International review of neurobiology最新文献

The methodology of Quantitative Sensory Testing (QST) comprises standardized testing procedures, which provide information of the integrity of the somatosensory nervous system. Over the years, different protocols have been established, which utilize similar but distinct testing procedures. They pursue the same overall objective to identify loss or gain of function of the respective sensory parameter to better understand the degree of abnormal nervous function and thereby improve patient care in the long-term. Laboratory-based QST protocols, which apply highly standardized testing procedures in pre-defined order and body regions, are considered as the gold standard in sensory testing. However, those protocols often require specifically trained personal, high equipment investment, and are time consuming. Thus, in recent years several attempts have been made to simplify testing protocols as well as reduce high costs of testing equipment such as thermal probe systems. These attempts have culminated in an array of sensory bedside testing protocols subserving the need for protocols that are easy to implement in and provide a standardized assessment within clinical trials. While laboratory and bedside QST that focus on static responses of single stimuli, protocols for testing dynamic QST focus on the functional response to pain also exist. Conditioned pain modulation (CPM) is often applied, which offers the ability to study endogenous inhibition of pain. All of these mentioned methodologies are considered as psychophysical measures and thus rely heavily on the cooperation of the patient or participant. In this chapter we provide an overview of QST along three main lines: (i) laboratory QST, (ii) bedside QST and (iii) dynamic QST. In addition, we discuss advantages and pitfalls of each modality. While we discuss along these lines, it should be noted that methodologies are overlapping: some bedside tests are similar or identical to lab-QST, many lab-QST protocols include a dynamic component, and assessment of dynamic QST requires to start with static assessments.

Alzheimer's disease (AD) stands as the most prevalent form of neuropsychiatric disorder among the elderly population, impacting a minimum of 50 million individuals worldwide. Current pharmacological treatments rely on the prescribing cholinesterase inhibitors and memantine. However,recently anecdotal findings based on low-quality real-world data had prompted physicians, patients, and their relatives to consider the use of cannabinoids, especially Cannabidiol (CBD), for alleviating of AD symptoms. CBD the primary non-psychotomimetic compound found in the Cannabis sp. plant, exhibits promising therapeutic potential across various clinical contexts. Pre-clinical and in vitro studies indicate that CBD could mitigate cognitive decline and amyloid-beta-induced neurodegeneration by modulating oxidative stress and neuroinflammation. In addition, CBD demonstrates significant effects in promoting neuroplasticity, particularly in brain regions such as the hippocampus. However, the available clinical evidence presents conflicting results, and no randomized placebo-controlled trials have been published to date. In conclusion, although pre-clinical and in vitro studies offer encouraging insights into the potential benefits of CBD in AD models, new and well-designed clinical trials are imperative to ascertain the clinical relevance of CBD use in the management of AD symptoms, especially in comparison to conventional treatments.

Cannabidiol (CBD) is a major phytocannabinoid in the Cannabis sativa plant. In contrast to Δ⁹-tetrahydrocannabinol (THC), CBD does not produce the typical psychotomimetic effects of the plant. In addition, CBD has attracted increased interest due to its potential therapeutic effects in various psychiatric disorders, including schizophrenia. Several studies have proposed that CBD has pharmacological properties similar to atypical antipsychotics. Despite accumulating evidence supporting the antipsychotic potential of CBD, the mechanisms of action in which this phytocannabinoid produces antipsychotic effects are still not fully elucidated. Here, we focused on the antipsychotic properties of CBD indicated by a series of preclinical and clinical studies and the evidence currently available about its possible mechanisms. Findings from preclinical studies suggest that CBD effects may depend on the animal model (pharmacological, neurodevelopmental, or genetic models for schizophrenia), dose, treatment schedule (acute vs. repeated) and route of administration (intraperitoneal vs local injection into specific brain regions). Clinical studies suggest a potential role for CBD in the treatment of psychotic disorders. However, future studies with more robust sample sizes are needed to confirm these positive findings. Overall, although more studies are needed, current evidence indicates that CBD may be a promising therapeutic option for the treatment of schizophrenia.

The target of alcohol's effect on the central nervous system has been sought for more than 50 years in the brain's GABA system. The behavioral and emotional effects of alcohol in humans and rodents are very similar to those of barbiturates and benzodiazepines, and GABA_A receptors have been shown to be one of the sites of alcohol action. The mechanisms of GABAergic inhibition have been a hotspot of research but have turned out to be complex and controversial. Genetics support the involvement of some GABA_A receptor subunits in the development of alcohol dependence and in alcohol use disorders (AUD). Since the effect of alcohol on the GABA_A system resembles that of a GABAergic positive modulator, it may be possible to develop GABAergic drug treatments that could substitute for alcohol. The adaptation mechanisms of the GABA system and the plasticity of the brain are a big challenge for drug development: the drugs that act on GABA_A receptors developed so far also may cause adaptation and development of additional addiction. Human polymorphisms should be studied further to get insight about how they affect receptor function, expression or other factors to make reasonable predictions/hypotheses about what non-addictive interventions would help in alcohol dependence and AUD.

Published works highlight the role of neuropeptides in both the development and treatment of AUD. Closely related hypothalamic neuropeptides, oxytocin (OT) and vasopressin (VP), initially recognized for their physiological hormone effects, are increasingly acknowledged for their behavioral influences. Studies consistently demonstrate that OT and VP impact alcohol consumption and related behaviors, implicating them in the neurobiology of addiction. Moreover, stress is a pivotal risk factor for alcohol use and relapse, with OT and VP playing an integral role in the body's stress response system. While previous work has explored the interaction of OT and VP with other substances of abuse, this review focuses on their roles in alcohol-associated behaviors specifically to better understand the role of OT and VP in AUD. Here we synthesize recent preclinical and clinical literature examining changes in OT and VP protein and receptor expression in response to alcohol, as well as research investigating the effects of modulating these systems on alcohol-related behaviors. This review aims to deepen the understanding of OT and VP in the context of AUD with the goal of facilitating future research and enhancing treatment outcomes.

Several pieces of evidence have implicated the endocannabinoid system on dopaminergic mesolimbic brain reward, as well as the potential role of cannabinoid receptors CB1 and CB2 on modulation of reinforced properties of drug abuse and consequently to the treatment of substance use disorder, including alcoholism. Moreover, growing evidence has been proposed that cannabis or cannabinoid compounds may be helpful to treat alcohol use disorder (AUD). Cannabis is prevalent among individuals who also consume alcohol. While some authors reported that cannabis may be a promising candidate as a substitute medication for AUD, some studies have demonstrated that concomitant use of alcohol and cannabis may increase the risk of adverse outcomes. Considering that advances in the legalization and decriminalization movements regarding cannabis have led to increased availability worldwide, the current chapter aims to provide evidence on the benefits and risks of combining alcohol and cannabis, as well as the potential therapeutic use of cannabinoid compounds in treating AUD.

This chapter aims to explain and evaluate the evidence for psychological, physical and complementary therapies as part of a holistic plan for managing neuropathic pain. Psychological therapies refer to interventions targeting mental health, while physical therapies refer to interventions designed to target movement and functional ability, and complementary therapies are those that attempt to target key mechanisms of change to alter brain and body functioning, or thought processes related to the experience of pain. Each therapeutic modality is discussed to narratively report on the evidence and provide implications for clinicians. Where evidence was unavailable for neuropathic pain populations, evidence from chronic pain populations more broadly was considered. Although promising, there is a lack of high-quality evidence investigating the benefits and safety of psychological, physical and complementary therapies for the management of neuropathic pain. The low certainty evidence and lack of evidence across different neuropathic pain conditions impacts the ability to make recommendations for clinical practice. However, there are several potential areas for future research. Psychological therapies that focus on the underlying mechanisms related to emotion regulation may improve mood and pain, while cognitive and behavioural based approaches may improve psychological comorbidities such as anxiety and depression. Physical therapies involving physical activity and exercise, education, and graded motor imagery may improve functioning and reduce pain. Finally, complementary therapies including electroencephalography neurofeedback, acupuncture, virtual reality, hypnosis and transcutaneous electrical nerve stimulation may provide promising reductions in pain. There is a clear need for further high-quality trials to evaluate the benefits and safety of psychological, physical and complementary therapies to guide the management of neuropathic pain.

