Supraspinal Mechanisms of Spinal Cord Stimulation for Modulation of Pain: Five Decades of Research and Prospects for the Future

Abstract

The field of spinal cord stimulation is expanding rapidly, with new waveform paradigms asserting supraspinal sites of action. The scope of treatment applications is also broadening from chronic pain to include cerebral ischemia, dystonia, tremor, multiple sclerosis, Parkinson disease, neuropsychiatric disorders, memory, addiction, cognitive function, and other neurologic diseases. The role of neurostimulation as an alternative strategy to opioids for chronic pain treatment is under robust discussion in both scientific and public forums. An understanding of the supraspinal mechanisms underlying the beneficial effects of spinal cord stimulation will aid in the appropriate application and development of optimal stimulation strategies for modulating pain signaling pathways. In this review, the authors focus on clinical and preclinical studies that indicate the role of supraspinal mechanisms in spinal cord stimulation-induced pain inhibition, and explore directions for future investigations.

Conflict of interest statement

Conflicts of Interest

Y.G. and S.R. received research grant support from Medtronic, Inc. B.L. is a consultant for Medtronic Inc., St Jude Medical, Boston Scientific, and Elekta AB. All other authors declare no competing interests.

Figures

Figure 1

Cross sectional representations of experiments that have examined supraspinal mechanisms of spinal cord stimulator therapy in chronological order. EEG: electroencephalogram, SCS: spinal cord stimulation, VPL: ventral posterolateral nucleus of the thalamus, GABA: γ-amino-butyric acid, APTN: anterior pretectal nucleus, PAG: periaqueductal grey.

Figure 2

Sagittal brain anatomy of regions involved in supraspinal mechanisms of spinal cord stimulation. *The thalamus insert depicts the thalamus corpus which is situated laterally to the midsagittal section as illustrated.

Figure 3

Cross sectional neuroanatomy of potential supraspinal pathways mediating spinal cord stimulation induced pain inhibition.

Figure 4

Schematic of historical perspective on pain modulation by spinal cord stimulation. Dorsal column stimulation results in direct presynaptic inhibition of small diameter sensory neurons and the activation of inhibitory interneurons producing an inhibitory effect on these neurons. Dorsal column stimulation also activates descending pain inhibitory pathways originating from the locus coeruleus and raphe nuclei.