Novel trigeminal slice preparation method for studying mechanisms of nociception transmission

J Neurosci Methods. 2017 Jul 15:286:6-15. doi: 10.1016/j.jneumeth.2017.05.019. Epub 2017 May 15.

Abstract

Background: The trigeminal subnucleus caudalis (Vc) plays a critical role in transmission and modulation of nociceptive afferent inputs, and exhibits a similar layer construction to the spinal dorsal horn. However, afferent inputs enter the brainstem and project to a separately located nucleus. It has previously been difficult to record responses of the Vc to afferent fiber activation in a brainstem slice preparation. The aim of the present study was to establish a novel brainstem slice preparation method to study trigeminal nociceptive transmission mechanisms.

New method: Thirty adult 6-7-week-old C57/BL6J male mice were included in the study. Obliquely sliced brainstem sections at a thickness of 600μm, which included the Vc and the root entry zone to the brainstem, were prepared. The Vc response to electrical stimulation of afferent fibers was observed as a change in intracellular calcium concentration by fluorescence intensity response.

Results: Electrical stimulation of afferent inputs to the trigeminal nerve increased fluorescent intensity in the Vc, which was completely diminished by tetrodotoxin and significantly suppressed by the AMPA/kainate antagonist CNQX (paired t-test, P<0.001), although the non-competitive NMDA antagonist (+)-MK801 maleate resulted in no changes. These results suggested a glutamate receptor-mediated response.

Comparison with existing methods/conclusion: This brainstem slice preparation will be useful for investigating nociceptive transmission mechanisms of the trigeminal nerve.

Keywords: Calcium imaging; Caudalis; Root entry; Slice; Trigeminal spinal nucleus.

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Afferent Pathways / physiology*
  • Animals
  • Calcium / metabolism
  • Dizocilpine Maleate / pharmacology
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Heterocyclic Compounds, 3-Ring / pharmacokinetics
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nociception / physiology*
  • Nociceptors / physiology*
  • Sodium Channel Blockers / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Tetrodotoxin / pharmacology
  • Time Factors
  • Trigeminal Nucleus, Spinal / drug effects
  • Trigeminal Nucleus, Spinal / physiology*

Substances

  • Excitatory Amino Acid Antagonists
  • Heterocyclic Compounds, 3-Ring
  • Sodium Channel Blockers
  • rhod-2
  • Tetrodotoxin
  • Dizocilpine Maleate
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Calcium