A Q&A on the Need for Pain Research

NOTE: Sections of this web page were excerpted for the September 2010 FAER Report in the ASA Newsletter.

The FAER Pain Research Council works to facilitate and promote opportunities for funding worthy science, new discoveries and specialized researchers that will enable anesthesiologists to evaluate and improve patient care in the area of pain medicine. To support this work, the Council has developed requests for FAER grant applications focused on two important areas of pain research: 1) Chronic opioid use and perioperative management and 2) Spinal cord stimulation and chronic pain.

To help illustrate the urgent need for research in these areas, Council members spoke to leading experts in these fields, Daniel B. Carr, MD, and Bengt Linderoth, MD, PhD.

Chronic Opioid Use and Perioperative Management: A Q&A with Dr. Daniel Carr

Daniel B. Carr, MD, is Saltonstall Professor of Pain Research in the Department of Anesthesia and Tufts Medical Center and Adjunct Professor of Anesthesiology at Tufts University School of Medicine in Boston, Massachusetts.

Q: What are the biggest challenges in providing acute postoperative pain care to patients taking chronic opioids?

A: In many preclinical models animals chronically exposed to opioids not only develop tolerance to their analgesic effects [1], but in the process, and via overlapping mechanisms, develop abnormally intense responses to painful stimuli. The latter state, termed “hyperalgesia,” is further exacerbated during acute opioid withdrawal. Clinical observations [2,3] confirm that postoperative opioid requirements in patients with preoperative chronic opioid use are several-fold greater than in patients without such prior exposure. Because increasing numbers of patients take opioids chronically, the numbers of such patients presenting for surgery are on the increase. Anesthesiologists have long known that acute perioperative pain management in patients chronically taking opioids is often challenging and time-consuming.

The biggest challenge in providing acute postoperative pain management for such patients is the absence of clear, evidence-based treatment protocols. Contrast the availability of consensus clinical pathways for perioperative insulin management of patients with diabetes mellitus, or perioperative hydrocortisone therapy in those with chronic glucocorticoid exposure, and the magnitude of this challenge becomes clear. Ad hoc decisions are made continually in this context, beginning with a guesstimate as to what opioid dosage and duration threshold is significant. Should we try to pre-empt pain by providing generous preoperative opioid doses or will doing so merely trigger (in Eisenach’s phrase [4]) “preemptive hyperalgesia”? Should every patient having chronic preoperative opioid exposure automatically receive a baseline opioid equivalent to, or some multiple of, the preoperative dose? How can one best select from the menu of promising multimodal analgesic therapies [5]? Should one relax the goals of pain therapy in such patients, mindful of how difficult it is to achieve them, or be particularly aggressive in an effort to reduce their risk of developing persistent postsurgical pain [6]? How should the presence of substance abuse affect management?

 

From a practical point of view, the physiological changes (central sensitization, mobilization of endogenous hyperalgesic systems, accumulation of hyperalgesic metabolites, etc. [7]) seen with chronic opioid use result in a “right-shift” of the pain intensity distribution after a surgical procedure [Figure 1]. The biggest management challenge is to efficiently apply our current analgesic armamentarium in each such patient, so as to optimize pain control in the face of a dysfunctional nociceptive system.
While not easy to solve, the problem is easy to state. For example, opioid-naïve patients undergoing a surgical procedure of mild to moderate invasiveness might well be treated with a weak NSAID or acetaminophen. Superimposing (in the mind’s eye) Figures 1 and 2, it is clear that opioid-tolerant patients who are hyperalgesic and undergo the identical procedure will experience greater pain intensity and require a stronger agent to secure meaningful pain relief.

Q: What are the biggest gaps in knowledge regarding perioperative care for patients taking chronic opioids?

A: The challenges identified in the response to Question 1 also apply, to some extent, to all patients. Increasingly, anesthesiologists are broadly applying multimodal techniques in concert with their surgical colleagues’ minimally invasive approaches to shift the distribution of postoperative pain intensity to the left and minimize the need for postoperative opioids [8].

For the subset of patients who come to the OR after chronic ongoing opioid exposure, important key knowledge gaps remain:

• What is the threshold for concern about opioid tolerance? Do different thresholds apply according to age, gender or genetic factors?
• Should baseline opioid dosing be augmented perioperatively even when the operation (e.g., replacement of an arthritic knee or hip) may eliminate pain and the need for analgesic medication?
• Is the benefit-to-risk ratio of opioid-sparing agents (gabapentin, NSAIDs, subanesthetic ketamine…) and techniques such as regional anesthesia sufficiently great that they should be the default standard of care for such patients?
• How can one make a smooth postoperative transition—presumably on an outpatient basis—to the new chronic opioid level?
• Would measures such as the above show any benefit upon functional outcomes, including a reduction in the incidence of persistent postsurgical pain [9]?
• What “red flags” (possibly including gene sequencing and single nucleotide polymorphisms in the future) should trigger a preoperative pain consultation [10]?

Q: Why is this relevant to anesthesiologists?

A: Effective pain control is integral to the practice of anesthesiology. When postoperative pain control is inadequate, anesthesiologists are the first to be called to bring the problem under control. On a daily basis, anesthesiologists intervene to improve short- and long-term outcomes of their patients through the skillful and timely application of their knowledge of analgesic pharmacology and regional anesthesia [11].  Pathbreaking work by leading anesthesiologists such as Bonica, Cousins, and others has brought the entire field of pain from the margins of medical practice to center stage in the clinical enterprise. Clinicians have intuitively recognized the benefits of regional anesthesia since its introduction into the operating room, and continue to define its benefits, including for opioid-tolerant patients [10,11].  Anesthesiologists have advocated that the control of pain is a fundamental human right [12], and they lead in research to achieve pain control in challenging patient populations and situations. Few things that anesthesiologists do are so certain to improve patient satisfaction and evoke their gratitude, as to solve—or better, to avert—complex acute and chronic pain problems.

Q: What changes do you think need to be made to provide improved perioperative pain care to this group of patients using currently available technology?

A: Experienced clinicians have described current approaches to perioperative pain care in this group of patients, as well as the subgroup whose chronic opioid exposure is further complicated by substance abuse [10,11,13]. This relevant literature accords with a comprehensive review by Carroll, Angst and Clark [14] published in 2004 which is still current, in my view. Carroll et al and these other clinicians conclude that optimal perioperative management of patients chronically consuming opioids involves:

• Identification of such patients preoperatively
• An opioid dose composed of the daily dose taken chronically before surgery supplemented by that made necessary by the surgery
• Use of adjuvant analgesics (ketamine, NSAIDs, acetaminophen, gabapentin, clonidine, dexmedetomidine…) [and I would add, non-drug therapies such as heat, cold, and cognitive-behavioral techniques]
• Regional anesthetic techniques
• Planning with the patient on the return to the preoperative opioid dose [and I would add, slow tapering and discontinuation of opioids if the operation is anticipated to be curative, such as replacement of an arthritic joint]

References

1. South S, Smith M. Analgesic tolerance to opioids. IASP Pain Clinical Updates 2001; 9: 1-9.
2. de Leon-Casasola OA, Myers DP, Donaparthi S, Bacon DR, Peppriell J, REmpel J, Lema MJ. A comparison of postoperative epidural analgesia between patients with chronic cancer taking high doses of oral opioids versus opioid-naïve patients. Anesth Analg 1993; 76: 302-307.
3. Rapp SE, Ready LB, Nessly ML. Acute pain management in patients with prior opioid consumption: a case-controlled retrospective review. Pain 1995; 61: 195-201.
4. Eisenach JC. Preemptive hyperalgesia, not analgesia? Anesthesiology 2000; 98: 308-309.
5. White PF, Kehlet H. Improving postoperative pain management: what are the unresolved issues? Anesthesiology 2010; 220-225.
6. Macrae W. Can we prevent chronic pain after surgery? In, Shorten G, Carr DB, Harmon D, Puig MM, Browne J (eds).  Postoperative Pain Management:  An Evidence-Based Guide to Practice.  Philadelphia: Saunders Elsevier, 2006, pp 259-264.
7. King T, Porreca F. Opioids in cancer pain: new considerations. IASP Pain Clinical Updates 2010; 18: 1-5.
8. Overdyk FJ. Postoperative opioids need system-wide overhaul. APSF Newsletter Winter 2009-2010; 24: 61.
9. Kehlet H, Rathmell JP. Persistent postsurgical pain: the path forward through better design of clinical studies. Anesthesiology 2010; 112: 514-515.
10. Nedeljkovic S S,Wasan AD. Postoperative pain management for patients with drug dependence. In: Shorten G, Carr DB, Harmon D, Puig MM, Browne J (eds).  Postoperative Pain Management:  An Evidence-Based Guide to Practice.  Philadelphia: Saunders Elsevier, 2006, pp 239-248.
11. Mcintyre PE, Scott DA. Acute pain management and acute pain services. In: Cousins MJ, Bridenbaugh PO, Carr DB, Horlocker TT (eds).  Cousins & Bridenbaugh's Neural Blockade In Clinical Anesthesia and Management of Pain, 4th ed.  Philadelphia: Lippincott Williams & Wilkins, 2009, p 1055.
12. Brennan F, Carr DB, Cousins MJ.  Pain management: A fundamental human right.  Anesth Analg  2007;105:205-221.
13. Carr DB, Jacox AK, Chapman CR, et al. Acute Pain Management: Operative or Medical Procedures and Trauma.  Clinical Practice Guideline.  Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health & Human Services; 1992, pp 60-62.
14. Carroll IR, Angst MS, Clark JD. Management of perioperative pain in patients chronically consuming opioids. Reg Anesth Pain Med 2004; 29: 576-591.

