• You-Qing Cai, Wei Wang, Yuan-Yuan Hou, and Zhizhong Z Pan.
• Department of Anesthesiology and Pain Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. zzpan@mdanderson.org.
• Mol Pain. 2014 Jan 1;10:70.

BackgroundThe 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.ResultsIn 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.ConclusionsThese results suggest that selective activation of RVM 5-HT neurons exerts a predominant effect of pain facilitation under control conditions.

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