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Neuropathic Pain in Neurodegenerative Diseases: Pathophysiology and Treatment Advances – Neurology
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<main class="site-main" id="main"> <article id="post-108" class="post-108 post type-post status-publish format-standard has-post-thumbnail hentry category-neurodegenerative-diseases tag-amyotrophic-lateral-sclerosis tag-central-sensitization tag-multiple-sclerosis tag-neurodegenerative-diseases tag-neuropathic-pain tag-non-pharmacological-treatments tag-pain-management tag-pathophysiology tag-pharmacological-treatments" itemtype="https://schema.org/CreativeWork" itemscope> <div class="inside-article"> <div class="featured-image page-header-image-single "> <img width="800" height="419" src="https://neurocare.blog/archive/wp-content/uploads/2024/11/banner-30.jpg" class="attachment-full size-full" alt="" itemprop="image" decoding="async" fetchpriority="high" srcset="https://neurocare.blog/archive/wp-content/uploads/2024/11/banner-30.jpg 800w, https://neurocare.blog/archive/wp-content/uploads/2024/11/banner-30-300x157.jpg 300w, https://neurocare.blog/archive/wp-content/uploads/2024/11/banner-30-768x402.jpg 768w" sizes="(max-width: 800px) 100vw, 800px" /> </div> <header class="entry-header"> <h1 class="entry-title" itemprop="headline">Neuropathic Pain in Neurodegenerative Diseases: Pathophysiology and Treatment Advances</h1> <div class="entry-meta"> <span class="posted-on"><time class="entry-date published" datetime="2024-11-08T18:50:45+05:30" itemprop="datePublished">November 8, 2024</time></span> <span class="byline">by <span class="author vcard" itemprop="author" itemtype="https://schema.org/Person" itemscope><a class="url fn n" href="https://neurocare.blog/archive/author/neurocare/" title="View all posts by neurocare" rel="author" itemprop="url"><span class="author-name" itemprop="name">neurocare</span></a></span></span> </div> </header> <div class="entry-content" itemprop="text"> <p><span style="font-weight: 400;">Neuropathic pain, a chronic and weakening condition, arises from direct rupture or disease affecting the somatosensory nervous system. This type of pain is not barely a symptom but a complex clinical entity that remarkably affects the quality of life in patients , mainly those with neurodegenerative diseases like amyotrophic lateral sclerosis(ALS) and Multiple sclerosis(MS) . The complex pathophysiology of neuropathic pain includes both peripheral and central nervous system mechanisms , paving way to altered neuronal excitability, inflammation and changes in synaptic function . In spite of notable developments in the underlying mechanisms, accurate cure remains uncertain. This article is involved in the pathophysiology of neuropathic pain involved with neurodegenerative diseases and highlights recent developments in its management.</span></p> <h4><b>Pathophysiology of Neuropathic Pain</b></h4> <p><span style="font-weight: 400;">The pathophysiology of neuropathic pain in neurodegenerative diseases is multidisciplinary including both peripheral and central nervous system changes . After nerve damage or degeneration , a series of events occurs at the molecular, cellular and systemic levels leading to pain. </span></p> <h4><b>Peripheral Mechanisms</b></h4> <p><span style="font-weight: 400;">In the peripheral nervous system, nerve injury usually paves way to the release of inflammatory mediators such as cytokines , chemokines and growth factors which sensitize nociceptors, the sensory neurons that transmit pain signals. Additionally changes in ion channel expression, particularly sodium, calcium and potassium channels,contribute to the hyperexcitability of damaged nerves. This hyperexcitability manifests as spontaneous pain or amplifies responses to normally non painful stimuli (allodynia) and increased pain response to painful stimuli ( hyperalgesia).</span></p> <p><span style="font-weight: 400;">One of the important features of neuropathic pain is the criteria of phenotypic switching in which injured sensory neurons alter their neurochemical profile. For instance, after nerve injury, neurons that mainly do not generate some neuropeptides or ion channels may begin to do so, paving way to altered pain signaling routes. Moreover, the sympathetic nervous system can become involved, where adrenergic receptors on non receptors enhance the sensitivity to noradrenaline, exacerbating pain.