scholarly journals TNFα in MS and Its Animal Models: Implications for Chronic Pain in the Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Aislinn D. Maguire ◽  
John R. Bethea ◽  
Bradley J. Kerr
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Animal Studies ◽  
Critical Factor ◽  
Autoimmune Encephalomyelitis ◽  
Cytokine Tumor Necrosis Factor ◽  
Central Nervous Systems ◽  
Severe Chronic Pain ◽  
Factor Α

Multiple Sclerosis (MS) is a debilitating autoimmune disease often accompanied by severe chronic pain. The most common type of pain in MS, called neuropathic pain, arises from disease processes affecting the peripheral and central nervous systems. It is incredibly difficult to study these processes in patients, so animal models such as experimental autoimmune encephalomyelitis (EAE) mice are used to dissect the complex mechanisms of neuropathic pain in MS. The pleiotropic cytokine tumor necrosis factor α (TNFα) is a critical factor mediating neuropathic pain identified by these animal studies. The TNF signaling pathway is complex, and can lead to cell death, inflammation, or survival. In complex diseases such as MS, signaling through the TNFR1 receptor tends to be pro-inflammation and death, whereas signaling through the TNFR2 receptor is pro-homeostatic. However, most TNFα-targeted therapies indiscriminately block both arms of the pathway, and thus are not therapeutic in MS. This review explores pain in MS, inflammatory TNF signaling, the link between the two, and how it could be exploited to develop more effective TNFα-targeting pain therapies.

Sympathetic component of neuropathic pain: Animal models and clinical diagnosis

1997 ◽  
Vol 20 (3) ◽  
pp. 468-469
Author(s):  
Laszlo A. Urban
Keyword(s):  
Experimental Data ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Clinical Diagnosis ◽  
Inflammatory Pain ◽  
Ongoing Debate ◽  
Pain Syndromes ◽  
Sympathetic Nervous

Although clinical studies and animal models seem to establish an important role for the sympathetic nervous system in many forms of neuropathic and inflammatory pain, there is an ongoing debate on the classification of pain syndromes with sympathetic components. The confusion originates from several sources: failure to acknowledge that the pathomechanism of chronic pain can change during the progress of the disease, which is now strongly underlined by experimental data from suitable animal models. Neuropathic pain is a vaguely defined collection of pain syndromes which includes painful conditions with diverse and largely unknown patho-mechanisms. Clinical diagnosis is difficult and well designed, placebo controlled sympathectomy is rarely performed. [blumberg et al.]

scholarly journals Modulation of Glia-Mediated Processes by Spinal Cord Stimulation in Animal Models of Neuropathic Pain

2021 ◽  
Vol 2 ◽  
Author(s):  
David L. Cedeño ◽  
Courtney A. Kelley ◽  
Krishnan Chakravarthy ◽  
Ricardo Vallejo
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Glial Cells ◽  
Mechanism Of Action ◽  
Spinal Cord Stimulation ◽  
Expression Levels ◽  
Gate Control Theory

Glial cells play an essential role in maintaining the proper functioning of the nervous system. They are more abundant than neurons in most neural tissues and provide metabolic and catabolic regulation, maintaining the homeostatic balance at the synapse. Chronic pain is generated and sustained by the disruption of glia-mediated processes in the central nervous system resulting in unbalanced neuron–glial interactions. Animal models of neuropathic pain have been used to demonstrate that changes in immune and neuroinflammatory processes occur in the course of pain chronification. Spinal cord stimulation (SCS) is an electrical neuromodulation therapy proven safe and effective for treating intractable chronic pain. Traditional SCS therapies were developed based on the gate control theory of pain and rely on stimulating large Aβ neurons to induce paresthesia in the painful dermatome intended to mask nociceptive input carried out by small sensory neurons. A paradigm shift was introduced with SCS treatments that do not require paresthesia to provide effective pain relief. Efforts to understand the mechanism of action of SCS have considered the role of glial cells and the effect of electrical parameters on neuron–glial interactions. Recent work has provided evidence that SCS affects expression levels of glia-related genes and proteins. This inspired the development of a differential target multiplexed programming (DTMP) approach using electrical signals that can rebalance neuroglial interactions by targeting neurons and glial cells differentially. Our group pioneered the utilization of transcriptomic and proteomic analyses to identify the mechanism of action by which SCS works, emphasizing the DTMP approach. This is an account of evidence demonstrating the effect of SCS on glia-mediated processes using neuropathic pain models, emphasizing studies that rely on the evaluation of large sets of genes and proteins. We show that SCS using a DTMP approach strongly affects the expression of neuron and glia-specific transcriptomes while modulating them toward expression levels of healthy animals. The ability of DTMP to modulate key genes and proteins involved in glia-mediated processes affected by pain toward levels found in uninjured animals demonstrates a shift in the neuron–glial environment promoting analgesia.

scholarly journals Neuropathic Pain in Multiple Sclerosis and Its Animal Models: Focus on Mechanisms, Knowledge Gaps and Future Directions

