RT Journal Article
T1 Small RNAs control sodium channel expression, nociceptor excitability, and pain thresholds
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 Richard
A1 Nassar, Mohammed A
A1 Abrahamsen, Bjarke
A1 Dickenson, Anthony
A1 Cobb, Bradly S
A1 Merkenschlager, Matthias
A1 Wood, John N
K1 Expresión génica
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.
PB Society for Neuroscience
YR 2010
FD 2010-08-11
LK https://hdl.handle.net/10630/36665
UL https://hdl.handle.net/10630/36665
LA eng
NO Zhao, J., Lee, M.-C., Momin, A., Cendan, C.-M., Shepherd, S. T., Baker, M. D., Asante, C., Bee, L., Bethry, A., Perkins, J. R., Nassar, M. A., Abrahamsen, B., Dickenson, A., Cobb, B. S., Merkenschlager, M., & Wood, J. N. (2010). Small RNAs control sodium channel expression, nociceptor excitability, and pain thresholds. The Journal of Neuroscience, 30(32), 10860–10871. https://doi.org/10.1523/JNEUROSCI.1980-10.2010
NO This work was supported by the Medical Research Council (J.Z., M.M., J.N.W.), Biotechnology and Biological Sciences Research Council (J.Z., J.N.W.), and the Wellcome Trust (M.A.N., J.N.W.) for support. This work was partially supported by grant no. R31-2008-000-10103-0 from the World Class University project of the Korean Ministry of Education, Science, and Technology and the National Research Foundation of Korea, and C.M.C. was supported by the Research Program of the University of Granada. We thank Marc Friedländer, Ziheng Yang, Huiliang Li, and Ann Sheasby for technical advice and Ramin Raouf and the London Pain Consortium for helpful discussions.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026