scholarly journals Potential Molecular Targets for Treating Neuropathic Orofacial Pain Based on Current Findings in Animal Models

2021 ◽  
Vol 22 (12) ◽  
pp. 6406
Author(s):  
Yukinori Nagakura ◽  
Shogo Nagaoka ◽  
Takahiro Kurose

This review highlights potential molecular targets for treating neuropathic orofacial pain based on current findings in animal models. Preclinical research is currently elucidating the pathophysiology of the disease and identifying the molecular targets for better therapies using animal models that mimic this category of orofacial pain, especially post-traumatic trigeminal neuropathic pain (PTNP) and primary trigeminal neuralgia (PTN). Animal models of PTNP and PTN simulate their etiologies, that is, trauma to the trigeminal nerve branch and compression of the trigeminal root entry zone, respectively. Investigations in these animal models have suggested that biological processes, including inflammation, enhanced neuropeptide-mediated pain signal transmission, axonal ectopic discharges, and enhancement of interactions between neurons and glial cells in the trigeminal pathway, are underlying orofacial pain phenotypes. The molecules associated with biological processes, whose expressions are substantially altered following trigeminal nerve damage or compression of the trigeminal nerve root, are potentially involved in the generation and/or exacerbation of neuropathic orofacial pain and can be potential molecular targets for the discovery of better therapies. Application of therapeutic candidates, which act on the molecular targets and modulate biological processes, attenuates pain-associated behaviors in animal models. Such therapeutic candidates including calcitonin gene-related peptide receptor antagonists that have a reasonable mechanism for ameliorating neuropathic orofacial pain and meet the requirements for safe administration to humans seem worth to be evaluated in clinical trials. Such prospective translation of the efficacy of therapeutic candidates from animal models to human patients would help develop better therapies for neuropathic orofacial pain.

Cephalalgia ◽  
2013 ◽  
Vol 33 (13) ◽  
pp. 1132-1136 ◽  
Author(s):  
Daniel YH Tan ◽  
Eu Tiong Chua ◽  
Kim Bock Ng ◽  
Kwang Ping Chan ◽  
John Thomas

Background The short-lasting unilateral neuralgiform headache associated with conjunctival injection and tearing or SUNCT syndrome was first described in the 1970s. This paper is the first in the literature that describes the successful use of stereotactic radiosurgery (SRS) using a non-invasive frameless technique, targeting both the trigeminal nerve and the sphenopalatine ganglion in the management of intractable SUNCT. We also discuss the role of selecting peripheral targets in the management of this rare headache syndrome. Methods Among patients treated for functional pain disorders in our radiosurgery unit using the frameless technique since August 2011, one patient with symptoms matching the International Classification of Headache Disorders-2 (ICHD-II) criteria of SUNCT syndrome was identified. The multi-disciplinary case records of this patient were retrospectively reviewed and reported. Results Our patient had symptoms resembling the ICHD-II diagnostic criteria of SUNCT, which was refractory to medical treatment. Ninety Gy was delivered to the trigeminal root entry zone and 80 Gy was delivered to the sphenopalatine ganglion. At 16 months’ follow-up, she was pain free with minimal side effects. Conclusions Frameless linear accelerator (linac)-based SRS targeting the trigeminal nerve and sphenopalatine ganglion remained successful in our patient at 16 months. Longer follow-up and further experience will determine the efficacy and safety of this approach. We suggest that frameless SRS is a convenient and attractive non-invasive option for patients with medically refractory SUNCT.


2021 ◽  
Vol 9 (3) ◽  
pp. 53
Author(s):  
Giuseppe Tardiolo ◽  
Pina Brianti ◽  
Daniela Sapienza ◽  
Pia dell’Utri ◽  
Viviane Di Dio ◽  
...  

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pathogen agent causing the coronavirus infectious disease (COVID-19). This novel virus originated the most challenging pandemic in this century, causing economic and social upheaval internationally. The extreme infectiousness and high mortality rates incentivized the development of vaccines to control this pandemic to prevent further morbidity and mortality. This international scenario led academic scientists, industries, and governments to work and collaborate strongly to make a portfolio of vaccines available at an unprecedented pace. Indeed, the robust collaboration between public systems and private companies led to resolutive actions for accelerating therapeutic interventions and vaccines mechanism. These strategies contributed to rapidly identifying safe and effective vaccines as quickly and efficiently as possible. Preclinical research employed animal models to develop vaccines that induce protective and long-lived immune responses. A spectrum of vaccines is worldwide under investigation in various preclinical and clinical studies to develop both individual protection and safe development of population-level herd immunity. Companies employed and developed different technological approaches for vaccines production, including inactivated vaccines, live-attenuated, non-replicating viral vector vaccines, as well as acid nucleic-based vaccines. In this view, the present narrative review provides an overview of current vaccination strategies, taking into account both preclinical studies and clinical trials in humans. Furthermore, to better understand immunization, animal models on SARS-CoV-2 pathogenesis are also briefly discussed.