</span></p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Yearwise Publication Trend on <b>“<a href="https://neurocare.blog/publication-trends/index/neurodegenerative diseases" target="_blank" title="neurodegenerative diseases - yearwise publication trends">neurodegenerative diseases</a>”</b></h2> </div> </div><div class="results-container"><div class="chart-block" style="padding:15px;"> <div class="left"> <div id="results" class="results"></div> </div> <div class="right"> <div class="chart-container"><canvas id="publicationChart"></canvas></div> </div> <div class="keywordsdiv"> <div style="text-align:center;"><b>Find publication trends on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-stats"></span> </div> </div></div></div><div class="inside-article"><style> table { margin: 0 0 1.5em; 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After peripheral nerve injury, enhanced activity in spinal dorsal horn neurons paving way to synaptic plasticity, featured by increased excitatory transmission and lowered inhibitory control. This results in a point where even low level stimuli can generate pain. </span></p> <p><span style="font-weight: 400;">Glial cells, mainly microglia and astrocytes , play an important role in having central sensitization. With nerve injury , these glial cells become activated , releasing pro inflammatory cytokines , chemokines and growth factors that perpetuate neuronal hyperexcitability.Including,the loss of inhibitory interneurons and the downregulation of GABAergic (Gamma – aminobutyric acid – producing) pathways further exacerbate central sensitization.</span></p> <p><span style="font-weight: 400;">Neurodegenerative diseases like ALS and MS, which includes progressive neuronal loss, contribute to the complexity of neuropathic pain. In ALS, for example , the degeneration of motor neurons paves way to both peripheral and central sensitization, while in MS, demyelination and subsequent axonal damage outcomes in abnormal pain processing.</span></p> <h4><b>Clinical Manifestations</b></h4> <p><span style="font-weight: 400;">Neuropathic pain in neurodegenerative diseases is often chronic and resistant to conventional analgesics. Patients may experience a range of symptoms, including burning sensations, electric shock like pain, and aching pain. These symptoms can increase in intensity and may be accompanied by sensory deficits such as numbness or tingling.</span></p> <p><span style="font-weight: 400;">In ALS , neuropathic pain is usually linked to the progressive loss of motor neurons, paving way to muscle wasting, spasticity and joint contractures which leads to pain. In MS, neuropathic pain can arise from lesions in both the central and peripheral nervous systems, with trigeminal neuralgia and Lhermitte’s signal ( a sudden electric shock sensation triggered by neck movement) being main pain syndromes related with the disease.</span></p> <h4><b>Advances in Treatment</b></h4> <p><span style="font-weight: 400;">The control of neuropathic pain in neurodegenerative diseases remains difficult due to the severity of the involved mechanisms and the chronic nature of the pain. However, recent innovations offer hope for more effective treatments.</span></p> <h3><b>Pharmacological Treatments</b></h3> <p><span style="font-weight: 400;">Several classes of drugs are commonly used to manage neuropathic pain, each targeting different aspects of the pain pathway.</span></p> <p><b>Antidepressants</b><span style="font-weight: 400;">: Tricyclic antidepressants (TCAs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are often the basic cure for neuropathic pain. They work by increasing the regulating inhibitory pain pathways in the central nervous system. However, their use in patients with neurodegenerative diseases may be less by side effects, especially in older patients.</span></p> <p><b>Anticonvulsants</b><span style="font-weight: 400;">:Gabapentin and pregabalin are commonly used anticonvulsants that inhibit excitatory neurotransmitter release by blocking voltage gated calcium channels. </span></p> <p><b>Opioids</b><span style="font-weight: 400;">: While opioids are efficient for many types of pain, their use in neuropathic pain is controversial due to the risk of tolerance, dependence, and side effects. They may be considered in cases where other treatments have failed, but long term use should be carefully analyzed.</span></p> <p><b>Topical Agents</b><span style="font-weight: 400;">: Lidocaine patches and capsaicin cream are topical cures that can be used to manage localized neuropathic pain. Lidocaine works by blocking sodium channels, thereby reducing neuronal excitability, a neuropeptide involved in pain transmission.