Journal of Pain and Symptom Management
Volume 38, Issue 2, Supplement , Pages S28-S38, August 2009

Spinal Cord and Peripheral Nerve Stimulation Techniques for Neuropathic Pain

  • Oscar A. de Leon-Casasola, MD

      Affiliations

    • Corresponding Author InformationAddress correspondence to: Oscar A. de Leon-Casasola, MD, Department of Anesthesiology, Critical Care & Pain Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

Department of Anesthesiology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo; and Department of Anesthesiology, Critical Care & Pain Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA

Accepted 20 May 2009.

Article Outline

Abstract 

When comprehensive medical pharmacological therapy titrated to maximum doses fails to provide an appropriate level of analgesia, or side effects associated with these therapies impair the ability to increase the doses to obtain appropriate therapeutic effects in patients with a variety of chronic neuropathic pain conditions, alternative methods, such as spinal cord stimulation and peripheral nerve stimulation, are effective alternative options. This article discusses important concepts to consider when implementing spinal cord and peripheral nerve stimulation therapy for the treatment of neuropathic pain conditions other than failed back surgery syndrome. The focus is primarily on post-surgical pain syndromes, which are frequently encountered in daily clinical practice.

Key Words: Spinal cord stimulation, peripheral nerve stimulation, chronic pain, refractory pain, electrode placement, clinical trials

 

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Introduction 

When comprehensive medical pharmacological therapy titrated to maximum doses fails to provide an appropriate level of analgesia, or side effects associated with these therapies impair the ability to increase the doses to obtain appropriate therapeutic effects in patients with a variety of chronic neuropathic pain conditions, alternative methods, such as spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS), are effective options. These technologies use high-frequency, low-stimulation currents, which are delivered by means of electrodes that are either percutaneously implanted in close proximity to peripheral nerves or implanted in the epidural space of the spine to stimulate either the dorsal columns or the nerve roots as they exit the spinal canal. These electrodes are then connected subcutaneously to an implanted generator unit.1 SCS has been used to relieve pain since 1967, when Shealy et al. pioneered the technology for a patient with metastatic cancer.2 Although the technique is used today most commonly to relieve chronic pain associated with failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), ischemic limb pain, and angina pectoris, it also has been implemented to address other intractable neuropathic and chronic visceral pain conditions. In most of the cases, SCS or PNS is used as a component of a multimodal therapeutic plan designed to control a patient's pain while decreasing the doses of analgesics, and in rare cases, pain medications are discontinued completely.

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Mechanisms of Action 

Thus far, there is no mechanistic explanation for the observed clinical benefits obtained from the use of either SCS or PNS. The long-lasting effects associated with SCS have, in part, been attributed to enhanced pain inhibition through supraspinal mechanisms involving a reduction of γ-aminobutyric acid levels in the periaqueductal gray matter.3 Modulation of descending inhibitory pathways through release of spinal dynorphin in the thoracic spinal cord and subsequent dampening of the nociceptive signal through the reduction of substance P release from dorsal horn laminae also have been implicated in the analgesic effects obtained with SCS, particularly for intractable chronic angina.4 The peripheral release of calcitonin gene-related peptide from sensory fibers also has been proposed as one of the mechanisms underlying pain relief induced by SCS.5, 6 In actuality, there may be different mechanisms responsible for relieving ischemic and neuropathic pain. Certainly, a satisfactory explanation remains to be established, and the gate control theory of pain developed by Melzack and Wall7 does not offer a full explanation for the analgesic effects obtained by SCS or PNS.

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Variables Affecting the Stimulation Threshold 

Despite our limitations in the understanding of the mechanism(s) of action of SCS and PNS, accumulated empirical observations lend useful insight into the implementation of these techniques. Indeed, a thorough comprehension of the variables affecting the stimulation threshold is required before initiating SCS or PNS therapy. Knowledge of the specific relevant characteristics of the patient, combined with an understanding of the somatotopic organization of the central nervous system, can enable the overlap of the area of induced analgesia with the pain region to best fit the necessary equipment for SCS or PNS and to create a good outcome.

The conductivity of tissues is a variable that significantly affects the outcome of SCS or PNS. Cerebrospinal fluid (CSF) has the greatest conductivity (range: 0.33–3.00S/m), followed by the white matter (range: 0.31–0.48S/m), and gray matter (range: 0.33–1.0S/m).8 The wider the CSF band between the epidural space and the spinal cord, the higher the stimulation threshold needed. Hence, stimulation of the dorsal column in the mid-thoracic region is more difficult, because this is where the spinal cord is the smallest and the CSF band is the widest. Furthermore, the thickness of the dorsal CSF space varies according to the body's position, such that the dorsal CSF layer is narrower when a patient is lying supine, making the position more suitable for low-output stimulation as the spinal cord is closer to the electrodes. The dorsal root entry zone (DREZ) is within the gray matter, which reduces the conductivity obtained therein. These and other factors (see later) will increase the stimulation threshold for DREZ stimulation.

Other anatomical factors that influence the stimulation threshold are the size of the fibers and the location and angulation of the nerve fibers as they exit the spinal cord. The larger the size of the fiber, the lower the stimulation threshold that is required to obtain a sensory response. The dorsal column fibers decrease in size as they ascend in the spinal cord; therefore, the stimulation threshold is lower in the lumbar and low thoracic regions when compared with the high thoracic and cervical regions. As noted, the location and angulations of the fibers as they exit the spinal cord also have an impact on the required stimulation threshold for SCS. The angle between the nerve roots and the spinal cord increases in the caudal direction; that is, in the cervical region, they exit at a 90° angle, whereas in the sacral area, the angle increases to approximately 170°. Dorsal root fibers with a sharper angle require a higher stimulation threshold.

The last key factor influencing stimulation threshold is the size of the dorsal column fibers. At any given level, the lateral dorsal column fibers are larger than the medial dorsal column fibers. Thus, leads placed at the physiologic midline of the epidural space will require higher energy output than those placed more laterally. Moreover, as the columns ascend in the spinal cord, they become smaller, generating one more factor to consider when planning stimulation patterns.

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Procedural Considerations for Spinal Cord and Peripheral Nerve Stimulation 

Lead placement with respect to the physiologic midline affects the neurophysiologic area that is targeted by SCS. A frequently used approach to SCS is to place the leads epidurally at the midline of the spinal cord to generate a stimulation field with the intent of reaching the dorsal columns. In contrast, gradually separating the leads laterally off the physiologic midline concentrates stimulation over the DREZ. With movement toward the lateral portion of the epidural space for DREZ stimulation, the output and frequency requirement increases, along with the risk of generating bothersome stimulation patterns. This technique can be used to provide relief of visceral pain, such as pancreatitis by means of left DREZ stimulation at T7 to T12 and angina pectoris by stimulation at T2 to T5. For relief of vulvar and vaginal pain, leads are placed at the physiologic midline between T9 and T12 (Fig. 1).

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Lead Placement According to Clinical Condition 

Spinal Cord Stimulation 

Although each individual is unique, many clinical conditions have typical neurological areas that are commonly responsive to lead placement therein. The following can be used as a guide for SCS lead placement when targeting neuropathic pain in select areas. For upper extremity pain, electrodes should be placed sequentially between C2 and C5. For chest pain (e.g., post-thoracotomy pain syndrome [Fig. 2], postmastectomy pain syndrome [Fig. 3], and angina), two leads are usually placed, one at the midline and the other more laterally between T1 and T4. For coverage of pain in the lower extremities near the thigh and knee, leads should be placed at T9 and T10, and for lower extremity pain in the calf and ankle regions, from T10 to T12 (Fig. 4). Lead position for coverage of pain within the dorsum may require even lower lead placement, between T11 and L1 (Fig. 5).9 Complex retrograde techniques may sometimes be needed to cover the ankle and the foot with lead placement directly at L4, L5, or close to the trunks of S1 and S2 (Fig. 6) in the posterior epidural space to stimulate the plantar portion of the foot.

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  • Fig. 2 

    Epidural spinal cord stimulation lead placement for post-thoracotomy pain syndrome. Note that one lead is used for anterior chest pain (medial lead), and the other for lateral and posterior chest pain (lateral lead).

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  • Fig. 3 

    Epidural spinal cord stimulation lead placement for postmastectomy pain syndrome. Note that one lead is used for axillary and lateral chest pain (medial lead), and the other for medial arm pain (lateral lead).

Patients with chemotherapy-induced peripheral neuropathy after treatment with vincristine, vinblastine, paclitaxel, docetaxel, cisplatin, vinorelbine, bortezomib, or thalidomide can develop both numbness and pain in their hands and/or feet. If pain control is not achieved with multimodal pharmacotherapies, epidural lead placement in the cervical region or between T10 and T12 can successfully reduce paresthesias (i.e., the sensation of pins and needles) in the hands and feet, respectively.

Peripheral Nerve Stimulation 

Peripheral subcutaneous nerve stimulation can be implemented to control pain associated with neuropathies affecting the greater occipital, auricotemporal, lesser occipital, ilioinguinal, iliohypogastric, and genitofemoral nerves, as well as the superficial cervical plexus and the V1 and V2 subdivisions of the trigeminal nerve. These nerves can be associated with a variety of chronic neuropathic pain syndromes, such as post-traumatic pain, postsurgical pain, occipital neuralgia, and CRPS Type II. The successful treatment of many of these syndromes by PNS has been documented in published studies and/or case reports.10 However, the use of PNS is limited for pain that requires lead placement through a joint; leads should not run through the course of a joint that has a significant angle of flexion or extension as it will likely result in migration of the lead. For this reason, we have limited the use of this technique to the aforementioned nerves.

Auriculotemporal and Lesser Occipital Nerve Stimulation 

Postcraniotomy pain syndromes may result in chronic headache in as much as 30% of the population undergoing this procedure; the pain syndrome has been linked to the development of other complications, such as depression and anxiety.11 Most commonly, pain after anterior craniotomies is associated with supraorbital and/or supratrochlear nerve injuries (see below). Postsurgical pain associated with lateral craniotomies involves injury to the auriculotemporal nerve (anterior to the ear) or lesser occipital nerve (posterior to the ear) (Fig. 7). For the treatment of these patients, a lead is introduced by means of a regular Tuohy needle through a small incision behind the ear, and advanced to the appropriate area where the nerve was likely injured so that the active portion of the lead is perpendicular to the nerve. For this purpose, fluoroscopy imaging is used to define the area where the skull was opened to help guide the lead insertion (Fig. 7). Care must be exercised so that injury to the vascular bundle does not occur during the needle insertion; ultrasound guidance may be useful toward this end. Once the lead is in place, it is tunneled around the ear, back to the infraclavicular region where it can be connected to the implanted pulse generator (IPG). For the tunneling process, we have used the same Tuohy needle without complications.

Nerve Stimulation of the Trigeminal V1 and V2 Subdivisions 

Injury to the V1 or V2 subdivisions because of enucleations or direct trauma to the eye can lead to chronic pain that responds very well to stimulation of the supratrochlear and supraorbital nerves (Fig. 8) or the infraorbital nerve (Fig. 9). In these circumstances, an eight-contact lead is placed through an epidural Tuohy needle that has been inserted through a small incision at the junction of the anterior portion of the ear and the face, and advanced to the medial aspect of the supraorbital area or the infraorbital area. As with the aforementioned procedures, to avoid migration of the lead, a 2-0 silk suture is tied around the lead with the help of an RB-1 needle (Ethicon sutures) at the site of needle insertion. The use of this type of needle facilitates securing the lead because of the size and angle at which the needle is constructed. Even though none of the manufacturers of spinal cord stimulators recommend tying a suture directly around the lead, we have not encountered problems with lead fracture when using this approach. As with the other procedures in the head and neck area, injury to the vascular bundle during the needle insertion is a risk that can be minimized by care and implementation of ultrasound guidance. Once the lead is in place, it is tunneled around the ear, and then back to the infraclavicular region where it can be connected to the IPG (Fig. 10). For the tunneling process, we have used the same Tuohy needle without problems.

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  • Fig. 10 

    Migration of subcutaneous lead to the infraclavicular region in a patient who was treated for lesser occipital nerve injury. The patient is an avid swimmer and experienced loss of stimulation after a prolonged swimming session.

Superficial Cervical Plexus or Branch Nerve Stimulation 

The superficial cervical plexus has four main cutaneous branches:

•The lesser occipital nerve that innervates the lateral part of the occipital region (C2, C3);

•The greater auricular nerve that innervates the skin near the concha auricle and the external acoustic meatus (C2 and C3);

•The transverse cervical nerves that innervate the anterior region of the neck (C2 and C3);

•The supraclavicular nerves that innervate the suprascapularis region, the shoulder, and the upper thoracic region (C3, C4).

During the course of a modified radical neck dissection, injury to any of these nerves may occur.12 Patients with postradical neck pain syndrome, who have injuries of the superficial cervical plexus, may experience pain in the anterior portion of the neck and the border of the mandible (transverse cervical nerve injury), auricular area (great auricular nerve injury), or even at the lateral aspect of the scalp (lesser occipital nerve injury). In particular, African Americans have a higher rate and increased risk of developing postsurgical chronic pain after neck surgery.13, 14 This predisposition may be related to differences within the alpha-2-adrenergic receptors, proteins that are involved in the regulation of sympathetic activity. Differences therein are also a potential cause for difficulties in controlling hypertension with blood pressure lowering medications within this population.15, 16 When comprehensive medical management has failed to provide pain relief, placing an octopolar lead along the sternal belly of the sternocleidomastoid muscle will be effective in treating these patients (Fig. 11). Injury of the greater auricular nerve is more frequent during these procedures; thus, placement of the lead high in the neck is recommended for these patients. Just as with the other indications, the lead is inserted by means of a Tuohy needle that has been introduced through a small skin incision at the junction of the neck and the supraclavicular region. Care must be exercised not to injure the anterior jugular vein during insertion. For this purpose, patients are asked to perform a Valsalva maneuver to help locate the vein. The lead is also anchored as described earlier. Just as with other peripheral stimulation techniques, programming does not require high-energy outputs or frequency rates.

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  • Fig. 11 

    Subcutaneous lead placement for superficial cervical plexus injury after a modified radical neck dissection. The patient experienced symptoms that suggested both greater auricular nerve and transverse nerve injury. Hence, a lead with eight contacts was chosen and the tip of the lead was placed at the angle of the mandible.

Ilioinguinal, Genitofemoral, and Iliohypogastric Nerve Stimulation 

Inguinal hernia repair and surgeries in the groin are associated with an 11%–30% incidence of postsurgical chronic pain.17 Patients undergoing inguinal lymph node resections for melanomas or sarcomas and hernia repairs also may experience ilioinguinal, genitofemoral, and/or iliohypogastric nerve injuries during these procedures. A history and physical evaluation will help define whether the pain is related to ilioinguinal or genitofemoral nerve injuries, or a combination of both. Patients with ilioinguinal nerve injury will complain of burning pain at the upper portion of the scrotum or labia, the superomedial portion of the thigh, and the medial portion of the groin. In contrast, patients with genitofemoral nerve injury will have pain at the bottom of the scrotum and the proximal medial portion of the thigh, and patients with iliohypogastric nerve injury will complain of pain throughout the groin area, extending to the anterior superior spine. These findings can be helpful in determining if a patient will need one or two leads subcutaneously inserted at the level of the anterior superior spine with typical placement above the surgical scar, and just beyond the boundaries of the medial aspect of the scar for patients with genitofemoral nerve injury, or below the scar in those with either iliohypogastric or ilioinguinal nerve injuries (Fig. 12).

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  • Fig. 12 

    Subcutaneous lead placement for both genitofemoral (superior lead) and ilioinguinal (inferior lead) nerve injuries after orchiectomy. The horizontal line shows the site of the incision, and the vertical lines show the medial and lateral boundaries of the incision.

Other 

There is no consensus as to whether connecting extensions should be implemented for SCS and PNS when stimulation is required in new areas. As a general rule, the lower the number of connections, the lower the failure rate. Still, revising the lead after migration has led to the loss of stimulation in the affected area involves opening both the wound where the lead is secured and the pocket where the generator is implanted. A radiograph should confirm correct placement of the connecting lead without wire kinking (which can cause the wire to break and stimulation to be halted) before the incision is closed. In the case of PNS of the head and neck region, the anatomical characteristics of the retroauricular area preclude the use of connecting extensions because of the risk of skin erosion at the site of the connection. Likewise, their use in the neck is not customary because of esthetic reasons. Consequently, despite the high risk of lead migration in these areas when the IPG is placed in the infraclavicular region (because of extreme shoulder abduction and extension, as occurs during swimming), the use of connecting extensions is precluded in these cases (Fig. 10).

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Potential Complications 

In general, severe complications after SCS or PNS device implantation are not common.9, 18, 19, 20, 21 Potential severe unwanted outcomes of SCS and PNS include spinal cord injury leading to paralysis or loss of sensation, and postdural puncture headache. Rarely, intracranial subdural hematomas develop secondary to dural puncture during the placement of an SCS device.22 A 3%–5% rate of infection and a 5% incidence of persistent pain at the implant site have been reported.9 Incident rates range from 11% to 45% depending on the specific equipment used. Potential long-term complications associated with the implant include electrode migration, equipment failure because of stress fracture or an electrical leak, and shifting of the generator's position (e.g., the device can flip over in its pocket if the pocket is too big).9, 19 These issues, and a lack of effective pain relief from SCS or PNS, can be resolved by electrode or generator repositioning.

Patients implanted with electrodes in the head and neck areas should be conservative in their shoulder movements, as they run the risk of displacing the electrodes from their implanted location back into the pocket where the generator was implanted (Fig. 10). With PNS, if all of the contacts are programmed to be negative electrodes while the generator is positive, unpleasant extraneous stimulation at the site of the implant can result. Other adverse effects include infection because of delayed hematogenous seeding or harbored from implantation without the usual immediate clinical signs, and skin irritation or erosion, especially in areas that endure friction or have been previously irradiated.

Individuals who have the types of pain treated by SCS or PNS may be genetically predisposed to develop neuropathic pain, such as CRPS Type II.23 Although the opportunity to implement alternative options, such as SCS, can cure a patient, there is also the risk that neuropathic pain can result at the site of the generator pocket. Pretreatment with 150mg pregabalin or 600mg gabapentin, a dose of 400mg of celecoxib,24, 25 and topical application of a eutectic mixture of lidocaine and prilocaine cream before surgery, as well as the use of local anesthetics during surgery, may help avoid sensitization of the nerves to pain and reduce the risk of inducing further neuropathic pain at the site of surgery.

Guidelines issued by the U.S. Food and Drug Administration state that magnetic resonance imaging (MRI) cannot be performed on patients with SCS or PNS. However, a study conducted in Spain with patients who had SCS leads implanted in their cervical or lumbar epidural space indicated that MRIs performed with a 1.5-T clinical use magnet and a specific absorption rate of no more than 0.9W/kg could be conducted without serious complications and with maximum patient satisfaction.26

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Guidelines and Published Evidence Regarding Treatment of Chronic Neuropathic Pain with Spinal Cord and Peripheral Nerve Stimulation 

In 2007, a task force assembled by the European Federation of Neurological Societies developed guidelines regarding the use of neurostimulation for treating chronic neuropathic pain refractory to pharmacotherapies.1 Another set of evidence-based recommendations assembled by the American Society of Interventional Pain Physicians, and a Cochrane Review, supported the implementation of SCS for select patients with FBSS and CRPS because of the potential for providing both short- and long-term pain relief.27, 28

