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While triptans are used to treat migraine, there is evidence that they also reduce inflammation induced pain at the spinal level. The cellular mechanisms underlying this spinal enhancement are unknown. We examined whether inflammation alters sumatriptan modulation of synaptic transmission in the rat spinal dorsal horn.
Learn More >Chronic migraine is a neurological disorder characterized by 15 or more headache days per month of which at least 8 days show typical migraine features. The process that describes the development from episodic migraine into chronic migraine is commonly referred to as migraine transformation or chronification. Ample studies have attempted to identify factors associated with migraine transformation from different perspectives. Understanding CM as a pathological brain state with trigeminovascular participation where biological changes occur, we have completed a comprehensive review on the clinical, epidemiological, genetic, molecular, structural, functional, physiological and preclinical evidence available.
Learn More >Migraine is a chronic, disabling neurological disease characterized by moderate-to-severe headache pain with other symptoms, including nausea, vomiting, and photophobia. Triptans, while generally effective, are insufficiently efficacious in 30-40% of patients and poorly tolerated by or contraindicated in others. We assessed the impact of insufficient response to triptans on health-related quality of life (HRQoL) and work productivity in patients currently receiving any prescribed triptan formulation as their only acute migraine medication.
Learn More >To assess the proportion of individuals who report dizziness and/or vertigo during the prodromal phase or headache phase of migraine.
Learn More >Diffuse noxious inhibitory controls (DNIC) as measured in rat and conditioned pain modulation (CPM), the supposed psychophysical paradigm of DNIC measured in humans, are unique manifestations of an endogenous descending modulatory pathway that is activated by application of a noxious conditioning stimulus. The predictive value of the human CPM processing is crucial when deliberating the translational worth of the two phenomena.
Learn More >The pathophysiological mechanism of medication overuse headache is uncertain; no distinctive markers have been described right now. The aim of this study was to conduct proteomic analyses on serum samples from patients with medication overuse headache and healthy individuals. Specifically, mono- (SDS-PAGE) and two-dimensional gel electrophoresis (2-DE) followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to evaluate changes in serum proteins.
Learn More >Morphine is frequently used for pain relief, but long-term morphine therapy in patients with chronic pain results in analgesic tolerance and hyperalgesia. There are no effective therapeutic treatments that limit these detrimental side effects. We found pretreatment with melatonin could decrease morphine-induced analgesic tolerance. There was a significant activation of the NLRP3 inflammasome in the prefrontal cortex and the peripheral blood of morphine-treated mice compared to control animals, which could be blocked by melatonin. The inflammasome activation induced by morphine was mediated by the microglia. SiRNA knockdown or pharmacological inhibition of the NLRP3 abolished the morphine-induced inflammasome activation. Co-administration of melatonin and low-dose morphine had better analgesia effects in the murine models of pain and led to a lower NLRP3 inflammasome activity in brain tissues. Mice deficient for Nlrp3 had a higher nociceptive threshold and were less sensitive to develop morphine-induced analgesic tolerance and acetic acid-induced pain relative to wild-type animals. Concordantly, we observed a significantly elevated level of serum IL-1β, which indicates an increase of NLRP3 inflammasome activity associated with the reduced level of serum melatonin, in heroin-addicted patients relative to healthy individuals. Our results provide a solid basis for conducting a clinical trial with the co-administration of melatonin and morphine for the relief of severe pain.
Learn More >The mu opioid receptor (MOR) is the primary target for analgesia of endogenous opioid peptides, alkaloids, synthetic small molecules with diverse scaffolds, and peptidomimetics. Peptide-based opioids are viewed as potential analgesics with reduced side effects and have received constant scientific interest over the years. This study focuses on three potent peptide and peptidomimetic MOR agonists, DALDA, [Dmt]DALDA, and KGOP01, and the prototypical peptide MOR agonist DAMGO. We present the first molecular modeling study and structure-activity relationships aided by in vitro assays and molecular docking of the opioid peptide analogues, in order to gain insight into their mode of binding to the MOR. In vitro binding and functional assays revealed the same rank order with KGOP01 > [Dmt]DALDA > DAMGO > DALDA for both binding and MOR activation. Using molecular docking at the MOR and three-dimensional interaction pattern analysis, we have rationalized the experimental outcomes and highlighted key amino acid residues responsible for agonist binding to the MOR. The Dmt (2',6'-dimethyl-L-Tyr) moiety of [Dmt]DALDA and KGOP01 was found to represent the driving force for their high potency and agonist activity at the MOR. These findings contribute to a deeper understanding of MOR function and flexible peptide ligand-MOR interactions, that are of significant relevance for the future design of opioid peptide-based analgesics.
Learn More >This special issue highlights emerging research spanning from epidemiology to diagnostic workup, pathogenesis, and therapeutics for patients suffering from chronic pruritus. The special issue contains 13 articles reporting relevant epidemiologic and experimental data on chronic pruritus.
Learn More >To investigate sensory changes, physical function (pF), quality of life (QoL) and pain intensity of patients with osteoarthritis (OA) in the natural course of disease, and patients undergoing total joint replacement therapy (TJR) 31 (20 females, mean age 64.6 ± 10.4 years), patients with OA were investigated with questionnaires and quantitative sensory testing (QST) in the area of referred pain at the thigh at baseline and follow-up 22-49 weeks later; changes were analyzed separately for patients with ( = 13) and without TJR ( = 18). In patients without TJR pain intensity, pF, QoL did not improve, and increased pain sensitivity to cold and a stronger loss of detection were observed. In patients after TJR, however, a reduction in mechanical pain sensitivity and allodynia occurred in accordance with a reduction of pain intensity and improvement of functionality while QoL did not improve. Additionally, an increased sensitivity to heat pain and a more pronounced loss of mechanical detection could be observed in this group. TJR seems to stop peripheral pain input leading to a reduction of pain intensity and central sensitization, but surgery-induced sensory changes such as peripheral sensitization and loss of detection occur. Furthermore, TJR has favorable effects on pain intensity and functionality but not QoL.
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