Gate Theory

The gate-control theory of pain transmission proposed by Melzack and Wall³ in 1965 describes a balance between small and large sensory fibers, with positive and negative feedback loops controlling the activity of the dorsal horn cells of the spinal cord. The gate theory postulates that a predominance of small-diameter sensory fiber activity opens “gates” within the dorsal horn of the spinal cord, whereas large-fiber dominance closes them. Shealy reasoned that because large fibers have a lower threshold for depolarization by an electrical field applied to a peripheral nerve, they may be recruited selectively by an externally applied field. Moreover, because large-diameter sensory fibers within peripheral nerves are segregated into the dorsal columns, they may be more selectively activated by electrical stimulation of the dorsal aspect of the spinal cord. It is for this reason that the primary electrical effect of SCS has been assumed to be mediated by the dorsal columns.

As elegant as it is, the gate theory alone does not fully explain the clinical effect seen with SCS. For example, there are many pain conditions that are not effectively treated by SCS, including the pain of acute injury.⁴ In contrast, SCS is effective at treating hyperalgesia, which is signaled by large fibers. This may indicate that relief of pain by electrical stimulation is due to frequency-related conduction block, acting at primary afferent branch points where dorsal column fibers and dorsal horn collaterals diverge.⁵ This suggests that other mechanisms involving interneurons in the dorsal horn or involving descending fibers or sympathetic mechanisms may exist.⁶

One of the major limitations in our understanding of the mechanisms underlying SCS has been the paucity of animal models that reproduce the human chronic pain condition. Initial animal models using acute tissue injury have given way to those employing peripheral nerve injury, in an effort to create a reliable chronic pain model. However, it has been difficult to develop a rat model of chronic pain because rats generally recover from painful insults without long-term pain.⁵ Even in humans, peripheral nerve injury does not reliably result in neuropathic pain, and objective assessment of pain in the rat relies on behavioral changes. We therefore rely largely on the data accumulated over the past three decades of human use to further elucidate a possible mechanism.

Neurotransmitters

To better clarify the mechanism of action of SCS, investigators have also examined the role of local neurotransmitters within the spinal cord on pain conduction. Early studies explored opioid receptors as the conventional model of pharmacologic analgesia. It was found that administration of the narcotic antagonist naloxone had no effect on the relief of pain by SCS.⁷ Other studies revealed that substance P is increased in the cerebrospinal fluid (CSF) following SCS. It has also been noted that SCS causes a decrease in the release of excitatory amino acids, such as glutamate and aspartate, while at the same time increasing the release of γ-aminobutyric acid (GABA).⁶ This evidence suggests that neuropathic pain may be a state of imbalance between excitatory and inhibitory neurotransmitters and that SCS may restore that balance (Fig. 167-1).⁵ This is further corroborated by studies that show that the GABA agonist baclofen improves the effect of SCS, whereas GABA antagonists inhibit its effect.⁸ These lines of research leave open the door for the possibility of adjunctive pharmacotherapy.

FIGURE 167-1 Schematic illustration of the postulated effect of spinal cord stimulation (SCS). A, Dorsal horn neurons under normal conditions. Afferent inputs release excitatory neurotransmitters into the synaptic cleft. Simultaneously, γ-aminobutyric acid (GABA) neurons are activated exerting both presynaptic and postsynaptic inhibition, balancing the state of excitation. B, After peripheral nerve injury, GABA-ergic activity is reduced, and excitatory neurotransmission is enhanced. These changes can give rise to allodynia and hyperalgesia. C, SCS activates dorsal column fibers, and the resulting nerve activity is antidromically mediated to neurons in the dorsal horn. The paresthesias experienced during SCS are due to orthodromic activation of the dorsal columns. D, SCS-evoked nerve activity induces the release of GABA from dorsal horn interneurons, reducing hyperexcitability. AMPA, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate; NMDA, N-methyl-D-aspartate.

(Adapted from Cui JG, O’Connor WT, Ungerstedt U, et al. Spinal cord stimulation attenuates augmented dorsal horn release of excitatory amino acids in mononeuropathy via a GABAergic mechanism. Pain. 1997;73:87.)

Summary of Mechanisms

The mechanisms underlying SCS-induced analgesia are still open to question. However, it is clearly related to modulation of signals mediated by dorsally located fibers within the spinal cord. Neurohumoral changes in the spinal cord may be secondary to such activity modulation and may explain poststimulation analgesia, which is quite prominent in some patients.⁹

Failed Back Surgery Syndrome

Chronic neuropathic pain is most commonly located in the back and legs. Of patients undergoing lumbosacral spine surgery for treatment of this pain, 10% to 40% eventually develop persistent or recurrent pain.¹¹ This postsurgery pain is often referred to as failed back surgery syndrome (FBSS). Patients commonly have complaints of axial low back pain and lower extremity pain. In general, SCS is indicated in patients with FBSS whose radicular leg symptoms are more severe than the component of axial back pain. Objective evidence for a source of their neuropathic pain should be sought, including radiographic evidence of an anatomically successful surgery for herniated disk with an appropriate radiculopathy, matching the pain complaint.

FBSS is the most common indication for SCS and has the most evidence supporting its use. The Prospective, Randomized, Controlled, Multicenter Study of Patients with Failed Back Surgery Syndrome (PROCESS) trial, a large, multicenter, randomized controlled trial of SCS, has provided some of the best evidence for the use of SCS in failed back surgery syndrome.^12–14 The data emerging from this ongoing trial, first presented in 2005, followed pain relief and cost-effectiveness when compared with conventional medical management. Pain relief was significantly better in patients treated with spinal cord stimulators than in those managed conventionally.¹³ Patients also reported significant improvement in health care–related quality of life. However, the most recent data from this study show that, at 6 months, health care costs were significantly higher in the SCS group, likely related to the costs of the device and implantation.¹⁴ Longer follow-up of these patients is required to assess the true cost of this therapy.

The role of SCS in the management of recurrent back and leg pain following spine surgery has been examined in a randomized controlled trial comparing this therapy with repeat lumbar spine surgery.¹⁵ In this series of 42 patients with operable spinal pathology, SCS proved more effective than redo spine surgery. Moreover, a significant proportion of patients who had been randomized to spine surgery and failed to benefit from it subsequently achieved good results with SCS. Finally, the cost of therapy with SCS proved lower than repeat lumbar spine surgery, despite the significant cost of the hardware used.¹⁶

Complex Regional Pain Syndrome

SCS has been in use for the treatment of complex regional pain syndrome (CRPS). Also known as reflex sympathetic dystrophy, this is a condition for which there are few effective treatment options. The pathophysiology is unclear, with pain, dysfunction, and trophic changes occurring in an affected limb following trauma or surgery to that limb.¹⁷ Kemler and colleagues¹⁸ have recently released the 5-year follow-up results of a randomized, controlled trial comparing SCS with physical therapy to physical therapy alone. They found significantly better relief of symptoms in SCS patients than in those conservatively managed during the first 3 years after implantation. However, a spontaneous improvement in the control group appears to gradually diminish the effect of SCS over longer periods, with no statistical difference between the groups at 5 years. Despite these results, 95% of patients with SCS reported that they would undergo implantation again.

Ischemic Pain

It has been noted that SCS may alter vascular tone and improve tissue perfusion. It is thought that, through a combination of sympathetic outflow modulation and antidromic activation of sensory fibers, SCS acts to dilate peripheral vasculature.¹⁹ The use of SCS in the treatment of peripheral vascular disease was first proposed in the 1970s.²⁰ Subsequently, stimulator placement in the low thoracic or lumbar region of the spine has been shown to be effective in the treatment of pain caused by lower extremity peripheral artery occlusive disease.^21–23 Placement of the stimulator electrode at higher thoracic levels has been used in the treatment of intractable angina, with studies showing improved exercise tolerance and less ST-segment changes with SCS treatment.¹⁹ Recently, the effect of cervical SCS on the cerebral vasculature has been explored, with focus on cerebral vasospasm following subarachnoid hemorrhage.²⁴

Psychological Screening

One of the practical issues in SCS is the screening of patients. Clearly, not every pain syndrome responds equally well to SCS. In the same vein, not every patient with chronic pain responds well to this therapy. In an effort to sort out who responds well to SCS, many practitioners have turned to psychological screening. Aside from its ability to identify patients with major psychiatric morbidity, psychological screening has been reported to have some predictive value in selecting patients who would benefit from the therapy.²⁵ Some studies have found that it is important to assess the psychological profile of the patient to determine the suitability of SCS for treatment of the patient’s pain. In particular, preimplantation screening protocols have examined overall stability of the patient and the patient’s defensiveness, self-confidence, and self-efficacy. Other aspects examined are the patient’s response to and concern about the illness and the patient’s ability to cope with setbacks. Family support and a willingness to be an active participant in the patient’s care are also important.²⁶ However, the utility of psychological screening is not uniformly accepted; there are also data that suggest that the predictive value of psychological testing is low.²⁷ In summary, data regarding the usefulness of psychological screening of patients before SCS are mixed. However, this type of screening continues to be widely practiced.