Intrathecal Metabotropic Glutamate Receptor Antagonists Do Not Decrease Mechanical Hyperalgesia in a Rat Model of Postoperative Pain

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Abstract
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 IT (+)-alpha-methyl-4-carboxyphenylglycine ([+]-MCPG), (S)-4-carboxyphenylglycine ([S]-4-CPG), (RS)-alpha-cyclopropyl-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)-4-CPG (30, 100 nmol), (RS)-CPPG (100, 500 nmol), or L-AP3 (10, 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. Implications: 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. (Anesth Analg 1998;87:1354-9)