PT  - JOURNAL ARTICLE
AU  - Zhao, Jing
AU  - Lee, Man-Cheung
AU  - Momin, Ali
AU  - Cendan, Cruz-Miguel
AU  - Shepherd, Samuel T.
AU  - Baker, Mark D.
AU  - Asante, Curtis
AU  - Bee, Lucy
AU  - Bethry, Audrey
AU  - Perkins, James R.
AU  - Nassar, Mohammed A.
AU  - Abrahamsen, Bjarke
AU  - Dickenson, Anthony
AU  - Cobb, Bradly S.
AU  - Merkenschlager, Matthias
AU  - Wood, John N.
TI  - Small RNAs Control Sodium Channel Expression, Nociceptor Excitability, and Pain Thresholds
AID  - 10.1523/JNEUROSCI.1980-10.2010
DP  - 2010 Aug 11
TA  - The Journal of Neuroscience
PG  - 10860--10871
VI  - 30
IP  - 32
4099  - http://www.jneurosci.org/content/30/32/10860.short
4100  - http://www.jneurosci.org/content/30/32/10860.full
SO  - J. Neurosci.2010 Aug 11; 30
AB  - 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.