CB2, in the antipruritic effects of the cannabinoid agonist WIN 55,212-2...
February 9, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29364174/molecular-understanding-of-the-activation-of-cb1-and-blockade-of-trpv1-receptors-implications-for-novel-treatment-strategies-in-osteoarthritis
#3
Jakub Mlost, Magdalena Kostrzewa, Natalia Malek, Katarzyna Starowicz
Osteoarthritis (OA) is a joint disease in which cartilage degenerates as a result of mechanical and biochemical changes. The main OA symptom is chronic pain involving both peripheral and central mechanisms of nociceptive processing. Our previous studies have implicated the benefits of dual- over single-acting compounds interacting with the endocannabinoid system (ECS) in OA treatment. In the present study, we focused on the specific molecular alterations associated with pharmacological treatment. OA was induced in Wistar rats by intra-articular injection of 3 mg of monoiodoacetate (MIA)...
January 24, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29355030/allosteric-modulators-of-cannabinoid-receptor-1-developing-compounds-for-improved-specificity
#4
Rachel Dopart, Dai Lu, Aron H Lichtman, Debra A Kendall
The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) that is located primarily in the central nervous system. CB1 is a therapeutic target which may impact pathways to mediate pain, neurodegenerative disorders, hunger, and drug-seeking behavior. Despite these benefits, development of orthosteric therapeutic compounds, which target the endogenous ligand-binding site of CB1, has been challenging due to detrimental side effects including psychoactivity, depression, and suicidal thoughts. However, CB1 also has an allosteric binding site(s), which is topographically distinct from the orthosteric site...
January 21, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29340966/cannabinomimetric-lipids-from-natural-extract-to-artificial-synthesis
#5
REVIEW
Ya-Ru Gao, Yong-Qiang Wang
Endocannabinoid system is related with various physiological and cognitive processes including fertility, pregnancy, during pre- and postnatal development, pain-sensation, mood, appetite, and memory. In the latest decades, an important milestone concerning the endocannabinoid system was the discovery of the existence of the cannabinoid receptors CB1 and CB2. Anandamide was the first reported endogenous metabolite, which adjusted the release of some neurotransmitters through binding to the CB1 or CB2 receptors...
January 16, 2018: Natural Products and Bioprospecting
https://www.readbyqxmd.com/read/29314831/a-fluorescent-probe-to-unravel-functional-features-of-cannabinoid-receptor-cb1-in-human-blood-and-tonsil-immune-system-cells
#6
Mar Martín-Fontecha, Alba Angelina, Beate Rückert, Ainoa Rueda-Zubiaurre, Leticia Martin-Cruz, Willem van de Veen, Mübeccel Akdis, Silvia Ortega-Gutierrez, María L López-Rodrí Guez, Cezmi Akdis, Oscar Palomares
The human endogenous cannabinoid system (ECS) regulates key physiological processes and alterations in its signalling pathways and endocannabinoid levels are associated to diseases such as neurological and neuropsychiatric conditions, cancer, pain and inflammation, obesity, metabolic and different immune related disorders. Immune system cells express the G-protein coupled cannabinoid receptor 1 (CB1) but its functional role has not been fully understood, likely due to the lack of appropriate tools. The availability of novel tools to investigate the role of CB1 in immune regulation might contribute to identify CB1 as a potential novel therapeutic target or biomarker for many diseases...
January 9, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29274880/cb1-cannabinoid-receptor-agonist-mouse-vd-hemopressin-%C3%AE-produced-supraspinal-analgesic-activity-in-the-preclinical-models-of-pain
#7
Ting Zheng, Run Zhang, Ting Zhang, Meng-Na Zhang, Biao Xu, Jing-Jing Song, Ning Li, Hong-Hai Tang, Pei Wang, Rui Wang, Quan Fang
Mouse VD-hemopressin(α) (VD-Hpα) is an undecapeptide that selectively activates CB1 cannabinoid receptor in in vitro functional tests, and exerts CB1-mediated central antinociception in the mouse tail-flick assay. The aim of the present study was to further investigate the analgesic properties of supraspinal mouse VD-Hpα in a range of preclinical pain models. Our results indicated that the classical cannabinoid agonist WIN 55,212-2 produced supraspinal analgesia in preclinical pain models, which was selectively antagonized by the CB1 antagonist/inverse agonist AM251, but not by the CB2 antagonist AM630...
December 21, 2017: Brain Research
https://www.readbyqxmd.com/read/29247851/the-involvement-of-the-endocannabinoid-system-in-the-peripheral-antinociceptive-action-of-ketamine
#8
Renata C M Ferreira, Marina G M Castor, Fabiana Piscitelli, Vincenzo Di Marzo, Igor D G Duarte, Thiago R L Romero
Ketamine has been widely used as an analgesic and produces dissociative anesthetic effects. The antinociceptive effects of ketamine have been studied, but the involvement of endocannabinoids in these effects has not yet been investigated. In this study, we evaluated the involvement of the endocannabinoid system in the peripheral antinociceptive effects induced by ketamine. All drugs were administered via the intraplantar route. To induce hyperalgesia, rat paws were injected with prostaglandin E2 (PGE2, 2 µg/paw)...
December 13, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29225040/differential-neuromodulatory-role-of-endocannabinoids-in-the-rodent-trigeminal-sensory-ganglion-and-cerebral-cortex-relevant-to-pain-processing
#9
Francesca Eroli, Inge C M Loonen, Arn M J M van den Maagdenberg, Else A Tolner, Andrea Nistri
Endocannabinoids are suggested to control pain, even though their clinical use is not fully validated and the underlying mechanisms are incompletely understood. To clarify the targets of endocannabinoid actions, we studied how activation of the endocannabinoid CB1 receptor (CB1R) affects neuronal responses in two in vitro preparations of rodents, namely the trigeminal sensory ganglion (TG) in culture and a coronal slice of the cerebral cortex. On TG small-medium size neurons, we tested whether submicromolar concentrations of the endogenous CB1R agonist anandamide (AEA) modulated inhibitory GABAA receptors and excitatory ATP-gated P2X3 receptors...
December 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29169951/regulation-of-noradrenergic-and-serotonergic-systems-by-cannabinoids-relevance-to-cannabinoid-induced-effects
#10
REVIEW
Aitziber Mendiguren, Erik Aostri, Joseba Pineda
The cannabinoid system is composed of Gi/o protein-coupled cannabinoid type 1 receptor (CB1) and cannabinoid type 2 (CB2) receptor and endogenous compounds. The CB1 receptor is widely distributed in the central nervous system (CNS) and it is involved in the regulation of common physiological functions. At the neuronal level, the CB1 receptor is mainly placed at GABAergic and glutamatergic axon terminals, where it modulates excitatory and inhibitory synapses. To date, the involvement of CB2 receptor in the regulation of neurotransmission in the CNS has not been clearly shown...
January 1, 2018: Life Sciences
https://www.readbyqxmd.com/read/29167401/acetaminophen-relieves-inflammatory-pain-through-cb1-cannabinoid-receptors-in-the-rostral-ventromedial-medulla
#11
Pascal P Klinger-Gratz, William T Ralvenius, Elena Neumann, Ako Kato, Rita Nyilas, Zsolt Lele, István Katona, Hanns Ulrich Zeilhofer
Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug with only incompletely understood mechanisms of action. Previous work, using models of acute nociceptive pain, indicated that analgesia by acetaminophen involves an indirect activation of CB1 receptors by the acetaminophen metabolite and endocannabinoid re-uptake inhibitor AM 404. However, the contribution of the cannabinoid system to anti-hyperalgesia against inflammatory pain, the main indication of acetaminophen, and the precise site of the relevant CB1 receptors have remained elusive...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29160600/current-evidence-of-cannabinoid-based-analgesia-obtained-in-preclinical-and-human-experimental-settings
#12
REVIEW
J Lötsch, I Weyer-Menkhoff, I Tegeder
Cannabinoids have a long record of recreational and medical use and become increasingly approved for pain therapy. This development is based on preclinical and human experimental research summarized in this review. Cannabinoid CB 1 receptors are widely expressed throughout the nociceptive system. Their activation by endogenous or exogenous cannabinoids modulates the release of neurotransmitters. This is reflected in antinociceptive effects of cannabinoids in preclinical models of inflammatory, cancer and neuropathic pain, and by nociceptive hypersensitivity of cannabinoid receptor-deficient mice...
November 21, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29145497/rare-genetic-variants-in-the-endocannabinoid-system-genes-cnr1-and-dagla-are-associated-with-neurological-phenotypes-in-humans
#13
Douglas R Smith, Christine M Stanley, Theodore Foss, Richard G Boles, Kevin McKernan
Rare genetic variants in the core endocannabinoid system genes CNR1, CNR2, DAGLA, MGLL and FAAH were identified in molecular testing data from 6,032 patients with a broad spectrum of neurological disorders. The variants were evaluated for association with phenotypes similar to those observed in the orthologous gene knockouts in mice. Heterozygous rare coding variants in CNR1, which encodes the type 1 cannabinoid receptor (CB1), were found to be significantly associated with pain sensitivity (especially migraine), sleep and memory disorders-alone or in combination with anxiety-compared to a set of controls without such CNR1 variants...
2017: PloS One
https://www.readbyqxmd.com/read/29127599/cb1-receptors-mediated-inhibition-of-atp-induced-ca-2-i-increase-in-cultured-rat-spinal-dorsal-horn-neurons
#14
Jingdong Long, Xiaolu Lei, Meiyun Chen, Shulei Yang, Tao Sun, Junwei Zeng, Deqian Yu, Hong Tian, Xiaohong Liu
Spinal cannabinoid receptor 1 (CB1R) and purinergic P2X receptors (P2XR) play a critical role in the process of pathological pain. Both CB1R and P2XR are expressed in spinal dorsal horn (DH) neurons. It is not clear whether CB1 receptor activation modulates the function of P2X receptor channels within dorsal horn. For this reason, we observed the effect of CP55940 (cannabinoid receptor agonist) on ATP-induced Ca(2+) mobilization in cultured rat DH neurons. The changes of intracellular calcium concentration ([Ca(2+)]i) were detected with confocal laser scanning microscopy using fluo-4/AM as a calcium fluorescent indicator...
November 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29111112/anti-migraine-effect-of-%C3%A2-9-tetrahydrocannabinol-in-the-female-rat
#15
Ram Kandasamy, Cole T Dawson, Rebecca M Craft, Michael M Morgan
Current anti-migraine treatments have limited efficacy and many side effects. Although anecdotal evidence suggests that marijuana is useful for migraine, this hypothesis has not been tested in a controlled experiment. Thus, the present study tested whether administration of ∆9-tetrahydrocannabinol (THC) produces anti-migraine effects in the female rat. Microinjection of the TRPA1 agonist allyl isothiocyanate (AITC) onto the dura mater produced migraine-like pain for 3h as measured by depression of home cage wheel running...
January 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29108858/increased-expression-of-type-1-cannabinoid-cb1-receptor-among-patients-with-rotator-cuff-lesions-and-shoulder-stiffness
#16
Shu-Jui Kuo, Feng-Sheng Wang, Jih-Yang Ko, Chih-Hsin Tang, Ka-Kit Siu, Ya-Hung Hsu, Tsai-Chen Tsai
BACKGROUND: Shoulder stiffness is a disease manifested by pain, limited range of motion, and functional disability. The inflammatory and fibrosis processes play a substantial role in the pathogenesis of shoulder stiffness. The CB1 receptor has been recognized to mediate the processes of pathologic fibrosis. This study investigated the role of the CB1 pathway in pathogenesis of rotator cuff lesions with shoulder stiffness. METHODS: All of the patients undergoing repair surgery for rotator cuff lesions were recruited and subcategorized into subjects with and without shoulder stiffness...
