Cholinergic, noradrenergic, and serotonergic inhibition of fast synaptic transmission in spinal lumbar dorsal horn of rat.
It is known that spinal nociceptive sensory transmission receives descending inhibitory and facilitatory modulation from supraspinal structures. Glutamate is the major fast excitatory transmitter between primary afferent fibers and spinal dorsal horn neurons. In whole-cell patch clamp recordings from dorsal horn neurons in spinal slices, we investigated synaptic mechanisms for inhibitory modulation at the lumbar level of the spinal cord. Application of the cholinergic receptor agonist carbachol produced a dose-dependent inhibition of glutamate-mediated excitatory postsynaptic currents (EPSCs) (IC(50) 13 microM). Postsynaptic injection of two different types of G-protein inhibitors, guanosine 5'-O-2-thiophosphate or guanosine 5'-O-3-thiotriphosphate, blocked the inhibition produced by carbachol. Clonidine, a selective alpha-adrenergic receptor agonist, also produced a dose-dependent inhibition of EPSCs (IC(50) 7 microM) that was reduced by postsynaptic inhibition of G-proteins. The inhibitory effect of serotonin was likewise mediated by postsynaptic G-proteins. Our results suggest that activation of postsynaptic neurotransmitter receptors plays a critical role in inhibition of glutamate mediated sensory responses by acetylcholine, norepinephrine, and serotonin. Our results support the hypothesis that descending sensory modulation may be mediated by multiple neurotransmitter receptors in the spinal cord.
Li
P
P
Department of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, St. Louis, MO 61103, USA.
Zhuo
M
M
D000109:Acetylcholine / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004525:Efferent Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D008159:Lumbar Vertebrae; D018721:Muscarinic Agonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013126:Spinal Nerve Roots / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D018721:Muscarinic Agonists; D018377:Neurotransmitter Agents; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018698:Glutamic Acid; D000109:Acetylcholine; D009638:Norepinephrine