Characterization of hyperpolarization-activated currents in deep dorsal horn neurons of neonate mouse spinal cordin vitro

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Abstract

Emerging evidence suggests that blockade of hyperpolarization-activated current (Ih) produces analgesia acting at peripheral sites. However, little is known about the role of this current in central pain-processing structures. The aim of the present work was to characterize the Ih in deep dorsal horn neurons and to assess the role of the current in the transmission of somatosensory signals across spinal circuits.

To these purpose in vitro preparations of the spinal cord from mice pups were used in combination with whole cell recordings to characterize the current in native neurons. Extracellular recordings from sensory and motor pathways were performed to assess the role of the current in spinal somatosensory processing. Cesium chloride and ZD7288 were used as current blockers.

Most deep dorsal horn neurons showed a functional Ih that was blocked by ZD7288 and cesium. Ih blockade caused hyperpolarization, increased input resistance and potentiation of synaptic responses. Excitatory effects of Ih blockade on synaptic transmission were confirmed in projecting anterolateral axons and ventral roots. Ih modulation by cAMP produced a rightward shift in the voltage dependency curve and blocked excitatory effects of ZD7288 on sensory pathways.

Results indicate that Ih currents play a stabilizing role in the spinal cord controlling transmission across sensory and motor spinal pathways via cellular effects on input resistance and excitability. In addition, results suggest that current modulation may alter significantly the role of the current in somatosensory processing.

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