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Merck

Optogenetic activation of brainstem serotonergic neurons induces persistent pain sensitization.

Molecular pain (2014-11-21)
You-Qing Cai, Wei Wang, Yuan-Yuan Hou, Zhizhong Z Pan
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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. 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. These results suggest that selective activation of RVM 5-HT neurons exerts a predominant effect of pain facilitation under control conditions.

MATERIALS
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Supelco
4-tert-Octylphenol monoethoxylate solution, 10 ฮผg/mL in acetone, analytical standard
Supelco
N,Nโ€ฒ-Bis(acryloyl)cystamine, BioReagent, suitable for electrophoresis
Sigma-Aldrich
Ammonium hydrogen difluoride, reagent grade, 95%
Sigma-Aldrich
Ammonium hydrogen difluoride, 99.999% trace metals basis