Windup of Nociceptive Flexion Reflex Depends on Synaptic and Intrinsic Properties of Dorsal Horn Neurons in Adult Rats

Abstract

Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive peripheral fibers, is a useful model to study central sensitization to pain. Windup is expressed by neurons in both the dorsal and ventral horn of the spinal cord. In juvenile rats, it has been demonstrated both in vivo and in vitro that windup depends on calcium-dependent intrinsic properties and their modulation by synaptic components. However, the involvement of these two components in the adults remains controversial. In the present study, by means of electromyographic and extracellular recordings, we show that windup in adults, in vivo, depends on a synaptic balance between excitatory N-methyl-D-aspartate (NMDA) receptors and inhibitory glycinergic receptors. We also demonstrate the involvement of L-type calcium channels in both the dorsal and ventral horn of the spinal cord. These results indicate that windup in adults is similar to juvenile rats and that windup properties are the same regardless of the spinal network, i.e., sensory or motor.