Optogenetic activation of brainstem serotonergic neurons induces persistent pain sensitization

Molecular Pain

Zhizhong Z Pan¹  Yuan-Yuan Hou¹  Wei Wang¹  You-Qing Cai¹ 

[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: Pain;    Rostral ventromedial medulla;    Descending facilitation;    Optogenetic;    5-HT;    Serotonin;   

Others  :  1135559
DOI  :  10.1186/1744-8069-10-70

 received in 2014-04-16, accepted in 2014-06-18,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Cai et al.; licensee BioMed Central Ltd.

【 图 表 】

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