FBSS is a common, often disabling condition of recurrent or continued symptoms despite surgery for various types of low back pain.29 Outcome data for FBSS in cohorts of younger patients and those over the age of 60 years, from well-designed randomized controlled trials (RCTs) and from other clinical studies, systematic reviews, published expert opinions, and case reports, have demonstrated a favorable risk-to-benefit ratio, supporting the usage of SCS, even when cost is taken into account.30, 31, 32, 33, 34 Authors of a study of 100 patients with FBSS and predominant leg pain of neuropathic radicular origin who were randomized to receive SCS plus conventional medical management or conventional medical management alone (control) for at least six months reported that 24 patients given SCS (48%) and four patients administered only the control management (9%) (P<0.001) achieved 50% or more pain relief in their legs.32A cost-effectiveness study of patients who had pain refractory to back surgery and were subsequently implanted with an SCS device found that although the alternative treatment is associated with high upfront average total health care costs (CAN$19,486 or €12,653 vs. CAN$3,994 or €2,594 for patients managed nonoperatively; mean adjusted difference: CAN$15,395 or €9997; P<0.001), the subsequent reduced use of analgesics, physical therapy, and/or chiropractic therapies offset the initial additional costs by 15% within six months after implantation.33 Importantly, the improvement in health-related quality of life among patients administered SCS compared with control groups over the same time period was markedly greater. In addition, another cost-effectiveness study based on an RCT found that SCS was less expensive and more effective than reoperation in selected patients with FBSS.34

Similarly, evidence accumulated primarily on CRPS Type I and some data on Type II from well-designed RCTs, other clinical studies, published expert opinions, and case reports also show a risk-to-benefit ratio in favor of including SCS as an option to provide relief of chronic, refractory neuropathic pain for both young and older adults.35, 36, 37, 38, 39 A prospective study of 29 patients with CRPS Type I found that deep pain and allodynia could be significantly reduced (P<0.01) with SCS, ultimately resulting in functional improvements.38 A five-year follow-up to an RCT of SCS treatment for CRPS indicated pain relief diminished with time compared with that attained by a control group.36 However, possibly because statistically significant pain relief was attained for the first three years, 95% of treated patients indicated that they would undergo the therapy again for the same result.35 Patients with CRPS Type II who have been resistant to pharmacological approaches also may respond to a combined therapeutic strategy of small doses of an anticonvulsant, the tricyclic antidepressant drug desipramine, and PNS.

Although clinical observations support the use of SCS or PNS for postherpetic neuralgia, postamputation pain, multiple sclerosis, peripheral diabetic neuropathy,40 spinal cord injury, spinal cord lesion, cauda equina syndrome, cervical root injury pain, and thoracic nerve root injury pain, data from RCTs have not been collected on these conditions to date. Results collected over 22 years from a group of 410 patients with chronic pain—caused by peripheral vascular disease, peripheral neuropathy, phantom limb or stump pain, multiple sclerosis, bone and joint pain syndromes, spinal cord injury, cauda equina syndrome, perirectal pain, or postherpetic neuralgia—suggest that long-term pain relief may be attained by SCS, even in older adults.39 A small, prospective study of patients with intractable pain because of postherpetic neuralgia who did not derive adequate analgesia from analgesics found that 23 (82%) of the patients derived long-term pain relief from SCS treatment (median decrease from 9 to 1 on a visual analog scale; P<0.001).41 The positive preliminary results of SCS for these pain conditions suggest that RCTs should be designed to assess the potential value of SCS and PNS as options for patients who have chronic neuropathic pain and inadequate responses to pharmacotherapies.

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Conclusions 

Although the mechanism of action of SCS and PNS is not well understood, it is clear that these are effective alternatives to treating neuropathic pain, and possibly, chronic visceral and ischemic pain. PNS is a viable, simple option for the treatment of pain related to peripheral nerve injury, such as CRPS Type II, in older adults. For older adult patients with chronic neuropathic pain who do not derive adequate pain relief from analgesics, or have side effects associated with the use of anticonvulsants and tricyclic antidepressants that limit titration to doses that provide acceptable analgesia, SCS and PNS should be considered as an alternative. Severe complications associated with these techniques are rare, and the recognition and implementation of preventative strategies may decrease the incidence of mild and moderate adverse outcomes, including the need to reposition the leads.

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PII: S0885-3924(09)00542-9

doi:10.1016/j.jpainsymman.2009.05.005

Journal of Pain and Symptom Management
Volume 38, Issue 2, Supplement , Pages S28-S38, August 2009

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