Neurokinin-1 receptor-expressing neurons that contain serotonin and gamma-aminobutyric acid in the rat rostroventromedial medulla are involved in pain processing

Tao Chen, Xiao Lin Wang, Juan Qu, Wei Wang, Ting Zhang, Yuchio Yanagawa, Sheng Xi Wu, Yun Qing Li

Research output: Contribution to journalArticlepeer-review

Abstract

The rostroventromedial medulla (RVM) is an important area of the endogenous pain-regulating system, in which 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) are 2 main transmitters involved in pain modulation. However, whether 5-HT and GABA are colocalized is poorly understood. By using glutamate decarboxylase 67-green fluorescence protein (GAD67-GFP) knock-in mouse, we confirmed the colocalization of 5-HT and GABA in the RVM, with a main distribution in the raphe magnus nucleus and paragigantocellular reticular nucleus. Interestingly, more than half (51.6%) of the 5-HT/GABA-immunoreactive (ir) neurons expressed neurokinin-1 receptors (NK-1R) and one-third (30.1%) of the 5-HT/GABA/NK-1R-ir neurons projected to the spinal cord, suggesting that substance P (SP) should regulate the activity of 5-HT/GABA-ir spinal cord-projecting neurons. By combining retrograde and anterograde tracing methods, we observed that the cuneiform nucleus, dorsal raphe nucleus, and lateral periaqueductal gray are the main origin nuclei for the SP-ir fibers and terminals in the RVM. Finally, after formalin injection into the mice hind paw, 29.2% SP-ir RVM-projecting neurons from supra-RVM nuclei and 33.1% NK-1R-ir spinal cord-projecting neurons in the RVM were activated. The present study provides potent morphological evidence that 5-HT and GABA are coexistent in RVM-spinal cord-projecting neurons that are also regulated by SPergic projections. Perspective: The results will greatly enhance our understanding for the modulation of nociceptive information in the descending pain-regulating system.

Original languageEnglish (US)
Pages (from-to)778-792
Number of pages15
JournalJournal of Pain
Volume14
Issue number8
DOIs
StatePublished - Aug 2013
Externally publishedYes

Keywords

  • GABA
  • GAD67-GFP knock-in mouse
  • Serotonin
  • neurokinin-1 receptor
  • rostroventromedial medulla

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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