Peripheral Nerve Stimulation for Chronic Pain Jaimie M. Henderson, MD
Corresponding author Jaimie M. Henderson, MD Stereotactic and Functional Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive, Edwards Building/R-227, Stanford, CA 94305, USA. E-mail:
[email protected] Current Pain and Headache Reports 2008, 12:28–31 Current Medicine Group LLC ISSN 1531-3433 Copyright © 2008 by Current Medicine Group LLC
Electrical stimulation has been used since ancient times to treat painful conditions. Electrotherapy for pain was largely consigned to the realm of quackery until the introduction of the Gate Control Theory by Melzack and Wall in 1965 provided a rationale for direct stimulation of peripheral nerves. Since that time, peripheral nerve stimulation has been applied to the treatment of painful conditions throughout the body, beginning with the major nerves of the extremities and culminating today in precise subcutaneous field stimulation targeted to specific areas of neuropathic pain. This article reviews the history, development, and current areas of interest in peripheral nerve stimulation for the treatment of neuropathic pain.
Introduction Electrical stimulation of the peripheral nervous system for the treatment of pain dates back to antiquity. The ancient Egyptians recognized that electrical fish such as the Nile catfish could produce analgesia and used their powerful electric shocks to treat painful conditions [1]. The use of electricity to treat pain began in earnest in the 18th century, based on the invention of the Leyden jar in 1745, which allowed for the storage of electrical charge. “Franklinism,” named for Benjamin Franklin’s famous 1775 kite experiment, was used by a number of physicians to treat maladies such as low back pain and gout [1]. The static discharge produced sudden shocks as well as sparks, sometimes to dramatic effect. In the early 19th century, the famous debate between Galvani and Volta regarding the nature of “animal electricity” gave rise to a gentler form of electrical treatment. “Galvanism” used electrical current generated by a battery of dissimilar metals that could be adminis-
tered without sparks or sudden shock. Therapy was usually administered by direct plate electrodes with the patient in a tub of water. Duchenne, the “father of electrotherapy,” introduced “Faradization” using electromagnetic induction in the late 1800s. By the turn of the century, electrotherapy was widespread, with quackery and false claims of efficacy obscuring much of the true therapeutic benefit. Around this time, a number of scientific breakthroughs, including vaccination, antiseptic surgery, and public sanitation, led the American Medical Association (AMA) to recommend adoption of a more rigorous scientific basis for medicine and medical education. The result of the AMA’s standardization efforts was the Flexner Report, published in 1910. This report denounced nonallopathic forms of medicine, and medical schools chose to drop these curricula (including bioelectric medicine) rather than face losing accreditation [2]. The “golden age of electrotherapy” came to an end, and physicians largely lost interest in the use of electricity to treat pain.
The Modern Era of Peripheral Nerve Stimulation The publication of the Gate Control Theory of pain by Melzack and Wall in 1965 presented a new way of thinking about modulation of pain circuitry and ushered in the modern era of neurostimulation. According to this theory, activation of large-diameter A-C fibers, which conduct innocuous stimuli such as vibration and position sensation, recruits inhibitory interneurons within the substantia gelatinosa of the spinal cord. These interneurons subsequently exert their inhibitory influence on both large- and small-diameter fibers synapsing onto wide-dynamic-range central transmission cells. Activation of this system in concert with small-diameter (nociceptive) input “closes the gate,” or inhibits transmission of nociceptive signals to the brain. Although some details of this theory have subsequently been refuted, the basic premise of large-fiber activation causing pain suppression spawned a series of experiments that established electrical stimulation as a viable option for the clinical treatment of pain. Because larger-diameter axons are activated at a lower electrical threshold than smaller-diameter axons, the Gate Control Theory predicts that electrical stimulation of a mixed
Peripheral Nerve Stimulation for Chronic Pain Henderson
nerve at an intensity high enough to produce sensory paresthesiae should also produce relief of pain. The first clinical verification of the theory was published in 1967 by Wall and Sweet [3]. Eight patients with chronic cutaneous pain underwent electrical stimulation of the affected peripheral nerve, either with implantable split-ring electrodes, percutaneous concentric bipolar electrodes, or skin surface electrodes. All eight patients experienced tingling paresthesias and dramatic pain relief, although two patients who had repeated stimulation over several months developed tolerance to the effect. At this time, Shealy et al. [4] also experimented with stimulation of the dorsal columns of the spinal cord, another potential site of modulation of large-diameter fibers. The early successes of spinal cord stimulation led to fully implanted systems with radiofrequency receivers, with the first implantable, battery-powered pulse generator developed by Cordis in 1976 [1]. With implantable electrodes and radiofrequency receivers, the stage was set for true therapeutic peripheral nerve stimulation (PNS) for the treatment of chronic pain.
Stimulation of Major Peripheral Nerves PNS was first applied in earnest for the treatment of neuropathic pain in the distribution of a specific peripheral nerve. Traumatic nerve injuries, painful neuromas, mononeuropathies, complex regional pain syndrome (CRPS), and chronic nerve entrapment all may respond to PNS to a significant degree [5]. Stanton-Hicks [6] has suggested several criteria for patient selection for PNS, including neuropathic pain in the appropriate nerve distribution, demonstration of pain relief by 1 to 3 targeted nerve blocks, exclusion of psychologic pathology, and positive response to transcutaneous electrical nerve stimulation (TENS). Campbell and Long [7] and Sweet [8] were early pioneers in the use of PNS for the treatment of neuropathic pain of various etiologies; their results were published in 1976. Although Sweet [8] did not rigorously analyze his results in terms of outcome, his anecdotal report on 69 patients treated over approximately 10 years gives a flavor of the uncharted territory that these investigators were navigating. Campbell and Long [7] treated 33 patients, with eight reporting “excellent” results and 17 classified as “failures,” with one “technical failure” and seven results reported as “intermediate.” Overall, both groups thought that upper-extremity pain responded to PNS better than did lower-extremity pain and noted that activation of motor fibers in some patients could limit stimulation intensities. Most investigators have described implantation via an open technique, exposing the nerve proximal to the site of injury or entrapment and applying an electrode directly to the nerve. The use of a cuff-style electrode as described in earlier reports [7–9] has largely been replaced by the use of flat, non-encircling electrodes that do not constrict
29
the nerve, lessening fibrosis and nerve injury. An excellent review by Stanton-Hicks [6] describes current surgical techniques and results from PNS. In a recent report, Eisenberg et al. [10] reviewed their long-term results in 46 patients followed for a median of 10.8 years after PNS of major peripheral nerves of the upper and lower extremities. Cuff or paddle electrodes were sutured directly to the affected peripheral nerves, proximal to the site of injury or entrapment. Thirty-six patients (78%) continued to experience at least 50% pain relief without any analgesic medications. The results were similar between patients with upper-extremity pain (83% good outcomes) and lowerextremity pain (73% good outcomes).
Trigeminal Nerve/Ganglion Stimulation Although there are many effective therapies for the treatment of classic trigeminal neuralgia, neuropathic pain in the trigeminal distribution due to other causes can be much more difficult to treat. Direct stimulation of the trigeminal ganglion [11–15] and trigeminal nerve branches [16,17•,18] has been used with some success for the treatment of neuropathic facial pain syndromes. Johnson and Burchiel [16] reported on 10 patients with post-herpetic or traumatic neuropathic pain treated by subcutaneous stimulation in the distribution of the supraorbital or infraorbital nerves. Seven of 10 (70%) reported reduction in pain of at least 50% at 24 months. Other investigators have reported similar encouraging results in the treatment of otherwise intractable facial pain of various causes [17•,18]. Direct stimulation of the trigeminal ganglion via either an open [11,12] or a percutaneous [13–15] approach can be effective for treating trigeminal neuropathic pain. In Steude’s [13] series of 182 patients, half reported greater than 50% pain relief and underwent placement of a permanent stimulation system, although no long-term follow-up data are given. However, technical factors can limit the clinical usefulness of this modality. In 2007, Machado et al. [15] analyzed the results of percutaneous stimulation of the trigeminal ganglion for neuropathic facial pain of varying etiologies. Ten patients underwent a percutaneous trial, eight of whom were implanted with a permanent stimulation system. Three patients achieved greater than 50% pain relief at 12-month follow-up. Electrode migration and loss of stimulation efficacy over time were the main reasons for poor response, in agreement with a previous report [14].
