Highlights of the 21st Annual Meeting of the American Academy of Pain Medicine

2005年2月23－27日

美国加利福尼亚州棕榈泉
February 23-27, 2005; Palm Springs, California

David L. Caraway, MD, PhD

The 21st Annual Meeting of the American Academy of Pain Medicine (AAPM) was held at the Palm Springs Convention Center, February 23-27, 2005. The goal of the meeting was to highlight multispecialty approaches to the diagnosis and treatment of chronic pain. A total of 18 update sessions with focused presentations on key clinical and practice management topics, multiple symposia offering insights into newer therapies, and several original scientific abstract and poster sessions provided an expansive selection of educational opportunities in pain medicine. This review highlights the topics that represented the state of the art in the nonpharmacologic treatment of chronic pain.

Spinal Cord Stimulation
In a preconference educational seminar on neuromodulation, Kenneth Follett discussed the history, current application, and future use of spinal cord stimulation (SCS) for the treatment of neuropathic pain.[1-7] SCS has been in clinical use for over 20 years. The primary indication of SCS is for the treatment of otherwise intractable neuropathic pain. The most common application of SCS is for persistent neuropathic pain in an extremity following spinal surgery (so-called failed back surgery syndrome). Outcomes of SCS treatment of such pain have been reported in a large number of publications, which show uniformly that pain improves substantially in approximately 55% to 65% of individuals. Analgesic use decreases in the majority of individuals who undergo SCS, and activities of daily living improve. SCS has been demonstrated to be superior to several other approaches to the treatment of pain related to failed back surgery syndrome (eg, dorsal root ganglionectomy, reoperation). Of importance, SCS is a cost-effective method of pain management.

Applications of SCS are expanding to ameliorate other types of neuropathic pain syndromes. These include complex regional pain syndrome (CRPS) (reflex sympathetic dystrophy) and some axial and peripheral neuropathic pain disorders. Complex regional pain syndrome has gained recognition in the past few years as a neuropathic pain disorder amenable to treatment with SCS. In fact, the best quality outcomes data for SCS to date pertain to the treatment of complex regional pain syndrome, supporting the utility of SCS for the treatment of this disease.

Other neuropathic pain disorders that may respond to SCS include peripheral neuropathies, such as chemotherapy-induced neuropathy, metabolic neuropathy (eg, diabetic neuropathy), and traumatic neuropathy. SCS may be more effective for diabetic neuropathy than for other types of peripheral neuropathy. In some instances, the pain of postherpetic neuralgia may also improve with SCS.

Two evolving SCS techniques include spinal nerve root stimulation (SNRS) and minimally invasive implantation of surgical laminotomy-type stimulation electrodes. SNRS may be useful for the targeted treatment of selected spinal nerves that innervate focal areas of neuropathic pain. This may be particularly useful for the treatment of some axial neuropathic pain disorders. SNRS has been used for the treatment of pain associated with interstitial cystitis by placing the stimulation electrodes in the epidural space overlying the sacral nerve roots.

SCS electrodes can be implanted percutaneously or via surgical exposure of the spinal epidural space (laminotomy). Surgically implanted electrodes are somewhat more complex to implant, but they have several advantages compared with percutaneously implanted stimulation electrodes. In particular, the stimulation amplitudes required for good pain relief are lower with surgical leads, extending the longevity of the subcutaneous stimulation pulse generators, resulting in fewer pulse generator replacement surgeries for the patients and greater long-term cost-effectiveness. Surgical leads can now be implanted with a minimally invasive technique that makes them even more desirable as a method of SCS. With a system of percutaneously placed cannulas, a channel can be fashioned that allows access to the spinal epidural space with less discomfort to the patient and, potentially, a shorter healing time, as opposed to traditional open methods for implantation of surgical-type electrodes.

Extensive clinical experience supports the utility and cost-effectiveness of SCS for the treatment of neuropathic pain. The development of new technologies will broaden the applications, improve the success rates, and further increase the acceptance of SCS for the treatment of intractable pain.

Spinal Neuromodulation
Oren Sagher discussed spinal neuromodulation in an update session on innovative surgical interventions for pain.[8] He noted that electrical stimulation of the spinal cord is routinely used for the relief of chronic radicular pain. The development of this popular technique in 1967 was entirely empirical, but its benefits for patients in chronic pain have proven to be robust over nearly 4 decades. The exact mechanisms underlying SCS-induced analgesia remain a hotly debated topic, but appear to involve direct electrical stimulation of tracts within the dorsal aspect of the spinal cord, as well as indirect neurochemical modulation within the dorsal horn.

Recent investigational and clinical data have suggested that SCS also exerts a potent, local sympatholytic effect.[9] This effect has allowed SCS to be used for the treatment of non-reconstructable peripheral limb ischemia and angina.[10,11] In addition, converging lines of evidence now suggest that SCS may be used to augment blood flow to the brain, thereby recommending its potential use in the prevention and treatment of some forms of stroke, as well as enhancing the regional delivery of chemotherapeutic agents in cancer.[12] The fact that SCS may be used to meaningfully improve regional blood flow is extremely exciting and indicates that in the future spinal neuromodulation may be used not only to control pain but also to ameliorate functional deficits within the spinal cord or periphery.

Web-Based Performance Registry
Evidence-based medicine and comprehensive analyses of the effectiveness of various therapies for the treatment of chronic pain are inadequate. The high acquisition costs and relative increased invasiveness of therapies, such as implantable systems, suggests a special need to more fully delineate efficacy, cost of care, appropriate indications, and complications. A Web-based performance registry has been designed to collect and analyze these important clinical data. Stearns and colleagues[13] presented the ambitious design of this data-collection platform in poster form at the 2005 AAPM.

The study authors state that the Implantable Systems Performance Registry (ISPR) is an ongoing, prospective, multicenter postmarket surveillance registry designed to monitor Medtronic infusion and neurostimulation systems in the United States. ISPR was developed as a follow-up to the National Outcomes Registry for Low Back Pain.[14,15] The vision for ISPR is to establish a robust data repository of representative implant and follow-up data, centers providing a forum where therapy effectiveness can be benchmarked across centers, product performance monitored, and hypotheses generated.

ISPR centers follow standard clinical practice and a common registry protocol. The centers are required to collect ISPR data at the time of implant (demographics, indication, device information, and implant technique), report the status of the patient at 6-month intervals, and report any ISPR "events," such as patient death or lost to follow-up, device explanted replaced/not replaced, other device-related surgical interventions, and therapy abandoned or resumed. ISPR collects data through a secure Web-based system, which enables electronic data capture from each center. Potential selection bias is minimized through 100% eligibility of all implanted devices at each center.

Since August 2003, 11 centers have actively contributed data for more than 900 patients with implantable systems. A multidisciplinary advisory board oversees registry reporting with the goal of peer-reviewed scientific presentation and publication. Information collected in ISPR will track therapy and device performance over extended follow-up intervals, thus providing long-term data not available in typical clinical trials, and more complete than what is possible with passive surveillance methods. Furthermore, information collected in ISPR may provide insight into the etiology of events and generate best practices on the basis of a comparison of outcomes associated with various practice techniques.

Controversies in Interventional Pain Management
A fascinating symposium[16] on controversies in the interventional pain management field offered the attendee a unique opportunity to hear and participate in a debate among opinion leaders on clinical areas pertinent to interventional pain therapies for which there have not been established clear treatment guidelines. The innovative format posed a question to 2 national experts, one of whom argued the pro aspects of the therapy and the other argued opinions opposing that position. Before the presentation, the audience was polled by the use of handheld transmitters regarding their views on the issues. After the presentations the audience was asked the same questions to see whether opinions had been swayed by the evidence and arguments presented.

Intrathecal Use of Non-US Food and Drug Administration Approved Drugs
Samuel Hassenbusch, a neurosurgeon from MD Anderson Hospital in Houston, Texas, and current president of the AAPM, argued that non-US Food and Drug Administration (FDA)-approved drugs infused through intrathecal pumps are widely used in practice, are allowed to be prescribed under Federal guidelines, and provide greater ability to control complex pain syndromes. Specifically, the use of various opioids, local anesthetics, midazolam, and other adjuvants seems to offer utility. The speaker cited a recent consensus paper supporting his position.[17]

Dr. Follett, Chair of Neurosurgery at the University of Nebraska-Lincoln, argued that the purpose of the FDA is to ensure the safety and efficacy of therapies prescribed by doctors. Without appropriate review by the agency, no such assurances can be given and the potential for harm outweighs any possible potential benefit. He argued that the only drugs approved for use in the intrathecal space are morphine, baclofen, and ziconotide. His position was that the vast majority of patients could be well controlled with these agents, and that if "off-label" medications were to be used, the patient should be informed of this with the use of a special consent.

