Zhao, J; Lee, MC; Momin, A; Cendan, CM; Shepherd, ST; Baker, MD; ... Wood, JN; + view all Zhao, J; Lee, MC; Momin, A; Cendan, CM; Shepherd, ST; Baker, MD; Asante, C; Bee, L; Bethry, A; Perkins, JR; Nassar, MA; Abrahamsen, B; Dickenson, A; Cobb, BS; Merkenschlager, M; Wood, JN; - view fewer (2010) Small RNAs Control Sodium Channel Expression, Nociceptor Excitability, and Pain Thresholds. J NEUROSCI , 30 (32) 10860 - 10871. 10.1523/JNEUROSCI.1980-10.2010.
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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.
|Title:||Small RNAs Control Sodium Channel Expression, Nociceptor Excitability, and Pain Thresholds|
|Keywords:||DORSAL-ROOT GANGLIA, INFLAMMATORY PAIN, NEUROPATHIC PAIN, MESSENGER-RNAS, IB4 BINDING, MICRORNAS, NEURONS, DICER, RAT, IDENTIFICATION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Wolfson Inst for Biomedical Research|
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