The Role of Type 1 Metabotropic Glutamate Receptors in the Generation of Dorsal Root Reflexes Induced by Acute Arthritis or the Spinal Infusion of 4-Aminopyridine in the Anesthetized Rat

Antidromically propagated action potentials can be recorded in the proximal end of the severed medial articular nerve (MAN) on mechanical stimulation of an inflamed knee in rats and are referred to as dorsal root reflex (DRR) activity. The absence of DRR activity in normal rats suggests that the activity could be the result of hyperexcitability of spinal neurons induced by inflammation. In this study, the role of spinal type 1 metabotropic glutamate (mGlu(1)) receptors in the generation of DRR activity in the MAN during acute knee inflammation was investigated. Four hours after an injection of a mixture of kaolin and carrageenan (k/c) into a knee joint, DRR activity could be evoked in the ipsilateral MAN by mechanical stimulation of the inflamed limb. Spinal application of a selective mGlu(1) receptor antagonist, [RS]-1-Aminoindan-1,5-dicarboxylic acid/UPF 523 (AIDA), or a potent, but less specific mGlu(1) receptor antagonist, LY393053, both depressed the DRR activity significantly. AIDA and LY39053 had no effect on recordings in the MAN from noninflamed control Animals. However, spinal administration of AIDA did suppress DRR activity generated by infusion of 4-aminopyridine (4-AP), a K(+) channel blocker, into the dorsal horn of noninflamed Animals. These observations suggest that mGlu(1) receptors support the generation of DRR activity in the MAN following sensitization of spinal cord neurons.