Painful diabetic neuropathy: an update

Kaur, Sharonjeet; Pandhi, P; Dutta, Pinaki

doi:10.5214/ans.0972.7531.1118409

Cited by 83 publications

(62 citation statements)

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“…NSAIDs have shown narrow therapeutic benefits, 73,74 but more work is needed to ascertain their benefits along with other pharmacological agents. 75 As a major inflammatory mediator in the diabetic milieu, COX-2 is implicated in diabetic neuropathy, and a more targeted approach to therapy will certainly prove more effective. Unlike nonselective NSAIDs, 76,77 COX-2 inhibitors show promise, with protection against nerve dysfunction and nerve fiber loss 78 as well as attenuated mechanical hyperalgesia 79 in experimental diabetes.…”

Section: Pge 2 In Hypertension and Diabetesmentioning

confidence: 99%

PGE2, Kidney Disease, and Cardiovascular Risk

Nasrallah

Hassouneh

Hébert

2016

Journal of the American Society of Nephrology

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An important measure of cardiovascular health is obtained by evaluating the global cardiovascular risk, which comprises a number of factors, including hypertension and type 2 diabetes, the leading causes of illness and death in the world, as well as the metabolic syndrome. Altered immunity, inflammation, and oxidative stress underlie many of the changes associated with cardiovascular disease, diabetes, and the metabolic syndrome, and recent efforts have begun to elucidate the contribution of PGE 2 in these events. This review summarizes the role of PGE 2 in kidney disease outcomes that accelerate cardiovascular disease, highlights the role of cyclooxygenase-2/microsomal PGE synthase 1/PGE 2 signaling in hypertension and diabetes, and outlines the contribution of PGE 2 to other aspects of the metabolic syndrome, particularly abdominal adiposity, dyslipidemia, and atherogenesis. A clearer understanding of the role of PGE 2 could lead to new avenues to improve therapeutic options and disease management strategies. 27: 666-676, 201627: 666-676, . doi: 10.1681 Accelerated cardiovascular disease is the leading cause of mortality in patients with kidney disease. 1,2 This implies that kidney disease has a major effect on global cardiovascular risk, affecting fluid (volume, BP), electrolyte, and acid base balance, among many other cardiovascular risk factors. In fact, renal transplantation ameliorates cardiovascular risk, improves quality of life, and reduces mortality. 2 PGs are important homeostatic regulators of kidney function. PGE 2 is the major product of cyclooxygenase (COX)-2 and microsomal PGE synthase 1 (mPGES1), and both of these enzymes are elevated in renal diseases. [3][4][5][6][7][8][9][10] PGE 2 binds four EP receptors (EP 1-4 ) to activate G protein signaling responses. Figure 1 illustrates the COX pathway leading to PGE 2 , as well as its target receptors. These receptors are often coexpressed in cells and usually have opposing effects (protective and harmful). PGE 2 acting on EP can alter vascular tone and influence renal blood flow and hemodynamics. 11-15 PGE 2 also stimulates the macula densa to activate the renin-angiotensin-aldosterone system, a key mediator of kidney injury. [16][17][18][19] Inflammatory, immune, and oxidative stress responses are influenced by PGE 2 , which are reported to alter growth, fibrosis, and apoptosis in renal cells. 20-26 PGE 2 also contributes to disturbances in collecting duct salt and water transport in polyuric diseases, 19,[27][28][29] and b cell defects in sodium and potassium handling associated with type I distal renal tubule acidosis. 30 PGE 2 /EP 4 also compensates for the loss of vasopressin V2 receptors in mouse diabetes insipidus. 28 Although attempts to block PGE 2 using COX-2 or mPGES1 inhibitors have failed, selective inhibition of EP receptors may prove to be quite useful in controlling the deleterious effects of COX-2/mPGES1/PGE 2 , while leaving the protective responses intact. EP 1 mediates many of the pathologic effects of PGE 2 in kidne...

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Section: Pge 2 In Hypertension and Diabetesmentioning

confidence: 99%

PGE2, Kidney Disease, and Cardiovascular Risk

Nasrallah

Hassouneh

Hébert

2016

Journal of the American Society of Nephrology

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“…Although several randomized controlled trials have shown that TCAs are effective for patients with post‐herpetic neuralgia and diabetic peripheral neuropathy, there are concerns with adverse effects such as orthostatic hypotension, urinary retention and drowsiness, so it may not be the appropriate choice for elderly patients . There are also concerns with the potential of TCAs to predispose patients to cardiac arrhythmias and heart block . Besides TCAs, other therapies that have been evaluated include opioids, anticonvulsants and topical treatments (lidocaine patch, capsaicin and ketamine).…”

