Animal Models of Peripheral Neuropathy and Neuropathic Pain

2017 ◽  
Author(s):  
Katelyn Donaldson ◽  
Ahmet Höke
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Animal Models ◽  
Human Disease ◽  
New Drugs ◽  
Molecular Pathways ◽  
Peripheral Neuropathies ◽  
Different Types

There are numerous types of peripheral neuropathies and conditions that cause neuropathic pain with varying symptoms and different mechanisms of pathogenesis. Therefore, it is not surprising that many different animal models of peripheral neuropathies and neuropathic pain have been developed with varying degrees of fidelity to recapitulate the human disease. Nevertheless, these models are useful in a deconstructive manner to examine role of specific molecular pathways in pathogenesis of different types of peripheral neuropathies and test potential new drugs.

scholarly journals The Role of Microglia in Neurodevelopmental Disorders and their Therapeutics

2020 ◽  
Vol 20 (4) ◽  
pp. 272-276
Author(s):  
Rachel Coomey ◽  
Rianne Stowell ◽  
Ania Majewska ◽  
Daniela Tropea
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Therapeutic Effect ◽  
Immune Cells ◽  
Neurodevelopmental Disorders ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Molecular Pathways ◽  
Present Evidence

The development of new therapeutics is critically dependent on an understanding of the molecular pathways, the disruption of which results in neurological symptoms. Genetic and biomarker studies have highlighted immune signalling as a pathway that is impaired in patients with neurodevelopmental disorders (NDDs), and several studies on animal models of aberrant neurodevelopment have implicated microglia, the brain’s immune cells, in the pathology of these diseases. Despite the increasing awareness of the role of immune responses and inflammation in the pathophysiology of NDDs, the testing of new drugs rarely considers their effects in microglia. In this brief review, we present evidence of how the study of microglia can be critical for understanding the mechanisms of action of candidate drugs for NDDs and for increasing their therapeutic effect.

scholarly journals Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 399
Author(s):  
Cristina Giorgio ◽  
Mara Zippoli ◽  
Pasquale Cocchiaro ◽  
Vanessa Castelli ◽  
Giustino Varrassi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Complement System ◽  
Critical Role ◽  
Peripheral Neuropathies ◽  
Adequate Pain Relief ◽  
Medical Need ◽  
New Strategy ◽  
The Complement System

The complement system is a key component of innate immunity since it plays a critical role in inflammation and defense against common pathogens. However, an inappropriate activation of the complement system is involved in numerous disorders, including peripheral neuropathies. Current strategies for neuropathy-related pain fail to achieve adequate pain relief, and although several therapies are used to alleviate symptoms, approved disease-modifying treatments are unavailable. This urgent medical need is driving the development of therapeutic agents for this condition, and special emphasis is given to complement-targeting approaches. Recent evidence has underscored the importance of complement component C5a and its receptor C5aR1 in inflammatory and neuropathic pain, indicating that C5a/C5aR1 axis activation triggers a cascade of events involved in pathophysiology of peripheral neuropathy and painful neuro-inflammatory states. However, the underlying pathophysiological mechanisms of this signaling in peripheral neuropathy are not fully known. Here, we provide an overview of complement pathways and major components associated with dysregulated complement activation in peripheral neuropathy, and of drugs under development targeting the C5 system. C5/C5aR1 axis modulators could represent a new strategy to treat complement-related peripheral neuropathies. Specifically, we describe novel C5aR allosteric modulators, which may potentially become new tools in the therapeutic armory against neuropathic pain.

scholarly journals Whole-body vibration as a modality for the rehabilitation of peripheral neuropathies: implications for cancer survivors suffering from chemotherapy-induced peripheral neuropathy

2015 ◽  
Author(s):  
Anna L.J. Verhulst ◽  
Hans H.C.M. Savelberg ◽  
Gerard Vreugdenhil ◽  
Massimo Mischi ◽  
Goof Schep
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Muscle Strength ◽  
Cancer Survivors ◽  
Methodological Quality ◽  
Whole Body Vibration ◽  
Whole Body ◽  
Peripheral Neuropathies ◽  
Body Vibration

The objective was to study the effect of whole-body vibration (WBV) on strength, balance and pain in patients with peripheral neuropathies and to consider its significance for the rehabilitation of patients suffering from chemotherapy-induced peripheral neuropathy (CIPN). Using a broad search strategy, PubMed was searched for clinical trials on WBV interventions aimed at improving strength, balance or pain in patients with peripheral neuropathies, which were published in English until 5th June 2014. The search was performed by the first author and generated a total of 505 results, which yielded 5 articles that met the inclusion criteria, being studies: i) published in English; ii) involving adult human subjects’ peripheral neuropathies; iii) evaluating the effect of WBV as a therapeutic intervention; and iv) reporting findings for at least one of the following outcomes: strength, balance or pain. Methodological quality of included studies was assessed independently by first and second author, using the physiotherapy evidence database scale. The overall methodological quality of included studies was low. Two studies found a beneficial effect of WBV on neuropathic pain, but another study failed to find the same effect. One study found significant improvements in both muscle strength and balance, while another study found improvements only in some, but not all, of the applied tests to measure muscle strength and balance. The results of this literature search suggest insufficient evidence to assess the effectiveness for the effects of WBV on neuropathic pain, muscle strength and balance in patients with peripheral neuropathies. More high-quality trials are needed to guide the optimization of rehabilitation programs for cancer survivors with CIPN in particular.

The role of brain-derived neurotrophic factor in different animal models of neuropathic pain

2010 ◽  
Vol 14 (5) ◽  
pp. 473.e1-473.e9 ◽  
Author(s):  
Pascal Vanelderen ◽  
Tom Rouwette ◽  
Tamas Kozicz ◽  
Eric Roubos ◽  
Jan Van Zundert ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Animal Models ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor

scholarly journals Sensory Neurons, Ion Channels, Inflammation and the Onset of Neuropathic Pain

2012 ◽  
Vol 39 (4) ◽  
pp. 416-435 ◽  
Author(s):  
Patrick L. Stemkowski ◽  
Peter A. Smith
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Pain Management ◽  
Sensory Neurons ◽  
Inflammatory Mediators ◽  
Primary Afferents ◽  
Ectopic Activity ◽  
Management Procedures

Neuropathic pain often fails to respond to conventional pain management procedures. here we review the aetiology of neuropathic pain as would result from peripheral neuropathy or injury. We show that inflammatory mediators released from damaged nerves and tissue are responsible for triggering ectopic activity in primary afferents and that this, in turn, provokes increased spinal cord activity and the development of ‘central sensitization’. Although evidence is mounting to support the role of interleukin-1β, prostaglandins and other cytokines in the onset of neuropathic pain, the clinical efficacy of drugs which antagonize or prevent the actions of these mediators is yet to be determined. basic science findings do, however, support the use of pre-emptive analgesia during procedures which involve nerve manipulation and the use of anti-inflammatory steroids as soon as possible following traumatic nerve injury.

Role of DAMPs and of Leukocytes Infiltration in Ischemic Stroke: Insights from Animal Models and Translation to the Human Disease

2020 ◽  
Author(s):  
Rosita Stanzione ◽  
Maurizio Forte ◽  
Maria Cotugno ◽  
Franca Bianchi ◽  
Simona Marchitti ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Animal Models ◽  
Human Disease

scholarly journals Reprogrammable Recognition Codes in Bicoid Homeodomain-DNA Interaction

2000 ◽  
Vol 20 (20) ◽  
pp. 7673-7684 ◽  
Author(s):  
Vrushank Dave ◽  
Chen Zhao ◽  
Fan Yang ◽  
Chang-Shung Tung ◽  
Jun Ma
Keyword(s):  
Dna Sequences ◽  
Human Disease ◽  
Dna Recognition ◽  
Dna Interaction ◽  
Morphogenetic Protein ◽  
Different Types ◽  
Disease Protein

