Research progress of mechanisms and drug therapy for neuropathic pain
TL;DR: The anatomical physiology, underlying mechanisms of neuropathic pain is overviewed to provide a better understanding in the initiation, development, maintenance, and modulation of this pervasive disease, and inspire research in the unclear mechanisms as well as potential targets.
About: This article is published in Life Sciences.The article was published on 2017-12-01. It has received 46 citations till now. The article focuses on the topics: Neuropathic pain.
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01 Jan 1909
TL;DR: Application of Principles of Steady-State Kinetics to the Estimation of Brain Acetyicholine Turnover Rate: Effects of Oxotremorine and Physostigmine and the Relationship between Nitro Group Reduction and the Intestinal Microflora.
774 citations
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01 Jan 1947
109 citations
TL;DR: The characteristics and clinical applications of dexmedetomidine are mainly focused on, especially the role of dex medetomidin in the nervous system and the use of DexmedetOMidine in the relief of neuropathic pain.
Abstract: Dexmedetomidin is a new-generation, highly selective α2 adrenergic receptor agonist with a large number of advantages, including its sedative and analgesic properties, its ability to inhibit sympathetic nerves, its reduced anesthetic dosage, its hemodynamic stability, its mild respiratory depression abilities, and its ability to improve postoperative recognition. Its safety and effectiveness, as well as its ability to provide a certain degree of comfort to patients, make it a useful anesthetic adjuvant for a wide range of clinical applications. For example, dexmedetomidine is commonly used in patients undergoing general anesthesia, and it also exerts sedative effects during tracheal intubation or mechanical ventilation in intensive care unit patients. In recent years, with the deepening of clinical research on dexmedetomidine, the drug is still applied in the treatment of spastic pain, myofascial pain, neuropathic pain, complex pain syndrome, and chronic headache, as well as for multimodal analgesia. However, we must note that the appropriateness of patient and dose selection should be given attention when using this drug; furthermore, patients should be observed for adverse reactions such as hypotension and bradycardia. Therefore, the safety and effectiveness of this drug for long-term use remain to be studied. In addition, basic experimental studies have also found that dexmedetomidine can protect important organs, such as the brain, heart, kidney, liver, and lung, through various mechanisms, such as antisympathetic effects, the inhibition of apoptosis and oxidative stress, and a reduction in the inflammatory response. Moreover, the neuroprotective properties of dexmedetomidine have received the most attention from scholars. Hence, in this review, we mainly focus on the characteristics and clinical applications of dexmedetomidine, especially the role of dexmedetomidine in the nervous system and the use of dexmedetomidine in the relief of neuropathic pain.
44 citations
Cites background from "Research progress of mechanisms and..."
...Currently, the incidence of neuropathic pain is high, and treatment is difficult, which seriously affects the work and quality of life of patients (Vranken, 2012; Yan et al., 2017)....
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TL;DR: A comprehensive review of the latest findings on VIPN in terms of symptoms, risk factors, potential mechanisms, and prevention and treatment measures was performed to help clinicians better understand and accurately diagnose VIPN, select appropriate intervention measures and reduce the damage to cancer patients.
Abstract: Vincristine (VCR), an alkaloid extracted from vinca, is often used in combination with other chemotherapeutic drugs to treat a variety of cancers, such as acute lymphoblastic leukaemia (ALL), malignant lymphoma, and neuroblastoma. However, VCR possesses dose-dependent neurotoxicity, which is the main factor restricting its application. Vincristine-induced peripheral neuropathy (VIPN) not only limits the dose of VCR and leads to the discontinuation of treatment but also triggers serious damage to the physical and mental health of patients. In addition, VIPN brings huge healthcare costs to patients and society. Individuals with VIPN often exhibit mechanical allodynia, sensory/tactile disorders, and numbness in the hands and feet. Unfortunately, VIPN is easily ignored due to its variable symptoms, which gives rise to insufficient research on the aetiology and pathogenesis of this disease, thereby resulting in a lack of appropriate preventive and therapeutic management. We performed a comprehensive review of the latest findings on VIPN in terms of symptoms, risk factors, potential mechanisms, and prevention and treatment measures. The purpose was to help clinicians better understand and accurately diagnose VIPN, select appropriate intervention measures and reduce the damage to cancer patients.
36 citations
References
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TL;DR: This guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.
Abstract: Importance Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose. Objective To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. Process The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category. Evidence Synthesis Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (≥1 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects. Recommendations There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone. Conclusions and Relevance The guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.
3,935 citations
"Research progress of mechanisms and..." refers background in this paper
...Gabapentinoids (Gabapentin and pregabalin (Lyrica)) are recommended as first-line agents for neuropathic pain by the Center for Disease Control and Prevention (CDC) (Dowell et al. , 2016)....
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TL;DR: Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.
3,394 citations
"Research progress of mechanisms and..." refers background in this paper
...…tropomyosin receptor kinase A (TrkA) receptors that bind to nerve growth factor (Chandran et al. ), whereas nonpeptidergic C fibers are mainly associated with expression of nonpeptide substance such as c-Ret neurotrophin receptors (Basbaum et al., 2009, Benarroch, 2016, Lewin and Nykjaer, 2014)....
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...Apart from inflammation, hemangiectasis or sympathetic excitation can also aid in release of these agents (Ballantyne et al. , 2006, Basbaum et al., 2009) (Fig 2)....
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...When noxious stimuli such as intense thermal, mechanical, and chemical stimuli are detected by the nervous system, acute pain is generated, rendering people conscious of the deleterious conditions, thus engaging appropriate behaviors to avoid being injured (Basbaum et al. , 2009)....
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TL;DR: A grading system of definite, probable, and possible neuropathic pain is proposed, which includes the grade possible, which can only be regarded as a working hypothesis, and the grades probable and definite, which require confirmatory evidence from a neurologic examination.
Abstract: Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes.
2,342 citations
University of Rochester1, University of Wisconsin-Madison2, University of Pennsylvania3, Aarhus University Hospital4, Helsinki University Central Hospital5, University of Washington6, University of California, San Francisco7, University of Liverpool8, Beth Israel Medical Center9, Imperial College London10, Oregon Health & Science University11, University of Mainz12, University of California, San Diego13
TL;DR: Patients with neuropathic pain are challenging to manage and evidence‐based clinical recommendations for pharmacologic management are needed, and medications should be individualized, considering side effects, potential beneficial or deleterious effects on comorbidities, and whether prompt onset of pain relief is necessary.
Abstract: Patients with neuropathic pain (NP) are challenging to manage and evidence-based clinical recommendations for pharmacologic management are needed. Systematic literature reviews, randomized clinical trials, and existing guidelines were evaluated at a consensus meeting. Medications were considered for recommendation if their efficacy was supported by at least one methodologically-sound, randomized clinical trial (RCT) demonstrating superiority to placebo or a relevant comparison treatment. Recommendations were based on the amount and consistency of evidence, degree of efficacy, safety, and clinical experience of the authors. Available RCTs typically evaluated chronic NP of moderate to severe intensity. Recommended first-line treatments include certain antidepressants (i.e., tricyclic antidepressants and dual reuptake inhibitors of both serotonin and norepinephrine), calcium channel alpha2-delta ligands (i.e., gabapentin and pregabalin), and topical lidocaine. Opioid analgesics and tramadol are recommended as generally second-line treatments that can be considered for first-line use in select clinical circumstances. Other medications that would generally be used as third-line treatments but that could also be used as second-line treatments in some circumstances include certain antiepileptic and antidepressant medications, mexiletine, N-methyl-D-aspartate receptor antagonists, and topical capsaicin. Medication selection should be individualized, considering side effects, potential beneficial or deleterious effects on comorbidities, and whether prompt onset of pain relief is necessary. To date, no medications have demonstrated efficacy in lumbosacral radiculopathy, which is probably the most common type of NP. Long-term studies, head-to-head comparisons between medications, studies involving combinations of medications, and RCTs examining treatment of central NP are lacking and should be a priority for future research.
1,962 citations
"Research progress of mechanisms and..." refers background in this paper
...The most frequent adverse effects of gabapentinoids include dizziness, somnolence, peripheral edema, asthenia, and headache (Dworkin et al. , 2007), while gabapentinoids can also induce a nontrivial side AC C EP TE D M AN U SC R IP T effect - cognitive difficulty....
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