Spinal Cord Stimulation and Chronic Pain: A Q&A with Dr. Bengt Linderoth

Bengt Linderoth, MD, PhD, is Professor of Functional Neurosurgery and Head of Functional Neurosurgery and the Applied Neuroscience Research Program at the Karolinska Institute in Stockholm, Sweden and Adjunct Professor of Physiology at the Department of Physiology at the University of Oklahoma Health Sciences Center in Oklahoma City, Oklahoma.

Q: What are the biggest challenges in providing spinal cord stimulation as an effective treatment for failed back surgery syndrome with persistent radiculopathy? Is there a difference in primary leg pain as compared to axial pain?

A: “Failed back surgery syndrome,” or even pain in the back and legs without previous surgery, often consists of several different pain components, where some are neuropathic and some are related to pathologies in muscles, ligaments and joints. The general experience that pain physicians and spinal cord stimulation (SCS) system implanters in this field have, is that it is mainly the neuropathic components, i.e. pains, that radiate into the legs (or the arms), that respond well to spinal cord stimulation. However, even for this type of pain, the response rates are below that for pain with ischemic pain components. Actually, in well-selected series, the response rates may vary—between 50 and 70% of patients respond well to SCS (more often between 60 and 75%). Most often, only the radiating pain component has been targeted, meaning that the stimulating poles of the lead have been placed on levels T11 to L1, or for the cervical medulla, between C3 and C5 a little off the midline towards the side of the pain.

Lately, however, evidence is accumulating that the axial components might also respond to stimulation. This might be due to a direct effect on presumed neuropathic mechanisms of this component—the reduction of radiating pain actually provides a relaxation of the paraspinal muscles. The challenge concerning treatment of the radiating component is that we do not presently have any good tools to pre-select suitable patients. Therefore, a test period with a percutaneous extension is the gold standard. This test period should last for at least one to two weeks or longer, and should involve the daily activities of the patient. At present, patients with semiologically similar pain syndromes might respond quite differently during the testing periods. The solution would be to develop instruments for pre-selecting patients prior to the first surgical implant. So far, this has not been accomplished, and test stimulation is still standard at most centers.

When it comes to the axial components, very few publications have directly targeted the fact that these electrodes should be positioned more rostrally, that is at levels above T10, e.g. T8, or even higher, depending on the localization of the principal axial pain component. The therapeutic algorithms for treating the radiating pain components with SCS might vary considerably. Most patients with typical irradiating neuropathic components are recommended to use 30-40 minutes of stimulation 3-5 times daily or as needed. Many patients end up using a rather weak stimulation all of their awake time. In the ideal case, 30-40 minutes of stimulation should provide a significant pain reduction for 3-4 hours, after which a new SCS period is needed. For the axial components, it seems that several hours of stimulation, or stimulation when the patient is awake, at low amplitude, is more beneficial. However, there is little firm scientific basis for this application of SCS.

Q: Have new leads made a difference in the more complicated patient?

A: The availability of octopolar leads, or the use of double octopolar leads with stimulators that can be multi-programmed, has made a huge difference in difficult cases. Before this modern era, experienced implanters used to cross over midline with one 4-polar lead to enable differentiated stimulation patterns. At present, the many different combinations of stimulating poles and programs that can be used have made it necessary for computers to aid the selection of the proper stimulation poles. But many physicians with a background in physiology and extensive experience pre-select, with a rather high precision, combinations that might be suitable in a single case. New leads, both using double or triple percutaneous, as well as plate leads with stimulation poles placed to enable steering of the paraesthesiae, aid considerably in the treatment of these cases. Use of multiprogramming will be further developed, and computer point-screens will be used to enable the patient to easily steer the paraesthesiae to the painful regions. However, we will still not be successful for some patients with symptomatologies and medical histories suitable for SCS—possibly due to some internal weakness of the patient`s pain-control systems that does not respond adequately to the stimulation. In such cases, drug-enhanced spinal stimulation could be a solution and the development of this on the basis of animal experiments has barely begun.