2021 ◽  
Vol 12 ◽  
Author(s):  
Ersilia Mirabelli ◽  
Stella Elkabes
Keyword(s):  
Multiple Sclerosis ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Future Research ◽  
Knowledge Gaps ◽  
Autoimmune Encephalomyelitis ◽  
Increased Sensitivity ◽  
Disease Stages

Multiple sclerosis (MS) is a multifaceted, complex and chronic neurological disease that leads to motor, sensory and cognitive deficits. MS symptoms are unpredictable and exceedingly variable. Pain is a frequent symptom of MS and manifests as nociceptive or neuropathic pain, even at early disease stages. Neuropathic pain is one of the most debilitating symptoms that reduces quality of life and interferes with daily activities, particularly because conventional pharmacotherapies do not adequately alleviate neuropathic pain. Despite advances, the mechanisms underlying neuropathic pain in MS remain elusive. The majority of the studies investigating the pathophysiology of MS-associated neuropathic pain have been performed in animal models that replicate some of the clinical and neuropathological features of MS. Experimental autoimmune encephalomyelitis (EAE) is one of the best-characterized and most commonly used animal models of MS. As in the case of individuals with MS, rodents affected by EAE manifest increased sensitivity to pain which can be assessed by well-established assays. Investigations on EAE provided valuable insights into the pathophysiology of neuropathic pain. Nevertheless, additional investigations are warranted to better understand the events that lead to the onset and maintenance of neuropathic pain in order to identify targets that can facilitate the development of more effective therapeutic interventions. The goal of the present review is to provide an overview of several mechanisms implicated in neuropathic pain in EAE by summarizing published reports. We discuss current knowledge gaps and future research directions, especially based on information obtained by use of other animal models of neuropathic pain such as nerve injury.

scholarly journals In-Depth Characterization of Somatic and Orofacial Sensitive Dysfunctions and Interfering-Symptoms in a Relapsing-Remitting Experimental Autoimmune Encephalomyelitis Mouse Model

2022 ◽  
Vol 12 ◽  
Author(s):  
Amélie Démosthènes ◽  
Benoît Sion ◽  
Fabrice Giraudet ◽  
Xavier Moisset ◽  
Laurence Daulhac ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Autoimmune Encephalomyelitis ◽  
Relapsing Remitting ◽  
Eae Model ◽  
Pain Symptoms ◽  
Experimental Autoimmune

Among the many symptoms (motor, sensory, and cognitive) associated with multiple sclerosis (MS), chronic pain is a common disabling condition. In particular, neuropathic pain symptoms are very prevalent and debilitating, even in early stages of the disease. Unfortunately, chronic pain still lacks efficient therapeutic agents. Progress is needed (i) clinically by better characterizing pain symptoms in MS and understanding the underlying mechanisms, and (ii) preclinically by developing a more closely dedicated model to identify new therapeutic targets and evaluate new drugs. In this setting, new variants of experimental autoimmune encephalomyelitis (EAE) are currently developed in mice to exhibit less severe motor impairments, thereby avoiding confounding factors in assessing pain behaviors over the disease course. Among these, the optimized relapsing-remitting EAE (QuilA-EAE) mouse model, induced using myelin oligodendrocyte glycoprotein peptide fragment (35–55), pertussis toxin, and quillaja bark saponin, seems very promising. Our study sought (i) to better define sensitive dysfunctions and (ii) to extend behavioral characterization to interfering symptoms often associated with pain during MS, such as mood disturbances, fatigue, and cognitive impairment, in this optimized QuilA-EAE model. We made an in-depth characterization of this optimized QuilA-EAE model, describing for the first time somatic thermal hyperalgesia associated with mechanical and cold allodynia. Evaluation of orofacial pain sensitivity showed no mechanical or thermal allodynia. Detailed evaluation of motor behaviors highlighted slight defects in fine motor coordination in the QuilA-EAE mice but without impact on pain evaluation. Finally, no anxiety-related or cognitive impairment was observed during the peak of sensitive symptoms. Pharmacologically, as previously described, we found that pregabalin, a treatment commonly used in neuropathic pain patients, induced an analgesic effect on mechanical allodynia. In addition, we showed an anti-hyperalgesic thermal effect on this model. Our results demonstrate that this QuilA-EAE model is clearly of interest for studying pain symptom development and so could be used to identify and evaluate new therapeutic targets. The presence of interfering symptoms still needs to be further characterized.