Occipital Nerve Stimulation Stimulation of the greater occipital nerve for the treatment of occipital neuralgia was first described by Weiner and Reed [19] in 1999. Before this report, numerous approaches to the treatment of occipital neuralgia, including chemical and radiofrequency neurolysis as well as
30 Anesthetic Techniques in Pain Management
surgical nerve transection, had been attempted, with mixed results. Their use of percutaneous stimulation electrodes was based on the success of PNS of major nerves for mononeuropathy and CRPS. Twelve of 13 patients in this initial series experienced greater than 50% reduction in pain over follow-up periods of 1.5 to 6 years. After the success of this initial series, several authors have reported on surgical results using various techniques [20–22]. In a series of 22 patients who underwent permanent PNS system implant for craniofacial pain syndromes, Slavin et al. [20] reported a reduction in Visual Analogue Scale score of greater than 50% in 14 patients (64%) over periods ranging from 1 month to over 3 years. The investigators in this study used cylindrical leads introduced at the level of C1 via a lateral-to-medial approach, beginning near the mastoid process. Although easy to place, cylindrical leads have disadvantages, including lead migration (due to the tendency of a uniform cylindrical lead to migrate through a circumferential anchor) and poor directionality of stimulation (related to the symmetry of the conductive surface). In an attempt to address these disadvantages, Kapural et al. [21] described the use of a paddle-style surgical lead introduced bilaterally via a midline approach. All six patients in this study experienced 50% or greater pain relief at 3-month follow-up. Occipital nerve stimulation has emerged as a viable alternative to other surgical techniques in the treatment of occipital neuralgia. Although further study is necessary, pain relief in preliminary reports has been robust and long lasting.
ments in technology coupled with the innovative work of numerous clinical investigators have given hope to many patients for whom no good treatment alternatives would otherwise exist. However, there are still ample opportunities for improvement in electrode and pulse generator design, as well as in the development of ever less invasive techniques for the delivery of stimulation. The recent innovations in subcutaneous PNS have the potential to fundamentally change the way we think about pain treatment. It is essential that these technologies be subjected to intense scrutiny and rigorous scientific evaluation before their widespread adoption, or else we risk losing the ability to use them properly for patients who could benefit the most. If carefully designed studies bear out the encouraging early results, the future for PNS is indeed bright.
Disclosure Dr. Henderson has done consulting for Medtronic Inc. (no stock or stock options).
References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
2.
Subcutaneous Field Stimulation
3.
The success of subcutaneous electrode placement in treating occipital neuralgia, facial pain, and headaches has led investigators to attempt subcutaneous stimulation for other disorders, such as inguinal neuralgia [23], abdominal pain [24], and low back pain [25•]. In a 2007 report, six patients with intractable low back pain were treated with subcutaneous field stimulation targeted to areas identified by patients as their most painful. One or two eight-contact electrodes were placed, and trial stimulation was carried out before permanent implant. Although follow-up times were not reported, all six patients were reported to have significant decrease in pain levels [25•]. Given the known success of TENS in the treatment of chronic pain [26] and the initial promising results with occipital nerve stimulation, subcutaneous nerve stimulation may be a promising treatment for many otherwise intractable pain syndromes. However, there is little more than anecdotal evidence for its use at present.
4. 5. 6.
7. 8. 9. 10. 11.
12.
