The selective activation of dorsal horn neurons by potassium stimulation of high threshold primary afferent neurons in vitro

Abstract

Intracellular recordings from neurons in the dorsal root ganglion and dorsal horn, in an in vitro spinal cord-dorsal root ganglion preparation, were used to investigate the role of large and small afferent fibers in the sensory synaptic transmission of the superficial dorsal horn. Raising the extracellular potassium concentration from 3.1 to 25–50mM in the dorsal root ganglion compartment evoked a large amplitude depolarization and blocked action potentials in the large neurons of the dorsal root ganglion, and it synaptically excited dorsal horn neurons. Excitatory postsynaptic potentials that were evoked by electrical stimulation of large myelinated fibers, but not those evoked by activation of small unmyelinated fibers, were blocked by the potassium treatment of the dorsal root. Tetrodotoxin (0.3−10 μM), when applied to the sensory neurons, abolished action potentials in large myelinated fibers but had no effect on the potassium-induced depolarization of the soma of large neurons of the dorsal root ganglion. Bath application of tetrodotoxin to the dorsal root ganglion blocked the postsynaptic potentials evoked in dorsal horn neurons by electrical stimulation of large fibers (stimulus intensity 10–20V, 0.02 ms) but failed to block postsynaptic potentials induced by electrical stimulation of slow fibers (stimulus intensity > 35 V, 0.5 ms). In addition, the tetrodotoxin failed to block the synaptic activation of dorsal horn neurons which was induced by the application of high potassium to sensory neurons. Capsaicin (10–100 μM, 10 s), applied to the sensory neurons, resulted in a prolonged synaptic activation of the dorsal horn neurons and a subsequent long lasting desensitization. During the period of capsaicin desensitization, synaptic activation of dorsal horn neurons by application of high potassium to the dorsal root ganglion and electrical stimulation of slow fibres was blocked. The opioid receptor agonist (D-Ala 2, D-Leu 5)-enkephalinamide (1 μM), applied to the spinal cord slice, abolished the dorsal horn neuron excitation evoked by electrical or chemical activation of slow primary afferent fibers. These findings indicate that high concentrations of K + applied to the dorsal root ganglia selectively activate a primary afferent input to the dorsal horn, which is capsaicin sensitive and tetrodotoxin resistant.