Articles: hyperalgesia.
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Behavioral neuroscience · Apr 2013
Inhibition of HCN channels within the periaqueductal gray attenuates neuropathic pain in rats.
Peripheral and spinal hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels play important roles in neuropathic pain by regulating neuronal excitability. However, the participation of HCN channels in the ventral-lateral periaqueductal gray (vlPAG) during neuropathic pain states has not been clarified. ⋯ Subsequently, the function of these upregulated channels was verified by the intravlPAG infusion of ZD7288, a specific HCN blocker, which significantly relieved mechanical allodynia and thermal hyperalgesia in CCI animals. These results suggest that the upregulation of vlPAG HCN channels plays an important role in pain maintenance and might be a target for attenuating pain.
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J. Pharm. Pharmacol. · Apr 2013
Establishment of a central post-stroke pain model using global cerebral ischaemic mice.
Stroke is the leading cause of disability in the world. Central post-stroke pain (CPSP), an intractable secondary disease, is a serious problem that occurs following cerebral stroke. However, the detailed mechanisms underlying CPSP and standard treatments for it are not well established. Therefore, we examined the nociceptive threshold and alterations in the current stimulus threshold of primary afferent neurons in bilateral carotid artery occlusion (BCAO) mice. ⋯ Our data show the development of bilateral hyperalgesia in this model. Potentially, C and Aβ fibre-specific hypersensitization after stroke may have contributed to these symptoms.
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We have demonstrated that the activation of P2X3 receptor on peripheral afferent neurons is critical to development of inflammatory hyperalgesia in peripheral tissue, although pharmacological administration of prostaglandin E(2) or sympathomimetic amines is enough to sensitize primary afferent neurons by acting directly in neuronal receptors. Therefore, to clarify this ambiguity this study verifies whether P2X3 receptor activation on primary afferent neurons enables the sensitization induced by prostaglandin E(2) or sympathomimetic amine. ⋯ Furthermore, because PKCɛ translocation induces an increase of neuronal susceptibility to inflammatory mediators, this study demonstrates that αβmeATP in peripheral tissue increases the expression of PKCɛ in cell membranes of DRG-L5, and in contrast, the administration of PKCɛ translocation inhibitor (1 μg/paw) in peripheral tissue 45 min before αβmeATP, prevented the hyperalgesia induced by sub-threshold dose of PGE(2) (4 ng/paw). In conclusion, this study suggests that neuronal P2X3 receptor activation and the consequent PKCɛ translocation increase the susceptibility of nociceptor to inflammatory mediators allowing the development of inflammatory hyperalgesia.
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Peripheral nerve injury induces the cleavage of CX3CL1 from the membrane of neurons, where the soluble CX3CL1 subsequently plays an important role in the transmission of nociceptive signals between neurons and microglia. Here we investigated whether CX3CL1 regulates microglia activation through the phosphorylation of extracellular signal-regulated protein kinase 5 (ERK5) in the spinal cord of rats with spinal nerve ligation (SNL). ERK5 and microglia were activated in the spinal cord after SNL. ⋯ The blockage of CX3CR1, the receptor of CX3CL1, significantly reduced the level of ERK5 activation following SNL. In addition, the antisense knockdown of ERK5 reversed the CX3CL1-induced hyperalgesia and spinal microglia activation. Our study suggests that CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through the ERK5 signaling pathway.
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Pharmaceutical biology · Apr 2013
Synergistic interaction between total glucosides and total flavonoids on chronic constriction injury induced neuropathic pain in rats.
Shaoyao Gancao Decoction (SGD), a famous herbal medicine, consists of two herbs (Paeoniae Radix and Glycyrrhizae Radix) and is traditionally used for the treatment of pain. ⋯ Analgesic effects of SGD may contribute to simultaneous inhibition of Sirt1 overexpression and could warrant further evaluation as a possible agent for the treatment of neuropathic pain.