scholarly journals The Use of Botulinum Toxin for the Treatment of Chronic Joint Pain: Clinical and Experimental Evidence

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 314 ◽  
Author(s):  
Nicole Blanshan ◽  
Hollis Krug

Chronic osteoarthritis pain is an increasing worldwide problem. Treatment for osteoarthritis pain is generally inadequate or fraught with potential toxicities. Botulinum toxins (BoNTs) are potent inhibitors of neuropeptide release. Paralytic toxicity is due to inhibition at the neuromuscular junction, and this effect has been utilized for treatments of painful dystonias. Pain relief following BoNT muscle injection has been noted to be more significant than muscle weakness and hypothesized to occur because of the inhibition of peripheral neuropeptide release and reduction of peripheral sensitization. Because of this observation, BoNT has been studied as an intra-articular (IA) analgesic for chronic joint pain. In clinical trials, BoNT appears to be effective for nociceptive joint pain. No toxicity has been reported. In preclinical models of joint pain, BoNT is similarly effective. Examination of the dorsal root ganglion (DRG) and the central nervous system has shown that catalytically active BoNT is retrogradely transported by neurons and then transcytosed to afferent synapses in the brain. This suggests that pain relief may also be due to the central effects of the drug. In summary, BoNT appears to be safe and effective for the treatment of chronic joint pain. The long-term effects of IA BoNT are still being determined.

Author(s):  
Maja Predojevic ◽  
Aida Salihagic Kadic

Abstract The human brain function is certainly one of the most amazing phenomena known. All behavior is the result of the brain function. The 100 billion nerve cells are the home to our centers of feelings and senses, pleasure and satisfaction; it is where the centers for learning, memory and creative work are located; where laughing and crying areas and the centers of our mind are. Our cognitive functions, such as thinking, speaking or creating works of art and science, all reside within the cerebral cortex. One of the tasks of the neural science is to explain how the brain marshals its millions of individual nerve cells to produce behavior and how these cells are affected by the environment.1 The brain function still remains shrouded in a veil of mystery. But what is known is that over 99 percent of the human neocortex is produced during the fetal period.2 Owing to the employment of state-of-the-art methods and techniques in prenatal investigations, a growing pool of information on the development of the central nervous system (CNS) and behavioral patterns during intrauterine life has been made available. This review outlines these events, along with the development of the fetal sensory system and circadian rhythms, the senses of vision and hearing, fetal learning and memory, and long-term effects of fetal stress on behavior. In brief, this review offers a glimpse of the fascinating world of the intrauterine life.


2017 ◽  
Vol 23 (6) ◽  
pp. 587-604 ◽  
Author(s):  
Julien Gibon ◽  
Philip A. Barker

Neurotrophins have been intensively studied and have multiple roles in the brain. Neurotrophins are first synthetized as proneurotrophins and then cleaved intracellularly and extracellularly. Increasing evidences demonstrate that proneurotrophins and mature neurotrophins exerts opposing role in the central nervous system. In the present review, we explore the role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) and their respective proform in cellular processes related to learning and memory. We focused on their roles in synaptic activity and plasticity in the brain with an emphasis on long-term potentiation, long-term depression, and basal synaptic transmission in the hippocampus and the temporal lobe area. We also discuss new findings on the role of the Val66Met polymorphism on the BDNF propeptide on synaptic activity.


2021 ◽  
Vol 21 (1) ◽  
pp. 36-40
Author(s):  
Justyna Wiśniowska ◽  
◽  
Kamilla Puławska ◽  

Fatigue is one of the most common symptoms seen in patients with multiple sclerosis. Cognitive-behavioural psychotherapy can be a non-pharmacological approach for these patients. Van Kessel and Moss-Morris developed a cognitive-behavioural model to explain multiple sclerosis-related fatigue (2006). According to this model, inflammatory and demyelinating factors present in the central nervous system trigger fatigue, while cognitive interpretation, anxiety, or depressive symptoms and resting lifestyle are maintaining factors. Based on the cognitive-behavioural model of fatigue in multiple sclerosis, a protocol encompassing 8 treatment sessions was developed. For over 10 years, studies have been conducted to verify the effectiveness of cognitive-behavioural psychotherapy in the treatment of fatigue in patients with multiple sclerosis. The so far obtained results show that cognitive-behavioural psychotherapy has a moderate short-term effect on reducing fatigue, while the effect size in the long-term is small. The obtained results were undoubtedly influenced by several factors: the heterogeneity of the procedures used, the size of the research groups, and the large number of disease-related intermediary variables. Further research should be conducted to identify specific factors responsible for the effectiveness of cognitive-behavioural psychotherapy in the treatment of fatigue and to assess the long-term effects of therapy.


