Articles: neuropathic-pain.
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Bioorganic chemistry · Feb 2014
Discovery of tetrahydropyrido[4,3-d]pyrimidine derivatives for the treatment of neuropathic pain.
A series of tetrahydropyridopyrimidine derivatives were synthesized and evaluated for neurotoxicity and peripheral analgesic activity followed by assessment of antiallodynic and antihyperalgesic potential in two peripheral neuropathic pain models, the chronic constriction injury (CCI) and partial sciatic nerve ligation (PSNL). Compounds (4b and 4d) exhibiting promising efficacies in four behavioral assays of allodynia and hyperalgesia (spontaneous pain, tactile allodynia, cold allodynia and mechanical hyperalgesia) were quantified for their ED50 values (15.12-65.10mg/kg). Studies carried out to assess the underlying mechanism revealed that the compounds suppressed the inflammatory component of the neuropathic pain and prevented oxidative and nitrosative stress.
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Nutritional neuroscience · Feb 2014
Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats.
This study was designed to investigate the ameliorative potential of Momordica charantia L. (MC) in tibial and sural nerve transection (TST)-induced neuropathic pain in rats. ⋯ Collectively, it is speculated that PPAR-gamma agonistic activity, anti-inflammatory, and antioxidative potential is critical for antinociceptive effect of MC in neuropathic pain.
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Neuroscience research · Feb 2014
Involvement of Wnt/β-catenin signaling in the development of neuropathic pain.
Despite tremendous research effort in the field, our current understanding of the molecular mechanisms underlying neuropathic pain is still incomplete. In the present study, our objective was to elucidate the involvement of the Wnt/β-catenin signaling pathway in the development of neuropathic pain. We showed that Wnt/β-catenin signaling is activated in the spinal cord dorsal horn after partial sciatic nerve ligation (PSL). ⋯ Moreover, we also found that PSL-induced microglial activation was significantly suppressed by intrathecal administration of XAV939 treatment. Because it was revealed that Wnt3a treatment triggered brain-derived neurotrophic factor (BDNF) release from microglial cells in vitro, it is possible that Wnt3a upregulation in the dorsal horn leads to the activation of microglial cells, then triggers BDNF secretion that is responsible for the establishment of neuropathic pain. Further studies will be needed for the comprehensive understanding of the roles of Wnt/β-catenin signaling in the development of neuropathic pain.
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The two most studied endocannabinoids are anandamide (AEA), principally catalyzed by fatty-acid amide hydrolase (FAAH), and 2-arachidonoyl glycerol (2-AG), mainly hydrolyzed by monoacylglycerol lipase (MGL). Inhibitors targeting these two enzymes have been described, including URB597 and URB602, respectively. Several recent studies examining the contribution of CB₁ and/or CB₂ receptors on the peripheral antinociceptive effects of AEA, 2-AG, URB597 and URB602 in neuropathic pain conditions using either pharmacological tools or transgenic mice separately have been reported, but the exact mechanism is still uncertain. ⋯ Furthermore, the antinociceptive effects for AEA and URB597 were observed in cnr2KO mice but absent in cnr1KO mice, whereas the effects of 2-AG, WIN and URB602 were altered in both of these transgenic mice. Complementary genetic and pharmacological approaches revealed that the anti-hyperalgesic effects of 2-AG and URB602 required both CB₁ and CB₂ receptors, but only CB₂ receptors mediated its anti-allodynic actions. The antinociceptive properties of AEA and URB597 were mediated only by CB₁ receptors.
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Chronic pain after surgery is a major public health problem and a major concern for perioperative physicians. Thoracic surgery presents a unique challenge, as thoracotomy is among the highest risk surgeries to develop persistent postsurgical pain. The purpose of this review is to discuss the relevance of research in pain epigenetics to patients with persistent pain after thoracic surgery. ⋯ The transition from acute to chronic pain after thoracic surgery may be mediated by epigenetics. Here, we discuss epigenetic modifications that have been discovered in animal models of chronic pain that may predispose patients to persistent neuropathic pain after thoracic surgery.