Behavioral evidence supporting a differential role for spinal group I and II metabotropic glutamate receptors in inflammatory hyperalgesia in sheep

Sharron Dolan, Andrea M. Nolan

Research output: Contribution to journalArticle

Abstract

A differential role for metabotropic glutamate receptors (mGluRs) in spinal nociception in normal animals has previously been identified. The present study examined the contribution of group I and group II mGluRs to the development and maintenance of inflammatory hyperalgesia produced by unilateral intradermal injection of carrageenan into the lower forelimb in sheep. Carrageenan (7.5 mg in 500 ìl) produced a significant bilateral reduction in forelimb mechanical withdrawal thresholds. Intrathecal administration of saline-vehicle or the group II mGluR antagonist (2S)-á-ethylglutamate (EGLU; 570 nmol) had no effect on either the development or maintenance of hyperalgesia. However, intrathecal administration of the group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 450 nmol) before carrageenan blocked the development of ipsilateral hyperalgesia, and when given 2 h after carrageenan, reversed both ipsilateral and contralateral hyperalgesia. Intrathecal administration of the group II mGluR agonist (2S,1S,2S)-2-(carboxycyclopropyl)glycine (L-CCG-I; 620 nmol) given either before or after carrageenan treatment produced analgesia and anti-hyperalgesia, an effect abolished by co-administration of EGLU (570 nmol). The magnitude of the analgesic response, assessed by the area under the response curve, was significantly greater than that produced by LCCG-I in normal animals. These data demonstrate that the development and maintenance of inflammatory hyperalgesia is dependent on activation of group I mGluRs in spinal cord. In addition, the analgesic and anti-hyperalgesic actions of group II mGluRs suggest that these receptors play a crucial role in modulating acute inflammatory hyperalgesia.

Original languageEnglish
JournalNeuropharmacology
DOIs
Publication statusPublished - 1 Sep 2002

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Metabotropic Glutamate Receptors
Hyperalgesia
Sheep
Carrageenan
Forelimb
Maintenance
Analgesics
Intradermal Injections
Nociception
Analgesia
Area Under Curve
Spinal Cord

Keywords

  • carrageenan
  • metabotropic glutamate receptors
  • inflammation
  • spinal cord
  • analgesia

Cite this

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title = "Behavioral evidence supporting a differential role for spinal group I and II metabotropic glutamate receptors in inflammatory hyperalgesia in sheep",
abstract = "A differential role for metabotropic glutamate receptors (mGluRs) in spinal nociception in normal animals has previously been identified. The present study examined the contribution of group I and group II mGluRs to the development and maintenance of inflammatory hyperalgesia produced by unilateral intradermal injection of carrageenan into the lower forelimb in sheep. Carrageenan (7.5 mg in 500 {\`i}l) produced a significant bilateral reduction in forelimb mechanical withdrawal thresholds. Intrathecal administration of saline-vehicle or the group II mGluR antagonist (2S)-{\'a}-ethylglutamate (EGLU; 570 nmol) had no effect on either the development or maintenance of hyperalgesia. However, intrathecal administration of the group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 450 nmol) before carrageenan blocked the development of ipsilateral hyperalgesia, and when given 2 h after carrageenan, reversed both ipsilateral and contralateral hyperalgesia. Intrathecal administration of the group II mGluR agonist (2S,1S,2S)-2-(carboxycyclopropyl)glycine (L-CCG-I; 620 nmol) given either before or after carrageenan treatment produced analgesia and anti-hyperalgesia, an effect abolished by co-administration of EGLU (570 nmol). The magnitude of the analgesic response, assessed by the area under the response curve, was significantly greater than that produced by LCCG-I in normal animals. These data demonstrate that the development and maintenance of inflammatory hyperalgesia is dependent on activation of group I mGluRs in spinal cord. In addition, the analgesic and anti-hyperalgesic actions of group II mGluRs suggest that these receptors play a crucial role in modulating acute inflammatory hyperalgesia.",
keywords = "carrageenan, metabotropic glutamate receptors, inflammation, spinal cord, analgesia",
author = "Sharron Dolan and Nolan, {Andrea M.}",
note = "Originally published in: Neuropharmacology (2002), 43 (3), pp.319-326.",
year = "2002",
month = "9",
day = "1",
doi = "10.1016/S0028-3908(02)00107-7",
language = "English",
journal = "Neuropharmacology",
issn = "0028-3908",
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TY - JOUR

T1 - Behavioral evidence supporting a differential role for spinal group I and II metabotropic glutamate receptors in inflammatory hyperalgesia in sheep

AU - Dolan, Sharron

AU - Nolan, Andrea M.