Meditation refers to a state of mind of relaxation and concentration, where generally the mind and body is at rest. The process of meditation reflects the state of the brain which is distinct from sleep or typical wakeful states of consciousness. Meditative practices usually involve regulation of emotions and monitoring of attention. Over the past decade there has been a tremendous increase in an interest to study the neural mechanisms involved in meditative practices. It could also be beneficial to explore if the effect of meditation is altered by the number of years of meditation practice. Functional Magnetic Resonance Imaging (fMRI) is a very useful imaging technique which can be used to perform this analysis due to its inherent benefits, mainly it being a non-invasive technique. Functional activation and connectivity analysis can be performed on the fMRI data to find the active regions and the connectivity in the brain regions. Functional connectivity is defined as a simple temporal correlation between anatomically separate, active neural regions. Functional connectivity gives the statistical dependencies between regional time series. It is a statistical concept and is quantified using metrics like Correlation. In this study, a comparison is made between functional connectivity in the brain regions of long term meditation practitioners (LTP) and short-term meditation practitioners (STP) to see the differences and similarities in the connectivity patterns. From the analysis, it is evident that in fact there is a difference in connectivity between long term and short term practitioners and hence continuous practice of meditation can have long term effects.


2013 ◽  
Vol 43 (1) ◽  
pp. 79
Author(s):  
R. Ghalamghash ◽  
H.Z. Mammedov ◽  
H. Ashayeri ◽  
A. Hosseini

Author(s):  
Angela Duckworth ◽  

For more than a century, scientists have known that acute stress activates the fight-or-flight response. When your life is on the line, your body reacts instantly: your heart races, your breath quickens, and a cascade of hormones sets off physiological changes that collectively improve your odds of survival. More recently, scientists have come to understand that the fight-or-flight response takes a toll on the brain and the body—particularly when stress is chronic rather than acute. Systems designed to handle transient threats also react to stress that occurs again and again, for weeks, months, or years. It turns out that poverty, abuse, and other forms of adversity repeatedly activate the fight-or-flight response, leading to long-term effects on the immune system and brain, which in turn increase the risk for an array of illnesses, including asthma, diabetes, arthritis, depression, and cardiovascular disease. Pioneering neuroscientist Bruce McEwen called this burden of chronic stress “allostatic load.”


2020 ◽  
pp. 000486742096147
Author(s):  
Christos Pantelis ◽  
Mahesh Jayaram ◽  
Anthony J Hannan ◽  
Robb Wesselingh ◽  
Jess Nithianantharajah ◽  
...  

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health.


2019 ◽  
Vol 46 (3) ◽  
pp. 484-495 ◽  
Author(s):  
Federico E Turkheimer ◽  
Pierluigi Selvaggi ◽  
Mitul A Mehta ◽  
Mattia Veronese ◽  
Fernando Zelaya ◽  
...  

Abstract The use of antipsychotic medication to manage psychosis, principally in those with a diagnosis of schizophrenia or bipolar disorder, is well established. Antipsychotics are effective in normalizing positive symptoms of psychosis in the short term (delusions, hallucinations and disordered thought). Their long-term use is, however, associated with side effects, including several types of movement (extrapyramidal syndrome, dyskinesia, akathisia), metabolic and cardiac disorders. Furthermore, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance and blunted affect, although the mechanisms driving the latter associations are not well understood. In this article, we propose a novel model of the long-term effects of antipsychotic administration focusing on the changes in brain metabolic homeostasis induced by the medication. We propose here that the brain metabolic normalization, that occurs in parallel to the normalization of psychotic symptoms following antipsychotic treatment, may not ultimately be sustainable by the cerebral tissue of some patients; these patients may be characterized by already reduced oxidative metabolic capacity and this may push the brain into an unsustainable metabolic envelope resulting in tissue remodeling. To support this perspective, we will review the existing data on the brain metabolic trajectories of patients with a diagnosis of schizophrenia as indexed using available neuroimaging tools before and after use of medication. We will also consider data from pre-clinical studies to provide mechanistic support for our model.


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