Spinal Cord and Peripheral Nerve Stimulation Techniques for Neuropathic Pain in Cancer
James Hitt, MD, PhD
Assistant Professor of Anesthesiology, Department of Anesthesiology
State University of New York at Buffalo - School of Medicine and Biomedical Sciences
Assistant Professor of Anesthesiology and Oncology, Department of Anesthesiology and Pain Medicine
Roswell Park Cancer Institute
Buffalo, New York
Oscar A. de Leon-Casasola, MD
Professor of Anesthesiology and Medicine
Senior Vice-Chair, Department of Anesthesiology
State University of New York at Buffalo - School of Medicine and Biomedical Sciences
Chief, Pain Medicine and Professor of Oncology
Department of Anesthesiology and Pain Medicine
Roswell Park Cancer Institute
Revised October 15, 2015
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 alternative options. These technologies use high-frequency, low-stimulation currents that are delivered via electrodes that are either percutaneously implanted in close proximity to peripheral nerves (PNS) or implanted in the epidural space of the spine to stimulate either the nerve roots or the dorsal columns as they exit the spinal canal (SCS). These electrodes are then connected subcutaneously to an implanted generator unit.
SCS has been utilized to relieve pain since 1967 when Shealy and colleagues pioneered the technology for a patient with metastatic cancer. Although the technique is employed 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 has also been implemented to address other intractable neuropathic and chronic visceral pain conditions. In the majority of 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.
Mechanisms of Action
Thus far, there is not a 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 (GABA) levels in the periaqueductal grey matter (PAG). In addition to the supraspinal GABAergic effects of SCS, it has also been shown to induce the release of GABA from dorsal horn spinal neurons in a rat model. 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 have also been implicated in the analgesic effects obtained with SCS, particularly for intractable chronic angina. The peripheral release of calcitonin gene-related peptide from sensory fibers has also been proposed as one of the mechanisms underlying pain relief induced by SCS.[6-7] 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 Wall does not offer a full explanation for the analgesic effects obtained by SCS or PNS.
It has been established that a significant percentage (30%-50%) of good SCS candidates fail to respond to the SCS trial, and up to 50% of responders loose analgesic benefit in the first few years of treatment. Given the theory that both GABA and acetylcholine modulated mechanisms (descending cortical inhibition) may contribute to the analgesic benefit of SCS, both neurotransmitters have been examined as intrathecal pharmacologic supplementation for SCS treatment failure. Initially, animal studies demonstrated that low doses of intrathecal baclofen could potentiate the effects of SCS in some animals and convert some animals who initially did not respond to the intervention. A pilot study and subsequent long-term followup demonstrated benefit of intrathecal baclofen in patients with suboptimal response to SCS for neuropathic pain conditions.[11,12]
Intrathecal clonidine has also been investigated as an adjunctive treatment in patients experiencing suboptimal analgesic benefit. Clonidine has been used to treat cancer-related pain and other somatic and neuropathic pain conditions[13,14] Animal studies have also suggested benefit when intrathecal clonidine is used to supplement SCS. A recent pilot study compared intrathecal baclofen and clonidine in neuropathic pain patients with suboptimal results from SCS; the study found that both medications could improve pain reduction from 32% to 82%.
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, in order 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 S/m–3.00 S/m), followed by the white matter (range 0.31 S/m–0.48 S/m), and gray matter (range 0.33 S/m–1.0 S/m). 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 described below 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 to 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 90º angle, while in the sacral area the angle increases to approximately 170º. 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.
Procedural Considerations for SCS and PNS
Lead placement with respect to the physiologic midline affects the neurophysiologic area that is targeted by SCS. A frequently employed approach to SCS is to place the leads epidurally at the midline of the spinal cord, in order 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 dorsal root entry zone (DREZ). With movement towards 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 via 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 (Figure 1).
Figure 1. Epidural spinal cord stimulation lead placement for vulvar pain. Note that the physiologic midline differs from the anatomic midline.
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 selected areas.
For upper extremity pain, electrodes should be placed sequentially between C2 and C5. For chest pain [e.g., postthoracotomy pain syndrome (Figure 2), postmastectomy pain syndrome (Figure 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 (Figure 4). Lead position for coverage of pain within the dorsum may require even lower lead placement, between T11 and L1 (Figure 5). 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 (Figure 6) in the posterior epidural space in order to stimulate the plantar portion of the foot.
Figure 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).
Figure 3. Epidural spinal cord stimulation lead placement for post-mastectomy 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).
Figure 4. Epidural spinal cord stimulation lead placement for lower extremity pain associated with chemotherapy induced peripheral neuropathy.
Figure 5. Epidural spinal cord stimulation lead placement for foot pain.
Figure 6. Epidural spinal cord stimulation lead placement for foot pain non-responsive to traditional placement as shown in Figure 5.
New Techniques in Neuromodulation
Given the significant proportion of patients who fail to obtain significant analgesic benefit from spinal cord stimulation or lose benefit after a few years of treatment, other strategies for neuromodulation have been investigated. Emerging new neuromodulation techniques include high frequency, dorsal root ganglion (DRG), and burst stimulation.
High frequency neuromodulation uses stimulation frequencies in the range of 2000 to 10,000 Hz and appears to produce analgesia by a distinct mechanism from conventional SCS. High frequency neuromodulation has some benefits over conventional SCS, including standard electrode placement in the region of T8 to T11, no need for sensory level testing during lead placement, and no discernable paresthesias experienced by patients.
Early clinical results have been promising, and results from a 24 month prospective study have shown safety with sustained efficacy. A high frequency neuromodulation system developed by Nevro Corporation (Menlo Park, CA, USA) received approval in Europe in 2011 and recent approval was granted by the FDA for use in the US. A prospective European study enrolled patients (N=83) with chronic back pain (with or without leg pain) who failed conventional treatment. The study reported an 86% stimulator trial success rate, and, of the patients who received an implanted system, the average 6 month VAS pain intensity was 2.7 as compared to 8.4 at baseline (a 78% median reduction in pain intensity). The same authors reported 24 month results that demonstrated sustained benefit (24 month VAS pain intensity of 3.3), and concomitant decreases in opioid use, disability scores, and sleep disturbance.
The DRG is a newer target for neuromodulation therapy. The DRG contains the cell bodies of the primary nociceptive afferent fibers and has been implicated in the development of chronic neuropathic pain states. The DRG is reliably located in close proximity to the neuroforamen between the medial and lateral boundaries of the spinal pedicle. While conventional spinal stimulation leads are not well suited to targeting the dorsal root entry zone (DREZ) within the neuroforamen, newer stimulation leads have been developed for the task. This approach may be of particular benefit to patients with pain difficult to localize by traditional SCS (eg, legs and feet).
A prospective pilot study of DRG stimulation conducted in 9 patients showed significant reduction in pain intensity along with a reduction in a majority of patients studied. A 12 month study examined the longer-term effects of DRG stimulation reported results in a patients with a variety chronic back and leg pain conditions; the results showed an average pain reduction of 56.3% and 60% of patients reporting more than 50% pain reduction. The results from the initial studies in DRG stimulation have demonstrated analgesic results at least comparable to conventional SCS with potential benefit in patients with well localized leg pain that can be difficult to target with conventional stimulation.
Peripheral Nerve Stimulation
Peripheral subcutaneous nerve stimulation can be implemented to control pain associated with neuropathies affecting the greater occipital, auriculotemporal, 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 posttraumatic pain, postsurgical pain, occipital neuralgia, and CRPS type II. Successful treatment of many of these syndromes by PNS has been documented in published studies and/or case reports. 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. Most commonly, pain following 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) (Figure 7). For the treatment of these patients, a lead is introduced via 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 in order to help guide the lead insertion (Figure 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.
Figure 7. Subcutaneous lead placement for lesser occipital nerve stimulation in a patient with post-craniotomy pain syndrome.
Nerve Stimulation of the Trigeminal V1 and V2 Subdivisions
Injury to the V1 or V2 subdivisions due to enucleations or direct trauma to the eye can lead to chronic pain that responds very well to stimulation of the supratrochlear and supraorbital nerves (Figure 8) or the infraorbital nerve (Figure 9). In these circumstances, an 8-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, in order 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 due to the size and angle with 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 (Figure 10). For the tunneling process, we have used the same Tuohy needle without problems.
