Exploration of the Supraspinal Hypotheses about Spinal Cord Stimulation and Dorsal Root Ganglion Stimulation: A Systematic Review

Abstract

Despite the established efficacy and effectiveness of Spinal Cord Stimulation (SCS), there is still no consensus on the supraspinal mechanisms of action of this therapy. The purpose of this study was to systematically review previously raised hypotheses concerning supraspinal mechanisms of action of SCS based on human, animal and computational studies. Searches were conducted using four electronic databases (PubMed, EMBASE, SCOPUS and Web of Science), backward reference searching and consultation with experts. The study protocol was registered prior to initiation of the review process (PROSPERO CRD42020161531). A total of 54 publications were included, 21 of which were animal studies, and 33 were human studies. The supraspinal hypotheses (n = 69) identified from the included studies could be categorized into six groups concerning the proposed supraspinal hypothesis, namely descending pathways (n = 24); ascending medial pathway (n = 13); ascending lateral pathway (n = 10); affective/motivational influences (n = 8); spinal–cerebral (thalamic)-loop (n = 3) and miscellaneous (n = 11). Scientific support is provided for the hypotheses identified. Modulation of the descending nociceptive inhibitory pathways, medial and lateral pathways were the most frequently reported hypotheses about the supraspinal mechanisms of action of SCS. These hypotheses were mainly supported by studies with a high or moderate confidence in the body of evidence.

Comparison of Spinal Cord Stimulation vs. Dorsal Root Ganglion Stimulation vs. Association of Both in Patients with Refractory Chronic Back and/or Lower Limb Neuropathic Pain: An International, Prospective, Randomized, Double-Blinded, Crossover Trial (BOOST-DRG Study)

“…Other animal studies have reported that cholinergic activation can enhance SCS pain relief [43,44]. Similarly, release of neurotransmitters such as adenosine, serotonin and noradrenaline by SCS could contribute to pain relief [43,45,46]. Recent studies have reported that 50% of the effects of conventional SCS in neuropathic pain imply supraspinal circuitry [45,47].…”

“…Recent studies have reported that 50% of the effects of conventional SCS in neuropathic pain imply supraspinal circuitry [45,47]. Assuming spinal and supraspinal activation during SCS or DRGS applied in an animal model [47], a recent systematic review synthesizes current literature on the supraspinal mechanisms of action underlying the pain-relieving effect of SCS and DRGS in animal and human studies [46]. Through 54 studies, Goudman et al [46] reported that three main supraspinal hypotheses indicate modulation of the descending nociceptive inhibitory pathways, followed by modulation of the ascending medial and lateral pathways.…”

“…Assuming spinal and supraspinal activation during SCS or DRGS applied in an animal model [47], a recent systematic review synthesizes current literature on the supraspinal mechanisms of action underlying the pain-relieving effect of SCS and DRGS in animal and human studies [46]. Through 54 studies, Goudman et al [46] reported that three main supraspinal hypotheses indicate modulation of the descending nociceptive inhibitory pathways, followed by modulation of the ascending medial and lateral pathways. The difference, in terms of mechanisms of action, between tonic conventional stimulation (TCS) and burst stimulation could be due to the more selective modulation of the medial pain pathway provided by burst stimulation, as evidenced on metabolic activation of the dorsal anterior cingulated cortex on a limited number of patients [48].…”

Combining Awake Anesthesia with Minimal Invasive Surgery Optimizes Intraoperative Surgical Spinal Cord Stimulation Lead Placement

“…This modulates temporal resolution of the electrical signal in view of obtaining better pain relief, less discomfort and more personalized therapy by selecting or even combining several signals at the same time [13][14][15][16][17][18]. This also identifies new SCS mechanisms of action conveyed by different patterns from the classical gate control theory [19][20][21][22]. -SCS spatial resolution has been optimized through multiplication of contacts at the surface of implanted leads, generating more precise and complex electrical fields, in view of enhancing spatial neural targeting [16,23].…”

Electrochemical Skin Conductance Alterations during Spinal Cord Stimulation: An Experimental Study

“…Since the late 1960s, with the introduction of the pain gate control theory [11], several complementary hypotheses based on spinal, segmental, and supraspinal elements have been proposed [12,13]. The hypotheses that have gained a lot of attention are the supraspinal mechanisms with modulations of the descending nociceptive inhibitory pathways [14], the ascending medial pathway [15], and the ascending lateral pathway [16,17]. More recent research has pointed towards the involvement of glial cells [18,19], gene expression [20], and local tissue temperature increases [21].…”