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Activation of metabotropic glutamate receptor 7 in spinal cord inhibits pain and hyperalgesia in a novel formalin model in sheep.

Publication ,  Journal Article
Dolan, S; Gunn, MD; Crossan, C; Nolan, AM
Published in: Behav Pharmacol
September 2011

This study set out to characterize the contribution of group III metabotropic glutamate receptor 7 activation to nociceptive behaviour and mechanical hypersensitivity in a novel formalin test in sheep. The mGlu receptor 7 allosteric agonist, N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082; 2-20 mM), the nonselective group III mGlu receptor agonist L-(+)-2-amino-4-phosphonobutyric acid (0.2-20 mM) and drug vehicle were injected intrathecally into naive subjects (n=7 per group), or 5 min preformalin (3%; 0.2 ml)/saline injection (intradermal), into the lower forelimb of adult female sheep (n=5-7 per group). Forelimb withdrawal thresholds to noxious mechanical stimulation and pain behaviours (time spent nonweight bearing or flinching) were assessed for up to 180 min. Formalin induced a characteristic biphasic pain-behaviour response and mechanical hyperalgesia between 1-5 and 30-120 min postinjection. Treatment with AMN082, but not L-(+)-2-amino-4-phosphonobutyric acid significantly inhibited both early and late phase formalin-induced hyperalgesia and pain behaviours. AMN082 also induced a rapid but short lasting analgesia in naive subjects. These data suggest that enhancing endogenous metabotropic glutamate receptor 7 activity in spinal cord, using the novel allosteric modulator, AMN082, blocks pain and hyperalgesia, and may be of therapeutic benefit for the treatment of inflammatory pain.

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Published In

Behav Pharmacol

DOI

EISSN

1473-5849

Publication Date

September 2011

Volume

22

Issue

5-6

Start / End Page

582 / 588

Location

England

Related Subject Headings

  • Sheep
  • Receptors, Metabotropic Glutamate
  • Pain
  • Neurology & Neurosurgery
  • Injections, Spinal
  • Inflammation
  • Hyperalgesia
  • Formaldehyde
  • Female
  • Dose-Response Relationship, Drug
 

Citation

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Dolan, S., Gunn, M. D., Crossan, C., & Nolan, A. M. (2011). Activation of metabotropic glutamate receptor 7 in spinal cord inhibits pain and hyperalgesia in a novel formalin model in sheep. Behav Pharmacol, 22(5–6), 582–588. https://doi.org/10.1097/FBP.0b013e3283478802
Dolan, Sharron, Mark Donald Gunn, Claire Crossan, and Andrea Mary Nolan. “Activation of metabotropic glutamate receptor 7 in spinal cord inhibits pain and hyperalgesia in a novel formalin model in sheep.Behav Pharmacol 22, no. 5–6 (September 2011): 582–88. https://doi.org/10.1097/FBP.0b013e3283478802.
Dolan, Sharron, et al. “Activation of metabotropic glutamate receptor 7 in spinal cord inhibits pain and hyperalgesia in a novel formalin model in sheep.Behav Pharmacol, vol. 22, no. 5–6, Sept. 2011, pp. 582–88. Pubmed, doi:10.1097/FBP.0b013e3283478802.
Dolan S, Gunn MD, Crossan C, Nolan AM. Activation of metabotropic glutamate receptor 7 in spinal cord inhibits pain and hyperalgesia in a novel formalin model in sheep. Behav Pharmacol. 2011 Sep;22(5–6):582–588.

Published In

Behav Pharmacol

DOI

EISSN

1473-5849

Publication Date

September 2011

Volume

22

Issue

5-6

Start / End Page

582 / 588

Location

England

Related Subject Headings

  • Sheep
  • Receptors, Metabotropic Glutamate
  • Pain
  • Neurology & Neurosurgery
  • Injections, Spinal
  • Inflammation
  • Hyperalgesia
  • Formaldehyde
  • Female
  • Dose-Response Relationship, Drug