2021 ◽  
Vol 22 (4) ◽  
pp. 1863
Author(s):  
Philippe A. Melas ◽  
Maria Scherma ◽  
Walter Fratta ◽  
Carlo Cifani ◽  
Paola Fadda

Cannabidiol (CBD) is the most abundant non-psychoactive component of cannabis; it displays a very low affinity for cannabinoid receptors, facilitates endocannabinoid signaling by inhibiting the hydrolysis of anandamide, and stimulates both transient receptor potential vanilloid 1 and 2 and serotonin type 1A receptors. Since CBD interacts with a wide variety of molecular targets in the brain, its therapeutic potential has been investigated in a number of neuropsychiatric diseases, including anxiety and mood disorders. Specifically, CBD has received growing attention due to its anxiolytic and antidepressant properties. As a consequence, and given its safety profile, CBD is considered a promising new agent in the treatment of anxiety and mood disorders. However, the exact molecular mechanism of action of CBD still remains unknown. In the present preclinical review, we provide a summary of animal-based studies that support the use of CBD as an anxiolytic- and antidepressant-like compound. Next, we describe neuropharmacological evidence that links the molecular pharmacology of CBD to its behavioral effects. Finally, by taking into consideration the effects of CBD on DNA methylation, histone modifications, and microRNAs, we elaborate on the putative role of epigenetic mechanisms in mediating CBD’s therapeutic outcomes.


Author(s):  
Ch Venkataramaiah ◽  
G Swathi ◽  
W Rajendra

 The morris water maze (MWM) was developed by morris as a device to investigate spatial learning and memory in laboratory rats. MWM has become one of the most frequently used laboratory tools in behavioral neuroscience. The MWM task has been often used in the validation of rodent models for neurocognitive disorders (e.g., Parkinson, Alzheimer, Epilepsy, and Schizophrenia), and the evaluation of possible neurocognitive treatments. It is also being used to assess the properties of established potential antipsychotics in animal models of Schizophrenia. The MWM task requires rats to find a hidden platform in a large, circular pool of water that is colored opaque with powdered non-fat milk (or) non-toxic tempera paint where they must swim to the hidden platform. Because they are in the opaque water, the animals cannot see the platform and cannot rely on scent to find the escape route. Instead, they must rely on extra-maze cues. The behavior of rat can be evaluated by analyzing the different parameters such as escape latency, swim speed, and path length, and probe trail. The purpose of this review is to briefly describe procedural aspects, interpretational difficulties of data and advantages of MWM. This paradigm has become a benchmark test for learning and memory difficulties in animal models and preclinical research in general.


Author(s):  
Ruiqing Ni

Animal models of Alzheimer’s disease amyloidosis that recapitulate cerebral amyloid-beta pathology have been widely used in preclinical research, and have greatly enabled the mechanistic understanding of Alzheimer’s disease and the development of therapeutics. Comprehensive deep phenotyping of the pathophysiological and biochemical features in these animal models are essential. Recent advances in positron emission tomography have allowed the non-invasive visualization of the alterations in the brain of animal models as well as in patients with Alzheimer’s disease, These tools have facilitated our understanding of disease mechanisms, and provided longitudinal monitoring of treatment effect in animal models of Alzheimer’s disease amyloidosis. In this review, we focus on recent positron emission tomography studies of cerebral amyloid-beta accumulation, hypoglucose metabolism, synaptic and neurotransmitter receptor deficits (cholinergic and glutamatergic system), blood-brain barrier impairment and neuroinflammation (microgliosis and astrocytosis) in animal models of Alzheimer’s disease amyloidosis. We further propose the emerging targets and tracers for reflecting the pathophysiological changes, and discuss outstanding challenges in disease animal models and future outlook in on-chip characterization of imaging biomarkers towards clinical translation.


2018 ◽  
Vol 64 (1) ◽  
pp. 5-17 ◽  
Author(s):  
Ian R. Winship ◽  
Serdar M. Dursun ◽  
Glen B. Baker ◽  
Priscila A. Balista ◽  
Ludmyla Kandratavicius ◽  
...  

Schizophrenia is a heterogeneous psychiatric disorder that is poorly treated with current therapies. In this brief review, we provide an update regarding the use of animal models to study schizophrenia in an attempt to understand its aetiology and develop novel therapeutic strategies. Tremendous progress has been made developing and validating rodent models that replicate the aetiologies, brain pathologies, and behavioural abnormalities associated with schizophrenia in humans. Here, models are grouped into 3 categories—developmental, drug induced, and genetic—to reflect the heterogeneous risk factors associated with schizophrenia. Each of these models is associated with varied but overlapping pathophysiology, endophenotypes, behavioural abnormalities, and cognitive impairments. Studying schizophrenia using multiple models will permit an understanding of the core features of the disease, thereby facilitating preclinical research aimed at the development and validation of better pharmacotherapies to alter the progression of schizophrenia or alleviate its debilitating symptoms.


2018 ◽  
Vol 57 (22) ◽  
pp. 3339-3340
Author(s):  
Arifumi Matsumoto ◽  
Kinya Hisanaga ◽  
Isao Nagano

Author(s):  
Asma Khan ◽  
Kenneth M. Hargreaves
Keyword(s):  

2018 ◽  
Vol 13 (10) ◽  
pp. 949-964 ◽  
Author(s):  
Heitor G. Araújo-Filho ◽  
Erik W.M. Pereira ◽  
Adriana Rolim Campos ◽  
Lucindo J. Quintans-Júnior ◽  
Jullyana S.S. Quintans

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