Intrathecal administration of the mGluR compound, (S)-4CPG, attenuates hyperalgesia and allodynia associated with sciatic nerve constriction injury in rats.
The present study examined the effects of intrathecal (i.t.) treatment (twice-daily injections on post-operative (PO) days 0-8) with the metabotropic glutamate receptor (mGluR) compound, (S)-4-carboxyphenylglycine ((S)-4CPG), or the non-competitive N-methyl-D-aspartate (NMDA) antagonist, dizocilipine maleate (MK-801), on mechanical allodynia and cold hyperalgesia associated with chronic constriction injury (CCI) of the sciatic nerve in rats. Also, the effects of early (twice-daily injections on days 0-3) or late (twice-daily injections on days 8-11) (S)-4CPG treatment on the injury-related mechanical allodynia and cold hyperalgesia were assessed in CCI rats. Results demonstrated that 8-day (S)-4CPG or MK-801 treatment attenuated mechanical allodynia (up to PO days 12 or 16, respectively) and cold hyperalgesia (up to PO days 8 or 16, respectively). Results also demonstrated that early (S)-4CPG treatment significantly attenuated the development of mechanical allodynia (90 and 270 nmol) and cold hyperalgesia (270 nmol). However, late treatment with (S)-4CPG did not reduce the nociceptive behaviours in either behavioural task. These data not only confirm that the NMDA receptor plays a role in chronic nociception, but also suggest that Group I mGluRs are more critically involved in the development, and not the maintenance, of mechanical allodynia and cold hyperalgesia associated with CCI in rats.
Fisher
Kim
K
Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, H2W 1R7, Canada Department of Psychology, McGill University, Montreal, Quebec, H2W 1R7, Canada Department of Physiology, McGill University, Montreal, Quebec, H2W 1R7, Canada Astra Research Centre Montreal, Montreal, Quebec, H2W 1R7, Canada Centre de recherche en sciences neurologiques et Département de médecine, Université de Montréal, Montreal, Quebec, H2W 1R7, Canada.
Fundytus
Marian E
ME
Cahill
Catherine M
CM
Coderre
Terence J
TJ
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D003080:Cold Temperature; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006930:Hyperalgesia / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D009408:Nerve Compression Syndromes / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects*; D013997:Time Factors
D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; C079693:4-carboxyphenylglycine; D005998:Glycine