Endocannabinoid-dependent plasticity at spinal nociceptor synapses

Abstract

Key points  Synaptic plasticity between primary nociceptors and second order dorsal horn neurons serves key roles in pain and analgesia  A contribution of NMDA receptors to long-term potentiation and long-term depression at these synapses has been demonstrated before, but much less is known about a possible role of endocannabinoids and cannabinoid (CB)(1) receptors.  Here we show that CB(1) receptors residing on the spinal terminals of primary nociceptors critically contribute to an NMDA receptor-independent form of long-term depression at these synapses, which requires simultaneous pre- and postsynaptic activity.  A similar long-lasting depression of nociceptive signal transmission can also be obtained with application of CB(1) receptor agonists in the presence of presynaptic stimulation alone.  These findings identify a previously unknown form of long-term depression at spinal nociceptor synapses, which may be important for our understanding of pain-related neural plasticity and analgesic actions of CB(1) receptor agonists.