Articles: neuralgia.
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Blood nerve barrier disruption and edema are common in neuropathic pain as well as in complex regional pain syndrome (CRPS). MicroRNAs (miRNA) are epigenetic multitarget switches controlling neuronal and non-neuronal cells in pain. The miR-183 complex attenuates hyperexcitability in nociceptors, but additional non-neuronal effects via transcription factors could contribute as well. ⋯ Cellular stress also compromised the microvascular barrier which was rescued either by miR-183 mimic via FoxO1 repression or by prior silencing of Foxo1. PERSPECTIVE: Low miR-183 leading to barrier impairment via FoxO1 and subsequent claudin-5 suppression is a new aspect in the pathophysiology of CRPS and neuropathic pain. This pathway might help untangle the wide symptomatic range of CRPS and nurture further research into miRNA mimics or FoxO1 inhibitors.
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This narrative review aims to summarize advances in the field of small fiber neuropathy made over the last decade, with emphasis on novel research highlighting the distinctive features of SFN. ⋯ While the management of SFNs is ideally aimed at treating the underlying cause, most patients will require pain control via multiple, concurrent therapies. Herein, we highlight the most up-to-date information for diagnosis, medication management, interventional management, and novel therapies on the horizon. Despite the prevalence of small fiber neuropathies, there is no clear consensus on guidelines specific for the treatment of SFN. Despite the lack of specific guidelines for SFN treatment, the most recent general neuropathic pain guidelines are based on Cochrane studies and randomized controlled trials (RCTs) which have individually examined therapies used for the more commonly studied SFNs, such as painful diabetic neuropathy and HIV neuropathy. The recommendations from current guidelines are based on variables such as number needed to treat (NNT), safety, ease of use, and effect on quality of life.
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Randomized Controlled Trial
A randomized, double-blind, placebo-controlled trial of ISC 17536, an oral inhibitor of TRPA1, in patients with painful diabetic peripheral neuropathy: impact of preserved small nerve fiber function.
Patients with chronic pain syndromes, such as those with painful peripheral neuropathy due to diabetes mellitus, have limited treatment options and suffer ongoing attrition of their quality of life. Safer and more effective treatment options are needed. One therapeutic approach encompasses phenotypic characterization of the neuropathic pain subtype, combined with the selection of agents that act on relevant mechanisms. ⋯ However, statistically significant and clinically meaningful improvement in pain were seen with ISC 17536 in an exploratory hypothesis-generating subpopulation of patients with preserved small nerve fiber function defined by quantitative sensory testing. These results may provide a mechanistic basis for targeted therapy in specific pain phenotypes in line with current approaches of "precision medicine" or personalized pain therapeutics. The hypothesis is planned to be tested in a larger phase 2 study.
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Many Americans cope with painful diabetic neuropathy (DN) as a sequela of high rates of diabetes mellitus in the US population. Appropriate management of this complex, debilitating chronic pain condition requires thorough evaluation through a biopsychosocial framework. This review aims to synthesize findings from original research studies and analyze the psychological factors that influence the experience of, and treatments for, DN pain. ⋯ Existing clinical literature suggests a wide breadth of psychological factors impacting DN pain. One research study detailed the demographic characteristics of DN patients most likely to have significant anxiety or depressive symptoms, and have emotional distress adversely impacting their response to therapies. A retrospective study demonstrated a correlation between patients' mindfulness-based stress reduction and improvement in DN pain severity. In addtion, a small-scale, randomized controlled pilot study supported cognitive-behavioral therapy as a superior intervention to conventional medical treatments in reducing DN patients' pain severity and pain interference, even when not accompanied by significant improvement in depressive symptoms. This review of investigations into psychological factors implicated in DN pain suggests that diagnosable mental health conditions as well as discrete, adverse thinking processes both exert significant influences on DN pain. This review further brings attention to the beneficial impact that psychotherapeutic modalities can have on DN pain.