Fig. 5.

Spinal cord stimulation (SCS) recruited GABAergic presynaptic inhibitory pathways observed as bicuculline-sensitive dorsal root potentials (DRPs) and dorsal root reflexes (DRRs). A: SCS-generated DRP with suprathreshold DRRs recorded at the L5 dorsal root entry zone. By convention, negativity is presented upwards to convey the DRP as primary afferent depolarization. Shaded box indicates the location of stimulus artifact and truncated direct antidromic axonal volley preceding the slow DRP. The average response (black) is presented overlying 10 individual events (gray) to demonstrate variability in timing of individual DRRs. B: SCS evokes DRP and DRRs that are blocked following application of the GABA_A receptor antagonist bicuculline (Bic; 10 μM). i: averages of 10 sweeps from the T13 dorsal root entry zone. Both DRP and DRRs are blocked after the addition of Bic (blue). ii: Bic-sensitive DRRs are shown in the absence of an underlying DRP. Shown are 6 events overlaid from an L2 DR recording obtained farther from the root entry zone. In both i and ii, shaded box indicates the location of stimulation artifact and direct primary afferent recruitment. C: schematic depicting possible circuitry responsible for GABAergic actions on afferent axons leading to a form of presynaptic inhibition called primary afferent depolarization (PAD), experimentally observed as DRPs and DRRs. SCS antidromically recruits Aαβ afferent axons responsible for recruiting the spinal circuit leading to PAD. Aαβ afferents synaptically recruit last-order GABAergic interneurons directly or via interposed interneurons (not shown). GABAergic axo-axonic synapses on primary afferents activate Bic-sensitive GABA_A receptors that mediate Cl⁻ efflux to produce PAD. Because these experiments cannot identify the afferent axons generating PAD, possible actions on all afferent classes are shown.