The role of neurokinin and N-methyl-d-aspartate receptors in synaptic transmission from capsaicin-sensitive primary afferents in the rat spinal cord in vitro

I. Nagy, C. A. Maggi, A. Dray, C. J. Woolf, L. Urban

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

The rat spinal cord with connected dorsal root ganglia was used to study neurokinin and N-methyl-d-aspartate receptors involved in the sensory synaptic transmission of dorsal horn cells. Selective C-fibre excitation was produced by capsaicin (200-500 nM) administered to the dorsal root ganglions. Sixty-nine per cent of dorsal horn cells responded with a postsynaptic depolarization and enhanced synaptic activity, recorded via intracellular electrodes, to capsaicin-activated primary afferent input. Dorsal horn neurons activated by the capsaicin-evoked input were also excited by a 1-min perfusion of the neurokinin-1 receptor agonists substance P methyl ester or GR73 632 and by the neurokinin-2 agonist neurokinin-A. These cells were also depolarized by N-methyl-d-aspartate. Responses to substance P methyl ester and GR73 632 were selectively reduced by the neurokinin-1 receptor antagonist CP96 345, and responses to neurokinin-A were completely blocked by the neurokinin-2 receptor antagonist MEN 10 376. The depolarization evoked by N-methyl-d-aspartate was not altered by either of the antagonists, but was completely blocked by the selective N-methyl-d-aspartate receptor antagonist (-)-2-amino-5-phosphonovaleric acid. Capsaicin-evoked responses in the dorsal horn were inhibited by MEN 10 376 (63 ± 13% inhibition) but no significant change was observed with CP96 345. The N-methyl-d-aspartate receptor antagonist (-)-2-amino-5-phosphonovaleric acid consistently inhibited the capsaicin-induced response by 76 ± 14%. Combination of (-)-2-amino-5-phosphonovaleric acid and MEN 10 376 produced an almost complete abolition of the capsaicin-evoked depolarization. However, when (-)-2-amino-5-phosphonovaleric acid and CP96 345 were perfused together there was no alteration from the response to (-)-2-amino-5-phosphonovaleric acid alone. These data suggest that activation of dorsal horn neurons by polymodal nociceptors, the most abundant type of capsaicin sensitive C-fibres, involve mainly neurokinin-2 rather than neurokinin-1 receptors. A strong N-methyl-d-aspartate receptor-mediated component is also involved. The N-methyl-d-aspartate and neurokinin-2 receptors may be co-activated by nociceptive input and act together to produce slow synaptic potentials and prolonged excitability changes.

Original languageEnglish
Pages (from-to)1029-1037
Number of pages9
JournalNeuroscience
Volume52
Issue number4
DOIs
Publication statusPublished - 1993

Fingerprint

Capsaicin
Synaptic Transmission
2-Amino-5-phosphonovalerate
Spinal Cord
Posterior Horn Cells
Neurokinin-2 Receptors
Aspartic Acid
Neurokinin A
Neurokinin-1 Receptors
Unmyelinated Nerve Fibers
Spinal Ganglia
Neurokinin-1 Receptor Antagonists
Synaptic Potentials
Nociceptors
aspartic acid receptor
In Vitro Techniques
Electrodes
Perfusion
Tyr(5)-Trp(6,8,9)-Lys(10)-neurokinin A(4-10)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The role of neurokinin and N-methyl-d-aspartate receptors in synaptic transmission from capsaicin-sensitive primary afferents in the rat spinal cord in vitro. / Nagy, I.; Maggi, C. A.; Dray, A.; Woolf, C. J.; Urban, L.

In: Neuroscience, Vol. 52, No. 4, 1993, p. 1029-1037.