Persistent Postsurgical Pain

2018 ◽  
Vol 129 (3) ◽  
pp. 590-607 ◽  
Author(s):  
Philippe Richebé ◽  
Xavier Capdevila ◽  
Cyril Rivat
Keyword(s):  
Chronic Pain ◽  
Postoperative Pain ◽  
Critical Factor ◽  
Major Complication ◽  
Science Research ◽  
Clinical Practices ◽  
Postsurgical Pain ◽  
Pain Sensitization ◽  
Central Nervous Systems ◽  
Persistent Postoperative Pain

Abstract The development of chronic pain is considered a major complication after surgery. Basic science research in animal models helps us understand the transition from acute to chronic pain by identifying the numerous molecular and cellular changes that occur in the peripheral and central nervous systems. It is now well recognized that inflammation and nerve injury lead to long-term synaptic plasticity that amplifies and also maintains pain signaling, a phenomenon referred to as pain sensitization. In the context of surgery in humans, pain sensitization is both responsible for an increase in postoperative pain via the expression of wound hyperalgesia and considered a critical factor for the development of persistent postsurgical pain. Using specific drugs that block the processes of pain sensitization reduces postoperative pain and prevents the development of persistent postoperative pain. This narrative review of the literature describes clinical investigations evaluating different preventative pharmacologic strategies that are routinely used by anesthesiologists in their daily clinical practices for preventing persistent postoperative pain. Nevertheless, further efforts are needed in both basic and clinical science research to identify preclinical models and novel therapeutics targets. There remains a need for more patient numbers in clinical research, for more reliable data, and for the development of the safest and the most effective strategies to limit the incidence of persistent postoperative pain.

Experimental pain models and clinical chronic pain: Is plasticity enough to link them?

1997 ◽  
Vol 20 (3) ◽  
pp. 458-459 ◽  
Author(s):  
Paolo Marchettini ◽  
Marco Lacerenza ◽  
Fabio Formaglio
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Experimental Pain ◽  
Experimental Models ◽  
Basic Information ◽  
Pain Models ◽  
Clinical Conditions

The central hyperexcitability observed in animal models supports a pathophysiological explanation for chronic human pain. Novel information on cholecystokinin (CCK) upregulation offers a rationale for reduced opioid response in neuropathic pain. However, the basic information provided by scientists should not lead clinicians to equate experimental models to chronic human conditions. Clinicians should provide careful reports and attempt to classify pathophysiologically clinical conditions that have so far been grouped generically. [blumberg et al.; coderre & katz; dickenson; wiesenfeld-hallin et al.]

scholarly journals Neuroimmune mechanisms of pain: Basic science and potential therapeutic modulators

2020 ◽  
Vol 48 (3) ◽  
pp. 167-178
Author(s):  
Jessica SY Lim ◽  
Peter CA Kam
Keyword(s):  
Chronic Pain ◽  
Animal Models ◽  
Glial Cells ◽  
Immune Cells ◽  
Animal Studies ◽  
Neuroimmune Interaction ◽  
Proinflammatory Mediators ◽  
Anaesthetic Agents ◽  
Sensory Processes

This narrative review aims to describe the role of peripheral and central immune responses to tissue and nerve damage in animal models, and to discuss the use of immunomodulatory agents in clinical practice and their perioperative implications. Animal models of pain have demonstrated that nerve injury activates immune signalling pathways that drive aberrant sensory processes, resulting in neuropathic and chronic pain. This response involves the innate immune system. T lymphocytes are also recruited. Glial cells surrounding the damaged nerves release cytokines and proinflammatory mediators that activate resident immune cells and recruit circulatory immune cells. Toll-like receptors on the glial cells play a crucial role in the pathogenesis of chronic pain. Animal models indicate an immune mechanism of neuropathic pain. Analgesic drugs and anaesthetic agents have varied effects on the neuroimmune interface. Evidence of a neuroimmune interaction is mainly from animal studies. Human studies are required to evaluate the clinical implications of this neuroimmune interaction.

scholarly journals Neuropathic Pain in Animal Models of Nervous System Autoimmune Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
David H. Tian ◽  
Chamini J. Perera ◽  
Gila Moalem-Taylor
Keyword(s):  
Nervous System ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Autoimmune Diseases ◽  
Experimental Autoimmune Neuritis ◽  
Autoimmune Encephalomyelitis ◽  
Pain Mechanisms ◽  
Sensory Abnormalities ◽  
Underlying Mechanisms ◽  
Experimental Autoimmune

Neuropathic pain is a frequent chronic presentation in autoimmune diseases of the nervous system, such as multiple sclerosis (MS) and Guillain-Barre syndrome (GBS), causing significant individual disablement and suffering. Animal models of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN) mimic many aspects of MS and GBS, respectively, and are well suited to study the pathophysiology of these autoimmune diseases. However, while much attention has been devoted to curative options, research into neuropathic pain mechanisms and relief has been somewhat lacking. Recent studies have demonstrated a variety of sensory abnormalities in different EAE and EAN models, which enable investigations of behavioural changes, underlying mechanisms, and potential pharmacotherapies for neuropathic pain associated with these diseases. This review examines the symptoms, mechanisms, and clinical therapeutic options in these conditions and highlights the value of EAE and EAN animal models for the study of neuropathic pain in MS and GBS.

Quantitative Sensory Testing in Animal Models of Chronic Pain: A Pilot Study

2018 ◽  
Author(s):  
B. Monteiro ◽  
M. Moreau ◽  
C. Otis ◽  
L. De Lorimier ◽  
J. Pelletier ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Pilot Study ◽  
Animal Models ◽  
Quantitative Sensory Testing ◽  
Sensory Testing
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