Revisiting SCS: stimulation or conduction block? - Pathos

SCS involves the implantation of electrodes in the epidural space. The first documented instance of this procedure was in 1967, when Shealy and colleagues 5 performed a thoracic laminectomy and implanted platinum plates that were sutured to the dura mater. This procedure became so widely used in the US during the second half of the 1960s that its indiscriminate use led to unsatisfactory results and a decline in interest in the method until the early 1970s. During this period, the percutaneous insertion of temporary electrodes was proposed as a means of testing patients prior to definitive implantation.10,11 Consequently, the percutaneous technique, which had been employed solely for testing, was subsequently adopted for definitive implantation.12 The initial proposal of spinal cord stimulation (SCS) was exclusively for the purpose of analgesia. However, it was subsequently recognised that SCS has the capacity to interfere with various autonomic functions. Its utilisation in the management of urinary retention in paraplegics13 has been documented, as has its application in the treatment of bladder incontinence,14 angina pectoris, and Raynaud's phenomenon in scleroderma. The utilisation of the aforementioned treatment has also been documented in the prevention of cerebral vasospasm-related damage.

It is evident that SCS exerts an analgesic effect in specific types of neuropathic pain, yet this effect is not observed in nociceptive pain. It has also been demonstrated to possess an autonomic-vasodilatory effect, which has significant applications in the treatment of peripheral artery disease and angina pectoris. Furthermore, due to its sympatholytic effect, SCS is an important contrast to CRPS in terms of pathogenesis.1

The hypotheses formulated to explain the mechanisms of action of SCS are summarised below: the theory of activation of large myelinated afferents; the theory of conduction block; and the theory of glial activation block.

Despite the ongoing discourse surrounding the gate control theory in this context as if it were a religious tradition, it is implicated only in the mechanism of action of SCS with regard to Aβ fibres that run parallel to the dorsal horn of the spinal cord and activate the inhibitory interneuron of the gelatinous substance. In reality, this has a modest analgesic effect that only affects nociceptive pain conducted by C fibres. In the case of SCS, this is of negligible relevance as it does not affect the control of neuropathic pain from axonal neuropathy, which is of greater importance.

Notwithstanding the various gate control theories, the theory of the activation of large myelinated afferents remains the most widely accepted of the proposed theories. According to this theory, the activation of Aβ fibres located in the posterior columns of the spinal cord instigates the generation of orthodromic impulses. Upon reaching the nuclei of the gracile and cuneate fascicles, these impulses activate supraspinal centres, from which descending inhibitory pathways originate in the dorsolateral funiculus (DLF). Antidromic impulses are known to travel along collaterals directed to the superficial layers of the dorsal horn of the spinal cord (Figure 1). In both pathways, Aβ fibres have been observed to activate inhibitory interneurons in the dorsal horn of the spinal cord. The descending pathways in the dorsal lateral funiculus (DLF) have been shown to activate the 5-HT inhibitory receptors of the second neuron, thereby explaining the analgesic effect observed in cases of axonal neuropathic pain. The collaterals directed to the superficial layers of the dorsal horn of the spinal cord activate the inhibitory interneurons of the gelatinous substance, as well as the GABA_B receptors in the second neuron and the GABA_B receptors in the neuron of sympathetic origin. This phenomenon contributes to the analgesic effect observed in cases of axonal neuropathic pain.

In comparison to the approach that was almost unquestioningly accepted until around 15 years ago, SCS must now be re-examined in light of new technological advances, such as high-frequency SCS and Burst SCS. The efficacy of these techniques in treating lumbar pain, which is often not clearly defined but is likely to be of a nociceptive nature, is well-documented. Furthermore, these techniques are easier to implement as they do not require the patient to cooperate by searching for paresthesia. Consequently, these procedures can be performed under the administration of general anaesthesia.

In order to facilitate the management of lumbosacral and lower limb discomfort, it is imperative to employ a double octopolar electrode configuration, meticulously positioned between the eighth and eleventh thoracic vertebrae. The initial contact of one electrode is to be situated at the uppermost border of the eighth thoracic vertebra's body, while the final contact of the second electrode is to be placed at the lowermost border of the eleventh thoracic vertebra's body (Figure 3). In order to facilitate the management of cervicobrachial and upper limb discomfort, it is recommended that a double octopolar electrode be positioned between C2 and C7 at the midline. This approach has been shown to minimise the potential for electrode displacement, thereby reducing the occurrence of undesirable variations in paresthesia intensity associated with alterations in position.

