Excitatory amino acid receptor-mediated neurotransmission from cutaneous afferents in rat dorsal horn in vitro.
1. The cutaneous mechanoreceptive fields (RFs) of forty-two lumbar dorsal horn neurones have been examined intracellularly using the hemisected spinal cord-hindlimb preparation of 10 to 14-day-old rats. The neurones were classified into three groups on the basis of their excitatory responses to innocuous and noxious mechanical stimulation; the majority (25/42) were activated by noxious and innocuous stimuli and were classed as 'wide-dynamic' type (WDR). 'Nociceptive-specific' neurones (NS) which were excited by noxious stimuli made up the next largest group (12/42) followed by 'low-threshold' neurones (LT, 5/42) which responded only weakly to noxious stimuli. Another fourteen neurones which did not respond to peripheral stimuli were used to test antagonist selectivity against excitatory amino acid agonists. 2. The response to light touch or pinch consisted of an initial EPSP and cell firing followed by subthreshold EPSPs. The mean +/- S.E.M. values for the amplitude (mV) and the duration (s) of the EPSP produced by noxious pinch were significantly greater than those to touch; in WDR neurones the respective values were 14.3 +/- 0.9 vs. 11.5 +/- 0.7 mV (P < 0.01) and 11.9 +/- 1.8 vs. 4.8 +/- 0.6 s (P < 0.01). 3. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 3-5 microM) antagonized DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)-induced depolarizations. The amplitude and duration of the EPSPs produced in response to low- and high-threshold mechanical stimulation were potently attenuated and cell firing was abolished in WDR, NS, LT neurones. A similar profile of antagonism was produced in five WDR neurones superfused with ACSF containing 1 mM D-serine. 4. The NMDA-receptor antagonist D-aminophosphonovalerate (D-AP5, 50 microM) attenuated the EPSP amplitude and duration but never abolished cell firing produced by low- and high-intensity cutaneous mechanical stimulation. A preferential effect of D-AP5 against the EPSP duration resulted in failure of longer latency spikes. 5. The data indicate that non-NMDA receptors contribute substantially to dorsal horn neurotransmission and somatosensory processing of noxious and innocuous cutaneous stimuli, while the role of NMDA receptors is restricted to longer latency synaptic components.
King
A E
AE
Department of Physiology, University of Leeds.
Lopez-Garcia
J A
JA
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017459:Receptors, Amino Acid / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D012867:Skin / Q000294:innervation; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D011810:Quinoxalines; D017459:Receptors, Amino Acid; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate