RT Journal Article
SR Electronic
T1 Small RNAs Control Sodium Channel Expression, Nociceptor Excitability, and Pain Thresholds
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10860
OP 10871
DO 10.1523/JNEUROSCI.1980-10.2010
VO 30
IS 32
A1 Zhao, Jing
A1 Lee, Man-Cheung
A1 Momin, Ali
A1 Cendan, Cruz-Miguel
A1 Shepherd, Samuel T.
A1 Baker, Mark D.
A1 Asante, Curtis
A1 Bee, Lucy
A1 Bethry, Audrey
A1 Perkins, James R.
A1 Nassar, Mohammed A.
A1 Abrahamsen, Bjarke
A1 Dickenson, Anthony
A1 Cobb, Bradly S.
A1 Merkenschlager, Matthias
A1 Wood, John N.
YR 2010
UL http://www.jneurosci.org/content/30/32/10860.abstract
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.