Painful diabetic polyneuropathy

Background and aims Preclinical data suggest that the chemokine receptor 2 (CCR2) is involved in the pathophysiology of neuropathic pain through modulation of neuronal excitability, synaptic transmission and activation of spinal cord microglia. CCR2-antagonists have shown to be effective in preclinical models of neuropathic pain. The aim of this study was to evaluate the analgesic efficacy, safety and tolerability of a novel CCR2-antagonist, AZD2423, in patients with painful diabetic neuropathy (PDN). Methods This was a double-blind, randomized, parallel-group, multi-center study in patients with symmetric distal sensory polyneuropathy due to type 1 or 2 diabetes and duration of neuropathic pain between 3 months and 5 years...

Background Neuropathic pain is usually treated with antidepressants and anticonvulsant. The use of systemic treatment is, however, limited due to poor tolerability and low efficacy. Qutenza, a topical capsaicin patch (8%), is a relatively new treatment for patients with peripheral neuropathic pain (PNP) conditions. The indication for using topical capsaicin treatment is peripheral neuropathic pain in patients without diabetes. Aim To describe the use of topical capsaicin treatment in a pain clinic in patients with PNP...

BACKGROUNDS: Patients with diabetic polyneuropathy commonly suffer from ongoing burning pain and dynamic mechanical allodynia. In this clinical and skin biopsy study, we aimed at assessing how intraepidermal regenerating nerve sprouts are associated with these two types of pain. METHODS: We consecutively enrolled 85 patients with diabetic polyneuropathy. All patients underwent skin biopsy at the distal leg. Intraepidermal nerve fibres were immunostained with the anti-protein gene product 9...

Background and aims Painful polyneuropathy (PPN) is a disabling complication of diabetes. This study aims to determine its prevalence and relationship with Quality of Life (QoL) in a nationwide prospective cohort of incident recently diagnosed Danish type 2 diabetic patients. Methods We sent a detailed questionnaire on neuropathy, pain and QoL to 6726 patients prospectively enrolled from general practitioners and hospital specialist outpatient clinics into the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort...

OBJECTIVE: To identify the risk factors for foot ulceration through the tracing of diabetic peripheral neuropathy and peripheral arterial disease in individuals with type I and II diabetes, who were assisted in reference centers of the Federal District, Brazil. METHOD: a cross-sectional and analytical study, with the assessment of 117 individuals in outpatient clinics of the Federal District. Continuous variables were compared through Mann-Whitney test, and categorized variables, through Chi-square test for univariate analysis and Logistics regression test for multivariate analysis...

Diabetes mellitus is the leading cause of polyneuropathy in the Western world. Diabetic neuropathy is a frequent complication of diabetes and may have great clinical transcendence due to pain and possible ulceration of the lower extremities. It is also a relevant cause of morbidity and mortality in patients with diabetes. Although the cause of polyneuropathy in patients with diabetes is only partially known, it has been associated with chronic hyperglycemia suggesting the possible etiopathogenic implication of advanced glycosylation end products...

BACKGROUND: Burrowing is a rodent behavior validated as a robust and reproducible outcome measure to infer the global effect of pain in several inflammatory pain models. However, less is known about the effect of analgesics on burrowing in neuropathic pain models and no studies have determined burrowing performance in models of diabetes-associated neuropathic pain. OBJECTIVE: To compare the sensitivity of the burrowing assay in different neuropathic pain models: mononeuropathic pain and diabetic polyneuropathy...

OBJECTIVE: We studied the performance of a 15-item, health-related quality-of-life polyneuropathy scale in the clinic setting in patients with diabetic distal sensorimotor polyneuropathy (DSPN). METHODS: Patients with DSPN from 11 academic sites completed a total of 231 Chronic Acquired Polyneuropathy Patient-Reported Index (CAPPRI) scales during their clinic visits. Conventional and modern psychometric analyses were performed on the completed forms. RESULTS: Conventional and modern analyses generally indicated excellent psychometric properties of the CAPPRI in patients with DSPN...

INTRODUCTION: Sex and gender play roles in the pain experience, such that pain is more frequent in women. Explanations for this observation range from factors related to biological sex to those related to psychosocial gender. OBJECTIVES: To explore neuropathic pain characteristics in females with diabetes with and without established polyneuropathy. METHODS: We compared the presence and intensity of pain in males and females in 2 separate cohorts of patients with type II diabetes, with and without established diabetic polyneuropathy...

AIMS: To evaluate the feasibility of a one-stop microvascular screening service for the early diagnosis of diabetic distal symmetrical polyneuropathy, painful distal symmetrical polyneuropathy and the at-risk diabetic foot. METHODS: People with diabetes attending retinal screening in hospital and community settings had their feet examined by a podiatrist. Assessment included: Toronto Clinical Neuropathy Score evaluation; a 10-g monofilament test; and two validated, objective and quick measures of neuropathy obtained using the point-of-care devices 'DPN-Check', a hand-held device that measures sural nerve conduction velocity and amplitude, and 'Sudoscan', a device that measures sudomotor function...

