This study aims to individualize the selection of drugs for neuropathic pain by examining the potential coupling of a given drug's mechanism of action with the patient's pain modulation pattern. The latter is assessed by the conditioned pain modulation (CPM) and temporal summation (TS) protocols. We hypothesized that patients with a malfunctioning pain modulation pattern, such as less efficient CPM, would benefit more from drugs augmenting descending inhibitory pain control than would patients with a normal modulation pattern of efficient CPM. Thirty patients with painful diabetic neuropathy received 1 week of placebo, 1 week of 30 mg/d duloxetine, and 4 weeks of 60 mg/d duloxetine. Pain modulation was assessed psychophysically, both before and at the end of treatment. Patient assessment of drug efficacy, assessed weekly, was the study's primary outcome. Baseline CPM was found to be correlated with duloxetine efficacy (r=0.628, P<.001, efficient CPM is marked negative), such that less efficient CPM predicted efficacious use of duloxetine. Regression analysis (R(2)=0.673; P=.012) showed that drug efficacy was predicted only by CPM (P=.001) and not by pretreatment pain levels, neuropathy severity, depression level, or patient assessment of improvement by placebo. Furthermore, beyond its predictive value, the treatment-induced improvement in CPM was correlated with drug efficacy (r=-0.411, P=.033). However, this improvement occurred only in patients with less efficient CPM (16.8±16.0 to -1.1±15.5, P<.050). No predictive role was found for TS. In conclusion, the coupling of CPM and duloxetine efficacy highlights the importance of pain pathophysiology in the clinical decision-making process. This evaluative approach promotes personalized pain therapy.

Both type 1 and type 2 diabetes adversely affect the microvasculature in multiple organs. Our understanding of the genesis of this injury and of potential interventions to prevent, limit, or reverse injury/dysfunction is continuously evolving. This statement reviews biochemical/cellular pathways involved in facilitating and abrogating microvascular injury. The statement summarizes the types of injury/dysfunction that occur in the three classical diabetes microvascular target tissues, the eye, the kidney, and the peripheral nervous system; the statement also reviews information on the effects of diabetes and insulin resistance on the microvasculature of skin, brain, adipose tissue, and cardiac and skeletal muscle. Despite extensive and intensive research, it is disappointing that microvascular complications of diabetes continue to compromise the quantity and quality of life for patients with diabetes. Hopefully, by understanding and building on current research findings, we will discover new approaches for prevention and treatment that will be effective for future generations.

Experimental findings in vitro and in vivo illustrate enhanced hypoxia and the formation of reactive oxygen species (ROS) within the kidney following the administration of iodinated contrast media, which may play a role in the development of contrast media-induced nephropathy. Clinical studies indeed support this possibility, suggesting a protective effect of ROS scavenging or reduced ROS formation with the administration of N-acetyl cysteine and bicarbonate infusion, respectively. Furthermore, most risk factors, predisposing to contrast-induced nephropathy are prone to enhanced renal parenchymal hypoxia and ROS formation. In this review, the association of renal hypoxia and ROS-mediated injury is outlined. Generated during contrast-induced renal parenchymal hypoxia, ROS may exert direct tubular and vascular endothelial injury and might further intensify renal parenchymal hypoxia by virtue of endothelial dysfunction and dysregulation of tubular transport. Preventive strategies conceivably should include inhibition of ROS generation or ROS scavenging.