Articles: neuropathic-pain.
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Neurobiology of disease · Feb 2014
Riluzole attenuates neuropathic pain and enhances functional recovery in a rodent model of cervical spondylotic myelopathy.
Cervical spondylotic myelopathy (CSM) is the commonest cause of spinal cord impairment worldwide and despite surgical treatment, it is commonly associated with chronic neuropathic pain and neurological impairment. Based on data suggesting a key role of sodium and glutamate mediated cellular injury in models of spinal cord compression, we examined whether riluzole, a sodium channel/glutamate blocker, could improve neurobehavioral outcomes in a rat model of CSM. To produce chronic progressive compression of the cervical spinal cord, we used an established model of graded mechanical cord compromise developed in our laboratory. ⋯ Riluzole also decreased the number of phosphorylated NR1 and phosphorylated NR2B positive cells in the dorsal horns and the microglia activation in the dorsal horns. Together, our results indicate that systemic riluzole administration during chronic cervical spinal cord compression is effective at protecting spinal cord tissue, preserving neurobehavioral function and alleviating neuropathic pain, possibly by decreasing NMDA receptor phosphorylation in astrocytes and by eliminating microglia activation. As such, riluzole represents a promising clinical treatment for CSM.
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Although nerve injury-induced long-term postsynaptic changes have been investigated, less is known regarding the molecular mechanisms within presynaptic axonal terminals. We investigated the molecular changes in presynaptic nerve terminals underlying chronic pain-induced plastic changes in the medial prefrontal cortex (mPFC). After neuropathic pain was induced by spared nerve injury (SNI) in rats, we assessed the release of the excitatory neurotransmitter glutamate by using in vitro synaptosomal preparations from the mPFC. ⋯ Chronic pain upregulated the phosphorylation of endogenous protein kinases, including extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Ca(2+)/calmodulin-dependent kinase II (CaMKII), and synapsin I, the primary presynaptic target of ERK1/2 and CaMKII. Both presynaptic proteins and protein kinases were upregulated after SNI in a time-dependent manner. These results indicate that the long-term neuropathic pain-induced enhancement of glutamate release in the mPFC is linked to increased synaptic vesicle proteins and the activation of the ERK1/2- and CaMKII-synapsin signaling cascade in presynaptic axonal terminals.
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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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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.