Background and purpose: 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.
Experimental approach: 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.
Key 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 and implications: 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.
© 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.