title: LIMK-dependent actin polymerization in primary sensory neurons promotes the development of inflammatory heat hyperalgesia in rats.
abstract: 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.
authors: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Health, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors: Yi
authors: Y
authors: Li
authors: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Health, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors: Fang
authors: F
authors: Hu
authors: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Health, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors: Hai-Jing
authors: HJ
authors: Chen
authors: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Health, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors: Yi-Juan
authors: YJ
authors: Du
authors: Beijing Huijia Private School, Beijing 102200, China.
authors: Zhi-Ying
authors: ZY
authors: Xie
authors: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Health, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors: Ying
authors: Y
authors: Zhang
authors: Department of Anatomy and Histology, School of Basic Medical Sciences, Peking University, Beijing 100191, China. wangy66@bjmu.edu.cn wangjun74008@bjmu.edu.cn.
authors: Jun
authors: J
authors: Wang
authors: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Health, School of Basic Medical Sciences, Peking University, Beijing 100191, China. PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China. wangy66@bjmu.edu.cn wangjun74008@bjmu.edu.cn.
authors: Yun
authors: Y
authors: Wang
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000378:metabolism; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000633:toxicity; D005727:Ganglia, Spinal / Q000166:cytology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D058105:Polymerization; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D000199:Actins; C495812:Cfl1 protein, rat; D051338:Cofilin 1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D005620:Freund's Adjuvant; D054461:Lim Kinases; C515894:Limk1 protein, rat; C490644:Limk2 protein, rat