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Spinal nociceptive transmission receives biphasic modulation from supraspinal structures. Recent studies demonstrate that the anterior cingulate cortex (ACC) facilitates spinal excitatory synaptic transmission and nociceptive reflex. However, whether the top-down descending facilitation can cause long-term synaptic changes in spinal cord remains unclear. In the present study, we recorded C-fiber evoked field potentials in spinal dorsal horn and found that the ACC stimulation caused enhancement of C fiber mediated responses. The enhancement lasted for more than a few hours. Spinal application of NMDA receptor antagonist D-AP5 abolished this enhancement, suggesting the activation of NMDA receptor is required. Furthermore, spinal application of methysergide, a serotonin receptor antagonist, also blocked the ACC induced spinal long-term potentiation (LTP). Our results suggest that the ACC stimulation can produce heterosynaptic form of LTP at the spinal cord dorsal horn, and this novel form of LTP may contribute to top-down long-term facilitation in chronic pain conditions.

Heterosynaptic long-term potentiation from the anterior cingulate cortex to spinal cord in adult rats