Local and diffuse mechanisms of primary afferent depolarization and presynaptic inhibition in the rat spinal cord

Abstract

Two types of dorsal root potential (DRP) were found in the spinal cord of urethane-anaesthetized rats. Local DRPs with short latency-to-onset were evoked on roots close to the point of entry of an afferent volley. Diffuse DRPs with a longer latency-to-onset were seen on more distant roots up to 17 segments from the volley entry zone. The switch to long latency-to-onset occurred abruptly as a function of distance along the cord and could not be explained by conduction delays within the dorsal columns. Long-latency DRPs were also present and superimposed on the short-latency DRPs on nearby roots. Both local and diffuse DRPs were evoked by light mechanical stimuli: von Frey hair thresholds were ≤ 1 gram force Changes in excitability of the terminals of sural nerve afferents were used to confirm that both local and diffuse DRPs were associated with primary afferent depolarization (PAD). These effects were potent: the area of the antidromic volley evoked in the sural nerve by intraspinal microstimulation in the L4/5 spinal segment was increased by 109 ± 50% (mean ± S.D.; n = 5) by nearby conditioning stimuli, and by 52 ± 12% (n = 6) with stimuli applied 9-13 mm (5-8 segments) away. The time course of the changes in terminal excitability closely matched those of the DRPs. Reduction of the field potentials evoked in the dorsal horn by stimulation of dorsal roots was also shown to accompany both local and diffuse DRPs. The area of the monosynaptically evoked field potential was reduced by 48 ± 19% (n = 7) with nearby conditioning stimulation and 16 ± 9% (n = 10) with stimulation 9-12 mm distant. Evidence is presented that this inhibition includes a presynaptic component. Similar effects were seen with field potentials evoked by sural nerve stimulation. It is concluded that diffuse DRPs are mediated through propriospinal networks which may contribute to the gating of sensory information flow during natural behaviour as they respond to weak mechanical stimuli and provoke presynaptic inhibition.

Monoaminergic Modulation of Spinal Viscero-Sympathetic Function in the Neonatal Mouse Thoracic Spinal Cord

“…This suggests that visceral afferent stimulation-induced PAD has a broad distribution, and is consistent with the reported actions of somatosensory evoked PAD [65]. While afferent volleys could be recruited at stimulus intensities as low as 8 µA, 50 µs, greater stimulus intensities were often required to elicit a DRP (Fig.…”

Lateral inhibition during nociceptive processing

“…In the spinal cord, both widespread and local primary afferent depolarization has been identified [16]. Such inhibition may contribute importantly to the dynamic regulation of the receptive field sizes of spinal cord neurons [38].…”

Distinct Modes of Presynaptic Inhibition of Cutaneous Afferents and Their Functions in Behavior

“…Electrical stimulation of sensory afferents or supraspinal centers, or mechanical stimulation of the skin, can evoke PAD in a number of afferent subtypes (Andersen et al, 1962;Carpenter et al, 1963;Eccles et al, 1963b;J€ anig et al, 1968;Jimé nez et al, 1987), and GABA A R antagonists diminish low-threshold cutaneous and proprioceptive afferent-evoked PAD in the cat, rat, turtle, and mouse (Eccles et al, 1963a;Russo et al, 2000;Shreckengost et al, 2010). PAD underlies PSI by paradoxically reducing transmitter release from afferent terminals (Eccles et al, 1963b;Lidierth, 2006), which may involve one or more hypothesized mechanisms: (1) shunting inhibition, caused by Cl À efflux leading to diminished action potential (AP) height and thus transmitter release; (2) inactivation of voltage-gated Na + channels, thereby diminishing AP height and transmitter release; and (3) inactivation of voltage-gated Ca + channels in terminals, reducing transmitter release (Rudomin and Schmidt, 1999). Experimentally, PAD can be measured in individual sensory neuron fibers or, more conveniently, with an extracellular recording electrode placed on the dorsal root and recording a dorsal root potential (DRP), which reflects back-propagating PAD in primary sensory neuron axons (Eccles et al, 1963b;Lidierth, 2006).…”

“…PAD underlies PSI by paradoxically reducing transmitter release from afferent terminals (Eccles et al, 1963b;Lidierth, 2006), which may involve one or more hypothesized mechanisms: (1) shunting inhibition, caused by Cl À efflux leading to diminished action potential (AP) height and thus transmitter release; (2) inactivation of voltage-gated Na + channels, thereby diminishing AP height and transmitter release; and (3) inactivation of voltage-gated Ca + channels in terminals, reducing transmitter release (Rudomin and Schmidt, 1999). Experimentally, PAD can be measured in individual sensory neuron fibers or, more conveniently, with an extracellular recording electrode placed on the dorsal root and recording a dorsal root potential (DRP), which reflects back-propagating PAD in primary sensory neuron axons (Eccles et al, 1963b;Lidierth, 2006).…”