</span></p> <p><b>NMDA Receptor Antagonists</b><span style="font-weight: 400;">: The N-methyl-D-aspartate (NMDA) receptor plays a crucial role in central sensitization. Ketamine, an NMDA receptor antagonist, has been shown to reduce pain in patients with neuropathic pain, although its use is often limited to refractory cases due to its psychotropic side effects.</span></p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Recent Publications on <b>“<a href="https://neurocare.blog/recent-publications/index/neurodegenerative diseases" target="_blank" rel="noopener" title="neurodegenerative diseases - yearwise publication list">neurodegenerative diseases</a>”</b></h2> </div> </div> <div class="pb-main"><div class="article-scroll"><div id="results_recent" class="results"></div></div><div class="keywordsdiv" style="margin: 0px 15px;margin-top:20px;"> <div style="text-align:center;"><b>Find publications on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-papers"></span> </div></div></div><div class="inside-article"> <style> .pb-main{ border: solid 1px #ccc; 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Alzheimer\\\\\\'s disease is Type 3 Diabetes: Evidences from Bench to Bedside.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38955264", "publishedDate": "2024" }, { "title": "No causal relationship between serum urate and neurodegenerative diseases: A Mendelian randomization study.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38955238", "publishedDate": "2024" }, { "title": "The lipid side of unfolded protein response.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38844203", "publishedDate": "2024" }, { "title": "Aerobic Exercise Ameliorates Cognitive Disorder and Declined Oxidative Stress via Modulating the Nrf2 Signaling Pathway in D-galactose Induced Aging Mouse Model.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38839706", "publishedDate": "2024" }, { "title": "CSF neurosecretory proteins VGF and neuroserpin in patients with Alzheimer\\\\\\'s and Lewy body diseases.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38850771", "publishedDate": "2024" }, { "title": "No trend to rising rates: A review of Parkinson\\\\\\'s prevalence studies in the United Kingdom.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38876845", "publishedDate": "2024" }, { "title": "Unveiling brain disorders using liquid biopsy and Raman spectroscopy.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38845582", "publishedDate": "2024" } ]; var keywordsArray = ["Neuropathic pain","neurodegenerative diseases","amyotrophic lateral sclerosis","multiple sclerosis","pathophysiology","pain management","central sensitization","pharmacological treatments","non-pharmacological treatments"]; displayResults_recent(recent_papers); displayKeywordPapers(keywordsArray); // function stripslashes(str) { // if (typeof str === 'string') { // return str.replace(/\/g, ''); // } // } </script></p> <h3><b>Non-Pharmacological Treatments</b></h3> <p><span style="font-weight: 400;">In addition to pharmacological interventions, non pharmacological treatments play an essential role in managing neuropathic pain in neurodegenerative diseases.</span></p> <p><b>Physical Therapy</b><span style="font-weight: 400;">: Physical therapy can help manage pain by improving muscle strength, flexibility, and mobility, thereby reducing the mechanical factors contributing to pain.</span></p> <p><b>Neuromodulation</b><span style="font-weight: 400;">: Techniques such as spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS) are used to modulate pain signals and provide relief in certain cases of neuropathic pain. These approaches are particularly useful when pain is localized and refractory to other treatments.</span></p> <h4><b>Future Directions</b></h4> <p><span style="font-weight: 400;">upcoming research into the mechanisms of neuropathic pain is routing the way for novel therapeutic methods. One promising area of research is the innovation of biologic agents that target specific pain pathways, such as monoclonal antibodies against nerve growth factor (NGF). Gene therapy and stem cell therapy also hold capability for routing the underlying causes of neurodegenerative diseases and their related pain syndromes.</span></p> <p><span style="font-weight: 400;">Additionally, improvements in neuroimaging techniques, such as functional MRI and PET scans, are increasing our understanding of the central mechanisms involved in neuropathic pain, leading to more targeted and personalized treatment approaches.</span></p> <h4><b>Conclusion</b></h4> <p><span style="font-weight: 400;">Neuropathic pain in neurodegenerative diseases is a difficult and challenging condition that importantly impacts patients quality of life. While important innovations have been made in understanding the underlying mechanisms and developing new treatments, much remains to be done. A multidisciplinary approach, combining pharmacological and non pharmacological treatments, offers the best way for effective pain management. As research continues to uncover the intricacies of neuropathic pain, new and more effective therapies will likely evolve, offering hope for enhanced results in patients with neurodegenerative diseases.</span></p> <p></p> <h4><strong>References</strong></h4> <ol> <li>H Vranken, J., 2012. <a href="https://www.ingentaconnect.com/content/ben/cnsamc/2012/00000012/00000004/art00006">Elucidation of pathophysiology and treatment of neuropathic pain.</a> <i>Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Central Nervous System Agents)</i>, <i>12</i>(4), pp.304-314.</li> <li>Bäumer, D., Talbot, K. and Turner, M.R., 2014. <a href="https://journals.sagepub.com/doi/full/10.1177/0141076813511451">Advances in motor neurone disease.</a> <i>Journal of the Royal Society of Medicine</i>, <i>107</i>(1), pp.14-21.</li> <li>O’Driscoll, B.R., Howard, L.S., Earis, J. and Mak, V., 2017. <a href="https://bmjopenrespres.bmj.com/content/4/1/e000170?fbclid=IwAR0X2cxx3j_0Jz2XxKBLT-Edgl5GXftaJC0lIR_YnlJBY8IChLAXue7LV7c">British Thoracic Society Guideline for oxygen use in adults in healthcare and emergency settings.</a> <i>BMJ open respiratory research</i>, <i>4</i>(1), p.e000170.</li> <li>Brettschneider, J., Kurent, J. and Ludolph, A., 2013. <a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005226.pub3/full">Drug therapy for pain in amyotrophic lateral sclerosis or motor neuron disease.</a> <i>Cochrane Database of Systematic Reviews</i>, (6).</li> <li>Rafiq, M.K., Proctor, A.R., McDermott, C.J. and Shaw, P.J., 2012. <a href="https://pn.bmj.com/content/12/3/166.short">Respiratory management of motor neurone disease: a review of current practice and new developments.</a> <i>Practical neurology</i>, <i>12</i>(3), pp.166-176.</li> <li>Tomik, B. and Guiloff, R.J., 2010. <a href="https://www.tandfonline.com/doi/abs/10.3109/17482960802379004">Dysarthria in amyotrophic lateral sclerosis: A review. </a><i>Amyotrophic Lateral Sclerosis</i>, <i>11</i>(1-2), pp.4-15.</li> <li>Belić, M., Bobić, V., Badža, M., Šolaja, N., Đurić-Jovičić, M. and Kostić, V.S., 2019. <a href="https://www.sciencedirect.com/science/article/abs/pii/S0303846719302380">Artificial intelligence for assisting diagnostics and assessment of Parkinson’s disease—A review.</a> <i>Clinical neurology and neurosurgery</i>, <i>184</i>, p.105442.</li> </ol> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Top Experts on “<b style="color:#000;font-size:22px;">neurodegenerative diseases</b>“</h2> </div> </div><div class="author-main"><div id="results_author"></div><div style="text-align: center;"><a class="register-button" href="https://neurocare.blog/expert-search" target="_blank" rel="noopener">Find experts on any field</a></div></div><div class="inside-article" style="background: none;border: none;box-shadow: none;margin-top: -70px;"> <style> .author-block { padding: 15px; 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", "email": "tasano@hiroshima-u.ac.jp", "slug_tail": "t-asano" } }; //console.log(authors_data); displayResults_author(authors_data); var keywordsArray = ["Neuropathic pain","neurodegenerative diseases","amyotrophic lateral sclerosis","multiple sclerosis","pathophysiology","pain management","central sensitization","pharmacological treatments","non-pharmacological treatments"]; displayKeywordAuthors(keywordsArray); </script></p> </div> <footer class="entry-meta" aria-label="Entry meta"> <span class="cat-links"><span class="gp-icon icon-categories"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M0 112c0-26.51 21.49-48 48-48h110.014a48 48 0 0143.592 27.907l12.349 26.791A16 16 0 00228.486 128H464c26.51 0 48 21.49 48 48v224c0 26.51-21.49 48-48 48H48c-26.51 0-48-21.49-48-48V112z" /></svg></span><span class="screen-reader-text">Categories </span><a href="https://neurocare.blog/archive/category/neurodegenerative-diseases/" 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