Approaches to Permanent Implantation of SCS Leads in the Spine
Jaimie Henderson, a neurosurgeon at Stanford University, Stanford, California, discussed the advantages of surgically placed spinal cord stimulator leads. He argued that the procedure, although involving a limited laminotomy, is safe and resists migration -- a frequent and expensive complication to percutaneously placed leads. Furthermore, the surgical lead is more efficient electrically, thus preserving generator life. Finally, the flow of current with a surgical lead is unidirectional, preventing unwanted stimulation of posterior structures, which can be painful.

Timothy Deer, a pain management specialist from Charleston, West Virginia, pointed out that most leads are, in fact, placed percutaneously with excellent success. Furthermore, exposing a patient to unnecessary spinal surgery when less invasive alternatives are readily available does not justify the risk. He admitted that the "paddle-style" lead used during laminotomy placement does have some inherent advantages, but that even this will be irrelevant as similar-style leads will soon be available that can be placed percutaneously.

High-Frequency Stimulation for CRPS
David Caraway, a pain management specialist and expert on SCS, from Huntington, West Virginia, argued that there is no scientific evidence to support the use of high-frequency (greater than 100 Hz) stimulation to treat complex regional pain syndrome. Dr. Caraway noted that only 1 reference in the literature describes successful use of the stimulation mode after lower frequency stimulation has failed.[18] However, this report included no control group, no dose-response data, and no mention of the duration of success of the therapy. Furthermore, animal data suggest that high-frequency stimulation may be unsafe.[19]

Claudio Feler, Associate Professor of Neurosurgery, The University of Tennessee, Knoxville, Tennessee, reported his experience with the high-frequency mode of stimulation.[18] He explained that in his study, 15% of patients failed low-frequency stimulation despite maintenance of appropriate paresthesias. This mode, in his experience and that of many other practices, has been safe and effective.

Innovative Procedures for Chronic Pain
Intractable, neuropathic facial pain is treatable by motor cortex stimulation, providing 75% good-to-excellent pain relief, according to Jeffrey A. Brown, MD, a neurosurgeon from Great Neck, New York. In the update session on cutting-edge treatments for chronic pain,[8] Dr. Brown reviewed the use of cortical stimulation for intractable pain entities, such as pain after stroke (Dejerine-Roussy syndrome), postherpetic neuralgia (shingles), trigeminal neuropathic pain, phantom limb pain, spinal cord injury pain, and complex regional pain syndromes.

In his prospective series of 10 patients with neuropathic facial pain, the mean McGill Pain Questionnaire pain rating index fell by 55% at 10 months.[20] Pain medication dosage also dropped by 50%. A trial of the procedure of motor cortex stimulation was first published in 1991, leading to many more recent studies. Cortical stimulation uses intraoperative computerized neuronavigational techniques and electrophysiological cortical mapping to position an electrode array over the contralateral motor cortex corresponding to the painful region. Observations of functional motor and sensory improvements during stimulation suggest that stimulation alters cortical plasticity and inhibits thalamic hyperactivity. Three patients with long-term facial weakness and numbness not only achieved pain relief, but regained their motor tone and sensation.[21] The field of restorative neurosurgery exemplified by this procedure represents an exciting development in modern neurosurgery.

Sympathetic Nervous System Blocks
In a review course designed to hone the skills of those beginning their careers in pain medicine, Sunil Panchal,[22] from the Moffitt Cancer Center in Tampa, Florida, discussed the clinical application of sympathetic nervous system blockade for various pain syndromes.

