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LIMK-dependent actin polymerization in primary sensory neurons promotes the development of inflammatory heat hyperalgesia in rats.

Authors: Li, Y  Hu, F  Chen, HJ  Du, YJ  Xie, ZY  Zhang, Y  Wang, J  Wang, Y 
Citation: Li Y, etal., Sci Signal. 2014 Jun 24;7(331):ra61. doi: 10.1126/scisignal.2005353.
Pubmed: (View Article at PubMed) PMID:24962708
DOI: Full-text: DOI:10.1126/scisignal.2005353

Changes in the actin cytoskeleton in neurons are associated with synaptic plasticity and may also be involved in mechanisms of nociception. We found that the LIM motif-containing protein kinases (LIMKs), which regulate actin dynamics, promoted the development of inflammatory hyperalgesia (excessive sensitivity to painful stimuli). Pain is sensed by the primary sensory neurons of dorsal root ganglion (DRG). In rats injected with complete Freund's adjuvant (CFA), which induces inflammatory heat hyperalgesia, DRG neurons showed an increase in LIMK activity and in the phosphorylation and thus inhibition of the LIMK substrate cofilin, an actin-severing protein. Manipulations that reduced LIMK activity or abundance, prevented the phosphorylation of cofilin, or disrupted actin filaments in DRG neurons attenuated CFA-induced heat hyperalgesia. Inflammatory stimuli stimulated actin polymerization and enhanced the response of the cation channel TRPV1 (transient receptor potential V1) to capsaicin in DRG neurons, effects that were reversed by the knockdown of LIMK or preventing cofilin phosphorylation. Furthermore, inflammatory stimuli caused the serine phosphorylation of TRPV1, which was abolished by preventing cofilin phosphorylation in DRG neurons. We conclude that LIMK-dependent actin rearrangement in primary sensory neurons, leading to altered TRPV1 sensitivity, is involved in the development of inflammatory hyperalgesia.

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RGD ID: 11570412
Created: 2016-12-14
Species: All species
Last Modified: 2016-12-14
Status: ACTIVE



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