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.

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 Special Issue: The Role of Complement in Cancer Immunotherapy

Antibodies ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 29
Author(s):  
Ronald P. Taylor
Keyword(s):  
Cancer Immunotherapy ◽  
Complement System ◽  
Immune Defense ◽  
Special Issue ◽  
The Complement System ◽  
Critical Aspects

The complement system plays an important role in critical aspects of immune defense and in the maintenance of homeostasis in the bloodstream, as well as in essentially all tissues and organs [...]

The role of the complement system in hereditary angioedema

2017 ◽  
Vol 89 ◽  
pp. 59-68 ◽  
Author(s):  
Dorottya Csuka ◽  
Nóra Veszeli ◽  
Lilian Varga ◽  
Zoltán Prohászka ◽  
Henriette Farkas
Keyword(s):  
Complement System ◽  
Hereditary Angioedema ◽  
The Complement System

Critical role of Cav3.2 T-type calcium channels in the peripheral neuropathy induced by bortezomib, a proteasome-inhibiting chemotherapeutic agent, in mice

Toxicology ◽  
2019 ◽  
Vol 413 ◽  
pp. 33-39 ◽  
Author(s):  
Shiori Tomita ◽  
Fumiko Sekiguchi ◽  
Tomoyo Deguchi ◽  
Takaya Miyazaki ◽  
Yuya Ikeda ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Calcium Channels ◽  
Chemotherapeutic Agent ◽  
Critical Role

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.

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.

The role of paramyosin from blood fluke Schistosoma mansoni in inhibition of the complement system

2008 ◽  
Vol 45 (16) ◽  
pp. 4172
Author(s):  
Lina Grekin ◽  
Ram Cohen ◽  
James M. Sodetz ◽  
Daniel Gold ◽  
Zvi Fishelson
Keyword(s):  
Schistosoma Mansoni ◽  
Complement System ◽  
Blood Fluke ◽  
The Complement System
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