The pharmacological effects of intrathecally administered excitatory amino acid receptor ligands in the formalin test

The aim of the current studies was to clarify the role of excitatory amino acids (EAAs) in the transmission of nociceptive signals produced by injection of formalin in conscious rats. Studies were conducted by identifying the responses to EAAs administered via chronically implanted intrathecal (i.t.) cannulae. I.t. administration of both GLU and ASP produced significantly increased nociceptive responses when injected prior to 1.0% formalin. Phase 1 (0-10 min) nociception was more sensitive to the spinal administration of both GLU and ASP, while Phase 2 (10-60 min) nociception was only increased following the administration of higher doses of GLU. Thus, GLU and ASP appear to have a role in the spinal processing of nociceptive inputs. I.t. administration of NMDA produced significant hyperalgesia during Phase 1 (0.75 and 1.0 nmol) but was without effect on Phase 2 nociception, suggesting that ASP-induced Phase 1 hyperalgesia was mediated via an NMDA receptor. I.t. administration of aminohydroxymethyl isoxazolapropionic acid (AMPA) or the EAA metabotropic receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (tACPD) were without effect on formalin-induced nociception in either Phase. I.t. administration of both kainic acid (KA) and domoic acid (DOM) prior to 2.5% formalin produced significant antinociceptive effects. The selective low-affinity KA receptor antagonist NS-102 significantly reversed KA-and DOM-induced antinociception indicating that the antinociception produced by both KA and DOM was mediated via low-affinity KA receptors. (Abstract shortened by UMI.).