IUPHAR review: Navigating the role of preclinical models in pain research

Pharmacological Research, Journal Year: 2024, Volume and Issue: 200, P. 107073 - 107073

Published: Jan. 18, 2024

Chronic pain is a complex and challenging medical condition that affects millions of people worldwide. Understanding the underlying mechanisms chronic key goal preclinical research so more effective treatment strategies can be developed. In this review, we explore nociception, pain, multifaceted factors lead to by focusing on models. We provide detailed look into inflammatory neuropathic models discuss most used animal for studying behind these conditions. Additionally, emphasize vital role in developing new pain-relief drugs, biologics therapeutic potential NMDA cannabinoid receptor antagonists. also challenges TRPV1 modulation treatment, clinical failures neurokinin (NK)− 1 antagonists, partial success story Ziconotide valuable lessons Finally, highlight overall limitations current treatments while providing critical insights development therapies alleviate burden pain.

Language: Английский

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Cannabidiol activates MAPK pathway to induce apoptosis, paraptosis, and autophagy in colorectal cancer cells

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(4)

Published: Feb. 15, 2024

Abstract Mitogen‐activated protein kinase (MAPK) activation by natural compounds is known to be involved in the induction of apoptosis, paraptosis, and autophagy. Cannabidiol (CBD), a bioactive compound found Cannabis sativa , endowed with many pharmacological activities. We investigated cytotoxic effect CBD panel colorectal cancer (CRC) cells (HT‐29, SW480, HCT‐116, HCT‐15). induced significant cytotoxicity as evidenced results MTT assay, live‐dead flow cytometric analysis. Since displayed against CRC cells, we examined on decreased expression antiapoptotic proteins increased Annexin‐V‐positive well TUNEL‐positive suggesting that induces apoptosis. ATF4 (activating transcription factor 4) CHOP (CCAAT/enhancer‐binding homologous protein), elevated endoplasmic reticulum stress, enhanced reactive oxygen species levels indicating also promotes paraptosis. Atg7, phospho‐Beclin‐1, LC3 accelerates Since, MAPK pathway common cascade regulation autophagy, JNK, p38, ERK pathways. activated all forms inhibition these reverted observed effects. Our findings implied could induce cell death activating autophagy through pathway.

Language: Английский

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What Do We Know about Nociplastic Pain?

Healthcare, Journal Year: 2023, Volume and Issue: 11(12), P. 1794 - 1794

Published: June 17, 2023

Nociplastic pain is a recently distinguished type of pain, distinct from neuropathic and nociceptive well described in the literature. It often mistaken for central sensitization. Pathophysiology has not been clearly established with regard to alteration concentration spinal fluid elements, structure white gray matter brain, psychological aspects. Many different diagnostic tools, i.e., painDETECT Douleur Neuropathique 4 questionnaires, have developed diagnose but they can also be applied nociplastic pain; however, more standardized instruments are still needed order assess its occurrence clinical presentation. Numerous studies shown that present many diseases such as fibromyalgia, complex regional syndrome 1, irritable bowel syndrome. Current pharmacological nonpharmacological treatments entirely suitable treating pain. There an ongoing effort establish most efficient way manage it. The significance this field led several trials being carried out short time. aim narrative review was discuss currently available evidence on pathophysiology, associated diseases, treatment possibilities, trials. important physicians widely acknowledge relatively new concept provide optimized control patients.

Language: Английский

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Emerging Therapeutic Potential of Cannabidiol (CBD) in Neurological Disorders: A Comprehensive Review

Behavioural Neurology, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 17

Published: Oct. 12, 2023

Cannabidiol (CBD), derived from Cannabis sativa, has gained remarkable attention for its potential therapeutic applications. This thorough analysis explores the increasing significance of CBD in treating neurological conditions including epilepsy, multiple sclerosis, Parkinson's disease, and Alzheimer's which present major healthcare concerns on a worldwide scale. Despite lack available therapies, been shown to possess variety pharmacological effects preclinical clinical studies, making it an intriguing competitor. review brings together most recent findings endocannabinoid neurotransmitter systems, as well anti-inflammatory pathways, that underlie CBD's modes action. Synthesized efficacy safety assessments range illnesses are included, covering human trials, vitro animal models. The investigation includes how could protect neurons, control neuroinflammation, fend off oxidative stress, manage neuronal excitability. study emphasizes existing studies future possibilities research, addressing research issues such regulatory complications contradicting results, advocates further ideal dose methodologies. By emphasizing improve patient well-being, this presents revised viewpoint suitability intervention illnesses.

Language: Английский

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Novel rapid treatment options for adolescent depression

Pharmacological Research, Journal Year: 2024, Volume and Issue: 201, P. 107085 - 107085

Published: Feb. 2, 2024

There is an urgent need for novel fast-acting antidepressants adolescent treatment-resistant depression and/or suicidal risk, since the selective serotonin reuptake inhibitors that are clinically approved age (i.e., fluoxetine or escitalopram) take weeks to work. In this context, one of main research lines our group characterize at preclinical level approaches rapid-acting adolescence. The present review summarizes potential use in adolescence non-pharmacological options, such as neuromodulators (electroconvulsive therapy and other innovative types brain stimulation), well pharmacological including consciousness-altering drugs (mainly ketamine but also classical psychedelics) cannabinoids cannabidiol), with promising responses. Following a brief analytical explanation depression, we general introduction each therapeutical approach together clinical evidence supporting its beneficial extrapolated from prior successful examples adults), then report recent ongoing studies will aid improving inclusion these therapies clinic, by considering sex-, age-, dose-related differences, factors might affect efficacy long-term safety. Finally, conclude providing future avenues maximize treatment response, more importance designing testing options safe depression.

Language: Английский

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Chiral drugs: Sources, absolute configuration identification, pharmacological applications, and future research trends

LabMed discovery., Journal Year: 2024, Volume and Issue: 1(1), P. 100008 - 100008

Published: July 29, 2024

Chirality is one of the essential attributes nature. Chiral drugs refer to a class containing chiral centers, and molecular stereo-structures their enantiomers are non-superimposable mirror images each other. Sixty percent commonly used drugs, including those from traditional Chinese medicine (TCM), chiral. Developing single enantiomer with high efficiency low toxicity has drawn considerable attention due significant differences in pharmacological activities, metabolic processes, exhibited by drugs. This review concisely summarizes sources, absolute configuration identification, applications, future research trends, particularly TCM.

Language: Английский

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Cannabinoids in neuropathic pain treatment: pharmacological insights and clinical outcomes from recent trials

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Language: Английский

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Cannabidiol and brain function: current knowledge and future perspectives

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 15, 2024

Cannabidiol (CBD) is a naturally occurring non-psychoactive cannabinoid found in Cannabis sativa , commonly known as cannabis or hemp. Although currently available CBD products do not meet the safety standards of most food authorities to be approved dietary supplement additive, has been gaining widespread attention recent years due its various potential health benefits. While primarily for therapeutic effects managing epileptic seizures, psychosis, anxiety, (neuropathic) pain, and inflammation, CBD’s influence on brain function also piqued interest researchers individuals seeking enhance cognitive performance. The primary objective this review gather, synthesize, consolidate scientifically proven evidence impact significance treating neurological mental disorders. First, basic background information CBD, including biomolecular properties mechanisms action presented. Next, human provided followed by discussion implications neurotherapeutic agent. effectiveness reducing chronic pain considered but symptoms disorders such epilepsy, Alzheimer’s, Huntington’s Parkinson’s disease. Additionally, using manage psychiatric conditions anxiety fear, depression, substance use are explored. An overview beneficial aspects behavior, sleep, motor control, cognition memory, then provided. As remain largely unregulated, it crucial address ethical concerns associated with their use, product quality, consistency, safety. Therefore, discusses need responsible research regulation ensure efficacy agent stimulate behavioral abilities healthy individuals.

Language: Английский

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Anxiety Modulation by Cannabinoids—The Role of Stress Responses and Coping

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15777 - 15777

Published: Oct. 30, 2023

Endocannabinoids were implicated in a variety of pathological conditions including anxiety and are considered promising new targets for anxiolytic drug development. The optimism concerning the potentials this system anxiolysis is probably justified. However, complexity mechanisms affected by endocannabinoids, discrepant findings obtained with various experimental approaches makes interpretation research results difficult. Here, we review anxiety-related effects three main interventions used to study endocannabinoid system: pharmacological agents active at endocannabinoid-binding sites present on both cell membrane cytoplasm, genetic manipulations targeting cannabinoid receptors, function-enhancers represented inhibitors degradation transport. Binding-site ligands provide inconsistent because they activate multitude concomitantly. More robust particularly function enhancers, which heighten ongoing activation rather than affecting all indiscriminately. enhancement activity appears ameliorate stress-induced without consistent general. Limited evidence suggests that effect achieved promoting coping styles critical situations. These suggest functional signaling development target stress-related disorders.

Language: Английский

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The safety and efficacy of cannabinoids for the treatment of mental health and substance use disorders: protocol for a systematic review and meta-analysis

Systematic Reviews, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 24, 2025

There has been a global increase in the use of cannabinoids as treatment for mental health (MH) and substance disorders (SUD). In 2016, an Australian government-funded review found that although medicinal accounted small reduction MH symptoms, results varied according to study design. since rise randomised controlled trials (RCTs) aiming examine efficacy SUD. Therefore, current systematic will (a) identify all RCTs examining treating SUD, (b) provide quantitative or narrative synthesis evidence efficacy, (c) synthesise adverse event data harm. Electronic databases (Ovid MEDLINE, PsychINFO, Cochrane Central Register Controlled Clinical Trials, Database Systematic Reviews, Embase) were searched from 1980 24 May 2023. The adheres Preferred Reporting Items Reviews Meta-Analysis Guidelines. Articles be screened capture peer-reviewed evaluating plant-based pharmaceutical reducing SUD among people any age. risk bias tool 2.0 used assess bias, while Grades Recommendation, Assessment, Development Evaluation (GRADE) quality each outcome. Study findings disseminated through published manuscripts, conferences, policy guidelines. registration PROSPERO CRD42023392718.

Language: Английский

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