These procedures have diagnostic, therapeutic, and prognostic utility. Dr. Panchal covered stellate ganglion blocks, celiac plexus block, thoracic and lumbar sympathetic chain blocks, and ganglion impar block. Indications for therapeutic application of these procedures include conditions, such as CRPS, herpes zoster, circulatory insufficiency (eg, Raynaud's disease), hyperhidrosis, refractory angina, phantom limb pain, abdominal visceral pain, and urogenital/perineal pain.[23]

CRPS type I develops after a noxious event (even as innocuous as an ankle sprain) with findings of allodynia, hyperalgesia, edema, and abnormal blood flow/sudomotor activity. CRPS type II is indistinguishable clinically but occurs after direct neural injury. Cyanotic and mottled appearance are common, as well as changes in hair growth and nail and skin texture. The historical rationale for the use of sympathetic blocks comes from the work of Walker and Nulsen[24] in which patients with CRPS type II had electrical stimulation of the sympathetic chain after undergoing a preganglionic sympathectomy. Stimulation of the postganglionic fibers resulted in a reproduction of their pain symptoms, leading to the assumption that the symptoms were maintained by sympathetic activity. We now know that this is an oversimplification, as there are CRPS patients who do not respond to sympathetic blocks, but they are valuable for the many patients who do respond.

The stellate ganglion is located over the neck of the first rib. The fibers that innervate the head and neck originate from the T1 and T2 spinal levels, whereas the fibers that innervate the upper extremities originate from T2 to T9. Therefore, ablation of the chain at the T3 level may provide relief to the upper extremity without causing a permanent Horner's syndrome. Complications may include intravascular injection, pneumothorax, intrathecal or epidural injection, brachial plexus block, or recurrent laryngeal or phrenic nerve block. The incidence of pneumothorax for thoracic sympathetic blocks is at 4%. Sympathetic innervation to the lower extremities travels via the L2-L4 paravertebral ganglia, and all must be blocked to provide a complete sympathectomy to the lower extremity. Complications at this level include intravascular injection, nerve root block, intrathecal or epidural injection, lumbar plexus block, and genitofemoral nerve injury.

Assessment of adequate blockade is essential to evaluating the results. For blockade of fibers that travel to the head and neck, a resulting Horner's syndrome (ptosis, pupillary miosis, and facial anhidrosis) is adequate. For the extremities, a rise in skin temperature (to approximately 35°C) to reflect the core body temperature is acceptable with the assumption that full vasodilation has occurred with a complete sympathectomy.

Finally, the ganglion impar, which is the terminal ganglion of the sympathetic chain, sits anterior to the sacrococcygeal ligament and innervates the perineum. There are no criteria to assess adequate block except for observing adequate spread of solution under fluoroscopy. Possible complications include rectal puncture, nerve root block, and rectal injection; however, there are currently no reported complications in the literature.

Dr. Panchal's presentation included fluoro images to demonstrate adequate needle placement as well as appropriate spread of contrast. He also demonstrated examples of inadequate spread with the aid of 3-dimensional reconstructed images.

Neurostimulation for Headache Syndromes
Intractable migraine and other headache syndromes affect approximately 30 million Americans and many more millions worldwide. Although there are many treatment protocols, primarily designed around medication regimens, at least 5% of these headache sufferers do not respond in a meaningful way to medications. These patients' lives can be severely restricted to darkened, quiet rooms; heavy doses of narcotics; failed personal relationships; and an overwhelming sense of hopelessness.

Subcutaneous occipital neurostimulation at the level of the C1 (occipitocervical junction) has been pioneered by Richard L. Weiner, MD, during the past 11 years and championed as a relatively simple, minimally invasive technique for treating many of these intractable headache syndromes.[25] He discussed this technique at a preconference seminar.[1] Using unilateral or bilateral electrodes percutaneously placed into the subcutaneous tissues, patients perceive a gentle paresthesia sensation to the back of the head, which blocks the painful areas from disorders, including chronic daily transformed migraines, occipital neuralgia, cervicogenic headaches, and deafferentation neuropathic pain. Not all patients are responders, however, and long-term follow-up to date consistently reflects a 75% to 80% success rate with greater than 50% pain reduction and diminished use of medications, particularly narcotics.

A multicenter, placebo-controlled study supported by Medtronic, Inc., is currently under way to obtain FDA approval for headache as an indication with standard products available for spinal cord and brain stimulation. Several hundred patients to date have been implanted with the off-label equipment currently available, and the emerging advances in stimulation technology hold significant promise for the successful treatment of a number of localized pain syndromes.

Supported by an independent educational grant from Medtronic.

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