Neuromodulation and Drug Delivery Systems - a Reversible Option

Chronic back and/or leg pain is a condition described as pain that is felt in the back and/or leg that may result from spinal diseases including: arachnoiditis, degenerative disc disease, epidural fibrosis, failed back syndrome, lumbar disc herniation, osteoporosis, and spinal stenosis. Back pain is often located in the lower back, but it may extend to other areas, such as the thighs, calves, and feet. Affected areas may feel tender or sore to the touch, and the pain may increase with movement. This type of pain can be felt as sharp or knife-like pain, a burning sensation, or as a dull muscular ache. Symptoms can range from mildly uncomfortable to completely disabling.

When pain persists (or recurs) for more than six months, it is said to be chronic and normal activities can become severely restricted or even impossible. Chronic pain may stem from an initial injury that has long since healed. Or, it may have an ongoing cause such as arthritis, cancer or infection.

How do you register pain?

When you feel pain, it is really a reaction to signals that are transmitted from the site of pain. These signals are sent from the pain source, through the nerves in the spinal cord, to your brain, where you perceive them as pain.
Neuropathic pain is caused by damage to nerve tissue. It is often felt as a burning or stabbing pain. One example of neuropathic pain is a pinched nerve.

Nociceptive pain is caused by an injury or disease outside the nervous system. It is often an ongoing dull ache or pressure, rather than the sharper, trauma-like pain more characteristic of neuropathic pain. One example of nociceptive pain is cancer pain.

Chronic pain often produces various harmful psychosocial effects including fear, anxiety, interference with work, decreased self-esteem, and problematic relationships. The physical effects of pain can include increased heart rate and blood pressure, increased blood sugar, decreased digestive activity, and reduced blood flow.

Is Your Pain Treatment Working for You?

Many different treatments may be used to manage chronic pain. Common pain medications include mild pain relievers, such as aspirin, weak opioids, such as codeine, and strong opioids, such as morphine. Pain can sometimes be difficult to control and can get in the way of daily activities for you and your family. If your current treatment is not providing enough pain relief, or is causing uncomfortable side effects talk to your doctor. He or she may be able to adjust your medication dosage, prescribe a different medication to reduce side effects, or offer you other options, such as neurostimulation and/or intrathecal drug delivery.

Pain Therapies which include intrathecal drug delivery and neurostimulation, are proven, effective treatment alternatives when other pain treatments provide unsatisfactory relief. Results may vary depending on the patient. Intrathecal drug delivery and neuromodulation work directly on the spinal cord, which is the highway for pain signals. These therapies are thought to work by interfering with pain signals before they reach the brain. They can offer good to excellent pain relief, and improve your ability to go about daily activities.

Overview of Indications

The etiology and pattern of the patient pain guide the selection of the appropriate Pain Therapy. Neurostimulation is indicated to aid in the management of chronic intractable pain of the trunk or limbs. In general, neurostimulation is used for neuropathic pain. Examples of neuropathic pain syndromes that typically respond well to neurostimulation are shown in Figure 1.

Nociceptive or somatic pain, pain in multiple or axial sites, and even pain with a changing pattern are better suited to intrathecal drug delivery. Pain syndromes that are typically most opioid responsive also appear in Figure 1.

Figure 1: Indications for Medtronic Pain Therapies

The intrathecal drug delivery system offers a fully implantable and programmable method of continuous drug delivery. In use clinically since 1982, and commercially since 1988, the programmability of the system allows the following: Dosages to be varied throughout the day and tailored to match your individual medication needs. The potential for a lower dose (compared to oral drugs), which may result in reduced side effects. Non-invasive dose changes. This device has been available for many years, and has been implanted in more than 50,000 patients worldwide. It is a totally implantable and programmable system, which consists of two parts - the catheter and the pump - that are both placed inside the body during an operation.

The physiology of pain begins with sensory neurons called nociceptors. A pain message is transmitted along these neurons to the dorsal horn of the spinal cord. In the dorsal horn, sensory neurons release several neurotransmitters that act on the dendrites of ascending neurons. Eventually, these ascending neurons carry the signal to the brain where it is perceived as pain. One of the key neurotransmitters in pain transmission is substance P. Opioids inhibit the release of substance P and other neurotransmitters by bonding to opioid receptors (e.g., morphine binds to Mu, Kappa and perhaps Delta receptors1). This, in effect, blocks the message before it reaches the brain and is perceived as pain.

Intrathecal drug delivery utilizes a small pump that is surgically placed under the skin in the abdomen. A pain relieving drug is contained inside the pump, and is delivered through a small, soft tube called a catheter, directly into the area surrounding the spinal cord (intrathecal space). The spinal cord is like a highway for pain signals on their way to the brain, where the feeling of pain is experienced by your body. As the pain relieving drug is delivered directly to the spinal cord where these pain signals travel, intrathecal drug delivery can offer significant pain control, with much lower doses of medication than would be required with pills. This helps to minimize side-effects that often accompany other treatments.

System Overview

An intrathecal drug delivery systems are composed of two implantable components: an infusion pump and an intraspinal catheter. The pump is placed abdominally in a subcutaneous pocket, while the catheter is inserted into the intrathecal space of the spine, tunneled under the skin and connected to the pump. Medication can be delivered at constant or variable flow rates.

Implantable Pump

Implantable pumps are battery-powered devices that store and dispense drugs according to instructions received from a programmer.

The pump contains a reservoir, reservoir fill port, and an optional catheter access port.

Reservoir: The reservoir is the cavity inside the pump where the medication is stored. Reservoir Fill Port: In the center of the pump is a raised area (called a "port") that is used for filling and emptying the pump. In the middle of this port is a self-sealing, silicone septum that is used during your pump refill procedure. Catheter Access Port: Most pumps feature a catheter access port. The catheter access port allows doctors to bypass the pump reservoir and send medications or sterile solutions directly into the implanted catheter. Doctors also may use the catheter access port for some diagnostic purposes, such as testing to ensure medication is able to flow through the length of the catheter.

Benefits of an Implantable, Programmable System

A totally implantable system may reduce the risk of infection compared to the long-term use of external systems.1 Because there are no external parts, the system usually does not restrict daily activities. A programmable pump allows clinicians to adjust doses non-invasively, minimizing patient discomfort. In addition, the pump can be programmed to deliver different doses at various times of the day--meeting patients' changing needs.

How effective is intrathecal drug delivery?

Intrathecal drug delivery has been shown to provide effective pain relief in 60–80% of patients. In addition, it has been shown to improve patients overall mood, as well as reducing the need for additional pain medications. This has helped many patients with severe pain improve their quality of life and participate more fully in daily activities, in many cases enabling patients to return to work.

Neurostimulation

Chronic pain is a common problem, affecting over 10% of the adult population worldwide. Although common pain medications or other types of treatment such as physiotherapy can provide adequate pain relief in many patients, this is not always the case. For people whose pain treatment is no longer effective, or which causes uncomfortable or unpleasant side-effects, neurostimulation may help to increase pain relief and comfort, whilst also improving quality of life. Neurostimulation has been used to treat chronic pain since the early 1970s. Currently, approximately 15,000 patients a year are treated with neurostimulation around the world.

Neurostimulation is an effective alternative to repeated back surgery, medication or other therapies. Neurostimulation has been shown to provide effective pain relief. Patients who have success with neurostimulation usually experience a 50–88% reduction in their pain and improved ability to participate in daily activities. Neurostimulation can also reduce or eliminate the need for additional pain medications and further surgeries.

To date, over 100,000 people worldwide have received neurostimulation systems for pain, with the first being introduced in 1967. Medtronic introduced programmable implantable neurostimulation systems in the U.S. in 1980 and now offers both fully implantable systems and an external radiofrequency-powered system.

What is neurostimulation and how does it work?

Neurostimulation uses a small system that is surgically placed under the skin to send precisely controlled mild electrical impulses (which are felt as pleasant tingling sensations) to your nervous system. These electrical impulses are delivered through a lead (a special medical wire or thread), that is also surgically implanted. The electrical impulses block the pain signal from reaching the brain, thereby alleviating the pain.

Neurostimulation delivers low voltage electrical stimulation to the spinal cord or targeted peripheral nerve to block the sensation of pain. One theory, the Gate Control Theory of pain developed by researchers Ronald Melzack and Patrick Wall, proposes that neurostimulation activates the body's pain inhibitory system. According to this theory, there is a gate in the spinal cord that controls the flow of noxious pain signals to the brain. The theory suggests that the body can inhibit these pain signals or "close the gate" by activating certain non-noxious nerve fibers in the dorsal horn of the spinal cord. The neurostimulation system, implanted in the epidural space, stimulates these pain-inhibiting nerve fibers, masking the sensation of pain with a tingling sensation (paresthesia).

As neurostimulation works in the area where pain signals travel, electrical impulses can be directed to cover the specific areas where you are feeling pain. Neurostimulation does not involve any medication, so there are very few of the side effects that often accompany other treatments.

Neurostimulation may be the appropriate treatment for the management of certain chronic pain conditions, including: Failed Back Syndrome (FBS), Complex Regional Pain Syndrome (CRPS), and arachnoiditis.

Benefits of Neurostimulation

The goal of neurostimulation is to reduce rather than eliminate pain. Published studies of the therapy have shown that when used on carefully selected chronic pain patients, neurostimulation may:

• Improve pain relief (a majority of patients may experience at least 50 percent reduction in pain)
• Increase activity levels
• Reduce use of narcotic medications

These results may also lead to reduced hospitalizations and surgical procedures, reduced health care costs, greater independence, and improved quality of life.

Patient Selection Criteria

Adherence to patient selection criteria is critical to long-term success. Experience has shown that these therapies work best in a carefully selected patient population. Here are seven patient selection criteria as published by Elliot Krames M.D., in The Journal of Pain and Symptom Management (J Pain & Symptom Mgt.,1996):

• More conservative therapies have failed
• An observable pathology exists that is concordant with the pain complaint
• Further surgical intervention is not indicated
• No serious untreated drug habituation exists
• Psychological evaluation and clearance for implantation has been obtained
• No contraindications to implantation exist
• A Screening test has been successful

Screening Test Period

The next step is the screening test period. This period of trial stimulation provides:

• Evaluation of the impact of stimulation on the patient’s pain and daily life
• A low-cost means of evaluating the effectiveness of the therapy
• Exclusion of non-responding patients prior to system implantation
• Identification of lead position and stimulation parameters
• A method of demonstrating efficacy to both third-party payers and review organizations

The screening test period is an opportunity for the patient to develop an understanding of the technology and realistic expectations of the therapy. During this time the patient is carefully educated and encouraged to try different parameter settings to optimize and fully "test" neurostimulation.

At the end of the screening test period, patients return to the physician's office for an assessment of their experience with the therapy. Each of the following questions should be addressed:

• Did the stimulation continue to "cover" the painful area with parathesia?
• Was the paresthesia an agreeable sensation?
• Did the paresthesia relieve the patient's pain during activities which typically provoke pain?
• What percentage pain relief was achieved with stimulation? (Was it 50 percent or greater?)
• Was the patient capable of understanding the technology and operating the screener?

If the patient does not respond positively to neurostimulation during the screening test period, the lead is removed. If the patient responds positively to a neurostimulation system during the test period, a complete neurostimulation system is implanted.

Equipment Overview - Fully Implanted System The fully implanted neurostimulation system consists of an implantable neurostimulator, an implantable lead and extension, a programmer used by physicians, a patient programmer or an external control magnet that turns the system on or off.

Neurostimulator

The implantable neurostimulator is the device that generates the exact electrical impulses that are sent to your spinal cord to control your pain. The neurostimulator contains a special battery and electronics to create these impulses. The device is most frequently placed under the skin in your abdomen.

Lead

Neurostimulation leads are special insulated wires designed to deliver neurostimulation to the spinal cord. A neurostimulation system may use one lead (single-channel) or two leads (dual-channel). The lead is about 28cm long and is placed under the skin near your spine. It contains a set of electrodes through which the electrical stimulation is delivered to the spinal cord.

Extension

The extension is a small cable about 51cm long that is placed under the skin and connects the lead to the neurostimulator used by physicians.

Programmer Used by Physicians The programmer lets your doctor adjust your neurostimulation system to the appropriate level for your pain. This programmer consists of a computer, programming head, and a printer. The programming head is placed over the area where the neurostimulator is implanted to program the settings by use of radio waves. This procedure is done through the skin and is generally considered to be painless. When you visit the doctor’s office, your neurostimulation system can be reprogrammed to more effectively deal with your pain. For example, the multiple electrodes on leads can be readjusted to provide differing patterns of pain coverage. The strength of the pain coverage can be altered to accommodate lesser or greater pain.

Programmer used by physicians

Patient Programmer The hand-held patient programmer allows you to program your own stimulation (within the settings your physician has selected. The patient programmer allows you to adjust the stimulation according to your pain between visits to the doctor’s office. Depending on your need for pain control, you can use the patient programmer to turn your system off and back on. You can also direct your system to provide greater or lesser pain relief (by increasing or decreasing the tingling), within limits set by your doctor. You will not be able to change those limits on your own, but you may discuss the need for possible changes with your doctor. A 9-volt battery is required to operate the programmer.

Programmer used by patients

Conclusion

Neuromodulation and Intrathecal Drug Delivery are two options available to patients with chronic pain. The benefit of these therapies are:

1. The therapies are safe with very few complications.
2. It is very effective in relieving pain.
3. Effective in improving function.
4. The therapy is totally reversible (i.e. non-destructive).
5. The implanting technique is minimally invasive