N1 - Originally published in: Neuropharmacology (2002), 43 (3), pp.319-326.

PY - 2002/9/1

Y1 - 2002/9/1

N2 - A differential role for metabotropic glutamate receptors (mGluRs) in spinal nociception in normal animals has previously been identified. The present study examined the contribution of group I and group II mGluRs to the development and maintenance of inflammatory hyperalgesia produced by unilateral intradermal injection of carrageenan into the lower forelimb in sheep. Carrageenan (7.5 mg in 500 ìl) produced a significant bilateral reduction in forelimb mechanical withdrawal thresholds. Intrathecal administration of saline-vehicle or the group II mGluR antagonist (2S)-á-ethylglutamate (EGLU; 570 nmol) had no effect on either the development or maintenance of hyperalgesia. However, intrathecal administration of the group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 450 nmol) before carrageenan blocked the development of ipsilateral hyperalgesia, and when given 2 h after carrageenan, reversed both ipsilateral and contralateral hyperalgesia. Intrathecal administration of the group II mGluR agonist (2S,1S,2S)-2-(carboxycyclopropyl)glycine (L-CCG-I; 620 nmol) given either before or after carrageenan treatment produced analgesia and anti-hyperalgesia, an effect abolished by co-administration of EGLU (570 nmol). The magnitude of the analgesic response, assessed by the area under the response curve, was significantly greater than that produced by LCCG-I in normal animals. These data demonstrate that the development and maintenance of inflammatory hyperalgesia is dependent on activation of group I mGluRs in spinal cord. In addition, the analgesic and anti-hyperalgesic actions of group II mGluRs suggest that these receptors play a crucial role in modulating acute inflammatory hyperalgesia.

AB - A differential role for metabotropic glutamate receptors (mGluRs) in spinal nociception in normal animals has previously been identified. The present study examined the contribution of group I and group II mGluRs to the development and maintenance of inflammatory hyperalgesia produced by unilateral intradermal injection of carrageenan into the lower forelimb in sheep. Carrageenan (7.5 mg in 500 ìl) produced a significant bilateral reduction in forelimb mechanical withdrawal thresholds. Intrathecal administration of saline-vehicle or the group II mGluR antagonist (2S)-á-ethylglutamate (EGLU; 570 nmol) had no effect on either the development or maintenance of hyperalgesia. However, intrathecal administration of the group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 450 nmol) before carrageenan blocked the development of ipsilateral hyperalgesia, and when given 2 h after carrageenan, reversed both ipsilateral and contralateral hyperalgesia. Intrathecal administration of the group II mGluR agonist (2S,1S,2S)-2-(carboxycyclopropyl)glycine (L-CCG-I; 620 nmol) given either before or after carrageenan treatment produced analgesia and anti-hyperalgesia, an effect abolished by co-administration of EGLU (570 nmol). The magnitude of the analgesic response, assessed by the area under the response curve, was significantly greater than that produced by LCCG-I in normal animals. These data demonstrate that the development and maintenance of inflammatory hyperalgesia is dependent on activation of group I mGluRs in spinal cord. In addition, the analgesic and anti-hyperalgesic actions of group II mGluRs suggest that these receptors play a crucial role in modulating acute inflammatory hyperalgesia.

KW - carrageenan

KW - metabotropic glutamate receptors

KW - inflammation

KW - spinal cord

KW - analgesia

U2 - 10.1016/S0028-3908(02)00107-7

DO - 10.1016/S0028-3908(02)00107-7

M3 - Article

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -