Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0423716 (Neuropathic pain)
 1,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain resulting from nerve lesions or dysfunction represents one of the most challenging neurological diseases to treat. A better understanding of the molecular mechanisms responsible for causing these maladaptive responses can help develop novel therapeutic strategies and biomarkers for neuropathic pain. We performed a miRNA expression profiling study of dorsal root ganglion (DRG) tissue from rats four weeks post spinal nerve ligation (SNL), a model of neuropathic pain. TaqMan low density arrays identified 63 miRNAs whose level of expression was significantly altered following SNL surgery. Of these, 59 were downregulated and the ipsilateral L4 DRG, not the injured L5 DRG, showed the most significant downregulation suggesting that miRNA changes in the uninjured afferents may underlie the development and maintenance of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs and it was found that the transcripts with multiple predicted target sites belong to neurologically important pathways. By employing different bioinformatic approaches we identified neurite remodeling as a significantly regulated biological pathway, and some of these predictions were confirmed by siRNA knockdown for genes that regulate neurite growth in differentiated Neuro2A cells. In vitro validation for predicted target sites in the 3'-UTR of voltage-gated sodium channel Scn11a, alpha 2/delta1 subunit of voltage-dependent Ca-channel, and purinergic receptor P2rx ligand-gated ion channel 4 using luciferase reporter assays showed that identified miRNAs modulated gene expression significantly. Our results suggest the potential for miRNAs to play a direct role in neuropathic pain.
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PMID:Dynamic changes in the microRNA expression profile reveal multiple regulatory mechanisms in the spinal nerve ligation model of neuropathic pain. 2142 2

Purinergic signalling in the brain is becoming an important focus in the study of CNS health and disease. Various purinergic receptors are found to be present in different brain cells in varying extent, which get activated upon binding of ATP or its analogues. Conventionally, ATP was considered only as a major metabolic fuel of the cell but its recognition as a neurotransmitter in early 1970s, brought meaningful insights in neuron glia crosstalk, participating in various physiological functions in the brain. P2X7R, a member of ligand gated purinergic receptor (P2X) family, is gaining attention in the field of neuroscience because of its emerging role in broad spectrum of ageing and age related neurological disorders. The aim of this review is to provide an overview about the structure and function of P2X7R highlighting its unique features which distinguish it from the other members of its family. This review critically analyzes the literature mentioning the details about the agonist and antagonist of the P2X7R. It also emphasizes the advancements in understanding the dual role of P2X7R in brain development and disorders inviting meaningful insights about its involvement in Alzheimer's disease, Huntington's disease, Multiple Sclerosis, Neuropathic pain, Spinal Cord Injury and NeuroAIDS. Exploring the roles of P2X7R in detail is critical to identify its therapeutic potential in the treatment of acute and chronic neurodegenerative diseases. Moreover, this review also helps to raise more interest in the neurobiology of the purinergic receptors and thus providing new avenues for future research.
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PMID:Emerging role of P2X7 receptors in CNS health and disease. 2647 5