title: Involvement of phosphatase and tensin homolog deleted from chromosome 10 in rodent model of neuropathic pain.
abstract: BACKGROUND
  Many cancer research studies have extensively examined the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) pathway. There are only few reports that suggest that PTEN might affect pain; however, there is still a lack of evidence to show the role of PTEN for modulating pain. Here, we report a role for PTEN in a rodent model of neuropathic pain.
  
  
  RESULTS
  We found that chronic constriction injury (CCI) surgery in rats could elicit downregulation of spinal PTEN as well as upregulation of phosphorylated PTEN (phospho-PTEN) and phosphorylated mammalian target of rapamycin (phospho-mTOR). After examining such changes in endogenous PTEN in neuropathic rats, we explored the effects of modulating the spinal PTEN pathway on nociceptive behaviors. The normal rats exhibited mechanical allodynia after intrathecal (i.t.) injection of adenovirus-mediated PTEN antisense oligonucleotide (Ad-antisense PTEN). These data indicate the importance of downregulation of spinal PTEN for nociception. Moreover, upregulation of spinal PTEN by i.t. adenovirus-mediated PTEN (Ad-PTEN) significantly prevented CCI-induced development of nociceptive sensitization, thermal hyperalgesia, mechanical allodynia, cold allodynia, and weight-bearing deficits in neuropathic rats. Furthermore, upregulation of spinal PTEN by i.t. Ad-PTEN significantly attenuated CCI-induced microglia and astrocyte activation, upregulation of tumor necrosis factor-α (TNF-α) and phospho-mTOR, and downregulation of PTEN in neuropathic rats 14 days post injury.
  
  
  CONCLUSIONS
  These findings demonstrate that PTEN plays a key, beneficial role in a rodent model of neuropathic pain.
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. johnjohnkings@gmail.com.|Center for Neuroscience, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. johnjohnkings@gmail.com.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Taipei, 11217, Taiwan. cssung@vghtpe.gov.tw.|School of Medicine, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei, 11221, Taiwan. cssung@vghtpe.gov.tw.
authors.forename: Chun-Sung
authors.initials: CS
authors.lastname: Sung
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. ma4949@cgmh.org.tw.|Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, DAPI Road, Kaohsiung, 83301, Taiwan. ma4949@cgmh.org.tw.|Department of Neurosurgery, Xiamen Chang Gung Memorial Hospital, No. 123, Xiafei Road, Fujian, 361026, China. ma4949@cgmh.org.tw.
authors.forename: Wu-Fu
authors.initials: WF
authors.lastname: Chen
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. anubis0620@gmail.com.|Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. anubis0620@gmail.com.
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. qscjuejuejue@gmail.com.|Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. qscjuejuejue@gmail.com.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Feng
authors.affiliation: School of Medicine, College of Medicine and Department of Pediatrics, E-DA Hospital, I-Shou University, No. 1, Yida Road, Kaohsiung, 82445, Taiwan. y520729@gmail.com.
authors.forename: San-Nan
authors.initials: SN
authors.lastname: Yang
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. hanchun25@gmail.com.|Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. hanchun25@gmail.com.
authors.forename: Han-Chun
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. chen06688@gmail.com.|Division of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, No. 2, Zhongzheng 1st Road, Kaohsiung, 80284, Taiwan. chen06688@gmail.com.
authors.forename: Nan-Fu
authors.initials: NF
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-sen University, #70 Lienhai Road, Kaohsiung, 80424, Taiwan. peyru.lin@msa.hinet.net.
authors.forename: Pey-Ru
authors.initials: PR
authors.lastname: Lin
authors.affiliation: Center for Neuroscience, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. chensancher@yahoo.com.tw.|Institute of Biomedical Sciences, National Sun Yat-sen University, #70 Lienhai Road, Kaohsiung, 80424, Taiwan. chensancher@yahoo.com.tw.
authors.forename: San-Cher
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. davidw@kmu.edu.tw.|Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, No. 100, Shiquan 1st Road, Kaohsiung, 80708, Taiwan. davidw@kmu.edu.tw.|Graduate Institute of Natural Products, Kaohsiung Medical University, No. 100, Shiquan 1st Road, Kaohsiung, 80708, Taiwan. davidw@kmu.edu.tw.|Center for Stem Cell Research, Kaohsiung Medical University, No. 100, Shiquan 1st Road, Kaohsiung, 80708, Taiwan. davidw@kmu.edu.tw.
authors.forename: Hui-Min David
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-sen University, #70 Lienhai Road, Kaohsiung, 80424, Taiwan. skbboyz0817@gmail.com.
authors.forename: Tian-Huei
authors.initials: TH
authors.lastname: Chu
authors.affiliation: Center for Neuroscience, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. minghongtai@gmail.com.|Institute of Biomedical Sciences, National Sun Yat-sen University, #70 Lienhai Road, Kaohsiung, 80424, Taiwan. minghongtai@gmail.com.|Department of Biological Sciences, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. minghongtai@gmail.com.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. wzh@mail.nsysu.edu.tw.|Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. wzh@mail.nsysu.edu.tw.|Marine Biomedical Laboratory and Center for Translational Biopharmaceuticals, Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung, 80424, Taiwan. wzh@mail.nsysu.edu.tw.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006930:Hyperalgesia; D008297:Male; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D017288:Pain Threshold; D051381:Rats; D017208:Rats, Wistar; D012585:Sciatica / Q000473:pathology* / Q000503:physiopathology; D020123:Sirolimus / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D039481:CD11b Antigen; D049452:Green Fluorescent Proteins; D051059:PTEN Phosphohydrolase; D020123:Sirolimus