Q: What will leads look like in the future?

A: In the future I presume leads will be directional to that in the percutaneous cylinder—like poles, there will be an insulation division between the anterior and posterior side, and maybe also subdivisions. When the lead is stabilized in the epidural tissue, a computer can select the couplings of the multitudes of poles, with the lowest resistance providing a good coverage of the painful region with pleasant paraesthesiae. I think such development will expand the use of percutaneous leads, and I believe surgical leads will be restricted to the most difficult pain conditions.

The possibility of implanting plate leads in spinal anesthesia below T8 as well as the use of minimal invasive techniques are also breakthroughs in this therapy form. I believe surgical leads will just have more poles and will be thinner in the future. The expanding use of MRI in a variety of diseases necessitates the development of non-magnetic, or MRI-safe equipment. This is an important innovation that is just around the corner!

Q: What are the keys to getting good outcomes with SCS in ischemic limb pain and refractory angina?

A: Studies during the last two decades have demonstrated that even when using such a crude criterium for success as amputation rate, SCS proves beneficial for subgroups of patients with PVD (or PAOD; peripheral arterial occlusive disease), while leg ischemia due to venous problems does not respond at all. Especially targeted in several multicenter studies have been patients belonging to the Fontaine III group, i.e. cases with severe rest and night pain as well as severe claudication, but without, or with only minor tissue involvement. For complete success, those patients should not have ischemic ulcers (or these should be below 3 cm in diameter). If not, arrest of tissue loss is the primary goal for the treatment.

It has proved difficult to demonstrate with statistical significance that SCS lowers amputation rate and reduces ischemic pain, but the Gothenburg randomized study, the Dutch multicenter randomized study and the EPOS non-randomized follow-up study together indicate that subgroups of patients can enjoy large benefits with SCS therapy.

Groups with a moderately compromised peripheral circulation, as indicated by several selection criteria, such as a TcpO2 between 10 and 30 mmHg, measured apically on the diseased extremity, should be targeted. There are also proposals, e.g. by Gersbach et al, that TcpO2 should be measured both in the supine and up-right position and that a gradient between the two of more than 15 mm mercury predicts a successful outcome. Persisting wall dynamic in the small arteries, as demonstrated using drugs or recording peripheral perfusion after inhalation of oxygen, has also been proposed as a criterium.

In all cases, trial stimulation is recommended. We now know that when starting the treatment with a PAOD case, a bolus stimulation with almost 8-10 h of stimulation a day for 2-3 days is necessary to start up the beneficial effects. During this testing period, TcpO2 should be measured daily and laser Doppler flowmetry measures can also be of help, along with daily ratings on a visual analog scale. In well-selected groups of patients suffering from PAOD, the success rate should be more than 70-75% and in patients with vasospastic disease, e.g. Raynaud’s phenomenon (rheumatic disease or certain skin diseases) is higher—around 80-90%. For vasospastic disease, the latency for a beneficial effect is also much shorter, usually below 1 h of stimulation. Thus, case selection and adhering to strict criteria are the keys to success!

For angina pectoris, the success rates are even higher—more than 80% of patients submitted to different revasculatory therapies without sufficient effect enjoy a dramatic reduction in the number of anginal attacks, hospital visits and consumption of nitrates and thus have an increased quality of life with SCS. The selection of patients is critical and inclusion criteria include:

• Patients should suffer from severe angina pectoris, giving a significant handicap to their life—belonging to the NYHA, or Canadian Cardiovascular Society classification class III-IV.
• Preferably, preoperative examinations should have demonstrated reversible myocardial ischemia as a cause of the symptoms and a simple step test or walking test using temporary TENS electrodes will preferably have demonstrated rapid symptom alleviation with high amplitude TENS, when the patient experiences angina.