The issue that remains to be resolved is the understanding of whether these novel techniques exert a "stimulation" and an "indirect inhibition" or whether they do something completely different. It is disconcerting that instead of developing new technologies to achieve a goal, we are compelled to question the mechanisms by which they achieve that goal.

Firstly, the question of whether high-frequency SCS and Burst SCS are synonymous remains unresolved. However, DeRidder et al. 23 posit that both modalities act by modulating the medial pain pathways, a term that remains undefined and may signify a reduction in nociceptive afferent fibre activity or an increase in the activity of fibres that activate inhibitory circuits. The two techniques would thus be equivalent insofar as they do not cause paresthesia, due to the low intensity of the current supplied being insufficient to activate the Aβ afferents of the posterior cords.

The majority of observers concur that high-frequency SCS is more efficacious than conventional SCS. Moreover, frequent reports indicate that, in contrast to traditional SCS, high-frequency SCS effectively controls lumbar pain.24-30

Burst SCS, first reported by DeRidder 31 consists of packets of 5 pulses with a frequency of 500 Hz and a PW of 1000 μsec that are sent 40 times per second, i.e. at intervals that mimic the natural tendency of the CNS to discharge and would produce an analgesic effect by "synchronizing" with them (Table 1).32,33

Frequency (Hz) PW (μseconds) Intensity (mA)

Traditional SCS 50–100 50–500 3–8

High-frequency SCS 10,000 30 1–6

Burst SCS 500

(intra-burst frequency) 40

(inter-burst frequency) 1,000 2–3

A thorough review of the extant literature on the subject reveals a paucity of clarity regarding the operational mechanisms of these novel techniques. The prevailing sentiment that emerges from this examination is one of disinterest in this particular aspect, suggesting a lack of engagement and exploration of the underlying principles. A review of the literature on the mechanisms of action reveals that Burst SCS exerts its effect by reducing the discharge of WDR-n in the CDMS. 34. Furthermore, it has been established that both high-frequency SCS and Burst SCS function by modulating the medial pain pathways [Bocci et al., 2018; Ahmed et al., 2018]. Additionally, it has been determined that the intensity of the current delivered to implement high-frequency SCS is lower than that required to activate large myelinated afferents and thus evoke paresthesias. However, it is sufficient to induce conduction block in small C fibres at the segmental level (perhaps in the Lissauer tract), which would be responsible for the analgesic effect.

In the case of high-frequency SCS and Burst-SCS, it appears imperative to postulate a distinct mechanism of action, divergent from that of Aβ fiber activation. Consequently, attention must be directed towards the mechanism of conduction block, not of Aβ fibers but of C fibers in the central pathways (Figure 4), i.e., in the ascending multisynaptic system (AMS). In summary, it can be hypothesised that, in the absence of activation of the Aβ fibres that ascend in the posterior columns and therefore of activation of the inhibitory mechanism that descends in the DLF, the analgesic effect of high-frequency SCS is due, as regards axonal neuropathy pain, to conduction block in the AMS, as regards nociceptive pain, to conduction block in Lissauer's tract (with segmental effect) and as regards sympathetic block, to block of the activation of neurons of sympathetic fiber origin (with segmental effect).

In view of the aforementioned considerations, it would appear that the term "stimulation" should be subjected to closer scrutiny. It is intuitively obvious when applying electrical current to a peripheral nerve, yet simultaneously misleading because it is quite different if, with the application of exogenous electrical current, the electrical activity in the nerve is increased (i.e., its "conduction is increased" and therefore "stimulating" it) or reduced (i.e., "blocking conduction"). Conversely, the substitution of the term "nerve stimulation" with "nerve conduction block" suggests the acknowledgement of a well-defined mechanism of action. Moreover, given the functional interruption of afferents for SCS, this approach conceptualises SCS as being more akin to neurolesive techniques, with the capacity to selectively act on the SAM. Consequently, this would render SCS effective in the management of pain from axonal neuropathy and potentially from deafferentation on the Lissauer tract. This would also make it effective in the management of nociceptive lumbar pain, as well as exerting a direct sympatholytic effect on cells of sympathetic origin.