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 mGluR1 in the hyperalgesia and allodynia associated with the CFA model of chronic inflammation. Here we show that antisense (AS) oligonucleotide knockdown of spinal mGluR1 attenuates thermal hyperalgesia and mechanical allodynia in rats injected with CFA in one hindpaw. When intrathecal infusion of mGluR1 AS oligonucleotide (50 microg/day) began prior to CFA injection, mechanical allodynia was attenuated from Days 1 to 8 following CFA injection, whereas heat hyperalgesia was attenuated on Day 1 and then from Days 4 to 8. When intrathecal infusion of mGluR1 AS oligonucleotide was begun 2 days after CFA injection, both mechanical allodynia and heat hyperalgesia were attenuated at all time points following the oligonucleotide infusion. Thus, the present data suggest a role for mGluR1 in persistent inflammatory nociception.
Department of Physiology, McGill University, Montreal, Canada. marian.fundytus@pharma.com
Marian E
ME
Fundytus
Michael G
MG
Osborne
James L
JL
Henry
Terence J
TJ
Coderre
Andy
A
Dray
D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D005620:Freund's Adjuvant; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D008297:Male; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D005620:Freund's Adjuvant