Involvement of phosphatase and tensin homolog deleted from chromosome 10 in rodent model of neuropathic pain

Journal of Neuroinflammation

Zhi-Hong Wen²  Ming-Hong Tai⁷  Tian-Huei Chu³  Hui-Min David Wang¹  San-Cher Chen⁷  Pey-Ru Lin³  Nan-Fu Chen⁶  Han-Chun Hung²  San-Nan Yang⁴  Chien-Wei Feng²  Chun-Hong Chen²  Wu-Fu Chen⁸  Chun-Sung Sung⁵  Shi-Ying Huang⁷ 

[1] Center for Stem Cell Research, Kaohsiung Medical University, No. 100, Shiquan 1st Road, Kaohsiung 80708, Taiwan;Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, No. 70, Lienhai Road, Kaohsiung 80424, Taiwan;Institute of Biomedical Sciences, National Sun Yat-sen University, #70 Lienhai Road, Kaohsiung 80424, Taiwan;School of Medicine, College of Medicine and Department of Pediatrics, E-DA Hospital, I-Shou University, No. 1, Yida Road, Kaohsiung 82445, Taiwan;School of Medicine, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan;Division of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, No. 2, Zhongzheng 1st Road, Kaohsiung 80284, Taiwan;Center for Neuroscience, National Sun Yat-sen University, No. 70, Lienhai Road, Kaohsiung 80424, Taiwan;Department of Neurosurgery, Xiamen Chang Gung Memorial Hospital, No. 123, Xiafei Road, Fujian 361026, China

关键词: Neuroinflammation;    Astrocyte;    Intrathecal;    Chronic constriction injury;   

Others  :  1227105
DOI  :  10.1186/s12974-015-0280-1

 received in 2014-10-22, accepted in 2015-03-07,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Huang et al.; licensee BioMed Central.

【 图 表 】

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