European journal of pain : EJP
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Fibromyalgia syndrome (FMS) is a common and intriguing condition, manifest by chronic pain and fatigue. Although the pathogenesis of FMS is not yet completely understood, predicting the future development of FMS and chronic pain is a major challenge with great potential advantages, both from an individual as well as an epidemiological standpoint. Current knowledge indicates a genetic underpinning for FMS, and as increasing data are accumulated regarding the genetics involved, the prospect of utilizing these data for prediction becomes ever more attractive. ⋯ Functional neuroimaging may help to elucidate the neural processes involved in central sensitization, and may ultimately also evolve into markers of predictive value. Last but not least, obesity and disturbed sleep are clinical (inter-related) features relevant for this spectrum. Future efforts will aim at integrating genetic, clinical and physiological data in the prediction of FMS and chronic pain.
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The alkaloid morphine is historically the oldest opiate, yet still today it has clinically important uses in analgesic therapies. The main analgesic effect of opioids, including synthetic opioids belonging to the family of 4-anilidopiperidines, is mediated via activation of opioid receptors spread throughout the peripheral and central nervous system. However, morphine acting as a 'dirty' drug also exhibits effects on other receptor systems, e.g., the serotonergic system and its 5-HT3 receptor. Therefore, this study focuses on the interaction of morphine and fentanyl-type opioids (alfentanil, remifentanil and sufentanil) with 5-HT3A receptors. ⋯ Morphine is an opioid compound exhibiting special antagonistic interaction with 5-HT3A receptors. This interaction is not shared by the newer synthetic derivatives of the fentanyl-type opioids in the clinical relevant concentration range.
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The UVB and heat rekindling (UVB/HR) model shows potential as a translatable inflammatory pain model. However, the occurrence of central sensitization in this model, a fundamental mechanism underlying chronic pain, has been debated. Face, construct and predictive validity are key requisites of animal models; electromyogram (EMG) recordings were utilized to objectively demonstrate validity of the rat UVB/HR model. ⋯ This study used objective outcome measures of secondary hyperalgesia to validate the rat UVB/HR model as a translational model of inflammatory pain.
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We have previously synthesized three esterified endomorphin-2 (EM-2) analogues 1-3 by substitution of C-terminus with methyl, ethyl and tert-butyl ester, respectively. Interestingly, the increase of EM-2 in bulkness of the esterified group decreased the μ-opioid receptor affinity but increased the δ-affinity. Presently, we extended our studies to investigate the antinociceptive potencies of these esterified analogues given intrathecally in the mouse tail-flick test. Also, the specific opioid receptor antagonists and antibodies against endogenous opioid peptides were used to determine whether there are any differential mechanisms on the antinociception produced by these analogues. ⋯ Our results demonstrated that EM-2 and its analogues 1-3 produced differential antinociceptive effects when administered intrathecally. We concluded that C-terminal amide to esterification conversion changed the antinociceptive potencies and properties of EM-2.
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This study aimed to characterize and compare the efficacy profile on six fibromyalgia syndrome (FM) core symptoms associated with pharmacologic and non-pharmacologic treatments. We screened PubMed, Embase and the Cochrane Library for FM articles from 1990 to September 2012 to analyse randomized controlled trials comparing pharmacologic or non-pharmacologic treatments to placebo or sham. Papers including assessments of at least 2 of the 6 main FM symptom domains - pain, sleep disturbance, fatigue, affective symptoms (depression/anxiety), functional deficit and cognitive impairment - were selected for analysis. ⋯ Differences between pharmacologic and non-pharmacologic approaches may be related to different modes of action, tolerability profiles and study designs. Very few drugs in well-designed clinical trials have demonstrated significant relief for multiple FM symptom domains, whereas non-pharmacologic treatments with weaker study designs have demonstrated multidimensional effects. Future therapeutic trials for FM should prospectively examine each of the core domains and should attempt to combine pharmacologic and non-pharmacologic therapies in well-designed clinical trials.