However, even patients suffering from typical anginal symptoms, but without significant occlusion of their cardiac arteries as demonstrated on the arteriogram (so-called syndrome X), may also benefit from SCS therapy. Exclusion criteria include:

• Acute myocardial infarction
• Other ongoing cardiac diseases
• Unstable angina or a need for an MRI study in the immediate future

Different therapeutic algorithms: Patients with ischemic peripheral arteriopathies should, after the initial bolus stimulation period, be instructed to use the stimulator for periods as many times as needed during the day. Many such patients eventually find out that they get the largest benefits from almost continuous stimulation.

For angina patients, the instruction is to use SCS 8-10 h or more daily at a very low amplitude, and increase the amplitude only if they suffer from an acute attack of angina, or before any physical exertion, such as walking up stairs or any activity that they foresee could provoke an anginal attack.

Although SCS in Europe up to the present has focused on treatment of refractory angina pectoris, a rather late symptom in the progression of ischemic heart disease, animal studies indicate that SCS could also be useful as therapy for other symptoms and signs of heart failure. This might be a future important field.

Q: What are the biggest gaps in knowledge regarding spinal cord stimulation as an effective treatment for patients with refractory spine-related and ischemic pain syndromes?

A: One of the biggest gaps in knowledge regarding SCS lies in our still fragmentary knowledge of the underlying physiological mechanisms. However, during the last decades we have started to map some of the major mechanisms behind the benefits of SCS both in neuropathic and ischemic pain syndromes.

In neuropathic pain, sensitized second order neurons in the dorsal horn seem to be one major trouble maker, and SCS-induced activation or GABA-ergic circuitry in the dorsal horn has been indicated as a pivotal component for pain relief with SCS. However, a multitude of neuronal circuits seem to be activated simultaneously, and also cholinergic and adenosinergic, as well as serotoninergic neurons, are involved in providing pain relief with SCS in neuropathy. Earlier we believed strongly that the major part of pain relief by SCS in neuropathic pain syndromes was due to the antidromic activation of the dorsal columns, activating primarily segmental mechanisms. However, further studies have stressed the importance of suprasegmental mechanisms activated by the orthodromic dorsal column action potentials, being channeled via circuitry in the brain stem, there starting up descending pathways, probably using serotonin and norepinephrin as transmitters and ending up on the local interneurons (some of them GABAergic) in the concerned dorsal horns. The research work is presently progressing rapidly, but unfortunately, only a few research groups around the world are focusing on the part played by spinal cord stimulation.

In ischemic pain several mechanisms also seem to act in parallel. The primary effect of SCS relates to a reduction of the local ischemia, and the effect on ischemic pain is secondary to that. The effect on the pain is indeed a paradox, since SCS seems to lack effect on other nociceptive pain components in ischemic syndromes, e.g. pain from ischemic ulcers, pains rising from the borders of gangrenous zones and pain caused by changing ulcer dressings.

There seem to be several routes by which spinal cord stimulation can relieve peripheral ischemia. One is by exerting an inhibitory influence on sympathetic efferent activity, especially that being transmitted via nicotinic receptors in the sympathetic ganglia, and mainly via α-1 receptors in the end-organs. This efference seems to constitute a mainly vasoconstrictive pathway. Other routes to exert a vasodilatory influence in the periphery is that spinal chord stimulation seems to activate antidromically part of the dorsal root reflex fibers releasing CGRP and nitric oxide in the periphery, in this way creating a chemical base for vasodilatation of fine caliber arterioles. Another contribution of SCS is that preemptive SCS—i.e., using SCS for long periods of time during which a period of ischemia occurs or executing the therapy before the ischemic event—seems to induce cytoprotective changes both intra- and extracellularly. This third component is less known than those previously mentioned. However, there are several studies clearly demonstrating the importance of this component.

In angina pectoris reduction of the cardiac ischemia seems to be the most important primary event as well, and alleviation of pain is secondary to this. Both clinical and animal studies have demonstrated that SCS induces changes in the cardiac circulation, promoting a reduction of ischemia, and cell survival in critical ischemic states as well. There is at present no good animal model for angina pectoris, although multiple animal strains have been used in the investigations. However, the human studies are so compelling there is no doubt the mechanisms here are also only fragmentarily mapped. Studies are ongoing. Stimulation of the spinal chord, primarily at the T1/T2 level has demonstrated, both in man and in animals, multiple beneficial effects. Also, a few clinical trials with cervical stimulation have provided pain relief from angina, and lately canine studies at a somewhat lower (midthoracic) level have shown that several indices of heart failure can be beneficially changed by long-term spinal cord stimulation.

