Antisense oligonucleotide knockdown of mGluR1 alleviates hyperalgesia and allodynia associated with chronic inflammation

Chronic inflammation induced by injection of complete Freund's adjuvant (CFA) into one hindpaw elicits thermal hyperalgesia and mechanical allodynia in the injected paw. Metabotropic glutamate receptors (mGluRs) have been implicated in dorsal horn neuronal nociceptive responses and pain associated with short-term inflammation. The goal of the present study was to assess the role of mGluR(1) in the hyperalgesia and allodynia associated with the CIA model of chronic inflammation. Here we show that antisense (AS) oligonucleotide knockdown of spinal mGluR(1) attenuates thermal hyperalgesia and mechanical allodynia in rats injected with CFA in one hindpaw. When intrathecal infusion of mGluR(1) AS oligonucleotide (50 mug/day) began prior to CFA injection, mechanical allodynia was attenuated from Days I to 8 following CFA injection, whereas heat hyperalgesia was attenuated on Day I and then from Days 4 to 8. When intrathecal infusion of mGluR(1) AS oligonucleotide was begun 2 days after CFA injection, both mechanical allodynia and beat hyperalgesia were attenuated at all time points following the oligonucleotide infusion. Thus, the present data suggest a role for mGluR(1) in persistent inflammatory nociception. (C) 2002 Elsevier Science Inc. All rights reserved.