European journal of pain : EJP
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Radiotherapy (XRT) is the gold standard treatment for cancer-induced bone pain (CIBP), but only 50% of patients achieve adequate pain relief within 6 weeks. No predictors of analgesic response to XRT are known. The aim of this preliminary study was to explore the effect of XRT on sensory changes in CIBP with a view to predicting response. ⋯ This is the first clinical study to demonstrate alterations in sensory responses in CIBP. Alterations in specific sensory characteristics seem to be associated with an increased likelihood of successful analgesia from palliative XRT. This supports the use of QST in further biomarker studies to predict response to therapy and aid clinical decision making.
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Pain and factors related to it constitute serious health problems in the older population. This populationbased cross-sectional study aimed to investigate whether musculoskeletal pain is associated with mobility limitation and whether the relationship between pain and mobility limitation varies according to the use of analgesics among community-dwelling older people. A total of 622 community-dwelling participants aged 75 years and older (mean age 80.4, 74% women) were interviewed about presence and severity of musculoskeletal pain. ⋯ The risk of mobility limitation was highest among those who reported severe or moderate pain (1.84; 1.13, 3.13) and among those who used analgesics (2.37; 1.37, 4.11). In conclusion, musculoskeletal pain increases the risk for mobility limitation. The present findings underline the importance of the careful assessment and pharmacological and nonpharmacological management of pain in promoting mobility in older age.
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Inflammatory and immune responses following nerve injury have been shown to play an important role in neuropathic pain. Lipoxins are endogenous lipoxygenase-derived eicosanoids performing protective roles in a range of pathophysiologic processes. Here, we examined the effects of intrathecal lipoxinA4 (LXA4) on NF-κB activation and pro-inflammatory cytokine (TNF-α, IL-1β and IL-6) expression in dorsal root ganglia (DRG) following chronic compression of DRG (CCD), a model of neuropathic pain. ⋯ CCD induced both mechanical allodynia and thermal hyperalgesia, and increased the expression of TNF-α, IL-1β, IL-6 and NF-κB. Intrathecal injection of LXA4 prevented the development of neuropathic pain and inhibited NF-κB activation and pro-inflammatory cytokine upregulation in a dose-dependent manner. In this study, we have shown the strong protective effect of intrathecal LXA4 on the development of nociceptive behaviors induced by CCD and that these effects might be associated with its anti-inflammatory and pro-resolution properties.
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Recent studies suggest that CNS phospholipase A(2) (PLA(2) ) isoforms play a role in nociception, but until now, direct evidence of increased brain PLA(2) activity during allodynia or hyperalgesia is lacking. The present study was carried out, using lipidomics or systems wide analyses of lipids using tandem mass spectrometry, to elucidate possible changes in rat brain lipids after inflammatory pain induced by facial carrageenan injection. The caudal medulla oblongata showed decreases in phospholipids including phosphatidylethanolamine and phosphatidylinositol species, but increases in lysophospholipids, including lysophosphatidylethanolamine, lysophosphatidylinositol and lysophosphatidylserine, indicating increased PLA(2) activity and release of arachidonic acid after facial carrageenan injection. ⋯ Increase in sPLA(2) -III mRNA expression was found in the caudal medulla of carrageenan-injected rats, although no difference in sPLA(2) -III protein expression was detected. The changes in lipids as determined by lipidomics were therefore consistent with an increase in PLA(2) enzyme activity, but no change in enzyme protein expression. Together, these findings indicate enhanced PLA(2) activity in the caudal medulla oblongata after inflammatory orofacial pain.
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Several studies have suggested that 5-HT(7) receptors are involved in nociceptive processing but the exact contribution of peripheral versus central 5-HT(7) receptors still needs to be elucidated. In the present study, the respective roles of peripheral and spinal 5-HT(7) receptors in the modulation of mechanical hypersensitivity were investigated under two different experimental pain conditions. In a first set of experiments, the selective 5-HT(7) receptor agonist, E-57431, was systemically, intrathecally or peripherally (intraplantarly) administered to rats sensitized by intraplantar injection of capsaicin. ⋯ Significant inhibition of nerve injury-induced mechanical hypersensitivity was found after intraperitoneal (10 mg/kg) as well as intrathecal (100 μg) administration of E-57431 in this chronic pain model. These studies provide evidence that, under sensitizing neurogenic/neuropathic conditions, activation of 5-HT(7) receptors exerts antinociceptive effects at the level of the spinal cord and pronociceptive effects at the periphery. The antinociceptive effect mediated by central 5-HT(7) receptors seems to predominate over the pronociceptive effect at the periphery when a selective 5-HT(7) receptor agonist is systemically administered.