Postsynaptic dorsal column pathway activation during spinal cord stimulation in patients with chronic pain

Abstract

Spinal cord stimulation (SCS) treatment for chronic pain relies on the activation of primary sensory fibres ascending to the brain in the dorsal columns. While the efficacy of SCS has been demonstrated, the precise mechanism of action and nature of the fibres activated by stimulation remain largely unexplored. Our investigation in humans with chronic neuropathic pain undergoing SCS therapy, found that post-synaptic dorsal column (PSDC) fibres can be activated synaptically by the primary afferents recruited by stimulation, and axonically by the stimulation pulses directly. Synaptic activation occurred in 9 of the 14 patients analysed and depended on the vertebral level of stimulation. A clear difference in conduction velocities between the primary afferents and the PSDC fibres were observed. Identification of PSDC fibre activation in humans emphasises the need for further investigation into the role they play in pain relief and the sensory response sensation (paraesthesia) experienced by patients undergoing SCS.

Keywords: electrophysiology; mechanism of action; neural response recordings; neuroanatomy; neuropathic pain; postsynaptic dorsal column pathway; spinal cord stimulation.

Figure 1

Example propagation plots for patient 13. Left: propagating ECAP observed for stimulation at T11 (stimulation pulse applied at time t = 748 μs). Right: propagation of the N1 peak latencies versus distance from stimulation. CV of the ECAP is taken as the inverse of the slope of the linear fit of these points. The CV in this case was found to be 52 m/s.

Figure 2

Orthodromic neural responses of Patients 07 and 11 when stimulating at T11/T12 intervertebral disc. (A) Elicitation of a primary ECAP alone in patient 11 and a secondary ECAP in patient 7 (stimulation pulse applied at time t = 958 μs). (B) Negative lobes of the primary and secondary ECAPs (labelled N1 and N2, respectively, normalised to the end of the stimulation pulse) propagate at distinct CVs away from the stimulus site (47.3 m/s and 94.8 m/s respectively). The secondary ECAP delay in initiation, measured as the difference of the y-intercepts of the linear fits of the N1 and N2 propagation plots, is approximately 1.46 milliseconds after the primary ECAP.

Figure 3

Fibre activation in patients undergoing spinal cord stimulation therapy for chronic neuropathic pain. (A) Propagation plot of 79 current sweeps conducted in fourteen patients. Delayed N2 peaks were observed in the orthodromic direction only. Note that by convention for this plot, negative values were attributed to distances in the antidromic direction. The antidromic N1 peaks originate from 13 patients, and 44 experiments. The orthodromic N1 peaks originate from 13 patients and 57 experiments, and the orthodromic N2 peaks from 9 patients and 23 experiments. Latencies normalised to the end of the stimulation pulse. (B) Representative example from patient 16 showing secondary fibre propagation only orthodromically. Stimulation on CH12 (located at the bottom of T10) at 40 mA, 30 Hz, 30us PW and recording at a distance of 24 mm from the stimulation in both the antidromic and orthodromic directions (stimulation pulse applied at time t = 748 μs). The secondary ECAP is only observed in the orthodromic direction.

Figure 4

(A) Secondary fibre activation prevalence according to vertebral level stimulation. (B) Representative example from patient 18. Stimulation at T10 elicits a secondary ECAP while stimulation at mid-T9 does not. Stimulation done at 30 Hz, 240us PW (stimulation pulse applied at time t = 958 μs).

Figure 5

Average conduction velocities separated by propagation direction (orthodromic/antidromic) and by the vertebral level of stimulation. ^*Student’s t-tests, p < 0.05; SEM, standard error of the means.

Figure 6

Peak conduction velocity recorded across all experiments with at least 3 datapoints available. (A) CV of N1 peaks propagating antidromically. (B) CV of N1 peaks propagating orthodromically. (C) CV of N2 peaks propagating orthodromically.

Figure 7

Schematic illustration of the primary sensory afferents (red) and postsynaptic dorsal column fibres (blue) activated by spinal cord stimulation. As shown in the traces from patient 17, the secondary ECAP is faster, but starts only after activation by the primary ECAP. The traces appear to “catch up” with each other as they ascend to the brain.