title: Optogenetic activation of brainstem serotonergic neurons induces persistent pain sensitization.
abstract: 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.
authors.forename: You-Qing
authors.initials: YQ
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Hou
authors.affiliation: Department of Anesthesiology and Pain Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. zzpan@mdanderson.org.
authors.forename: Zhizhong Z
authors.initials: ZZ
authors.lastname: Pan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D000075402:Channelrhodopsins; D005260:Female; D006930:Hyperalgesia / Q000473:pathology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D062308:Optogenetics; D017288:Pain Threshold / Q000502:physiology; D059326:Serotonergic Neurons / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase