An introduction to operative neuromodulation and functional neuroprosthetics, the new frontiers of clinical neuroscience and biotechnology.

Operative neuromodulation is the field of altering electrically or chemically the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks and produce therapeutic effects. It is a rapidly evolving biomedical and high-technology field on the cutting-edge of developments across a wide range of scientific disciplines. The authors review relevant literature on the neuromodulation procedures that are performed in the spinal cord or peripheral nerves in order to treat a considerable number of conditions such as (a) chronic pain (craniofacial, somatic, pelvic, limb, or due to failed back surgery), (b) spasticity (due to spinal trauma, multiple sclerosis, upper motor neuron disease, dystonia, cerebral palsy, cerebrovascular disease or head trauma), (c) respiratory disorders, (d) cardiovascular ischemia, (e) neuropathic bladder, and (f) bowel dysfunction of neural cause. Functional neuroprosthetics, a field of operative neuromodulation, encompasses the design, construction and implantation of artificial devices capable of generating electrical stimuli, thereby, replacing the function of damaged parts of the nervous system. The present article also reviews important literature on functional neuroprostheses, functional electrical stimulation (FES), and various emerging applications based on microsystems devices, neural engineering, neuroaugmentation, neurostimulation, and assistive technologies. The authors highlight promising lines of research such as endoneural prostheses for peripheral nerve stimulation, closed-loop systems for responsive neurostimulation or implanted microwires for microstimulation of the spinal cord to enable movements of paralyzed limbs. The above growing scientific fields, in combination with biological regenerative methods, are certainly going to enhance the practice of neuromodulation. The range of neuromodulatory procedures in the spine and peripheral nerves and the dynamics of the biomedical and technological domains which are reviewed in this article indicate that new breakthroughs are likely to improve substantially the quality of life of patients who are severely disabled by neurological disorders.

Interventional pain management. Appropriate when less invasive therapies fail to provide adequate analgesia.

Unrelieved chronic pain is costly to patients and society. Noninvasive and less costly therapies should be used before more invasive and more costly therapies. Therapies for pain control should be used according to a pain treatment continuum. Nerve-blocking techniques, neurolytic techniques, and implantable neuromodulatory technologies, such as SCC and spinal delivery of analgesics, are cost-effective when less invasive therapies fail to provide adequate analgesia.

Intraspinal opioid therapy for chronic nonmalignant pain: current practice and clinical guidelines.

The multidimensional nature of chronic nonmalignant pain lends itself to numerous treatment options, which vary in cost and invasiveness. Based on the principle that less invasive and less costly interventions for pain treatment should be attempted first, a continuum of interventions for chronic pain states is presented. Although intraspinal opioid therapy is a relatively invasive and costly modality for pain treatment, it has a rational place in the treatment continuum for some chronic nonmalignant pain patients. A thorough review of the literature, supplemented by clinical experience, provides a foundation for the development of management guidelines.

Intrathecal infusional therapies for intractable pain: patient management guidelines.

This article focuses on appropriate patient selection for and management of patients selected for continuous spinal infusional opioid therapy. Patients with cancer-related pain who have undergone sequential strong opioid drug trials, who have intractable, unmanageable side effects, and who have undergone a successful spinal opioid efficacy trial are candidates for implantable spinal infusional therapy. Patients with noncancer-related chronic pain, who have failed all conventional syndrome-specific therapies before neuroablative surgical procedures, including sequential strong opioid drug trials, who have intractable, unmanageable side effects, and who have undergone successful spinal opioid efficacy trial are deemed candidates for implantable spinal infusional therapy. Patients with chronic noncancer-related pain and patient with cancer-related pain who have life expectancies greater than 3 mo all have implanted programmable infusion pumps. Patients with cancer-related pain who have life expectancies less than 3 mo have implanted permanent epidural catheters connected to external pump systems. Management guidelines for complications of therapy broadly categorized as surgical, mechanical, and pharmacologic are presented.

Clinical realities and economic considerations: patient selection in intrathecal therapy.

Chronic nonmalignant pain, persisting more than 6 months, affects 15%-30% of the United States population. The majority of chronic pain patients respond to a combination of physical modalities and non-opioid analgesics. However, approximately 20% do not derive sufficient pain relief from traditional measures (back surgery, oral drugs, etc.). An additional percentage of patients do not achieve a favorable balance between analgesia and side effects with systemic opioid therapy. For these patients, intraspinal delivery of opioids may improve pain relief, reduce suffering, and enhance quality of life and functional ability. Patient selection is a significant determinant of the success of this approach. Because pain is a biopsychosocial phenomenon, psychological and social assessment are essential along with adequate trials of opioid responsiveness. There are several valid approaches to conducting trials of intraspinal pain therapy including epidural and intrathecal trials. Other important issues concern trial length, the utility of placebo trials, and drug selection in cases where morphine alone provides insufficient analgesia.

Intrathecal infusional analgesia for nonmalignant pain: analgesic efficacy of intrathecal opioid with or without bupivacaine.

We report on the analgesic efficacy of intrathecal infusions of opioids alone or in combination with bupivacaine in 16 nonmalignant pain patients with implanted pumps. Three patients had nociceptive pain, five had neuropathic pain, and 8 had mixed pain syndromes. Infusional therapy was delivered over a combined monthly total of 445 mo of therapy (mean, 27.8 mo). Dose requirements appeared to be stable with a mean dose increase of 0.26 mg/mo. Bupivacaine was added to the opioid to enhance pain control in 13 patients who received combination therapy for an average of 11.7 mo/patient. Thirteen patients (81%) reported good to excellent results with opioid alone or opioid combined with bupivacaine. The addition of bupivacaine improved analgesia in two of three patients with nociceptive pain (66.7%), compared to eight of ten patients with a pure or mixed neuropathic component to their pain (80%). We conclude that intrathecal opioids alone or in combination with bupivacaine are efficacious for the treatment of nonmalignant pain states and are relatively free of significant side effects or tolerance.

Practical issues when using neuraxial infusion.

The pharmacologic tailoring guidelines of the World Health Organization represent the accepted treatment algorithm for the management of cancer-related pain syndromes. Unfortunately, the guidelines are only effective in 70% to 90% of patients, leaving a substantial population with intractable pain. In fact, recent surveys have shown that, in the United States, only 50% of hospitalized terminally ill patients die comfortably. When patients do not respond to the WHO guidelines, practitioners should abandon the therapy and not the patient. Interventional pain management approaches including intraspinal delivery of analgesics may be an effective alternative. Before a more permanent system for intraspinal therapy is implemented, a trial must be performed to assure efficacy, rule out toxicity, and establish that the positive response to the intrathecal agent trialed is not due to placebo effects. An external drug delivery system is appropriate if the patient has less than 3 months to live. If the patient is expected to survive more than 3 months, a totally implanted system is appropriate and cost-effective. Although morphine remains the gold standard for intrathecal pain therapy, other opioids such as fentanyl, hydromorphone, sufentanil, and meperidine are now being used in patients who do not tolerate morphine. Nonopioid agents for intrathecal use in patients who have pain syndromes that are poorly responsive to opioids include local anesthetics, such as bupivacaine, and clonidine.

Pain management: Establishing a role for implantable technologies.

Pain due to terminal illness such as AIDS and cancer-related pain should be managed according to the guidelines set forth by the World Health Organization. These guidelines suggest a pharmacologic tailoring approach to the level and intensity of the patient's pain. These guidelines obey the KISS principal (keep it simple) suggesting the use of less potent analgesic agents before utilizing more potent agents. Likewise, the treatment of non-malignant pain should be based on the same KISS principal utilizing least costly and least invasive therapies either in series or in parallel until the patient's pain is well managed. Interventional strategies and certainly implantable technologies for pain control have a place as 'tools' for the management of cancer, AIDS, and non-malignant-related pain syndromes. Since these therapies are costly and invasive, they should be used only after the failure of more conservative, less invasive and less costly therapies. This paper outlines a rational place for the use of implantable modalities for the treatment of cancer, AIDS and non-malignant pain.

