Up-regulation of metabotropic glutamate receptor subtypes 3 and 5 in spinal cord in a clinical model of persistent inflammation and hyperalgesia

Evidence from experimental pain research has revealed that metabotropic glutamate receptors (mGluRs) play a pivotal role in nociceptive processing, inflammatory pain and hyperalgesia. The aim of this study was to characterise expression of group I and II mGluRs in spinal cord in a model of naturally occurring persistent inflammation (sheep with unilateral lameness due to inflammation of the digital tissues of the feet, estimated to have been affected by the condition for >2 weeks) and an experimental model of acute inflammation (injection of intradermal carrageenan into lower forelimb in sheep). Animals with unilateral clinical inflammation displayed significant mechanical hyperalgesia on the affected limb. Carrageenan treatment produced significant bilateral limb mechanical hyperalgesia 3 h post-injection. Up-regulation of mGluR3 and mGluR5 mRNA was observed in ipsilateral spinal cord recovered from clinically lame animals, restricted to laminae II–V and I–II, respectively. Western blot analyses of protein extracts revealed a bilateral increase in mGluR2/3 and mGluR5. No change was detected in spinal cord mGluR1 or mGluR2 mRNA. There was no change in mGluR1,2,3,5 subtype mRNA or proteins in spinal cord recovered from animals 3 h post-carrageenan. These results demonstrate for the first time that mGluR subtypes are differentially expressed in spinal cord dorsal horn in response to persistent inflammation, and suggest that mGluR activity may be involved in mediating altered behaviours associated with clinical inflammatory pain.