Spinal Cord Stimulation for Peripheral Neuropathic Pain

Overview

In Western countries neuromodulation is increasingly used for peripheral neuropathic pain (PNP). To know the indications for neuromodulation therapies and understand how to diagnose PNP disorders, one must be familiar not only with the principles of the techniques, but also with (the basics of) the nervous system and its diseases. Detailed information about the relevant anatomy of the nervous system can be found in Chapter 3 . This chapter can be considered as guidance for the clinician who intends to implement neuromodulation therapies in patients with PNP.

According to the definition of the International Association for the Study of Pain, neuropathic pain is pain that arises as a direct consequence of a lesion or disease affecting the somatosensory system. The prevalence of neuropathic pain is estimated to be between 3.3% and 8.2% ( ). Neuropathic pain is associated with a high social and economic burden and therefore should be a priority in research ( ). Clinical assessment of neuropathic pain is very important for selecting the most optimal treatment, but can be difficult. The assessment should contain a careful history and neurological examination, and, if possible, be based on objective diagnostic tests ( ).

In diagnosing a neurological disorder of either central or peripheral origin it is helpful to distinguish the symptoms that belong to a default/defect in the central nervous system (CNS) (brain, spinal cord) from those of the peripheral nervous system (PNS) (spinal roots, plexus, peripheral nerves); see Fig. 49.1 . A lesion in the PNS can lead to weakness, atrophy, diminished reflexes, hypotonia, sensory loss (pain, touch, thermal sense), and/or hypersensitivity and pain, and usually has a specific neuro-anatomical distribution (see Fig. 49.2 ).

Until now, the first steps in treatment of PNP have been based on noninvasive pharmacological interventions. Pharmacological intervention used for treatment of neuropathic pain usually consists of antidepressant, antiepileptic, and opioid medications ( Table 49.1 ). These medications, however, may have unsatisfactory results and often unacceptable side-effects ( ). If pharmacological intervention does not result in adequate pain reduction, neuromodulation via SCS of the dorsal columns may be a second-line treatment option. The history and mechanisms of SCS of the dorsal columns, the proposed techniques, and current indications are discussed in this chapter.

History and Mechanisms of Action of Spinal Cord Stimulation

The mechanisms of action (MOAs) of SCS in humans are difficult to study, so various animal models have been used. Based on a translational, experimental animal model of chronic PNP, were the first to study the pain-relieving effects of SCS at the cellular and biochemical levels. Furthermore, with this experimental animal model, conventional SCS settings (approximately 50 Hz, 0.2 ms, 1.4 mA) of dorsal column stimulation results in a comparable pain-relieving effect and percentage of responders as observed in patients ( ).

In these chronic PNP animal models SCS significantly decreases the tactile hypersensitivity (responders to SCS), and this behavioral effect is correlated with a decreased intracellular GABA level and an increased extracellular GABA level in the DH ( ). Moreover, SCS of the dorsal columns induces a decrease in release of glutamate, the predominant neurotransmitter of nociceptive afferent neurons ( ). Interestingly, in nonresponders to SCS the effect on GABA release in the DH is less prominent, further substantiating the pivotal effect of SCS on GABA interneurons in the DH network ( ).

In SCS responders, intrathecal (IT) application of a selective GABA-B antagonist can prevent the SCS-induced glutamate decrease. This phenomenon is in line with the gate-control theory, where GABAergic interneurons presynaptically modulate the glutamate release of nociceptive afferents in the DH ).

Likewise, the IT application of a subeffective dose of baclofen could potentiate the attenuation of neuropathic pain by conventional SCS ( ). The importance of glutamate and its receptor was further substantiated by the fact that nonresponders to conventional SCS could be turned into responders when a subeffective dose of ketamine, a N -methyl- d -aspartate (NMDA) glutamate receptor antagonist, was additionally applied ( ). The latter is notable, as the NMDA receptor is very important for the increased sensitivity of glutamate transmission or central sensitization ( ).

The question still remains whether SCS is mainly acting via a segmental (antidromic) or a suprasegmental (orthodromic) mechanism (see Fig. 49.3 ).

Electrophysiological evidence showed that in rats with neuropathic pain, SCS induces long-lasting depression of hyperexcitable wide dynamic range neurons by attenuating both spontaneous and evoked after-discharges, and that SCS of the dorsal columns at the same time reduces the C-fiber evoked central sensitization ( ). These results indicate a spinal segmental modulation of excitatory and inhibitory molecules to be pivotal in the MOA underlying the pain-relieving effects of SCS. Although dorsal nociception is now known to be much more complicated than the gate-control network originally presented by Melzack and Wall in , the balance between many inhibitory and excitatory cells forms the essence of the concept.

This so-called DH gate-control network ( ) is a network triggered by conventional SCS and the antidromic stimulation of AB-fibers in the dorsal columns. In an elegant series of experiments where the leads were positioned either very close to the level where activated nociceptive afferents enter the spinal cord or much more rostrally, the pain-relieving effect of SCS was shown to be predominantly segmental ( ).

Although the primary effect of conventional SCS has been attributed to the antidromic activation of ascending dorsal column fibers inducing segmental neurochemical changes in the DH, there is evidence that orthodromic activation also involves supraspinal mechanisms via a loop in which the descending dorsolateral funiculus plays a role in the attenuation of neuropathic pain ( ).

Peripheral Neuropathic Pain and Conventional Spinal Cord Stimulation