ABSTRACT We describe experiments to determine how the homeodomain of the Drosophila morphogenetic protein Bicoid recognizes different types of DNA sequences found in natural enhancers. Our chemical footprint analyses reveal that the Bicoid homeodomain makes both shared and distinct contacts with a consensus site A1 (TAATCC) and a nonconsensus site X1 (TAAGCT). In particular, the guanine of X1 at position 4 (TAAGCT) is protected by Bicoid homeodomain. We provide further evidence suggesting that the unique arginine at position 54 (Arg 54) of the Bicoid homeodomain enables the protein to recognize X1 by specifically interacting with this position 4 guanine. We also describe experiments to analyze the contribution of artificially introduced Arg 54 to DNA recognition by other Bicoid-related homeodomains, including that from the human disease protein Pitx2. Our experiments demonstrate that the role of Arg 54 varies depending on the exact homeodomain framework and DNA sequences. Together, our results suggest that Bicoid and its related homeodomains utilize distinct recognition codes to interact with different DNA sequences, underscoring the need to study DNA recognition by Bicoid-class homeodomains in an individualized manner.

A 68-Year-Old Male with Progressive Numbness and Gait Difficulties

2016 ◽  
Author(s):  
Jeffrey A. Cohen ◽  
Justin J. Mowchun ◽  
Victoria H. Lawson ◽  
Nathaniel M. Robbins
Keyword(s):  
Peripheral Neuropathy ◽  
Monoclonal Gammopathy ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Peripheral Neuropathies ◽  
Hematologic Disease ◽  
Monoclonal Protein ◽  
Inflammatory Demyelinating Polyneuropathy ◽  
Management Approaches ◽  
Hematological Evaluation

Paraproteinemic demyelinating peripheral neuropathies require specific diagnostic and management approaches. The clinical features as well as the type of monoclonal protein and possible associated antibodies are all important considerations in evaluation and management of these complex presentations. It is important to recognize anti-myelin associated glycoproteins positive peripheral neuropathy, which is associated with IgM gammopathy, and typically presents with a sensory ataxia. Hematologic disease may mimic chronic inflammatory demyelinating polyneuropathy. This chapter also describes the role of hematological evaluation for patients with peripheral neuropathy and a monoclonal gammopathy.

scholarly journals Complex Regional Pain Syndrome (CRPS/RSD) and Neuropathic Pain: Role of Intravenous Bisphosphonates as Analgesics

2008 ◽  
Vol 8 ◽  
pp. 229-236 ◽  
Author(s):  
Jennifer Yanow ◽  
Marco Pappagallo ◽  
Letha Pillai
Keyword(s):  
Clinical Trials ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Complex Regional Pain Syndrome ◽  
Bone Pain ◽  
Treatment Options ◽  
Pain Syndrome ◽  
Pain Pathways ◽  
Intravenous Bisphosphonates

Neuropathic pain is a sequela of dysfunction, injuries, or diseases of the peripheral and/or central nervous system pain pathways, which has historically been extremely difficult to treat. Complex regional pain syndrome (CRPS) types 1 and 2 are neuropathic pain conditions that have a long history in the medical literature but whose pathophysiology remains elusive and whose available treatment options remain few. While an exact animal model for CRPS doesn't yet exist, there are several animal models of neuropathic pain that develop behaviors of hypersensitivity, one of the hallmark signs of neuropathic pain in humans.Bisphosphonates have been used for pathologic conditions associated with abnormal bone metabolism, such as osteoporosis, Paget’s disease and cancer-related bone pain for many years. More recently, results of clinical trials have indicated the potential role of bisphosphonates in the treatment of CRPS/RSD.In this paper we will review the preclinical studies regarding the use of bisphosphonates as analgesics in animal models of neuropathic pain, and also summarize the clinical trials that have been done to date. We will give an overview of bisphosphonate pharmacology and discuss several potential mechanisms by which bisphosphonates may be analgesic in CRPS/RSD and bone pain of noncancer origin.

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