PMID- 12763091
OWN - NLM
STAT- MEDLINE
DCOM- 20030708
LR  - 20190726
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 44
IP  - 8
DP  - 2003 Jun
TI  - Role of metabotropic glutamate receptor subtype 5 (mGluR5) in the maintenance of 
      cold hypersensitivity following a peripheral mononeuropathy in the rat.
PG  - 983-93
AB  - The present series of experiments were designed to examine the contribution of 
      metabotropic glutamate receptor subtype 5 (mGluR5) to neuropathic pain by 
      determining the effects of the selective mGluR5 antagonist MPEP 
      (2-methyl-6-(phenylethynyl)-pyridine) on neuropathy-induced cold 
      hypersensitivity. Unilateral chronic constriction injury (CCI) to the sciatic 
      nerve in rats produced an increase in the number of hind paw withdrawals from a 
      cold surface (4 +/- 2 degrees C) which was dose-dependently inhibited by systemic 
      (i.p.) injection of MPEP (ID(50) = 11.3 mg/kg). In vivo brain mGluR5 receptor 
      occupancy following systemic (i.p.) MPEP revealed that >90% occupancy is required 
      for behavioral efficacy. Intracerebroventricular (i.c.v.) injection of MPEP 
      dose-dependently inhibited CCI-induced cold hypersensitivity (ID(50) = 123.5 
      nmol), while microinjection of MPEP directly into the rostral ventromedial 
      medulla (RVM) potently inhibited this hypersensitivity (ID(50) = 1.3 pmol). A 
      role for mGluR5 in the RVM was further supported by the observation that 
      intra-RVM injection of the mGluR5 agonist CHPG (10 nmol; 
      2-chloro-5-hydroxyphenylglycine) produced cold hypersensitivity in naive rats 
      that was blocked by pretreatment with intra-RVM MPEP (3 nmol). Intrathecal (500 
      nmol; i.t.) or intraplantar (300 nmol; i.pl.) injection of MPEP was ineffective 
      in reversing CCI-induced cold hypersensitivity. These results demonstrate that 
      mGluR5 contributes to cold hypersensitivity following peripheral neuropathy 
      exclusively at supraspinal sites in the CNS. Additionally, mGluR5 in the RVM 
      significantly contributes to the maintenance of cold hypersensitivity, likely via 
      activation of descending nociceptive facilitatory systems.
FAU - Urban, M O
AU  - Urban MO
AD  - Department of Behavioral Pharmacology, Merck Research Laboratories, San Diego, CA 
      92121, USA. mark_urban@merck.com
FAU - Hama, A T
AU  - Hama AT
FAU - Bradbury, M
AU  - Bradbury M
FAU - Anderson, J
AU  - Anderson J
FAU - Varney, M A
AU  - Varney MA
FAU - Bristow, L
AU  - Bristow L
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Grm5 protein, rat)
RN  - 0 (Pyridines)
RN  - 0 (Receptor, Metabotropic Glutamate 5)
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - 7VC0YVI27Y (6-methyl-2-(phenylethynyl)pyridine)
SB  - IM
MH  - Animals
MH  - *Cold Temperature
MH  - Constriction, Pathologic
MH  - Excitatory Amino Acid Antagonists/administration & dosage/pharmacology
MH  - Injections, Intraventricular
MH  - Injections, Spinal
MH  - Male
MH  - Medulla Oblongata
MH  - Microinjections
MH  - Pain/etiology/*metabolism
MH  - Peripheral Nervous System Diseases/complications/*metabolism
MH  - Pyridines/administration & dosage/pharmacology
MH  - Radioligand Assay
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Metabotropic Glutamate 5
MH  - Receptors, Metabotropic Glutamate/*metabolism
MH  - Sciatic Nerve
EDAT- 2003/05/24 05:00
MHDA- 2003/07/09 05:00
CRDT- 2003/05/24 05:00
PHST- 2003/05/24 05:00 [pubmed]
PHST- 2003/07/09 05:00 [medline]
PHST- 2003/05/24 05:00 [entrez]
AID - S0028390803001187 [pii]
AID - 10.1016/s0028-3908(03)00118-7 [doi]
PST - ppublish
SO  - Neuropharmacology. 2003 Jun;44(8):983-93. doi: 10.1016/s0028-3908(03)00118-7.