• Jing Zhao, Man-Cheung Lee, Ali Momin, Cruz-Miguel Cendan, Samuel T Shepherd, Mark D Baker, Curtis Asante, Lucy Bee, Audrey Bethry, James R Perkins, Mohammed A Nassar, Bjarke Abrahamsen, Anthony Dickenson, Bradly S Cobb, Matthias Merkenschlager, and John N Wood.
• 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
• J. Neurosci. 2010 Aug 11;30(32):10860-71.

AbstractTo 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.

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