Articles: hyperalgesia.
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(-)-Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent found in green tea. It has been reported that may be a natural agent for reducing thermal and mechanical pain after nervous system injuries. However, the molecular pathways implicated in these beneficial effects have not been completely elucidated. This study aimed to assess the EGCG treatment effects on thermal hyperalgesia, spinal cord gliosis and modulation of Ras homologue gene family member A (RhoA), fatty acid synthase (FASN) and tumour necrosis factor alpha (TNF-α) expression after spinal cord contusion in mice. ⋯ These findings suggest that at short time EGCG treatment reduces thermal hyperalgesia and gliosis via FASN and RhoA pathway, causing a decrease in cytokines in spinal cord.
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Combining drugs not only reduces specific adverse effects of each of the drug at a higher dose but also may lead to enhanced efficacy. Tapentadol is a recently discovered analgesic possessing μ-opioid receptor agonism and noradrenaline re-uptake inhibition in a single molecule. Taking into consideration, the pharmacological similarities between opioids and cannabinoids, we assumed that combination of cannabinoids with noradrenaline re-uptake inhibitors might also be effective. We therefore aimed to determine whether combining 1:1, 1:3 and 3:1 fixed ratios of the synthetic cannabinoid WIN 55,212-2 and the selective noradrenaline re-uptake inhibitor maprotiline exert anti-allodynic synergy on nerve-injured neuropathic mice. ⋯ Overall, our data suggest that combination of a cannabinoid with a selective noradrenaline re-uptake inhibitor may offer a beneficial treatment option for neuropathic pain.
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The assessment of facial expressions associated with pain has been used to evaluate pain in humans and has recently found application in non-human mammals. These so called 'grimace scales' have the potential to be developed into a widely accepted non-invasive method of measuring pain in laboratory rodents. Currently, common methodologies to assess pain rely on nociceptive tests that assess stimulus evoked withdrawal responses. These tests, however, are limited to the assessment of a reflexive response without an affective component. This study aimed to use the recently developed Rat Grimace Scale (RGS) and assess its relationship with a conventional nociceptive test (the application of von Frey filaments). ⋯ This study confirms that the three pain models induce pain in rodents and showed that peak pain coincided with peak mechanical hypersensitivity. However, mechanical hypersensitivity remained once pain subsided, mimicking the human experience of CFA injection. These findings further our understanding of the roles of, and relationship between, these assays in the assessment of nociception and pain.
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We have recently shown that repeated exposure of the peripheral terminal of the primary afferent nociceptor to the mu-opioid receptor (MOR) agonist DAMGO ([D-Ala, N-Me-Phe, Gly-ol]-enkephalin acetate salt) induces a model of transition to chronic pain that we have termed type II hyperalgesic priming. Similar to type I hyperalgesic priming, there is a markedly prolonged response to subsequent administration of proalgesic cytokines, prototypically prostaglandin E2 (PGE2). However, type II hyperalgesic priming differs from type I in being rapidly induced, protein kinase A (PKA), rather than PKCε dependent, not reversed by a protein translation inhibitor, occurring in female as well as in male rats, and isolectin B4-negative neuron dependent. ⋯ In this study, we demonstrate that priming induced by repeated exposure to this A1-adenosine receptor agonist shares the same mechanisms, as MOR-agonist induced priming. However, the prolongation of PGE2 hyperalgesia induced by repeated administration of CPA depends on G-protein αi subunit activation, differently from DAMGO-induced type II priming, in which it depends on the β/γ subunit. These data implicate a novel form of Gi-protein signaling pathway in the type II hyperalgesic priming induced by repeated administration of an agonist at A1-adenosine receptor to the peripheral terminal of the nociceptor.
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Physical and psychological symptoms of individuals with chronic whiplash-associated disorders (WAD) are modulated by successful treatment with cervical radiofrequency neurotomy (cRFN). However, not all individuals respond to cRFN, and it is unknown which clinical features predict successful response to cRFN. ⋯ Low levels of pain catastrophizing and disability independently predicted a successful response to cRFN in patients with chronic WAD.