Enkephalins modulate excitatory synaptic transmission in the superficial dorsal horn by acting at mu-opioid receptor sites.
The effect of opioids on synaptic potentials of dorsal horn (DH) neurons has been investigated in a rat spinal cord DH slice-dorsal root ganglion (DRG) in vitro preparation. Conventional intracellular recording from DH and DRG neurons using 3 M potassium acetate-filled electrodes was employed. Dorsal roots were electrically isolated from the spinal cord slice and stimulated with pulses of different intensity and duration to evoke afferent action potentials monitored intracellularly from DRG neurons. Low-intensity single-shock stimulation of the dorsal roots (8-20 V pulses of 0.02-0.05 ms duration) activated large primary afferents and elicited excitatory postsynaptic potentials (EPSP) in all of the neurons tested. High-intensity stimulation of the dorsal roots (over 35 V pulses of 0.5 ms duration), sufficient to excite small myelinated and unmyelinated primary afferents resulted in a large and prolonged depolarization of DH neurons associated with firing of action potentials. Bath application (D-Ala2,N-Me-Phe4,Gly5-ol)-enkephalin (DAGO), (D-Ala2,D-Leu5)-enkephalinamide (DADLEA), or (D-Ala2,D-Met5)-enkephalinamide (DADMEA) produced dose-dependent, reversible hyperpolarization in about 75% of the neurons tested. The hyperpolarization was associated with a fall in neuronal input resistance. In addition, opioids depressed the synaptic transmission in all of the neurons examined. This depressant effect of opioids was independent from their effects on resting membrane potential. Delta specific receptor opioid agonists (D-Pen2.5)-enkephalin (DPDPE) and (D-Pen2,L-Pen5)-enkephalin (DPLPE), were completely ineffective in producing an effect on neuronal membrane or synaptic transmission. All opioid effects were antagonized by naloxone.
Jeftinija
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Department of Veterinary Anatomy, Iowa State University, Ames 50011.
D000818:Animals; D004745:Enkephalins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu; D012016:Reference Values; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D004745:Enkephalins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone