N-arachidonyl-glycine modulates synaptic transmission in superficial dorsal horn.
OBJECTIVE
The arachidonyl-amino acid N-arachidonyl-glycine (NAGly) is an endogenous lipid, generated within the spinal cord and producing spinally mediated analgesia via non-cannabinoid mechanisms. In this study we examined the actions of NAGly on neurons within the superficial dorsal horn, a key site for the actions of many analgesic agents.


METHODS
Whole cell patch clamp recordings were made from lamina II neurons in rat spinal cord slices to examine the effect of NAGly on glycinergic and NMDA-mediated synaptic transmission.


RESULTS
N-arachidonyl-glycine prolonged the decay of glycine, but not β-alanine induced inward currents and decreased the amplitude of currents induced by both glycine and β-alanine. NAGly and ALX-1393 (inhibitor of the glycine transporter, GLYT2), but not the GLYT1 inhibitor, ALX-5407, produced a strychnine-sensitive inward current. ALX-5407 and ALX-1393, but not NAGly prolonged the decay phase of glycine receptor-mediated miniature inhibitory postsynaptic currents (IPSCs). NAGly prolonged the decay phase of evoked IPSCs, although to a lesser extent than ALX-5407 and ALX-1393. In the presence of ALX-1393, NAGly shortened the decay phase of evoked IPSCs. ALX-5407 increased and NAGly decreased the amplitude of evoked NMDA-mediated excitatory postsynaptic currents.


CONCLUSIONS
Our results suggest that NAGly enhanced inhibitory glycinergic synaptic transmission within the superficial dorsal horn by blocking glycine uptake via GLYT2. In addition, NAGly decreased excitatory NMDA-mediated synaptic transmission. Together, these findings provide a cellular explanation for the spinal analgesic actions of NAGly.
Jeong
Hyo-Jin
HJ
Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, University of Sydney at Royal North Shore Hospital, NSW, Australia. jeong@med.usyd.edu.au
Vandenberg
Robert J
RJ
Vaughan
Christopher W
CW
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000378:metabolism; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012521:Sarcosine / Q000031:analogs & derivatives / Q000494:pharmacology; D012694:Serine / Q000031:analogs & derivatives / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
C510369:(R)-(N-(3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl))sarcosine; C539864:ALX 1393; D001095:Arachidonic Acids; C465623:N-arachidonylglycine; D012694:Serine; D016202:N-Methylaspartate; D005998:Glycine; D012521:Sarcosine