In vivo antinociceptive activity of anti-rat mGluR1 and mGluR5 antibodies in rats.
To examine the specific roles of group I metabotropic glutamate receptors (mGluRs) in nociceptive processing, we examined the effects of intrathecal (i.t.) treatment with antibodies raised against the C-terminals of mGluR1 and mGluR5 in various rat pain models. The effects of anti-mGluR1 IgG and anti-mGluR5 IgG were assessed in a model of persistent pain induced by intrathecal administration of the mGluR1/5 agonist DHPG, as well as in models of heat pain (plantar test), chemical pain (formalin test) and neuropathic pain. DHPG-induced spontaneous nociceptive behaviours (SNB) were significantly attenuated by i.t. treatment with either anti-mGluR1 IgG (30 microg) or anti-mGluR5 IgG (10 and 30 microg). Neither anti-mGluR1 IgG (30 microg) nor anti-mGluR5 IgG (30 microg) significantly increased response latencies to noxious heat in the plantar test, compared with anti-rat IgG (control IgG). Moreover, neither antibody (30 microg) significantly reduced formalin pain scores as compared to control IgG. However, i.t. treatment with anti-mGluR1 IgG (30 microg) or anti-mGluR5 IgG (30 microg) significantly reduced cold hypersensitivity exhibited 8 days after constriction injury of the sciatic nerve, supporting the contention that group I mGluRs play a role in the development of neuropathic pain. Because these antibodies were effective against neuropathic pain, and not acute heat or chemical noxious stimuli, these results suggest that mGluRs are involved in nociceptive processing in chronic pain states rather than signaling acute noxious stimuli, and that DHPG-induced pain may be mediated by similar mechanisms as neuropathic pain.
Fundytus
M E
ME
Department of Physiology, McGill University, ASTRA Research Centre, Montréal, Québec, Canada.
Fisher
K
K
Dray
A
A
Henry
J L
JL
Coderre
T J
TJ
D000700:Analgesics; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000503:physiopathology* / Q000517:prevention & control; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D012118:Resorcinols / Q000008:administration & dosage / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D007074:Immunoglobulin G; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C104077:metabotropic glutamate receptor type 1; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine