Optogenetic activation of brainstem serotonergic neurons induces persistent pain sensitization

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• 作者：You-Qing Cai (1)
  Wei Wang (1)
  Yuan-Yuan Hou (1)
  Zhizhong Z Pan (1)
  
  1. Department of Anesthesiology and Pain Medicine ; The University of Texas MD Anderson Cancer Center ; 1515 Holcombe Boulevard ; Houston ; Texas ; 77030 ; USA
  
• 关键词：Serotonin ; 5 ; HT ; Optogenetic ; Descending facilitation ; Rostral ventromedial medulla ; Pain
• 刊名：Molecular Pain
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：10
• 期：1
• 全文大小：3,339 KB
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• 刊物主题：Pain Medicine; Molecular Medicine;
• 出版者：BioMed Central
• ISSN：1744-8069

文摘

Background The rostral ventromedial medulla (RVM) is a key brainstem structure that conveys powerful descending influence of the central pain-modulating system on spinal pain transmission and processing. Serotonergic (5-HT) neurons are a major component in the heterogeneous populations of RVM neurons and in the descending pathways from RVM. However, the descending influence of RVM 5-HT neurons on pain behaviors remains unclear. Results In this study using optogenetic stimulation in tryptophan hydroxylase 2 (TPH2)- Channelrhodopsin 2 (ChR2) transgenic mice, we determined the behavioral effects of selective activation of RVM 5-HT neurons on mechanical and thermal pain behaviors in vivo. We found that ChR2-EYFP-positive neurons strongly co-localized with TPH2-positive (5-HT) neurons in RVM. Optogenetic stimulation significantly increased c-fos expression in 5-HT cells in the RVM of TPH2-ChR2 mice, but not in wild type mice. Behaviorally, the optogenetic stimulation decreased both mechanical and thermal pain threshold in an intensity-dependent manner, with repeated stimulation producing sensitized pain behavior for up to two weeks. Conclusions These results suggest that selective activation of RVM 5-HT neurons exerts a predominant effect of pain facilitation under control conditions.