Section: What Is Known and Objectivementioning

confidence: 99%

Systematic review of topical amitriptyline for the treatment of neuropathic pain

Thompson

Brooks

2015

J Clin Pharm Ther

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Summary What is known and objective Neuropathic pain is a common disorder for which patients seek treatment. The most common causes of neuropathic pain are diabetes, herpetic infection and chemotherapy‐induced neuropathy. Oral administration of amitriptyline has traditionally been used for treating neuropathic pain; however, it has dose‐related anticholinergic effects, which may limit its use in some individuals. Pharmacotherapeutic agents that are commonly used to treat neuropathic pain include antidepressants, anticonvulsants, opioids and opioid‐like substances, and topical medications. The objective of this paper is to review the effectiveness of topical amitriptyline in patients with neuropathic pain. Methods We utilized the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines to provide a systematic and transparent reporting method. The literature search was performed using PubMed (1966 through October 2014) applying the MeSH ‘amitriptyline’ and ‘drug administration, topical’ and ‘neuropathy’. Web of Science (1945 through October 2014) was searched using the text words ‘amitriptyline’ and ‘neuropathy’. Bibliographies of retrieved articles were scanned for relevant articles. Cochrane databases were also searched for methods to treat neuropathic pain. Broad subject headings, including ‘neuropathic pain’, were used to search the database for review articles. All data sources in English and in humans were considered for inclusion. Results and discussion Topical application of amitriptyline has the theoretical advantage of local effects with fewer systemic side effects. The clinical trials and case reports describing the use of topical amitriptyline we reviewed show mixed results concerning the efficacy and the presence of adverse reactions. Controlled clinical trials reveal that topical amitriptyline is not effective in treating neuropathic pain. The uncontrolled clinical trials did support efficacy of topical amitriptyline; however, the data from these trials may be biased due to the nature of the study design. Finally, there have been several case reports that claim patients achieved pain relief with the use of topical amitriptyline. Data from these cases are limited due to the fact that there were no controls to which the amitriptyline treatments could be compared, and the majority of the patients in these cases were on other analgesics. What is new and conclusion Although there are reports that describe the benefits of topical amitriptyline for neuropathic pain, data from evidence‐based controlled clinical trials do not support efficacy in patients who use topical amitriptyline for neuropathic pain control.

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“…Oxidative stress arises in the hyperglycemic state from an increased production of reactive oxygen species, which is due to the auto-oxidation of the excess glucose and a failure in antioxidant mechanisms [60]. These oxygen-free radicals mediate endothelial dysfunction by inhibiting nitric oxide, leading to ischemic nerve damage.…”

Section: α-Lipoic Acidmentioning

confidence: 99%

Treating Diabetic Neuropathy: Present Strategies and Emerging Solutions

Javed¹,

Alam²,

Malik³

2015

Rev Diabet Stud

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■ AbstractDiabetic peripheral neuropathies (DPN) are a heterogeneous group of disorders caused by neuronal dysfunction in patients with diabetes. They have differing clinical courses, distributions, fiber involvement (large or small), and pathophysiology. These complications are associated with increased morbidity, distress, and healthcare costs. Approximately 50% of patients with diabetes develop peripheral neuropathy, and the projected rise in the global burden of diabetes is spurring an increase in neuropathy. Distal symmetrical polyneuropathy (DSPN) with painful diabetic neuropathy, occurring in around 20% of diabetes patients, and diabetic autonomic neuropathy (DAN) are the most common manifestations of DPN. Optimal glucose control represents the only broadly accepted therapeutic option though evidence of its benefit in type 2 diabetes is unclear. A number of symptomatic treatments are recommended in clinical guidelines for the management of painful DPN, including antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids, and topical agents such as capsaicin. However, monotherapy is frequently not effective in achieving complete resolution of pain in DPN. There is a growing need for head-to-head studies of different single-drug and combination pharmacotherapies. Due to the ubiquity of autonomic innervation in the body, DAN causes a plethora of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. The current treatment of DAN is largely symptomatic, and does not correct the underlying autonomic nerve deficit. A number of novel potential candidates, including erythropoietin analogues, angiotensin II receptor type 2 antagonists, and sodium channel blockers are currently being evaluated in phase II clinical trials.

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Painful diabetic neuropathy: an update

Cited by 83 publications

References 1 publication

PGE2, Kidney Disease, and Cardiovascular Risk

PGE2, Kidney Disease, and Cardiovascular Risk

Systematic review of topical amitriptyline for the treatment of neuropathic pain

Treating Diabetic Neuropathy: Present Strategies and Emerging Solutions

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