Figure 8. Subcutaneous lead placement for supratrochlear and supraorbital nerves stimulation in a patient with post-eye enucleation pain syndrome.
Figure 9. Subcutaneous lead placement for infraorbital nerve stimulation in a patient with pain after excision of a basal cell carcinoma of the face.
Figure 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 innervates the lateral part of the occipital region (C2, C3)
- The greater auricular nerve innervates the skin near the concha auricle and the external acoustic meatus (C2 and C3)
- The transverse cervical nerves innervate the anterior region of the neck (C2 and C3)
- The supraclavicular nerve innervates 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. Patients with post radical 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.[25-26] This predisposition may be related to differences within the alpha2-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.[27-28]
When comprehensive medical management fails to provide pain relief, placing an octopolar lead along the sternal belly of the sternocleidomastoid muscle will be effective in treating these patients (Figure 11). The greater auricular nerve is more frequently injured 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 via 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 in order to help locate the vein. The lead is also anchored as described above. Just as with other peripheral stimulation techniques, programming does not require high energy outputs or frequency rates.
Figure 11. Subcutaneous lead placement for superficial cervical plexus injury after a modified radical neck dissection. The patient experienced symptoms suggestive of both greater auricular nerve and transverse nerve injury; thus the choice is to place a lead with 8 contacts, and the tip of the lead 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% to 30% incidence of postsurgical chronic pain. Patients undergoing inguinal lymph node resections for melanomas or sarcomas and hernia repairs may also 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 whole 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 iliac 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 injury (Figure 12).
Figure 12. Subcutaneous lead placement for both genitofemoral (superior lead) and ilio-inguinal (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.
Figure 13. Typical programming for peripheral subcutaneous nerve stimulation. In this case, for post-radical neck dissection syndrome.
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. An x-ray 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 peripheral nerve stimulation 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 due to esthetic reasons. Consequently, despite the high risk of lead migration in these areas when the IPG is placed in the infraclavicular region (due to extreme shoulder abduction and extension, as occurs during swimming), the use of connecting extensions is precluded in these cases (Figure 10).
In general, severe complications following SCS or PNS device implantation are not common.[30-33] 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 hematoma develops secondary to dural puncture during the placement of an SCS device. A 3% to 5% rate of infection and a 5% incidence of persistent pain at the implant site have been reported.17 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 due to stress fracture or an electrical leak, and shifting of the generator’s position (e.g., the device can flip over if the pocket is too big).[17,31] These issues, as well as a lack of effective pain relief from SCS or PNS, can be resolved by repositioning of the electrode or generator.
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 were the generator was implanted (Figure 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 due to 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 pain amendable to SCS or PNS treatment may be genetically predisposed to develop neuropathic pain, such as CRPS type II. 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 pregabalin 150 mg or gabapentin 600 mg, celecoxib 400 mg,[36-37] and topical application of a eutectic mixture of lidocaine and prilocaine cream before surgery, as well as the use of local anesthetics during surgery, can help avoid sensitization of the nerves to pain and reduce the risk of inducing further neuropathic pain at the site of surgery.
Current FDA guidelines recommend that MRIs 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 0.9 W/kg could be conducted without serious complications and with maximum patient satisfaction.
Guidelines and Published Evidence Regarding Treating Chronic Neuropathic Pain With SCS and PNS
In 2007, a task force assembled by the European Federation of Neurological Societies (EFNS) developed guidelines regarding the use of neurostimulation for treating chronic neuropathic pain refractory to pharmacotherapy. Another set of evidence-based recommendations assembled by the American Society of Interventional Pain Physicians, as well as a Cochrane Review, supported the implementation of SCS for select patients with FBSS and CRPS due to the potential for providing both short-term and long-term pain relief.[39-40]
Failed back surgery syndrome (FBSS) is a common, often-disabling condition of recurrent or continued symptoms despite surgery for various types of low back pain. Outcome data for FBSS in cohorts of younger patients, as well as those over the age of 60, 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 usage of SCS, even when cost is taken into account.[42-46] 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 6 months reported that 24 patients given SCS (48%) and 4 patients administered only the control management (9%) (P< 0.001) achieved 50% or more pain relief in their legs.
A 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 versus CAN$3,994 or €2,594 for patients managed non-operatively; 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 6 months after implantation. Importantly, the improvement in health-related quality of life among patients administered SCS compared to 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 re-operation in selected patients with FBSS.
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.[47-51] 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. A 5-year follow-up to an RCT of SCS treatment for CRPS indicated pain relief diminished with time compared to that attained by a control group. 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. Patients with CRPS type II who have been resistant to pharmacological approaches may also respond to a combined therapeutic strategy of small doses of an anticonvulsant, the tricyclic antidepressant drug desipramine, and PNS.
Although well-designed clinical trial evidence supports the use of SCS or PNS for postherpetic neuralgia, post amputation pain, multiple sclerosis, peripheral diabetic neuropathy, spinal cord injury, spinal cord lesion, cauda equina syndrome, cervical root injury pain, and thoracic nerve root injury pain, RCT data have not been collected on these conditions as of yet. Results collected over 22 years from a study 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—demonstrated that long-term pain relief could be attained by SCS, even within older adults. A small, prospective study of patients with intractable pain due to 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 VAS; P<0.001). The positive preliminary results of SCS for these pain conditions suggest that randomized controlled studies 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.
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, within 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 the 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.
- Cruccu G, Aziz TZ, Garcia-Larrea L, et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. European journal of neurology : the official journal of the European Federation of Neurological Societies 2007;14:952-70.
- Shealy CN, Mortimer JT, Reswick JB. Electrical inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. Anesthesia and analgesia 1967;46:489-91.
- Stiller CO, Linderoth B, O'Connor WT, et al. Repeated spinal cord stimulation decreases the extracellular level of gamma-aminobutyric acid in the periaqueductal gray matter of freely moving rats. Brain research 1995;699:231-41.
- Stiller CO, Cui JG, O'Connor WT, Brodin E, Meyerson BA, Linderoth B. Release of gamma-aminobutyric acid in the dorsal horn and suppression of tactile allodynia by spinal cord stimulation in mononeuropathic rats. Neurosurgery 1996;39:367-74; discussion 74-5.
- Ding X, Hua F, Sutherly K, Ardell JL, Williams CA. C2 spinal cord stimulation induces dynorphin release from rat T4 spinal cord: potential modulation of myocardial ischemia-sensitive neurons. American journal of physiology Regulatory, integrative and comparative physiology 2008;295:R1519-28.
- Tanaka S, Barron KW, Chandler MJ, Linderoth B, Foreman RD. Low intensity spinal cord stimulation may induce cutaneous vasodilation via CGRP release. Brain research 2001;896:183-7.
- Wu M, Komori N, Qin C, Farber JP, Linderoth B, Foreman RD. Roles of peripheral terminals of transient receptor potential vanilloid-1 containing sensory fibers in spinal cord stimulation-induced peripheral vasodilation. Brain research 2007;1156:80-92.
- Melzack R, Wall PD. Pain mechanisms: a new theory. Science (New York, NY) 1965;150:971-9.
- Schechtmann G, Lind G, Winter J, Meyerson BA, Linderoth B. Intrathecal clonidine and baclofen enhance the pain-relieving effect of spinal cord stimulation: a comparative placebo-controlled, randomized trial. Neurosurgery 2010;67:173-81.
- Cui JG, Linderoth B, Meyerson BA. Effects of spinal cord stimulation on touch-evoked allodynia involve GABAergic mechanisms. An experimental study in the mononeuropathic rat. Pain 1996;66:287-95.
- Lind G, Meyerson BA, Winter J, Linderoth B. Intrathecal baclofen as adjuvant therapy to enhance the effect of spinal cord stimulation in neuropathic pain: a pilot study. European journal of pain (London, England) 2004;8:377-83.
- Lind G, Schechtmann G, Winter J, Meyerson BA, Linderoth B. Baclofen-enhanced spinal cord stimulation and intrathecal baclofen alone for neuropathic pain: Long-term outcome of a pilot study. European journal of pain (London, England) 2008;12:132-6.
- Eisenach JC, DuPen S, Dubois M, Miguel R, Allin D. Epidural clonidine analgesia for intractable cancer pain. The Epidural Clonidine Study Group. Pain 1995;61:391-9.
- Martin TJ, Eisenach JC. Pharmacology of opioid and nonopioid analgesics in chronic pain states. The Journal of pharmacology and experimental therapeutics 2001;299:811-7.
- Schechtmann G, Wallin J, Meyerson BA, Linderoth B. Intrathecal clonidine potentiates suppression of tactile hypersensitivity by spinal cord stimulation in a model of neuropathy. Anesthesia and analgesia 2004;99:135-9.
- Van Uitert R, Johnson C, Zhukov L. Influence of head tissue conductivity in forward and inverse magnetoencephalographic simulations using realistic head models. IEEE transactions on bio-medical engineering 2004;51:2129-37.
- Falowski S, Celii A, Sharan A. Spinal cord stimulation: an update. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 2008;5:86-99.
- Van Buyten JP, Al-Kaisy A, Smet I, Palmisani S, Smith T. High-frequency spinal cord stimulation for the treatment of chronic back pain patients: results of a prospective multicenter European clinical study. Neuromodulation : journal of the International Neuromodulation Society 2013;16:59-65; discussion -6.
- Al-Kaisy A, Van Buyten JP, Smet I, Palmisani S, Pang D, Smith T. Sustained effectiveness of 10 kHz high-frequency spinal cord stimulation for patients with chronic, low back pain: 24-month results of a prospective multicenter study. Pain medicine (Malden, Mass) 2014;15:347-54.
- Deer TR, Grigsby E, Weiner RL, Wilcosky B, Kramer JM. A prospective study of dorsal root ganglion stimulation for the relief of chronic pain. Neuromodulation : journal of the International Neuromodulation Society 2013;16:67-71; discussion -2.
- Liem L, Russo M, Huygen FJ, et al. One-year outcomes of spinal cord stimulation of the dorsal root ganglion in the treatment of chronic neuropathic pain. Neuromodulation : journal of the International Neuromodulation Society 2015;18:41-9.
- Slavin KV. Peripheral nerve stimulation for neuropathic pain. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 2008;5:100-6.
- Rocha-Filho PA, Gherpelli JL, de Siqueira JT, Rabello GD. Post-craniotomy headache: characteristics, behaviour and effect on quality of life in patients operated for treatment of supratentorial intracranial aneurysms. Cephalalgia : an international journal of headache 2008;28:41-8.
- Sist T, Miner M, Lema M. Characteristics of postradical neck pain syndrome: a report of 25 cases. Journal of pain and symptom management 1999;18:95-102.
- Eversley R, Estrin D, Dibble S, Wardlaw L, Pedrosa M, Favila-Penney W. Post-treatment symptoms among ethnic minority breast cancer survivors. Oncology nursing forum 2005;32:250-6.
- Jayadevappa R, Johnson JC, Chhatre S, Wein AJ, Malkowicz SB. Ethnic variation in return to baseline values of patient-reported outcomes in older prostate cancer patients. Cancer 2007;109:2229-38.
- Bruehl S, Chung OY, Diedrich L, Diedrich A, Robertson D. The relationship between resting blood pressure and acute pain sensitivity: effects of chronic pain and alpha-2 adrenergic blockade. Journal of behavioral medicine 2008;31:71-80.
- Kurnik D, Friedman EA, Muszkat M, et al. Genetic variants in the alpha2C-adrenoceptor and G-protein contribute to ethnic differences in cardiovascular stress responses. Pharmacogenetics and genomics 2008;18:743-50.
- Nienhuijs SW, Rosman C, Strobbe LJ, Wolff A, Bleichrodt RP. An overview of the features influencing pain after inguinal hernia repair. International journal of surgery (London, England) 2008;6:351-6.
- Cameron T. Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: a 20-year literature review. Journal of neurosurgery 2004;100:254-67.
- Kumar K, Wilson JR, Taylor RS, Gupta S. Complications of spinal cord stimulation, suggestions to improve outcome, and financial impact. Journal of neurosurgery Spine 2006;5:191-203.
- Rosenow JM, Stanton-Hicks M, Rezai AR, Henderson JM. Failure modes of spinal cord stimulation hardware. Journal of neurosurgery Spine 2006;5:183-90.
- Turner JA, Loeser JD, Deyo RA, Sanders SB. Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and complications. Pain 2004;108:137-47.
- Chiravuri S, Wasserman R, Chawla A, Haider N. Subdural hematoma following spinal cord stimulator implant. Pain physician 2008;11:97-101.
- Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet 2006;367:1618-25.
- Buvanendran A, Kroin JS, Della Valle CJ, Kari M, Moric M, Tuman KJ. Perioperative oral pregabalin reduces chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial. Anesthesia and analgesia 2010;110:199-207.
- Hurley RW, Cohen SP, Williams KA, Rowlingson AJ, Wu CL. The analgesic effects of perioperative gabapentin on postoperative pain: a meta-analysis. Regional anesthesia and pain medicine 2006;31:237-47.
- De Andres J, Valia JC, Cerda-Olmedo G, et al. Magnetic resonance imaging in patients with spinal neurostimulation systems. Anesthesiology 2007;106:779-86.
- Boswell MV, Trescot AM, Datta S, et al. Interventional techniques: evidence-based practice guidelines in the management of chronic spinal pain. Pain physician 2007;10:7-111.
- Mailis-Gagnon A, Furlan AD, Sandoval JA, Taylor R. Spinal cord stimulation for chronic pain. The Cochrane database of systematic reviews 2004:Cd003783.
- Chou R. Generating evidence on spinal cord stimulation for failed back surgery syndrome: not yet fully charged. The Clinical journal of pain 2008;24:757-8.
- Bala MM, Riemsma RP, Nixon J, Kleijnen J. Systematic review of the (cost-)effectiveness of spinal cord stimulation for people with failed back surgery syndrome. The Clinical journal of pain 2008;24:741-56.
- Kumar K, Taylor RS, Jacques L, et al. Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicentre randomised controlled trial in patients with failed back surgery syndrome. Pain 2007;132:179-88.
- Manca A, Kumar K, Taylor RS, et al. Quality of life, resource consumption and costs of spinal cord stimulation versus conventional medical management in neuropathic pain patients with failed back surgery syndrome (PROCESS trial). European journal of pain (London, England) 2008;12:1047-58.
- North RB, Kidd D, Shipley J, Taylor RS. Spinal cord stimulation versus reoperation for failed back surgery syndrome: a cost effectiveness and cost utility analysis based on a randomized, controlled trial. Neurosurgery 2007;61:361-8; discussion 8-9.
- Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for chronic back and leg pain and failed back surgery syndrome: a systematic review and analysis of prognostic factors. Spine 2005;30:152-60.
- Harke H, Gretenkort P, Ladleif HU, Rahman S. Spinal cord stimulation in sympathetically maintained complex regional pain syndrome type I with severe disability. A prospective clinical study. European journal of pain (London, England) 2005;9:363-73.
- Kemler MA, Barendse GA, van Kleef M, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. The New England journal of medicine 2000;343:618-24.
- Kemler MA, de Vet HC, Barendse GA, van den Wildenberg FA, van Kleef M. Spinal cord stimulation for chronic reflex sympathetic dystrophy--five-year follow-up. The New England journal of medicine 2006;354:2394-6.
- Kemler MA, de Vet HC, Barendse GA, van den Wildenberg FA, van Kleef M. Effect of spinal cord stimulation for chronic complex regional pain syndrome Type I: five-year final follow-up of patients in a randomized controlled trial. Journal of neurosurgery 2008;108:292-8.
- Kumar K, Hunter G, Demeria D. Spinal cord stimulation in treatment of chronic benign pain: challenges in treatment planning and present status, a 22-year experience. Neurosurgery 2006;58:481-96; discussion -96.
- de Vos CC, Rajan V, Steenbergen W, van der Aa HE, Buschman HP. Effect and safety of spinal cord stimulation for treatment of chronic pain caused by diabetic neuropathy. Journal of diabetes and its complications 2009;23:40-5.
- Harke H, Gretenkort P, Ladleif HU, Koester P, Rahman S. Spinal cord stimulation in postherpetic neuralgia and in acute herpes zoster pain. Anesthesia and analgesia 2002;94:694-700; table of contents.
Order byNewest on top Oldest on top