Conclusions PNS has emerged as a promising treatment option for neuropathic pain of multiple etiologies. Continued improve-
Rossi U: The history of electrical stimulation of the nervous system for the control of pain. In Electrical Stimulation and the Relief of Pain. Edited by Simpson BA. Amsterdam: Elsevier; 2003:5–16. Beck AH: The Flexner Report and the standardization of American medical education. JAMA 2004, 291:2139–2140. Wall PD, Sweet WH: Temporary abolition of pain in man. Science 1967, 155:108–109. Shealy CN, Mortimer JT, Reswick JB: Electrical inhibition of pain by stimulation of the dorsal columns: a preliminary clinical report. Anesth Analg 1967, 46:489–491. Weiner RL: Peripheral nerve neurostimulation. Neurosurg Clin N Am 2003, 14:401–408. Stanton-Hicks M: Transcutaneous and peripheral nerve stimulation. In Electrical Stimulation and the Relief of Pain. Edited by Simpson BA. Amsterdam: Elsevier; 2003:37–55. Campbell JN, Long DM: Peripheral nerve stimulation in the treatment of intractable pain. J Neurosurg 1976, 45:692–699. Sweet WH: Control of pain by direct electrical stimulation of peripheral nerves. Clin Neurosurg 1976, 23:103–111. Law JT, Sweet J, Kirsch W: Retrospective analysis of 22 patients with chronic pain treated by peripheral nerve stimulation. J Neurosurg 1980, 52:482–485. Eisenberg E, Waisbrod H, Gerbeshagen HU: Long-term peripheral nerve stimulation for painful nerve injuries. Clin J Pain 2004, 20:143–146. Meyerson BA, Håkansson S: Alleviation of atypical trigeminal pain by stimulation of the gasserian ganglion via an implanted electrode. Acta Neurochir Suppl (Wien) 1980, 30:303–309. Meyerson BA, Håkansson S: Suppression of pain in trigeminal neuropathy by electric stimulation of the gasserian ganglion. Neurosurgery 1986, 18:59–66.
Peripheral Nerve Stimulation for Chronic Pain Henderson 13.
Steude U: Chronic trigeminal nerve stimulation for the relief of persistent pain. In Textbook of Stereotactic and Functional Neurosurgery. Edited by Gildenberg PL, Tasker RR. New York: McGraw Hill; 1998:1557–1564. 14. Taub E, Munz M, Tasker RR: Chronic electrical stimulation of the gasserian ganglion for the relief of pain in a series of 34 patients. J Neurosurg 1997, 86:197–202. 15. Machado AG, Ogrin M, Rosenow JM, Henderson JM: A 12-month prospective study of gasserian ganglion stimulation for trigeminal neuropathic pain. Stereotact Funct Neurosurg 2007, 85:216–224. 16. Johnson MD, Burchiel KJ: Peripheral stimulation for treatment of trigeminal postherpetic neuralgia and trigeminal posttraumatic neuropathic pain: a pilot study. Neurosurgery 2004, 55:135–142. 17.• Slavin KV, Colpan ME, Munawar N, et al.: Trigeminal and occipital peripheral nerve stimulation for craniofacial pain: a single-institution experience and review of the literature. Neurosurg Focus 2006, 21:E6. Current state of the art in PNS for craniofacial pain. 18. Dunteman E: Peripheral nerve stimulation for unremitting ophthalmic postherpetic neuralgia. Neuromodulation 2002, 5:32–37. 19. Weiner RL, Reed KL: Peripheral neurostimulation for control of intractable occipital neuralgia. Neuromodulation 1999, 2:217–221. 20. Slavin KV, Nersesyan H, Wess C: Peripheral neurostimulation for treatment of intractable occipital neuralgia. Neurosurgery 2006, 58:112–119.
21.
31
Kapural L, Mekhail N, Hayek SM, et al.: Occipital nerve electrical stimulation via the midline approach and subcutaneous surgical leads for treatment of severe occipital neuralgia: a pilot study. Anesth Analg 2005, 101:171–174. 22. Oh MY, Ortega J, Bellotte JB, et al.: Peripheral nerve stimulation for the treatment of occipital neuralgia and transformed migraine using a C1-2-3 subcutaneous paddle style electrode: a technical report. Neuromodulation 2004, 7:103–112. 23. Stinson LW, Roderer GT, Cross NE, Davis BE: Peripheral subcutaneous electrostimulation for control of intractable post-operative inguinal pain: a case report series. Neuromodulation 2001, 4:99–104. 24. Paicius RM, Bernstein CA, Lempert-Cohen C: Peripheral nerve field stimulation in chronic abdominal pain. Pain Physician 2006, 9:261–266. 25.• Paicius RM, Bernstein CA, Lempert-Cohen C: Peripheral nerve field stimulation for the treatment of chronic low back pain: preliminary results of long-term follow-up: a case series. Neuromodulation 2007, 10:279–290. Interesting pilot study that suggests the use of subcutaneous field stimulation may have a role in the treatment of chronic back pain. 26. Mannheimer JS, Lampe GN: Clinical Transcutaneous Electrical Nerve Stimulation. Philadelphia: FA Davis Company; 1984.
