The N-methyl-D-aspartate (NMDA) receptor is postsynaptic to substance P- containing axon terminals in the rat superficial dorsal horn

Sue Aicher, Sarita Sharma, Peter Y. Cheng, Virginia M. Pickel

Research output: Contribution to journalArticle

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Abstract

The N-methyl-D-aspartate (NMDA) receptor is thought to mediate the postsynaptic effects of excitatory amino acids released from primary afferent terminals in the superficial layers of the dorsal horn of the spinal cord where synergistic associations with substance P (SP) have been implicated in the production of hyperalgesia. We examined the electron microscopic dual immunocytochemical localization of SP and the R1 subunit of the NMDA receptor (NMDAR1) in this region to determine the cellular basis for interactions between SP and NMDA receptor ligands. Of 971 profiles immunolabeled for NMDAR1, 40% were dendrites and the remainder were primarily unmyelinated axons and astrocytic processes. In dendrites, NMDAR1-like immunoreactivity (NMDAR1-LI) was associated with synaptic and non-synaptic portions of the plasma membrane, as well as intracellular membranes including smooth endoplasmic reticulum. These NMDAR1-labeled dendrites received synaptic input from unlabeled terminals and from terminals containing SP and/or NMDAR1-LI and they occasionally (25/389) also contained SP. In contrast, of 540 SP- immunoreactive profiles, 60% were axon terminals and the majority (252/324) of these SP-labeled terminals were presynaptic to NMDAR1-containing dendrites. These results provide anatomical evidence that the synergistic nociceptive effects of SP and NMDA ligands are attributed mainly to dual modulation of the activity of single dendritic targets in the dorsal horn of the spinal cord. They also suggest that activation of NMDA receptors may also play a role in the modulation of SP neurons, presynaptic release of SP or other neurotransmitters, and in glial function in the dorsal horn.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalBrain Research
Volume772
Issue number1-2
DOIs
StatePublished - Oct 24 1997
Externally publishedYes

Fingerprint

Presynaptic Terminals
Substance P
N-Methyl-D-Aspartate Receptors
Dendrites
Spinal Cord Dorsal Horn
Ligands
Smooth Endoplasmic Reticulum
Intracellular Membranes
Excitatory Amino Acids
Hyperalgesia
N-Methylaspartate
NMDA receptor A1
Neuroglia
Neurotransmitter Agents
Axons
Cell Membrane
Electrons
Neurons

Keywords

  • Dorsal horn
  • NMDA receptor
  • Nociception
  • Pain
  • Primary afferent
  • Substance P

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The N-methyl-D-aspartate (NMDA) receptor is postsynaptic to substance P- containing axon terminals in the rat superficial dorsal horn. / Aicher, Sue; Sharma, Sarita; Cheng, Peter Y.; Pickel, Virginia M.

In: Brain Research, Vol. 772, No. 1-2, 24.10.1997, p. 71-81.

Research output: Contribution to journalArticle

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