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Hyperglycemia is considered a key risk factor for development of diabetic complications including neuropathy. There is strong scientific evidence showing a primary role of aldose reductase, the first enzyme of the polyol pathway, in the cascade of metabolic imbalances responsible for the detrimental effects of hyperglycemia. Aldose reductase is thus considered a significant drug target. We investigated the effects of cemtirestat, a novel aldose reductase inhibitor, in the streptozotocin-induced rat model of uncontrolled type 1 diabetes in a 4-month experiment. Markedly increased sorbitol levels were recorded in the erythrocytes and the sciatic nerve of diabetic animals. Osmotic fragility of red blood cells was increased in diabetic animals. Indices of thermal hypoalgesia were significantly increased in diabetic rats. Tactile allodynia, recorded in diabetic animals in the early stages, turned to mechanical hypoalgesia by the end of the experiment. Treatment of diabetic animals with cemtirestat (i) reduced plasma triglycerides and TBAR levels; (ii) did not affect the values of HbA1c and body weights; (iii) reversed erythrocyte sorbitol accumulation to near control values, while sorbitol in the sciatic nerve was not affected; (iv) ameliorated indices of the erythrocyte osmotic fragility; and (v) attenuated the symptoms of peripheral neuropathy more significantly in the middle of the experiment than at the end of the treatment. Taking into account the lipid metabolism as an interesting molecular target for prevention or treatment of diabetic peripheral neuropathy, the triglyceride-lowering effect of cemtirestat should be considered in future studies. The most feasible mechanisms of triglyceride-lowering action of cemtirestat were suggested.
Learn More >Neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) is a novel hypnotic and voltage-dependent blocker of T-type calcium channels. Here we examine its potential analgesic effects and adjuvant anesthetic properties using a post-surgical pain model in rodents.
Learn More >An estimated 2.5-3.1% of people with episodic migraine develop chronic migraine in a year. Several risk factors are associated with an increased risk for this transformation. We conducted a systematic review and meta-analysis to provide quantitative and qualitative data on predictors of this transformation.
Learn More >Children of individuals with chronic pain have an increased vulnerability to experience pain problems, possibly through observation of pain in their parents. As pain-related fear (PRF) is a critical factor in the development and maintenance of chronic pain, the current experimental study examined the acquisition of PRF through observational learning and subsequent extinction after first-hand experience of the feared stimulus.
Learn More >The influence of the genetic polymorphism of enzymes and receptors involved in paracetamol metabolism and mechanism of action has not been investigated. This trial in healthy volunteers investigated the link between paracetamol pain relief and the genetic polymorphism of 23 enzymes and receptors.
Learn More >Chronic pain has a tremendous personal and socioeconomic impact and remains difficult to treat. Therefore, it seems important to provide an update on the current understanding regarding lifestyle factors in people with chronic pain across the lifespan, and explaining that clinicians should address various lifestyle factors concomitantly into an individually-tailored multimodal lifestyle intervention for people having chronic pain. Lifestyle factors such as physical (in)activity, sedentary behaviour, stress, poor sleep, unhealthy diet and smoking are associated with chronic pain severity and sustainment. This applies to all age categories, that is, chronic pain across the lifespan. Yet current treatment options often do not, or only partly address the many lifestyle factors associated with chronic pain, or attempt to address them in a standard format rather than providing an individually tailored multimodal lifestyle intervention. The evidence regarding lifestyle factors is available in adults, but limited in children and elderly having chronic pain, providing important avenues for future research. In conclusion, it is proposed that treatment approaches for people having chronic pain should address all relevant lifestyle factors concomitantly into an individually-tailored multimodal intervention. Ultimately, this should lead to a higher clinical impact with higher effect sizes and subsequently decreasing the psychological and socio-economic burden of chronic pain in the Western world. This article is protected by copyright. All rights reserved.
Learn More >Efficacy of galcanezumab, a monoclonal antibody for migraine prevention, has been demonstrated in two pivotal trials in patients with episodic migraine.
Learn More >Despite the availability of measures for assessing physical, psychological, and health impact in children with chronic pain, there are not established guidelines for interpretation of children's pain outcomes following psychological treatment. The purpose of this topical review is to discuss clinical significance as a neglected area of consideration in pediatric chronic pain assessment and to make recommendations on how the field can move toward benchmarking on core outcome domains.
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