Topical treatment of peripheral neuropathic pain: applying the evidence

Patients with peripheral neuropathic pain (NP) may only achieve partial pain relief with currently recommended first-line oral treatments, which are also associated with systemic adverse events. Topical treatments are currently considered second- or third-line options, but a recent pharmacologic treatment algorithm has called for broader first-line use of these agents. This has highlighted a need to communicate the benefits associated with topical agents, in particular around the efficacy, targeted local action, and limited systemic availability resulting in minimal systemic adverse events and drug-drug interactions

High-Dose Capsaicin for the Treatment of Neuropathic Pain: What We Know and What We Need to Know

Neuropathic pain is a frequent and disabling condition with diverse underlying etiologies and is often difficult to treat. Systemic drug treatment is often limited in efficacy. Furthermore, adverse effects may be a limiting factor when trying to reach the necessary dose. Analgesics that can be applied topically have the potential to largely overcome this problem. They may be of particular advantage in localized neuropathic pain syndromes such as postherpetic neuralgia or small fiber neuropathy. Capsaicin, the pungent component of chili peppers, is a natural ligand of the transient receptor potential vanilloid 1 channel and has long been used as topically applicable cream with concentrations of 0.025 to 0.075%. In 2009, a high-concentration transdermal capsaicin 8% patch (Qutenza ; Acorda Therapeutics, Inc., Ardsley, NY, USA; Astellas Pharma Europe Ltd., Chertsey, Surrey, UK) was introduced for the treatment of peripheral neuropathic pain syndromes other than of diabetic origin in adults. It has since been widely used in diverse neuropathic pain disorders. In this review article, we summarize current knowledge on Qutenza, its advantages and problems, and expose unmet needs

Resolvins and inflammatory pain

Resolvins are a group of molecules derived from omega-3 fatty acids. They are part of a biochemical program that allows inflamed tissues to return to homeostasis once the need for the inflammatory response is over. Resolvins act in very low dose ranges in vitro and in vivo. New data suggest that they might have the potential to become very potent analgesic drugs in inflammatory pain

Ökonomischer Erfolg durch ökologisches Handeln: der FirmenUmweltIndex FUX für nachhaltiges Wirtschaften

Der vorliegende Beitrag ist ein Ergebnis der studentischen Forschungs- und Arbeitsgruppe sO2lutions der Technischen Hochschule Wildau (FH). Er geht der Frage nach, wie umweltfreundliches Verhalten eines Unternehmens beeinflusst und gefördert werden kann. Dazu werden zunächst die Eckpfeiler Ökonomie, Ökologie und Ethik und deren Zusammenwirken in einer realökonomischen an Stelle einer geldökonomischen Unternehmensführung erörtert. Anschließend wird der FirmenUmweltIndex FUX als Beitrag zur Verwirklichung umweltgerechter, realökonomischer Unternehmensführung vorgestellt und diskutiert. Dieser personenbezogene Ansatz kann in jedweder organisatorischen Einheit und damit beispielsweise in Wohnungsunternehmen oder auch in Krankenhäusern zur Realisierung von Nachhaltigkeit eingesetzt werden.This report is a result of the research activities of the working group sO2lutions of the Technical University of Applied Sciences Wildau. The main question is how we can realize a positive impact on environmentally friendly behavior of managers and employees in a company. Therefore the report examines the key elements of sustainability: (1) economy, (2) ecology and (3) ethics. The combination of these three parts should be the challenge for corporations world-wide instead of money economic based management. Furthermore, the report presents the FirmenUmweltIndex FUX (Company Environment Index), established by sO2lutions, as a contribution to the implementation of a sustainable management based on economy, ecology and ethics. This approach can be used to realize economic leadership and management under consideration of environmental needs. It can be implemented in each organizational unit e. g. in housing companies or hospitals

Tips in navigating the diagnostic complexities of chronic inflammatory demyelinating polyradiculoneuropathy

The 2021 guideline of the European Academy of Neurology/Peripheral Nerve Society on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) includes important revisions to the previous 2010 guideline. This article highlights the new criteria and recommendations for the differential diagnosis of CIDP. In the revised guideline, the CIDP spectrum has been modified to include typical CIDP and four well-characterized CIDP variants, namely distal, multifocal/focal, motor and sensory CIDP, replacing the term ‘atypical’ CIDP. To improve the diagnosis of CIDP, the revised guideline attempts to improve the specificity of the diagnostic criteria for typical CIDP and the four CIDP variants. Specific clinical and electrodiagnostic (including both motor and sensory conduction) criteria are provided for typical CIDP and each of the CIDP variants. The levels of diagnostic certainty have been changed to CIDP and possible CIDP, with the removal of probable CIDP (due to the lack of difference in the accuracy of the electrodiagnostic criteria for probable CIDP) and definite CIDP (due to the lack of a gold standard for diagnosis). If the clinical and electrodiagnostic criteria allow only for a diagnosis of possible CIDP, cerebrospinal fluid analysis, nerve ultrasound, nerve magnetic resonance imaging, objective treatment response, and nerve biopsy can be used as supportive criteria to upgrade the diagnosis to CIDP. Although the revised guideline needs to be validated and its strengths and weaknesses assessed, using the guideline will likely improve the accuracy of diagnosis of CIDP and variants of CIDP, and aid in distinguishing CIDP from conditions with similar features.</p

New treatment options for fibromyalgia: critical appraisal of duloxetine

Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain, tender points, fatigue, and sleep disturbance. FMS leads to high disability levels, poor quality of life, and extensive use of medical care. Effective pharmacological treatment options are rare, and treatment effects are often of limited duration. Duloxetine is a new selective serotonin and norepinephrine reuptake inhibitor that is licensed for the treatment of pain in diabetic neuropathy. So far two randomized, placebo-controlled trials have investigated the short-term safety and efficacy of duloxetine 60 mg/day and 120 mg/day in patients suffering from FMS over a period of 12 weeks. Both dosages were superior to placebo in pain relief, and improvement in quality of life and depressive symptoms. The analgesic effect was largely independent of the antidepressant action of duloxetine. The higher dose of 120 mg/day further reduced the tender point count and elevated the tender point pain thresholds. Only mild to moderate adverse effects were reported. Duloxetine 60 mg/day and 120 mg/day has proven to be beneficial in the treatment of FMS symptoms. As true for other antidepressants further studies are needed to assess the long-term efficacy and safety of duloxetine as an additional pharmacological treatment option in FMS

Signal characteristics of focal bone marrow lesions in patients with multiple myeloma using whole body T1w-TSE, T2w-STIR and diffusion-weighted imaging with background suppression

Objective: This study analyses the diagnostic potential of Diffusion-Weighted Imaging with Background Suppression (DWIBS) in the detection of focal bone marrow lesions from multiple myeloma. The signal and contrast properties of DWIBS are evaluated in correlation with the serum concentration of M-component (MC) and compared with established T1- and T2-weighted sequences. Methods: Data from 103 consecutive studies in 81 patients are analysed retrospectively. Signal intensities and apparent Diffusion Coefficients (ADC) of 79 focal lesions in the lumbar spine or pelvis of 38 patients are determined and contrast-to-noise-ratio (CNR) is calculated. Data from patients with low (20g/dL) MC are evaluated separately. Results: Signal intensities of focal myeloma lesions on T2w-STIR vary significantly depending on the MC, which leads to a loss in CNR in patients with high MC. No signal variation is observed for T1w-TSE and DWIBS. The CNR values provided by DWIBS in patients with high MC are slightly higher than those of T2w-STIR. ADC values in patients with low MC are significantly higher than in patients with high MC. Conclusion: Whole-body DWIBS has the potential to improve the conspicuity of focal myeloma lesions and provides additional biological information by ADC quantificatio

Stable Metabolic Control but Increased Demand for Professional Support in Children with Type 1 Diabetes in the Past Ten Years in Bern/Switzerland: A Quality Control Study.

Introduction Lower HbA1c targets and increasingly complex diabetes management with substantially increasing costs dominate today's type 1 diabetes therapy in children and adolescents. Objective To evaluate metabolic control in children and adolescents with type 1 diabetes and assess associated factors, evaluate determinants for frequency of healthcare contacts, and compare actual with historical data. Method This cross-sectional observational study collected data on 178 children and adolescents with type 1 diabetes treated at the University Children's Hospital in Bern. Results Mean HbA1c was 7.9% (63 mmol/mol), 33.1% (59/178) of children reached the target of HbA1c < 7.5% (<59 mmol/mol), and 18.0% (32/178) had an HbA1c value < 7.0% (<53 mmol/mol). Compared to historical data, stable HbA1c levels appeared with a doubled proportion of individuals using insulin pumps. Metabolic control was worse with a longer duration of diabetes and younger age at diagnosis but better when parents came from a Western European country. Age at the consultation, use of diabetes technology and native language influenced the number of healthcare contacts. Younger patients, patients using CSII, and patients without an official Swiss language as mother tongue had more consultations with a healthcare professional than older and native language individuals. Conclusion The metabolic targets in childhood and adolescent type 1 diabetes are still unmet despite a shift towards more technology. Our study documents a higher demand for support and supervision in specific patient groups. An investment to increase healthcare contacts could help combat the increase in total diabetes cost and significantly improve metabolic control

Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice

<p>Abstract</p> <p>Background</p> <p>Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process.</p> <p>Results</p> <p>Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1β), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1β. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1β, and IL-10 following CFA, overall corroborating the inhibitor data.</p> <p>Conclusion</p> <p>These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.</p