Curr Pain Headache Rep (2014) 18:397 DOI 10.1007/s11916-013-0397-9
NEUROMODULATION (M GOFELD, SECTION EDITOR)
New Horizons in Neuromodulation Michael Gofeld
Published online: 6 February 2014 # Springer Science+Business Media New York 2014
Abstract Electrical stimulation of the nervous system is a method used for several centuries which just in the past decades received wide recognition as an effective and safe modality in the management of neuropathic pain and other maladies. Explosion of new technologies and discovery of new neuromodulation targets are two parallel and interconnected processes. Using a paraphrase from the famous novel of Samuel Sham, The House of God, one can say that there is no nervous tissue in the human body that cannot be reached with a stimulating lead directed by a good strong arm. Neuromodulation devices are being used for the stimulation of the entire nervous system, from the cutaneous terminals to brain centers. Autonomic regulation is also subject to stimulation via implanted devices. Future research and development is tightly related to the process of discovery, experimental courage, and philosophical exploration of neurobehavioral mechanisms. Keywords Neurostimulation . Neuromodulation . Electrical Stimulation . Nervous System
Introduction In the past two decades, the field of neuromodulation has been exploding. New methods and devices have been introduced to treat multiple maladies and conditions including pelvic floor syndromes, obesity, depression, movement disorders, and This article is part of the Topical Collection on Neuromodulation M. Gofeld University of Toronto, Toronto, ON, Canada M. Gofeld (*) St Michael’s Hospital, 30 Bond Street, Toronto, ON M5B 1 W8, Canada e-mail: [email protected]
chronic pain. In this volume Dr. Kumar and Dr. Rizvi have highlighted the history, the present, and new developments in electrical modulation of chronic pain. This review will outline philosophical concepts of neurostimulation and will shed light on some disruptive technologies that might achieve the status of future clinical applications. The fundamental question is “Why is implantation of external energy sources into a human body medically sound?” The appreciation of electricity as a curative power is not original. For ages, electrical and other energies have been implemented in medicine. The ancient concept of Yin and Yang is based on the theory of an eternal energy flow through meridians maintaining health and wellbeing. A block or imbalance of the flow was claimed to be the ultimate source of human illness, suffering, and death. Thus, stimulation of the nervous system may serve as a “jump-start” or “energetic harmonizer” of this internal energy. Seemingly obsolete from the modern Western medicine point of view, this postulate is not without merit. Clinical studies showed benefit of electrical stimulation of the tibial nerve to control urinary incontinence [1]. There is no solid anatomical basis to link an irritation of a remote peripheral nerve and a centrally governed disorder. However, the so-called Kidney meridian is closely aligned with the course of the tibial nerve in the leg and ankle. The powerful acupuncture points Kidney 3–7 are extensively used in traditional Chinese medicine to treat the same condition, urinary urgency, and they are located exactly at the site which was recommended for the device application (Fig. 1). Another, more pragmatic, appeal is likely related to overutilization of pharmaceutical and surgical methods. Overuse of opioids for treatment of chronic non-malignant pain in the last two decades has resulted in a national epidemic of substance abuse, addiction, and deadly overdoses [2]. It appears that even short-term opioid administration may result in irreversible changes of the human brain [3•]. Moreover, polypharmacy has been introduced as an inevitable
397, Page 2 of 4
Fig. 1 Posterior tibial nerve stimulator (a) with the active electrode (EMG-type needle) inserted at the anatomical site corresponding with the acupuncture point K7 (b)
consequence to counterbalance side effects. Along with opioids, many patients have to take laxatives, antiemetics, diuretics, and sex hormones. The lack of therapeutic benefits of chronic opioid therapy has been sobering as well. Narcotics failed to significantly relieve pain and improve function [4]. On the other hand, surgical treatment of chronic pain has also fallen into disfavor. Surgical repair of injured nerves, removal of neuromas, and surgical neurectomies are usually ineffective to control neuropathic pain. Spinal fusions and laminectomies not only failed to improve chronic low back pain, but by themselves created a new diagnosis – the failed back surgery syndrome [5, 6]. In view of the disappointment from medical and surgical options, neuromodulation appears to be safe, reasonably effective, and reversible. It perfectly suits the goals of chronic illness management by providing chronic intervention (stimulation). It does not cure chronic pain, but it helps to maintain the pain-free status by blocking nociception and stimulating neuroadaptive mechanisms. In a sense, it is similar to the insulin pump. Diabetes mellitus is a chronic incurable disease, but the infusion of exogenic insulin maintains the homeostatic balance. Conceivably, neuromodulation of chronic pain will continue to evolve and expand. Even now, the method is gaining momentum and changing its position in the analgesic ladder. It is no longer considered a salvage procedure for an end-stage chronic pain syndrome. It has been rather recommended as a method of choice for early irreversible conditions of chronic regional pain syndrome, chronic postoperative pain, and neuralgias [7, 8•]. A market research report published in January 2013 is predicting that the global market for neuromodulation devices will grow to $6.8 billion by 2017 [9]. More than 80 start-up companies related to neuromodulation are registered today. The majority will never achieve the status of approved-forhuman-use applications. However, this number surpasses corresponding enterprises in the orthopedic industry. It is fascinating to observe how clinical observations and anecdotal
Curr Pain Headache Rep (2014) 18:397
reports took off and resulted in development and regulatory approval of new devices. A small case-series report of sphenopalatine ganglion (SPG) stimulation for the treatment of cluster headache was published just a while ago [10]. Even though the prevalence of this syndrome is relatively low (one in 1,000 people suffers from cluster headache), the severity of pain and its relief achieved by SPG stimulation prompted Autonomic Technologies, Inc. to invest in the development of a specialized device (ATI™ Neurostimulation System ) and its commercialization. A tiny, externally powered, on-demand stimulator is effective to abort an attack of cluster headache (Fig. 2). A recently published randomized, controlled study confirmed the efficacy of this method [11]. Likewise, the first technical report of the dorsal root ganglion stimulation was published in 1999 [12]. Six years later, the Spinal Modulation company was founded, and the first specialized device for the dorsal root ganglion stimulation was eventually launched. A multicenter trial has been completed and published, and the device has received the CE mark [13]. Another way technological progress evolves is based on translational research and mathematical modeling. Development of miniature electrodes for peripheral nerve stimulation (e.g., Bioness Inc., Boston Scientific) and burst electrical stimulation (St Jude Medical) are examples of the former and latter, respectively. A keyword search for “neuromodulation+pain” yielded 30 results for “spinal cord stimulation,” 76 for “peripheral nerve stimulation+pain,” and 71 for “brain stimulation+pain” from 151 results regarding clinical trials registered at www. clinicaltrials.gov. It is intriguing to see the burgeoning research of brain neuromodulation. Indeed, pain is a function of the brain. Perhaps it represents a renaissance of brain modulation after initial attempts at regulatory approval of deep brain stimulation for pain indications failed. Although
Fig. 2 Artist drawing of ATI™ Neurostimulation System implanted to provide stimulation of the sphenopalatine ganglion
Curr Pain Headache Rep (2014) 18:397
the majority of the registered trials are post-marketing device evaluations, registries, and routine comparison studies, some of them deserve attention as disruptive innovations that, if proved to be successful, will revolutionize the field. A randomized clinical trial of a wireless stimulation of peripheral nerves is currently recruiting patients (Bioness® StimRouter™ Neuromodulation System for Chronic Pain Therapy NCT01592344). Traditionally it was accepted that electrical stimulation modulates transmission of the nociceptive signals. However, pain is not nociception, but rather a complex brain experience influenced by emotional, cognitive, social, cultural, and other factors. Thus, perhaps new areas of modulation will soon appear. For instance, a fascinating piece of research found that passion associated with romantic relations act as a powerful analgesic [14]. The results suggest that an emotional activation of neural reward systems via non-pharmacologic means can reduce the experience of pain. This is closely linked to the center of pleasure and reward, the nucleus accumbens, the same brain center linked to addiction disorders. Conceivably, electrical stimulation of the nucleus may produce a feeling of happiness and block physical and emotional suffering. Likewise, it was shown that distraction can help in treating chronic pain. That is why chronic pain sufferers are advised to find activities they enjoy such as walking on the ocean beach, reading, being involved in church choirs, etc. These activities are building new and constructive habits that eventually would substitute for bad habits of avoidance, inactivity, and pill popping. However, building new good habits and giving up bad habits is a very difficult process. Given the decreased cognitive abilities of chronic pain patients, this task may be unachievable in many cases. It is known that the basal ganglia are the center of habit formation. This paleocephalic region of the brain forms habits in humans and rats alike. Conceivably, stimulation of this brain area during multidisciplinary rehabilitation of complicated disabled individuals may expedite the building of new adaptive habits and can prevent relapse. Another area is the development of non-invasive neuromodulation methods such as transcranial magnetic stimulation (TMS) and percutaneous peripheral nerve stimulation (PCPNS). In a certain sense, it can be seen as a step back from sophisticated implanted systems to previously popular transcutaneous nerve stimulation (TENS). However, new percutaneous methods appear to be effective for treatment of intractable pain syndromes, where the implanted systems did not show dramatic benefit. As an example, Scrambler therapy showed significant improvement of chronic neuropathic pain [15].
Page 3 of 4, 397
anatomical targets and devices will likely be studied and implemented in the ensuing years. Disruptive neuromodulation technology is a product of both solid scientific foundations and non-traditional thinking. Compliance with Ethics Guidelines Conflict of Interest Dr. Gofeld is a consultant for Medtronic Inc., St. Jude Medical, and Boston Scientific (Cardiovascular Division), and has received grants from St. Jude Medical in the past. Dr. Gofeld serves as a section editor for Current Pain and Headache Reports. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References Papers of particular interest, published recently, have been highlighted as: • Of importance
1.
2.
3.•
4.
5.
6. 7.
8.•
Conclusion Neuromodulation of chronic pain is a rapidly evolving area in clinical practice, research, and medical industry. New
9.
Peters KM, Carrico DJ, Wooldridge LS, Miller CJ, MacDiarmid SA. Percutaneous tibial nerve stimulation for the long-term treatment of overactive bladder: 3-year results of the STEP study. J Urol. 2013;189:2194–21201. Sullivan MD, Howe CQ. Opioid therapy for chronic pain in the United States: Promises and perils. Pain. 2013. doi:10.1016/j.pain. 2013.09.009. Younger JW, Chu LF, D’Arcy N, Trott K, Jastrzab LE, Mackey SC. Prescription opioid analgesics rapidly change the human brain. Pain. 2011;152(8):1803–10. The results of this study suggest that even short-term administration of opioids may irreversibly change brain gray matter in certain regions including the amygdala, hypothalamus, inferior frontal gyrus, ventral posterior cingulated, and caudal pons. Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S. Turk DC Opioids compared to placebo or other treatments for chronic low-back pain. Cochrane Database Syst Rev. 2013;8, CD004959. doi:10.1002/14651858.CD004959.pub4. Froholdt A, Reikeraas O, Holm I, Keller A, Brox JI. No difference in 9-year outcome in CLBP patients randomized to lumbar fusion versus cognitive intervention and exercises. Eur Spine J. 2012;21(12):2531–8. Chan CW, Peng P. Failed back surgery syndrome. Pain Med. 2011;12(4):577–606. Poree L, Krames E, Pope J, Deer TR, Levy R, Schultz L. Spinal cord stimulation as treatment for complex regional pain syndrome should be considered earlier than last resort therapy. Neuromodulation. 2013;16(2):125–41. Kumar K, Rizvi S, Nguyen R, et al. Impact of wait-times on spinal cord stimulation therapy outcomes. Pain Pract 2013. This paper illustrates how the long-term efficacy of SCS is inversely proportional to implantation delay. The key to success is early SCS implantation and adherence to rigorous patient selection. http://www.marketsandmarkets.com/Market-Reports/ neurostimulation-devices-market-921.html. Last accessed October 2013
397, Page 4 of 4 10.
Ansarinia M, Rezai A, Tepper SJ, Steiner CP, Stump J, Stanton-Hicks M, et al. Electrical stimulation of sphenopalatine ganglion for acute treatment of cluster headaches. Headache. 2010;50(7):1164–74. 11. Schoenen J, Jensen RH, Lantéri-Minet M, Láinez MJ, Gaul C, Goodman AM, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: A randomized, sham-controlled study. Cephalalgia. 2013;33(10):816–30. 12. Alo KM, Yland MJ, Feler C, Oakley J. A study of electrode placement at the cervical and upper thoracic nerve roots using an anatomic trans-spinal approach. Neuromodulation. 1999;2:222–7. 13. Liem L, Russo M, Huygen FJ, Van Buyten JP, Smet I, Verrills P, et al. A multicenter, prospective trial to assess the safety and
Curr Pain Headache Rep (2014) 18:397 performance of the spinal modulation dorsal root ganglion neurostimulator system in the treatment of chronic pain. Neuromodulation. 2013. doi:10.1111/ner.12072. 14. Younger J, Aron A, Parke S, Chatterjee N. Mackey S Viewing pictures of a romantic partner reduces experimental pain: involvement of neural reward systems. PLoS One. 2010;5(10):e13309. doi: 10.1371/journal.pone.0013309. 15. Marineo G, Iorno V, Gandini C, Moschini V, Smith TJ. Scrambler therapy may relieve chronic neuropathic pain more effectively than guideline-based drug management: results of a pilot randomized, controlled trial. J Pain Symptom Manage. 2012;43(1):87–95.
NEUROMODULATION (M GOFELD, SECTION EDITOR)
New Horizons in Neuromodulation Michael Gofeld
Published online: 6 February 2014 # Springer Science+Business Media New York 2014
Abstract Electrical stimulation of the nervous system is a method used for several centuries which just in the past decades received wide recognition as an effective and safe modality in the management of neuropathic pain and other maladies. Explosion of new technologies and discovery of new neuromodulation targets are two parallel and interconnected processes. Using a paraphrase from the famous novel of Samuel Sham, The House of God, one can say that there is no nervous tissue in the human body that cannot be reached with a stimulating lead directed by a good strong arm. Neuromodulation devices are being used for the stimulation of the entire nervous system, from the cutaneous terminals to brain centers. Autonomic regulation is also subject to stimulation via implanted devices. Future research and development is tightly related to the process of discovery, experimental courage, and philosophical exploration of neurobehavioral mechanisms. Keywords Neurostimulation . Neuromodulation . Electrical Stimulation . Nervous System
Introduction In the past two decades, the field of neuromodulation has been exploding. New methods and devices have been introduced to treat multiple maladies and conditions including pelvic floor syndromes, obesity, depression, movement disorders, and This article is part of the Topical Collection on Neuromodulation M. Gofeld University of Toronto, Toronto, ON, Canada M. Gofeld (*) St Michael’s Hospital, 30 Bond Street, Toronto, ON M5B 1 W8, Canada e-mail: [email protected]
chronic pain. In this volume Dr. Kumar and Dr. Rizvi have highlighted the history, the present, and new developments in electrical modulation of chronic pain. This review will outline philosophical concepts of neurostimulation and will shed light on some disruptive technologies that might achieve the status of future clinical applications. The fundamental question is “Why is implantation of external energy sources into a human body medically sound?” The appreciation of electricity as a curative power is not original. For ages, electrical and other energies have been implemented in medicine. The ancient concept of Yin and Yang is based on the theory of an eternal energy flow through meridians maintaining health and wellbeing. A block or imbalance of the flow was claimed to be the ultimate source of human illness, suffering, and death. Thus, stimulation of the nervous system may serve as a “jump-start” or “energetic harmonizer” of this internal energy. Seemingly obsolete from the modern Western medicine point of view, this postulate is not without merit. Clinical studies showed benefit of electrical stimulation of the tibial nerve to control urinary incontinence [1]. There is no solid anatomical basis to link an irritation of a remote peripheral nerve and a centrally governed disorder. However, the so-called Kidney meridian is closely aligned with the course of the tibial nerve in the leg and ankle. The powerful acupuncture points Kidney 3–7 are extensively used in traditional Chinese medicine to treat the same condition, urinary urgency, and they are located exactly at the site which was recommended for the device application (Fig. 1). Another, more pragmatic, appeal is likely related to overutilization of pharmaceutical and surgical methods. Overuse of opioids for treatment of chronic non-malignant pain in the last two decades has resulted in a national epidemic of substance abuse, addiction, and deadly overdoses [2]. It appears that even short-term opioid administration may result in irreversible changes of the human brain [3•]. Moreover, polypharmacy has been introduced as an inevitable
397, Page 2 of 4
Fig. 1 Posterior tibial nerve stimulator (a) with the active electrode (EMG-type needle) inserted at the anatomical site corresponding with the acupuncture point K7 (b)
consequence to counterbalance side effects. Along with opioids, many patients have to take laxatives, antiemetics, diuretics, and sex hormones. The lack of therapeutic benefits of chronic opioid therapy has been sobering as well. Narcotics failed to significantly relieve pain and improve function [4]. On the other hand, surgical treatment of chronic pain has also fallen into disfavor. Surgical repair of injured nerves, removal of neuromas, and surgical neurectomies are usually ineffective to control neuropathic pain. Spinal fusions and laminectomies not only failed to improve chronic low back pain, but by themselves created a new diagnosis – the failed back surgery syndrome [5, 6]. In view of the disappointment from medical and surgical options, neuromodulation appears to be safe, reasonably effective, and reversible. It perfectly suits the goals of chronic illness management by providing chronic intervention (stimulation). It does not cure chronic pain, but it helps to maintain the pain-free status by blocking nociception and stimulating neuroadaptive mechanisms. In a sense, it is similar to the insulin pump. Diabetes mellitus is a chronic incurable disease, but the infusion of exogenic insulin maintains the homeostatic balance. Conceivably, neuromodulation of chronic pain will continue to evolve and expand. Even now, the method is gaining momentum and changing its position in the analgesic ladder. It is no longer considered a salvage procedure for an end-stage chronic pain syndrome. It has been rather recommended as a method of choice for early irreversible conditions of chronic regional pain syndrome, chronic postoperative pain, and neuralgias [7, 8•]. A market research report published in January 2013 is predicting that the global market for neuromodulation devices will grow to $6.8 billion by 2017 [9]. More than 80 start-up companies related to neuromodulation are registered today. The majority will never achieve the status of approved-forhuman-use applications. However, this number surpasses corresponding enterprises in the orthopedic industry. It is fascinating to observe how clinical observations and anecdotal
Curr Pain Headache Rep (2014) 18:397
reports took off and resulted in development and regulatory approval of new devices. A small case-series report of sphenopalatine ganglion (SPG) stimulation for the treatment of cluster headache was published just a while ago [10]. Even though the prevalence of this syndrome is relatively low (one in 1,000 people suffers from cluster headache), the severity of pain and its relief achieved by SPG stimulation prompted Autonomic Technologies, Inc. to invest in the development of a specialized device (ATI™ Neurostimulation System ) and its commercialization. A tiny, externally powered, on-demand stimulator is effective to abort an attack of cluster headache (Fig. 2). A recently published randomized, controlled study confirmed the efficacy of this method [11]. Likewise, the first technical report of the dorsal root ganglion stimulation was published in 1999 [12]. Six years later, the Spinal Modulation company was founded, and the first specialized device for the dorsal root ganglion stimulation was eventually launched. A multicenter trial has been completed and published, and the device has received the CE mark [13]. Another way technological progress evolves is based on translational research and mathematical modeling. Development of miniature electrodes for peripheral nerve stimulation (e.g., Bioness Inc., Boston Scientific) and burst electrical stimulation (St Jude Medical) are examples of the former and latter, respectively. A keyword search for “neuromodulation+pain” yielded 30 results for “spinal cord stimulation,” 76 for “peripheral nerve stimulation+pain,” and 71 for “brain stimulation+pain” from 151 results regarding clinical trials registered at www. clinicaltrials.gov. It is intriguing to see the burgeoning research of brain neuromodulation. Indeed, pain is a function of the brain. Perhaps it represents a renaissance of brain modulation after initial attempts at regulatory approval of deep brain stimulation for pain indications failed. Although
Fig. 2 Artist drawing of ATI™ Neurostimulation System implanted to provide stimulation of the sphenopalatine ganglion
Curr Pain Headache Rep (2014) 18:397
the majority of the registered trials are post-marketing device evaluations, registries, and routine comparison studies, some of them deserve attention as disruptive innovations that, if proved to be successful, will revolutionize the field. A randomized clinical trial of a wireless stimulation of peripheral nerves is currently recruiting patients (Bioness® StimRouter™ Neuromodulation System for Chronic Pain Therapy NCT01592344). Traditionally it was accepted that electrical stimulation modulates transmission of the nociceptive signals. However, pain is not nociception, but rather a complex brain experience influenced by emotional, cognitive, social, cultural, and other factors. Thus, perhaps new areas of modulation will soon appear. For instance, a fascinating piece of research found that passion associated with romantic relations act as a powerful analgesic [14]. The results suggest that an emotional activation of neural reward systems via non-pharmacologic means can reduce the experience of pain. This is closely linked to the center of pleasure and reward, the nucleus accumbens, the same brain center linked to addiction disorders. Conceivably, electrical stimulation of the nucleus may produce a feeling of happiness and block physical and emotional suffering. Likewise, it was shown that distraction can help in treating chronic pain. That is why chronic pain sufferers are advised to find activities they enjoy such as walking on the ocean beach, reading, being involved in church choirs, etc. These activities are building new and constructive habits that eventually would substitute for bad habits of avoidance, inactivity, and pill popping. However, building new good habits and giving up bad habits is a very difficult process. Given the decreased cognitive abilities of chronic pain patients, this task may be unachievable in many cases. It is known that the basal ganglia are the center of habit formation. This paleocephalic region of the brain forms habits in humans and rats alike. Conceivably, stimulation of this brain area during multidisciplinary rehabilitation of complicated disabled individuals may expedite the building of new adaptive habits and can prevent relapse. Another area is the development of non-invasive neuromodulation methods such as transcranial magnetic stimulation (TMS) and percutaneous peripheral nerve stimulation (PCPNS). In a certain sense, it can be seen as a step back from sophisticated implanted systems to previously popular transcutaneous nerve stimulation (TENS). However, new percutaneous methods appear to be effective for treatment of intractable pain syndromes, where the implanted systems did not show dramatic benefit. As an example, Scrambler therapy showed significant improvement of chronic neuropathic pain [15].
Page 3 of 4, 397
anatomical targets and devices will likely be studied and implemented in the ensuing years. Disruptive neuromodulation technology is a product of both solid scientific foundations and non-traditional thinking. Compliance with Ethics Guidelines Conflict of Interest Dr. Gofeld is a consultant for Medtronic Inc., St. Jude Medical, and Boston Scientific (Cardiovascular Division), and has received grants from St. Jude Medical in the past. Dr. Gofeld serves as a section editor for Current Pain and Headache Reports. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References Papers of particular interest, published recently, have been highlighted as: • Of importance
1.
