Intrathecal metabotropic glutamate receptor antagonists do not decrease mechanical hyperalgesia in a rat model of postoperative pain.
Spinal metabotropic glutamate receptors (mGluR) have been implicated in hyperalgesia after injury. The purpose of this study was to examine the effects of intrathecal (IT) mGluR antagonists on mechanical hyperalgesia in a rat model of human postoperative pain. The hindpaw withdrawal threshold to punctate stimulation using von Frey filaments and the response frequency to a nonpunctate stimulus applied directly to the wound were also measured. The effects of 1T (+)-alpha-methyl-carboxyphenylglycine ([+]-MCPG), (S)-carboxyphenylglycine ([S]-4-CPG), (RS)-alphacyclopropyl-4-phosphonophenylglycine ([RS]-CPPG) and L-2-amino-3-phosphonopropionic acid (L-AP3) on incision-induced mechanical hyperalgesia were examined. The withdrawal thresholds to punctate stimuli were not different from vehicle treatment after the IT administration of (+)-MCPG (100, 500 nmol), (S)4CPG (30, 100 nmol), (RS)-CPPG (100, 500 nmol), or L-AP3 (1, 30, 100 nmol). None of the IT mGluR antagonists decreased the response frequency to the nonpunctate stimulus. The largest dose of (+)-MCPG produced sufficient receptor antagonism because spontaneous nociceptive behaviors caused by the IT administration of a mGluR agonist were reduced.


CONCLUSIONS
Spinal metabotropic glutamate receptors antagonists, antinociceptive in some models of persistent pain, are not necessary for the maintenance of mechanical hyperalgesia in this rat model, which suggests that blockade of spinal metabotropic glutamate receptors may not be useful for the treatment of pain after surgery.
Zahn
P K
PK
Department of Anesthesia, University of Iowa, Iowa City, USA.
Brennan
T J
TJ
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D008297:Male; D017288:Pain Threshold; D010149:Postoperative Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate