European journal of pain : EJP
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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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To determine the association of severe pain with socioeconomic characteristics. ⋯ This study demonstrated significant associations between pain and socio-economic disadvantage. Apart from the direct impact upon the individual, this clearly has wider societal implications in terms of additional health and social care costs for affected people.
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Comparative Study
Social comparison performance standards, threat, and tolerance for experimentally-induced pain.
Social modelling experiments have illustrated how upward social comparisons (i.e., observing pain tolerant role models) can facilitate tolerance relative to downward social comparison (i.e., observing pain intolerant alternatives). However, because clinical studies suggest that people prefer to make downward social comparisons with less fortunate others when they are threatened or overwhelmed with pain or illness, it seems plausible that upward social comparisons confer fewer benefits when pain is appraised as threatening. ⋯ Conversely, the average tolerance time for participants presented with the higher threat orienting prime and upward comparison standard did not differ from that of either downward comparison group. The research highlighted powerful situational influences on tolerance for experimental pain and identified conditions under which verbally-presented upward social comparison standards may facilitate and hinder the capacity to bear pain.
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Peripheral neuropathy (PN) is a common impairment which may impact upon quality of life (QoL). Neuropathic pain (NeP) occurs in up to 50% of patients with PN. We hypothesized that disability and impaired quality of life resulting from PN is primarily associated with presence of NeP. ⋯ Our results confirm that NeP is a primary indicator for worsening QoL and diminished overall wellbeing in PN patients. The etiology of PN did not influence levels of NeP-related compromise of QoL. Further studies are needed to determine optimal methods for management of PN+NeP patients subjected to a significant physiological, psychological and functional burden.
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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.