Research output: Contribution to journalArticle

@article{75ec369859ef49d691475b99c15b8161,
title = "The role of neurokinin and N-methyl-d-aspartate receptors in synaptic transmission from capsaicin-sensitive primary afferents in the rat spinal cord in vitro",
abstract = "The rat spinal cord with connected dorsal root ganglia was used to study neurokinin and N-methyl-d-aspartate receptors involved in the sensory synaptic transmission of dorsal horn cells. Selective C-fibre excitation was produced by capsaicin (200-500 nM) administered to the dorsal root ganglions. Sixty-nine per cent of dorsal horn cells responded with a postsynaptic depolarization and enhanced synaptic activity, recorded via intracellular electrodes, to capsaicin-activated primary afferent input. Dorsal horn neurons activated by the capsaicin-evoked input were also excited by a 1-min perfusion of the neurokinin-1 receptor agonists substance P methyl ester or GR73 632 and by the neurokinin-2 agonist neurokinin-A. These cells were also depolarized by N-methyl-d-aspartate. Responses to substance P methyl ester and GR73 632 were selectively reduced by the neurokinin-1 receptor antagonist CP96 345, and responses to neurokinin-A were completely blocked by the neurokinin-2 receptor antagonist MEN 10 376. The depolarization evoked by N-methyl-d-aspartate was not altered by either of the antagonists, but was completely blocked by the selective N-methyl-d-aspartate receptor antagonist (-)-2-amino-5-phosphonovaleric acid. Capsaicin-evoked responses in the dorsal horn were inhibited by MEN 10 376 (63 ± 13{\%} inhibition) but no significant change was observed with CP96 345. The N-methyl-d-aspartate receptor antagonist (-)-2-amino-5-phosphonovaleric acid consistently inhibited the capsaicin-induced response by 76 ± 14{\%}. Combination of (-)-2-amino-5-phosphonovaleric acid and MEN 10 376 produced an almost complete abolition of the capsaicin-evoked depolarization. However, when (-)-2-amino-5-phosphonovaleric acid and CP96 345 were perfused together there was no alteration from the response to (-)-2-amino-5-phosphonovaleric acid alone. These data suggest that activation of dorsal horn neurons by polymodal nociceptors, the most abundant type of capsaicin sensitive C-fibres, involve mainly neurokinin-2 rather than neurokinin-1 receptors. A strong N-methyl-d-aspartate receptor-mediated component is also involved. The N-methyl-d-aspartate and neurokinin-2 receptors may be co-activated by nociceptive input and act together to produce slow synaptic potentials and prolonged excitability changes.",
author = "I. Nagy and Maggi, {C. A.} and A. Dray and Woolf, {C. J.} and L. Urban",
year = "1993",
doi = "10.1016/0306-4522(93)90549-U",
language = "English",
volume = "52",
pages = "1029--1037",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "4",

}

TY - JOUR

T1 - The role of neurokinin and N-methyl-d-aspartate receptors in synaptic transmission from capsaicin-sensitive primary afferents in the rat spinal cord in vitro

AU - Nagy, I.

AU - Maggi, C. A.

AU - Dray, A.

AU - Woolf, C. J.

AU - Urban, L.