The study of pain mechanisms has advanced significantly with the development of innovative in vitro models. This chapter explores those already used in or potentially useful for neuropathic pain research, emphasizing the complementary roles of animal and human cellular models to enhance translational success. Traditional animal models have provided foundational insights into the neurobiology of pain and remain invaluable for understanding complex pain pathways. However, integrating human cellular models addresses the need for better replication of human nociceptors. The chapter details methodologies for culturing rodent and human primary sensory neurons, including isolation and culture techniques, advantages, and limitations. It highlights the application of these models in neuropathic pain research, such as identifying pain-associated receptors and ion channels. Recent advancements in using induced pluripotent stem cell (iPSC)-derived sensory neurons are also discussed. Finally, the chapter explores advanced in vitro models, including 2D co-cultures and 3D organoids, and their implications for studying neuropathic pain. These models offer significant advantages for drug screening and ethical research practices, providing a more accurate representation of human pain pathways and paving the way for innovative therapeutic strategies. Despite challenges such as limited access to viable human tissue and variability between samples, these in vitro models, alongside traditional animal models, are indispensable for advancing our understanding of neuropathic pain and developing effective treatments.

Alcohol use disorder (AUD) is a multifactorial disorder arising from a complex interplay of various genetic, environmental, psychological, and social factors. Environmental factors influence alcohol misuse and can lead to AUD. While stress plays a crucial role in the onset and progression of this disorder, environmental enrichment (EE) also influences ethanol-induced behavioral and neurobiological responses. These alterations include reduced ethanol consumption, diminished operant self-administration, attenuated behavioral sensitization, and enhanced conditioned place preference. EE exerts modulatory effects on multiple neurobiological processes, such as the brain-derived neurotrophic factor/TrkB signaling pathway, the oxytocinergic system, and the hypothalamic-pituitary-adrenal axis. EE, which includes stimulating activities to counteract ethanol effects in animal studies, has parallels in human intervention that have shown potential benefits. Physical activity, cognitive behavioral therapy, and meditation, alongside techniques involving cognitive stimulation, social interaction, and recreational activities, may lead to more effective therapeutic outcomes in treatments of AUD.

Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach can offer a more cost-effective and time-efficient alternative to developing new drugs from scratch. Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate. Acamprosate was developed specifically for AUD, while disulfiram's alcohol-deterrent effects were discovered incidentally. Naltrexone and nalmefene were originally approved for opioids but found secondary applications in AUD. Baclofen and sodium oxybate were repurposed from neurological conditions. Other drugs show promise. Topiramate and zonisamide, anticonvulsants, demonstrate efficacy in reducing alcohol consumption. Another anticonvulsant, gabapentin has been disappointing overall, except in cases involving alcohol withdrawal symptoms. Varenicline, a nicotinic receptor agonist, benefits individuals with less severe AUD or concurrent nicotine use. Ondansetron, a 5-HT3 antagonist, has potential for early-onset AUD, especially when combined with naltrexone. Antipsychotic drugs like aripiprazole and quetiapine have limited efficacy. Further investigation is needed for potential repurposing of α1 adrenergic receptor antagonists prazosin and doxazosin, glucocorticoid receptor antagonist mifepristone, the phosphodiesterase inhibitor Ibudilast, the cysteine prodrug N-acetylcysteine, and the OX1R and OX2R blocker Suvorexant. This review supports repurposing drugs as an effective strategy for expanding treatment options for AUD.