November 3, 2017: Journal of Shoulder and Elbow Surgery
https://www.readbyqxmd.com/read/29046638/blockade-of-cannabinoid-cb1-receptors-in-the-dorsal-periaqueductal-gray-unmasks-the-antinociceptive-effect-of-local-injections-of-anandamide-in-mice
#17
Diego C Mascarenhas, Karina S Gomes, Tatiani Sorregotti, Ricardo L Nunes-de-Souza
Divergent results in pain management account for the growing number of studies aiming at elucidating the pharmacology of the endocannabinoid/endovanilloid anandamide (AEA) within several pain-related brain structures. For instance, the stimulation of both Transient Receptor Potential Vanilloid type 1 (TRPV1) and Cannabinoid type 1 (CB1) receptors led to paradoxical effects on nociception. Here, we attempted to propose a clear and reproducible methodology to achieve the antinociceptive effect of exogenous AEA within the dorsal periaqueductal gray (dPAG) of mice exposed to the tail-flick test...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29017758/in-vitro-and-in-vivo-pharmacological-characterization-of-asp8477-a-novel-highly-selective-fatty-acid-amide-hydrolase-inhibitor
#18
Tomonari Watabiki, Noriko Tsuji, Tetsuo Kiso, Tohru Ozawa, Fumie Narazaki, Shuichiro Kakimoto
Although exogenous agonists for cannabinoid (CB) receptors are clinically effective for treating chronic pain, global activation of brain CB receptors causes frequent central nervous system (CNS) side-effects. Fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme for anandamide (AEA), an endogenous CB. Recently, we discovered a novel FAAH inhibitor, 3-pyridyl 4-(phenylcarbamoyl)piperidine-1-carboxylate (ASP8477). In vitro studies demonstrated that ASP8477 inhibited human FAAH-1, FAAH-1 (P129T) and FAAH-2 activity with IC50 values of 3...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28980210/photobiomodulation-therapy-improves-acute-inflammatory-response-in-mice-the-role-of-cannabinoid-receptors-atp-sensitive-k-channel-p38-mapk-signalling-pathway
#19
Laís M S Neves, Elaine C D Gonçalves, Juliana Cavalli, Graziela Vieira, Larissa R Laurindo, Róli R Simões, Igor S Coelho, Adair R S Santos, Alexandre M Marcolino, Maíra Cola, Rafael C Dutra
Although photobiomodulation therapy (PBM) has been applied clinically for the treatment of pain and inflammation, wound healing, sports and soft tissue injuries, as well as to repair injured spinal cords and peripheral nerves, it remains unclear which molecular substrates (receptor) are implicated in the cellular mechanisms of PBM. Here, we reported that PBM (660 nm, 30 mW, 0.06 cm2, 50 J/cm2, plantar irradiation) significantly inhibited carrageenan-induced paw oedema, but not noxious thermal response, through positive modulation to both CB1 and CB2 cannabinoid receptors...
October 4, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28975684/salvinorin-a-reduces-neuropathic-nociception-in-the-insular-cortex-of-the-rat
#20
U Coffeen, A Canseco-Alba, K Simón-Arceo, A Almanza, F Mercado, M León-Olea, F Pellicer
BACKGROUND: Neuropathic pain is one of the most important challenges in public health. The search for novel treatments is important for an adequate relief without adverse effects. In this sense salvinorin A (SA), the main diterpene of the medicinal plant Salvia divinorum is an important antinociceptive compound, which acts as a potent agonist of kappa opioid receptor (KOR) and cannabinoid CB1 receptors. METHODS: We evaluated nociceptive responses in a neuropathic pain model induced by the sciatic nerve ligature (SNL) in the right hind paw, after the microinjection of SA, Salvinorin B (SB), KOR and CB1 antagonists directly in the insular cortex (IC) in male wistar rats...
October 4, 2017: European Journal of Pain: EJP
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