The above-mentioned mechanisms that are effective in peripheral ischemic diseases, might also be active when treating angina pectoris. However, communication between the spinal cord and the heart passes via small clusters of neurons in fat pads situated on the outer heart wall—the intrinsic cardiac neurons. These neuronal clusters which comprise a mixture of somatosensory and autonomic cells are actually the surveyors of the cardiac function and signal by altering their firing frequency—the presence of ischemia in some part of the heart significantly increases the firing. Several studies clearly demonstrate that spinal cord stimulation may control and stabilize the activity of these neurons. Thus, SCS also seems to involve antiarrythmic effects. This has been confirmed in controlled canine studies focused on ventricular dysrhythmias.

Another benefit clearly demonstrated in animal experiments stresses the use of chronic stimulation at a low amplitude in angina pectoris, since the protective mechanisms seem to be put in action only if the stimulation starts before the critical ischemic period. Certain pharmaceutical treatments may also counteract the beneficial effect of stimulation. This is presently being studied.

Another gap in our knowledge is that we do not know exactly how SCS should be applied to provide the maximum effect. For a long time it has been assumed that all frequencies between 30 and 100 Hz would be beneficial. Recently frequencies between 50 and 60 Hz have been most frequently used, but new animal studies actually demonstrate that much higher frequencies might be beneficial to increase the peripheral circulation, and these effects seem to be transmitted via small caliber fibres antidromically. The pulse forms should also be studied. We have for a long time used monophasic rectangular pulses. Some years ago, modulation of frequencies and pulse length were provided by manufacturers, but these features were eventually deleted because they were rarely used. Recorded or simulated “natural nerve activity” has also been considered but never practically used. So there are still big gaps to fill.

Q: Why is this topic relevant to anesthesiologists? How do different specialties approach these problems with SCS? Are there differences?

A: Although the two groups initially focusing on stimulation methods were physiologists and neurosurgeons, during the 80s and 90s and especially in the 20th Century, anesthesiologists and pain physicians have taken over. The physiologists have returned to the lab and the neurosurgeons to more invasive therapies, while the minimal invasiveness of the new techniques has appealed to anesthesiologists readily adopting percutaneous approaches. In many centers neurosurgeons are only called in when there is a need to implant the surgical lead. At present, the typical user of SCS has a background in anesthesiology with extended knowledge in physiology and pain therapy. Initially, a practice in a center with invasive implantation can be of importance for the anesthesiologist, but eventually, the anesthesiologist will manage the full implantation autonomically.

Q: What changes do you think need to be made to provide improved perioperative pain care to this group of patients using currently available technology?

A: In our center during the early and mid 80s we were performing the procedure alone, with the patient in a sitting position. Today, most patients are implanted in the prone position and the scrub nurse and nurse anesthetist take care of the instrumentation and the patient during the procedure. Most patients are medicated preoperatively with 5-10 mg benzodiazepine perorally one hour before surgery. During surgery, the patient should be awake and able to report on the distribution of the paresthesiae during test stimulation. Alphentanyl or remiphentanyl can be given by the nurse anesthetist in small doses during surgery as needed. Local anesthetic, preferably with adrenaline (if not an angina patient), should be used both for the primary incision and also in deeper tissues and with long needles subcutaneously along the route where tunneling will be performed.

The clinical application of spinal cord stimulation is spreading. Recently, large multicenter, well-controlled clinical studies on the use of SCS in neuropathic pain after spine surgery have been published, which clearly demonstrate that spinal cord stimulation provides superior pain relief when compared to repeat surgery. Use of SCS for ischemic syndromes has decreased in most countries, but I firmly believe that using more strict selection criteria will bring SCS back into the therapeutic armamentarium in pain clinics.

During the 2000s, SCS has also been used for certain sorts of intestinal pains and at present controlled trials are being carried out on irritable bowel syndrome. For some nerve territories, the placement of leads close to major nerve trunks might actually be more suitable than stimulation of the spinal chord. Use of peripheral nerve stimulation is spreading again after many years of being restricted to certain centers with a special interest in this modality.

At present, it is my opinion that spinal cord stimulation is probably an underused therapeutic modality. Regarding the unknown side effects of long-term treatment of pain syndromes with pharmaceutical regimens, even colleagues who earlier resisted invasive techniques have come to consider SCS a minimally invasive therapy with very few severe side effects that should be considered after trials with low-level drugs.

Click here to view a list of works alluded to in Dr. Linderoth ’s Q&A.