Reliability and clinical utility of an implanted intraspinal catheter used in the treatment of spasticity and pain.

Objectives. To examine the performance and reliability of a redesigned implantable intrathecal catheter. Materials and Methods. A total of 212 catheters were implanted in 202 patients in this 22-center prospective study of an implantable catheter/pump system used to deliver intrathecal drugs for the treatment of pain and spasticity. Along with physician assessments of ease of use, the rates of common catheter complications (dislodgments, disconnections, fractures, and kinks) experienced during the study were analyzed in relation to implant conditions (catheter entry site, tip position, and anchoring method). Results. A cumulative total of 3112.8 months of patient experience (average: 15.4 months; range: 0-30.2 months per catheter) revealed an overall catheter-caused complication rate of 0.3% per patient month. Physician assessments were favorable with 89% rating this catheter as better than previously used intraspinal catheters. A measure of catheter survival estimates (Kaplan-Meier) at nine months was 89% including all complications. Comparison of data relating to implant techniques demonstrated a variety of catheter implant techniques (entry, positioning, anchoring) with no correlation between any one technique and the common complications. Conclusions. Performance data and physician assessments indicate that this catheter is an improvement over the previously available catheter.

Intraspinal analgesia for nonmalignant pain: a retrospective analysis for efficacy, safety and feasability in 50 patients.

Objectives. To test the efficacy and safety of intraspinal opioids for patients with nonmalignant pain. Design. A retrospective analysis on 50 patients, 37 females and 13 males, who prior to intraspinal analgesia failed all conventional therapies including strong oral opioid trials. Patients were divided into three groups according to pain type: neuropathic, nociceptive, mixed neuropathic/nociceptive. Morphine equivalent doses were noted at intervals of 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, and 72 months. Global evaluation of pain relief (poor, fair, good, excellent) was obtained at each return visit. Dose requirements, escalations, and decreases were noted and analyzed. Side effects and complications of drug infusion or mechanical devises were noted and tabulated. Results. 7 of 7 patients with nociceptive pain had good (29%) to excellent (71%) pain relief. Sixty percent of the 16 patients with neuropathic pain had good (47%) to excellent (13%) pain relief. Seventy-two percent of the total of patients with mixed pain had good (40%) to excellent (32%) pain relief. When further subdivided, only 59% of the failed back/arachnoiditis sufferers had good (41%) to excellent (18%) pain relief while 100% of the mixed group with non-FBSS diagnoses had good (37%) to excellent (63%) pain relief. Conclusions. Long-term intrathecal opioids are efficacious, practical, and safe for the treatment of nonmalignant pain syndromes. FBSS patients respond similarly to intraspinal analgesia as the patients with neuropathic pain, while the group with mixed pain from other non-FBSS causes respond similarly to the nociceptive pain patients.

Continuous infusion of spinally administered narcotics for the relief of pain due to malignant disorders.

The INFUSAID model #400 totally implantable drug delivery system was implanted in 17 patients for the continuous infusion of spinally administered preservative-free morphine sulfate. Sixteen patients had pain of malignant origin, and one patient had pain secondary to meningomyelocele. Over time, there was a consistent mean improvement in analgesia scores ranging from 50% to 70% of the control levels for 16 of the patients with cancer-related pain. This form of pain therapy was not successful in treating the benign pain of the patient with meningomyelocele. Overall, the patients with cancer were pleased with their pain therapy, experienced few complications, and reported improved quality of life. Continuous infusion of spinally administered narcotics using a totally implantable drug delivery system such as the INFUSAID model #400 is a safe, complication-free procedure for the control of cancer-related pain.