Optogenetic activation of brainstem serotonergic neurons induces persistent pain sensitization

YQ Cai, W Wang, YY Hou, ZZ Pan - Molecular pain, 2014 - journals.sagepub.com
YQ Cai, W Wang, YY Hou, ZZ Pan
Molecular pain, 2014journals.sagepub.com
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 …
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.
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