Nicotinic receptor modulation of primary afferent excitability with selective regulation of Aδ-mediated spinal actions.

Somatosensory input strength can be modulated by primary afferent depolarization (PAD) generated predominantly via presynaptic GABA receptors on afferent terminals. We investigated whether ionotropic nicotinic acetylcholine receptors (nAChRs) also provide modulatory actions, focusing on myelinated afferent excitability in in vitro murine spinal cord nerve-attached models. Primary afferent stimulation-evoked synaptic transmission was recorded in the deep dorsal horn as extracellular field potentials (EFPs), whereas concurrently recorded dorsal root potentials (DRPs) were used as an indirect measure of PAD.

Presynaptic inhibition of primary afferents by depolarization: observations supporting nontraditional mechanisms.

Primary afferent neurotransmission is the fundamental first step in the central processing of sensory stimuli and is controlled by pre- and postsynaptic inhibitory mechanisms. Presynaptic inhibition (PSI) is probably the more powerful form of inhibitory control in all primary afferent fibers. A major mechanism producing afferent PSI is via a channel-mediated depolarization of their intraspinal terminals, which can be recorded extracellularly as a dorsal root potential (DRP).

Bicuculline-sensitive primary afferent depolarization remains after greatly restricting synaptic transmission in the mammalian spinal cord.

Primary afferent neurotransmission is the fundamental first step in the central processing of sensory stimuli. A major mechanism producing afferent presynaptic inhibition is via a channel-mediated depolarization of their intraspinal terminals which can be recorded extracellularly as a dorsal root potential (DRP). Based on measures of DRP latency it has been inferred that this primary afferent depolarization (PAD) of low-threshold afferents is mediated by minimally trisynaptic pathways with GABAergic interneurons forming last-order axoaxonic synapses onto afferent terminals.