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- Title
Small RNAs Control Sodium Channel Expression, Nociceptor Excitability, and Pain Thresholds.
- Authors
Jing Zhao; Man-Cheung Lee; Momin, Ali; Cendan, Cruz-Miguel; Shepherd, Samuel T.; Baker, Mark D.; Asante, Curtis; Bee, Lucy; Bethry, Audrey; Perkins, James R.; Nassar, Mohammed A.; Abrahamsen, Bjarke; Dickenson, Anthony; Cobb, Bradly S.; Merkenschlager, Matthias; Wood, John N.
- 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.
- Subjects
RNA; GENE expression; PAIN; MESSENGER RNA; INFLAMMATION; LABORATORY mice
- Publication
Journal of Neuroscience, 2010, Vol 30, Issue 32, p10860
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1980-10.2010