title: Small RNAs control sodium channel expression, nociceptor excitability, and pain thresholds.
abstract: To examine the role of small RNAs in peripheral pain pathways, we deleted the enzyme Dicer in mouse postmitotic damage-sensing neurons. We used a Nav1.8-Cre mouse to target those nociceptors important for inflammatory pain. The conditional null mice were healthy with a normal number of sensory neurons and normal acute pain thresholds. Behavioral studies showed that inflammatory pain was attenuated or abolished. Inflammatory mediators failed to enhance excitability of Nav1.8+ sensory neurons from null mutant mice. Acute noxious input into the dorsal horn of the spinal cord was apparently normal, but the increased input associated with inflammatory pain measured using c-Fos staining was diminished. Microarray and quantitative real-time reverse-transcription PCR (qRT-PCR) analysis showed that Dicer deletion lead to the upregulation of many broadly expressed mRNA transcripts in dorsal root ganglia. By contrast, nociceptor-associated mRNA transcripts (e.g., Nav1.8, P2xr3, and Runx-1) were downregulated, resulting in lower levels of protein and functional expression. qRT-PCR analysis also showed lowered levels of expression of nociceptor-specific pre-mRNA transcripts. MicroRNA microarray and deep sequencing identified known and novel nociceptor microRNAs in mouse Nav1.8+ sensory neurons that may regulate nociceptor gene expression.
authors: Molecular Nociception Group, Wolfson Institute for Biomedical Research, Research Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom. jing02.zhao@ucl.ac.uk
authors: Jing
authors: J
authors: Zhao
authors: Man-Cheung
authors: MC
authors: Lee
authors: Ali
authors: A
authors: Momin
authors: Cruz-Miguel
authors: CM
authors: Cendan
authors: Samuel T
authors: ST
authors: Shepherd
authors: Mark D
authors: MD
authors: Baker
authors: Curtis
authors: C
authors: Asante
authors: Lucy
authors: L
authors: Bee
authors: Audrey
authors: A
authors: Bethry
authors: James R
authors: JR
authors: Perkins
authors: Mohammed A
authors: MA
authors: Nassar
authors: Bjarke
authors: B
authors: Abrahamsen
authors: Anthony
authors: A
authors: Dickenson
authors: Bradly S
authors: BS
authors: Cobb
authors: Matthias
authors: M
authors: Merkenschlager
authors: John N
authors: JN
authors: Wood
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002531:Cerebellum / Q000166:cytology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000172:deficiency; D004195:Disease Models, Animal; D004722:Endoribonucleases / Q000172:deficiency; D005260:Female; D005620:Freund's Adjuvant / Q000009:adverse effects; D005727:Ganglia, Spinal / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000502:physiology; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010146:Pain / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism; D058477:Receptors, Purinergic P2X3; D043244:Ribonuclease III; D011984:Sensory Receptor Cells / Q000502:physiology*; D015222:Sodium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000503:physiopathology; D013997:Time Factors
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D035683:MicroRNAs; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C546409:P2rx3 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; C493726:Runx1 protein, mouse; C568318:Scn10a protein, mouse; D015222:Sodium Channels; D005620:Freund's Adjuvant; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases