Authors: Y Qiu W Y Chen Z Y Wang F Liu M Wei C Ma Y G Huang
Publish Date: 2016/05/23
Volume: 41, Issue: 9, Pages: 2457-2469
Abstract
Neuropathic pain occurs due to deleterious changes in the nervous system caused by a lesion or dysfunction Currently neuropathic pain management is unsatisfactory and remains a challenge in clinical practice Studies have suggested that actin cytoskeleton remodeling may be associated with neural plasticity and may involve a nociceptive mechanism Here we found that the RhoA/LIM kinase LIMK/cofilin pathway which regulates actin dynamics was activated after chronic constriction injury CCI of the sciatic nerve Treatments that reduced RhoA/LIMK/cofilin pathway activity including simvastatin the Rho kinase inhibitor Y27632 and the synthetic peptide TatS3 attenuated actin filament disruption in the dorsal root ganglion and CCIinduced neuropathic pain Overactivation of the cytoskeleton caused by RhoA/LIMK/cofilin pathway activation may produce a scaffold for the trafficking of nociceptive signaling factors leading to chronic neuropathic pain Here we found that simvastatin significantly decreased the ratio of membrane/cytosolic RhoA which was significantly increased after CCI by inhibiting the RhoA/LIMK/cofilin pathway This effect was highly dependent on the function of the cytoskeleton as a scaffold for signal trafficking We conclude that simvastatin attenuated neuropathic pain in rats subjected to CCI by inhibiting actinmediated intracellular trafficking to suppress RhoA/LIMK/cofilin pathway activity
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