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

Chapman, V; Dickenson, AH; (1995) Time-related roles of excitatory amino acid receptors during persistent noxiously evoked responses of rat dorsal horn neurones. BRAIN RES , 703 (1-2) 45 - 50.

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Abstract

The responses of convergent dorsal horn neurones to peripheral injection of formalin (5% formaldehyde, 50 mu l 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 mu g), 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 mu g) facilitated the second phase of the response (47 +/- 19% facilitation, P < 0.05), and the higher dose (50 mu g) 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 mu g) 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 mu g), 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 mu g 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.

Type: Article
Title: Time-related roles of excitatory amino acid receptors during persistent noxiously evoked responses of rat dorsal horn neurones
Keywords: NMDA receptor, AMPA receptor, spinal cord, nociception, central hypersensitivity, rat, NMDA RECEPTOR, SPINAL-CORD, FORMALIN TEST, GLYCINE SITE, CENTRAL SENSITIZATION, NOCICEPTIVE NEURONS, ANTAGONISTS, PAIN, GLUTAMATE, INVOLVEMENT
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/132353
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