Time-related roles of excitatory amino acid receptors during persistent noxiously evoked responses of rat dorsal horn neurones.

The responses of convergent dorsal horn neurones to peripheral injection of formalin (5% formaldehyde, 50 microliters volume) were recorded extracellularly in the halothane anaesthetized rat. The control response of dorsal horn neurones to formalin was biphasic, with a first phase from 0-10 min and the second inflammatory phase from 10-60 min. Pre-administered intrathecal CNQX (5, 50 and 500 micrograms), 5 min before formalin injection, significantly reduced both the first phase (40 +/- 22, 52 +/- 20 and 40 +/- 28% inhibition, respectively, P < 0.05) and the second phase of the formalin response (40 +/- 20% inhibition, P < 0.05, 93 +/- 4% inhibition, P < 0.0001 and 65 +/- 17% inhibition, P < 0.05, respectively). Post-administered CNQX, administered 5 min after the peripheral injection of formalin, was less efficacious, as compared to pre-administered CNQX, at reducing the second phase of the formalin response. The lowest dose of post-administered CNQX (5 micrograms) facilitated the second phase of the response (47 +/- 19% facilitation, P < 0.05), and the higher dose (50 micrograms) produced smaller inhibitions of the response (42 +/- 10% inhibition, P < 0.05) than those observed with pre-administration of the same dose. However, the highest dose of CNQX (500 micrograms) studied produced similar inhibitions of the second phase of the formalin response, irrespective of the timing of administration. Intrathecal administration of 7-chlorokynurenate (7CK, 0.25-2.5 micrograms), a functional antagonist at the glycine site of the NMDA receptor, did not alter the first phase of the formalin response. The second phase of the formalin response was significantly inhibited, and to a similar extent, by both pre- and post-administration of 2.5 micrograms of 7CK (67 +/- 10% and 56 +/- 7% inhibition respectively, P < 0.05 for both). Overall, our results clearly demonstrate differential time-related roles of different transmitter systems in the induction and maintenance of inflammatory evoked persistent pain responses, and such events may become increasingly relevant to the control of pain in the clinic.