PY - 1993

Y1 - 1993

N2 - The rat spinal cord with connected dorsal root ganglia was used to study neurokinin and N-methyl-d-aspartate receptors involved in the sensory synaptic transmission of dorsal horn cells. Selective C-fibre excitation was produced by capsaicin (200-500 nM) administered to the dorsal root ganglions. Sixty-nine per cent of dorsal horn cells responded with a postsynaptic depolarization and enhanced synaptic activity, recorded via intracellular electrodes, to capsaicin-activated primary afferent input. Dorsal horn neurons activated by the capsaicin-evoked input were also excited by a 1-min perfusion of the neurokinin-1 receptor agonists substance P methyl ester or GR73 632 and by the neurokinin-2 agonist neurokinin-A. These cells were also depolarized by N-methyl-d-aspartate. Responses to substance P methyl ester and GR73 632 were selectively reduced by the neurokinin-1 receptor antagonist CP96 345, and responses to neurokinin-A were completely blocked by the neurokinin-2 receptor antagonist MEN 10 376. The depolarization evoked by N-methyl-d-aspartate was not altered by either of the antagonists, but was completely blocked by the selective N-methyl-d-aspartate receptor antagonist (-)-2-amino-5-phosphonovaleric acid. Capsaicin-evoked responses in the dorsal horn were inhibited by MEN 10 376 (63 ± 13% inhibition) but no significant change was observed with CP96 345. The N-methyl-d-aspartate receptor antagonist (-)-2-amino-5-phosphonovaleric acid consistently inhibited the capsaicin-induced response by 76 ± 14%. Combination of (-)-2-amino-5-phosphonovaleric acid and MEN 10 376 produced an almost complete abolition of the capsaicin-evoked depolarization. However, when (-)-2-amino-5-phosphonovaleric acid and CP96 345 were perfused together there was no alteration from the response to (-)-2-amino-5-phosphonovaleric acid alone. These data suggest that activation of dorsal horn neurons by polymodal nociceptors, the most abundant type of capsaicin sensitive C-fibres, involve mainly neurokinin-2 rather than neurokinin-1 receptors. A strong N-methyl-d-aspartate receptor-mediated component is also involved. The N-methyl-d-aspartate and neurokinin-2 receptors may be co-activated by nociceptive input and act together to produce slow synaptic potentials and prolonged excitability changes.

AB - The rat spinal cord with connected dorsal root ganglia was used to study neurokinin and N-methyl-d-aspartate receptors involved in the sensory synaptic transmission of dorsal horn cells. Selective C-fibre excitation was produced by capsaicin (200-500 nM) administered to the dorsal root ganglions. Sixty-nine per cent of dorsal horn cells responded with a postsynaptic depolarization and enhanced synaptic activity, recorded via intracellular electrodes, to capsaicin-activated primary afferent input. Dorsal horn neurons activated by the capsaicin-evoked input were also excited by a 1-min perfusion of the neurokinin-1 receptor agonists substance P methyl ester or GR73 632 and by the neurokinin-2 agonist neurokinin-A. These cells were also depolarized by N-methyl-d-aspartate. Responses to substance P methyl ester and GR73 632 were selectively reduced by the neurokinin-1 receptor antagonist CP96 345, and responses to neurokinin-A were completely blocked by the neurokinin-2 receptor antagonist MEN 10 376. The depolarization evoked by N-methyl-d-aspartate was not altered by either of the antagonists, but was completely blocked by the selective N-methyl-d-aspartate receptor antagonist (-)-2-amino-5-phosphonovaleric acid. Capsaicin-evoked responses in the dorsal horn were inhibited by MEN 10 376 (63 ± 13% inhibition) but no significant change was observed with CP96 345. The N-methyl-d-aspartate receptor antagonist (-)-2-amino-5-phosphonovaleric acid consistently inhibited the capsaicin-induced response by 76 ± 14%. Combination of (-)-2-amino-5-phosphonovaleric acid and MEN 10 376 produced an almost complete abolition of the capsaicin-evoked depolarization. However, when (-)-2-amino-5-phosphonovaleric acid and CP96 345 were perfused together there was no alteration from the response to (-)-2-amino-5-phosphonovaleric acid alone. These data suggest that activation of dorsal horn neurons by polymodal nociceptors, the most abundant type of capsaicin sensitive C-fibres, involve mainly neurokinin-2 rather than neurokinin-1 receptors. A strong N-methyl-d-aspartate receptor-mediated component is also involved. The N-methyl-d-aspartate and neurokinin-2 receptors may be co-activated by nociceptive input and act together to produce slow synaptic potentials and prolonged excitability changes.

UR - http://www.scopus.com/inward/record.url?scp=0027472096&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027472096&partnerID=8YFLogxK

U2 - 10.1016/0306-4522(93)90549-U

DO - 10.1016/0306-4522(93)90549-U

M3 - Article

C2 - 7680798

AN - SCOPUS:0027472096

VL - 52

SP - 1029

EP - 1037

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 4

ER -