2.
3.•
4.
5.
6. 7.
8.•
Conclusion Neuromodulation of chronic pain is a rapidly evolving area in clinical practice, research, and medical industry. New
9.
Peters KM, Carrico DJ, Wooldridge LS, Miller CJ, MacDiarmid SA. Percutaneous tibial nerve stimulation for the long-term treatment of overactive bladder: 3-year results of the STEP study. J Urol. 2013;189:2194–21201. Sullivan MD, Howe CQ. Opioid therapy for chronic pain in the United States: Promises and perils. Pain. 2013. doi:10.1016/j.pain. 2013.09.009. Younger JW, Chu LF, D’Arcy N, Trott K, Jastrzab LE, Mackey SC. Prescription opioid analgesics rapidly change the human brain. Pain. 2011;152(8):1803–10. The results of this study suggest that even short-term administration of opioids may irreversibly change brain gray matter in certain regions including the amygdala, hypothalamus, inferior frontal gyrus, ventral posterior cingulated, and caudal pons. Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S. Turk DC Opioids compared to placebo or other treatments for chronic low-back pain. Cochrane Database Syst Rev. 2013;8, CD004959. doi:10.1002/14651858.CD004959.pub4. Froholdt A, Reikeraas O, Holm I, Keller A, Brox JI. No difference in 9-year outcome in CLBP patients randomized to lumbar fusion versus cognitive intervention and exercises. Eur Spine J. 2012;21(12):2531–8. Chan CW, Peng P. Failed back surgery syndrome. Pain Med. 2011;12(4):577–606. Poree L, Krames E, Pope J, Deer TR, Levy R, Schultz L. Spinal cord stimulation as treatment for complex regional pain syndrome should be considered earlier than last resort therapy. Neuromodulation. 2013;16(2):125–41. Kumar K, Rizvi S, Nguyen R, et al. Impact of wait-times on spinal cord stimulation therapy outcomes. Pain Pract 2013. This paper illustrates how the long-term efficacy of SCS is inversely proportional to implantation delay. The key to success is early SCS implantation and adherence to rigorous patient selection. http://www.marketsandmarkets.com/Market-Reports/ neurostimulation-devices-market-921.html. Last accessed October 2013
397, Page 4 of 4 10.
Ansarinia M, Rezai A, Tepper SJ, Steiner CP, Stump J, Stanton-Hicks M, et al. Electrical stimulation of sphenopalatine ganglion for acute treatment of cluster headaches. Headache. 2010;50(7):1164–74. 11. Schoenen J, Jensen RH, Lantéri-Minet M, Láinez MJ, Gaul C, Goodman AM, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: A randomized, sham-controlled study. Cephalalgia. 2013;33(10):816–30. 12. Alo KM, Yland MJ, Feler C, Oakley J. A study of electrode placement at the cervical and upper thoracic nerve roots using an anatomic trans-spinal approach. Neuromodulation. 1999;2:222–7. 13. Liem L, Russo M, Huygen FJ, Van Buyten JP, Smet I, Verrills P, et al. A multicenter, prospective trial to assess the safety and
Curr Pain Headache Rep (2014) 18:397 performance of the spinal modulation dorsal root ganglion neurostimulator system in the treatment of chronic pain. Neuromodulation. 2013. doi:10.1111/ner.12072. 14. Younger J, Aron A, Parke S, Chatterjee N. Mackey S Viewing pictures of a romantic partner reduces experimental pain: involvement of neural reward systems. PLoS One. 2010;5(10):e13309. doi: 10.1371/journal.pone.0013309. 15. Marineo G, Iorno V, Gandini C, Moschini V, Smith TJ. Scrambler therapy may relieve chronic neuropathic pain more effectively than guideline-based drug management: results of a pilot randomized, controlled trial. J Pain Symptom Manage. 2012;43(1):87–95.
