European journal of pain : EJP
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Low back pain is a common and expensive health complaint. Many low back pain trials have been conducted, but these are reported in a variety of ways and are often difficult to interpret. ⋯ A group of back pain experts reached a high level of consensus on a statement recommending reporting methods for patient-reported outcomes in future low back pain trials. The statement has the potential to increase interpretability and improve patient care.
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Randomized Controlled Trial Multicenter Study
Clinical trial of the p38 MAP kinase inhibitor dilmapimod in neuropathic pain following nerve injury.
Current treatments of neuropathic pain arising from conditions such as nerve injury/compression are only partially effective, and limited in their use by side-effects. p38 mitogen-activated protein kinase (MAPK) is involved in the regulation and synthesis of inflammatory mediators, and is the target for a novel class of cytokine-suppressive anti-inflammatory drugs. p38 inhibitors may reduce neuronal sensitisation in preclinical models of neuropathic pain, particularly where there is a substantial inflammatory component. An exploratory, multicentre, double-blind, placebo-controlled, two-period, cross-over trial was undertaken to evaluate the effect of dilmapimod (SB-681323), a selective p38 MAPK inhibitor, on neuropathic pain symptoms and signs. Fifty patients with nerve trauma, radiculopathy or carpal tunnel syndrome were randomised; 43 patients completed the study. ⋯ There was a statistically significant reduction in the primary endpoint of average daily pain score during the second week of treatment among patients treated with dilmapimod (15 mg/day) compared to placebo using NRS [0.80; 95% CI (0.28, 1.33); p=0.0034]. A similar trend for effect was seen in some secondary endpoints. Dilmapimod was well tolerated, with no clinically relevant safety findings. p38 MAPK inhibitors merit further evaluation for neuropathic pain in larger clinical trials, particularly for clinically meaningful analgesic effect size.
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Under-treatment of pain is a worldwide problem. We examine how often pain was addressed and the factors that influence how much time was spent on treating pain. We analyzed 385 videotapes of routine office visits in several primary care practices in the Southwest and Midwest regions of the United States. ⋯ Time constraints and racial concordance significantly influenced the length of discussion. We conclude that despite repeated calls for addressing under-treatment for pain, only a limited amount of time is used to address pain among elderly patients. This phenomenon could contribute to the under-treatment of pain.
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Targeting supraspinal pain control centers by gene transfer is known to induce sustained analgesia. In this study, we evaluated the effects of injecting a Herpes Simplex Virus type 1 vector which expresses enkephalin (HSV-ENK vector) in the lateralmost part of the caudal ventrolateral medulla (VLMlat), a pain control center that exerts mainly descending inhibitory effects on pain modulation. Overexpression of enkephalin at the VLMlat reduced the number of flinches during the early and delayed phases of the formalin test and decreased c-fos expression in the spinal cord. ⋯ Virally driven-enkephalin was expressed from transduced neurons located in the VLMlat and, at lower extent, in the rostral ventromedial medulla. Our results show that HSV-mediated expression of enkephalin in the VLMlat induced antinociceptive effects, likely due to an enhancement of the opioidergic input to the VLMlat which accounted for descending inhibition of the nociceptive transmission at the spinal cord. This study also demonstrates the value of HSV-1 derived vectors to manipulate, in a sustained and directed manner, pain modulatory pathways in the brain, which is important in the study of supraspinal pain control circuits.
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Shakuyakukanzoto (SKT) has been shown to modulate nociception in streptozotocin-induced diabetic mice via selective activation of the descending noradrenergic systems. However, the active components of SKT that exert the analgesic effect remain unknown. Here, we administered Glycyrrhizae radix (G. radix), Paeoniae radix (P. radix), and the two active constituents of P. radix, paeoniflorin and albiflorin, to determine the components that stimulate spinal α₂-adrenoceptors by promoting noradrenaline release. ⋯ Our findings suggest that paeoniflorin is the key antinociceptive component in SKT that increases noradrenaline release and activates α₂-adrenoceptors to modulate spinal nociceptive transmission in diabetic neuropathy.