Background: Familial transthyretin amyloidosis is a life-threatening disease presenting with sensorimotor and autonomic polyneuropathy. Delayed diagnosis has a detrimental effect on treatment and prognosis. To facilitate diagnosis, we analyzed data patterns of patients with transthyretin familial amyloid polyneuropathy (TTR-FAP) and compared them to polyneuropathies of different etiology for clinical and electrophysiological discriminators. Methods: Twenty-four patients with TTR-FAP and 48 patients with diabetic polyneuropathy (dPNP) were investigated (neurological impairment score NIS; neurological disability score NDS) in a cross-sectional design...

Tapentadol is an analgesic that acts as an agonist of µ opioid receptors (MOR) and that inhibits noradrenaline reuptake. Data from healthy rats show that tapentadol inhibits neuronal activity in the locus coeruleus (LC), a nucleus regulated by both the noradrenergic and opioid systems. Thus, we set out to investigate the effect of tapentadol on LC activity in streptozotocin (STZ)-induced diabetic rats, a model of diabetic polyneuropathy, by analyzing single-unit extracellular recordings of LC neurons. Four weeks after inducing diabetes, tapentadol dose-response curves were obtained from animals pre-treated with RX821002 or naloxone (alpha2-adrenoceptors and opioid receptors antagonists, respectively)...

Small fiber neuropathy (SFN) is a common feature of many inflammatory diseases, often presenting with pain and disability. SFN is diagnosed using symptoms, thermal threshold testing, and intra-epidermal nerve fiber quantification. Corneal confocal microscopy (CCM) is an ophthalmic imaging technique which non-invasively quantifies corneal nerve fiber (CNF) density, branch density and length, and has comparable diagnostic and superior ability to identify nerve regeneration compared to skin biopsy. CNF size (width and area) depends upon the number of fibers within each nerve, as well as pathology (e...

OBJECTIVES: This study utilizes a model of long-term spinal cord stimulation (SCS) in experimental painful diabetic polyneuropathy (PDPN) to investigate the behavioral response during and after four weeks of SCS (12 hours/day). Second, we investigated the effect of long-term SCS on peripheral cutaneous blood perfusion in experimental PDPN. METHODS: Mechanical sensitivity was assessed in streptozotocin induced diabetic rats (n = 50) with von Frey analysis. Hypersensitive rats (n = 24) were implanted with an internal SCS battery, coupled to an SCS electrode covering spinal levels L2-L5...

AIMS: We conducted a nationwide educational initiative to determine the prevalence and risk factors of diagnosed and undiagnosed painful and painless distal sensory polyneuropathy (DSPN). METHODS: Among 1850 participants, 781 had no history of diabetes (ND), 126 had type 1 diabetes (T1D), and 943 had type 2 diabetes (T2D). Painful DSPN was defined as polyneuropathy detected by bedside tests with pain and/or burning in the feet, while painless DSPN was defined as polyneuropathy with paresthesias, numbness, or absence of symptoms...

BACKGROUND: Polyneuropathies (peripheral neuropathies) are the most common type of disorder of the peripheral nervous system in adults, and specifically in the elderly, with an estimated prevalence of 5-8%, depending on age. The options for treatment depend on the cause, which should therefore be identified as precisely as possible by an appropriate diagnostic evaluation. METHODS: This review is based on the current guidelines and on large-scale cohort studies and randomized, controlled trials published from 2000 to 2017, with an emphasis on non-hereditary types of polyneuropathy, that were retrieved by a selective search in PubMed...

The descending pain modulatory system represents one of the oldest and most fundamentally important neurophysiological mechanisms relevant to pain. Extensive work in animals and humans has shown how a functional imbalance between the facilitatory and inhibitory components is linked to exacerbation and maintenance of persistent pain states. Forward translation of these findings into clinical populations is needed to verify the relevance of this imbalance. Diabetic polyneuropathy is one of the most common causes of chronic neuropathic pain; however, the reason why ∼25-30% of patients with diabetes develop pain is not known...

BACKGROUND: Several anticonvulsant drugs are used in the management of neuropathic pain. Oxcarbazepine is an anticonvulsant drug closely related to carbamazepine. Oxcarbazepine has been reported to be efficacious in the treatment of neuropathic pain, but evidence from randomised controlled trials (RCTs) is conflicting. Oxcarbazepine is reportedly better tolerated than carbamazepine. This is the first update of a review published in 2013. OBJECTIVES: To assess the benefits and harms of oxcarbazepine for different types of neuropathic pain...

Peripheral neuropathy is one of the most common and serious complications of type-2 diabetes. Diabetic neuropathy is characterized by a distal symmetrical sensorimotor polyneuropathy, and its incidence increases in patients 40 years of age or older. In spite of extensive research over decades, there are few effective treatments for diabetic neuropathy besides glucose control and improved lifestyle. The earliest changes in diabetic neuropathy occur in sensory nerve fibers, with initial degeneration and regeneration resulting in pain...

OBJECTIVE: Evidence from prospective studies for long-term treatment efficacy of spinal cord stimulation (SCS) in painful diabetic peripheral neuropathy (PDPN) is not available. We report prospective data on the effect of SCS on pain ratings, treatment success and failure, and complications during a 5-year follow-up in patients with PDPN. RESEARCH DESIGN AND METHODS: Patients with PDPN ( n = 48) were included in this prospective multicenter study. The Michigan Diabetic Neuropathy Score (MDNS) was used to assess the severity of neuropathy...