Introduction
In the U.S., unrelieved chronic pain and disability arising from chronic pain is, and will continue to be, a major problem until appropriate, cost-effective treatments are introduced. Upwards of 70 million people suffer from some form of chronic pain. The direct, hard costs of unrelieved pain to these pain sufferers and their families are loss of job, income, savings (and, therefore, security), insurance, and self-esteem. Less tangible, but no less important, is that chronic, unrelieved pain leads to depression, anger, frustration, and suffering.

Clearly, the result of untreated chronic pain is overwhelming, and it is just not acceptable today for doctors to abandon patients when less invasive therapies fail to relieve their pain and suffering. Patients should be allowed to try implantable technologies, such as spinal cord stimulation (SCS) systems and implantable drug delivery systems (also known as implantable drug pumps) before doctors tell them that nothing more can be done. These implantable technologies do work to relieve some types of pain and should be tried in appropriate patients. This article provides an overview of spinal cord stimulation implantable technologies and implantable drug delivery systems. It does not include information on deep brain stimulation or motor cortex stimulation for pain control nor does it give information on stimulation for movement disorders.  Words or phrases that are hyperlinked are defined in the glossary of terms at the end of the article. Click on the hyperlinked term to read the definition.

Treatment Options for Chronic Pain
Pain is not only biologic in nature—the end result of nervous system input—but is emotional and perceptual as well. To receive proper treatment for chronic pain and its multiple dimensions, patients need the expert care of health care providers, including doctors, nurses, psychologists, and physical therapists, who understand the problem.

Before starting any pain treatment plan, patients must understand that all pain treatments have some degree of risk. Consequently, their doctors usually will try less invasive therapies before trying more invasive therapies or procedures. Because spinal cord stimulation systems and implantable drug delivery systems are more costly and invasive than oral medications, physical or occupational therapies, or psychologic pain management, they are considered therapies of last resort to be used only when the less costly and less invasive procedures have failed to provide pain relief.  Sometimes your doctor may foresee that an implantable procedure like spinal cord stimulation (SCS) is the right therapy for you and should be tried before trying all of the less invasive therapies.  This decision should be left up to you and your doctor to decide. (Figure 1).

Figure 1: The Chronic Pain Treatment Continuum.

Spinal Cord Stimulation
Spinal cord stimulation for pain control was first used in 1967 by neurosurgeon Dr. Norman Shealy and his colleagues in response to the newly proposed gate control theory of pain. Published in 1965 by Melzack and Wall, this theory states that reception of large nerve fiber information, such as touch, sense of cold, or vibration, would turn off or close the gate to reception of painful small nerve fiber information. The expected end result would, therefore, be pain relief.

Based on the gate control theory, Shealy felt that, by electrically stimulating large fibers of the spinal cord, painful small fiber information would be shut down at that spinal segment and all other information downstream from that segment would be shut down as well. This electrical stimulation of the spinal cord, once known as dorsal column stimulation, is now referred to as spinal cord stimulation or SCS.

What is it?
Spinal cord stimulation (SCS) is a therapy used for pain control. An SCS system produces an electrical field over the spinal cord, which blocks some, but not all, types of pain. For example, pain from surgery, stomach ache, or tissue injury will not respond to spinal cord stimulation. These types of pains are called nociceptive pain. SCS can only control pain that comes from damage to the nervous system or that is caused by abnormal processes of this system. This type of pain is called neuropathic pain.

SCS systems have either an external or an internal source of power that produces the electric field. SCS systems with an external power source, called radio-frequency (RF) systems, send an electrical pulse through a flat rubber antenna worn by the patient on the skin over a small implanted receiver. The receiver is inserted into the patient's body through a surgical procedure. This receiver, which is about the size of a half dollar, receives electric information from the external generator, and sends this information to an implanted lead(s) that is placed over the spinal cord. Leads are catheter-like configurations containing electrodes that send out an electric field. Current U.S. Food and Drug Administration (FDA)-cleared or approved RF systems include ANS Renew® systems (Figure 2) and Medtronics Mattrix® (Figure 3).

Figure 2:  Renew® RF SCS system (Advanced Neuromodulation Systems, Inc.; Plano, TX)	Figure 3:  Mattrix® SCS system (Medtronic, Inc; Minneapolis, MN)

SCS systems with an implanted power source, or implantable pulse generator (IPG) SCS systems, are similar to pacemakers. IPG spinal cord stimulation systems are totally implanted under the skin within the body and generate power directly to the lead(s) over the spinal cord. IPGs can be controlled by the patient with a simple programmer outside the body (Figures 4, 5, and 6).

Figure 4. Synergy® IPG SCS system (Medtronic, Inc.; Minneapolis, MN)	Figure 5. Versetrel® IPG SCS system (Medtronic, Inc.; Minneapolis, MN)
Figure 6. GenesisXP™ IPG SCS system (Advanced Neuromodulation Systems, Inc.; Plano, TX)

The leads for SCS are placed directly over the spinal cord segment that processes the pain. These leads can be placed through a needle and buried under the skin (percutaneous leads), or they can be placed directly by an operation through a mini laminotomy, a small surgically created hole in the bone that covers the spinal cord (paddle leads) (Figures 7, 8, and 9).

 

Figure 7. Percutaneous and laminotomy leads from Advanced Neuromodulation Systems. (Plano, TX)	Figure 8. Percutaneous leads from Medtronic Inc. (Minneapolis, MN)
Figure 9. Laminotomy leads from Medtronic Inc. (Minneapolis, MN)

The decision to place percutaneous (through a needle) leads or surgical leads usually is made by the doctor who is to perform the operation. Some doctors only use percutaneous leads and some doctors only place surgical leads. Some doctors do both.  Sometimes a test for "good pain control" is performed using a percutaneous lead (through the skin) and the final system, by doctor choice, is converted to a laminectomy surgical system. Sometimes the test or trial and the final system used is, again by doctor choice, a percutaneous lead system. You should discuss these options and choices with your doctor before proceeding with the procedure.

Before the early 1990s, most lead systems were single quadrapolar (4 electrode) or single octopolar (8 electrode) leads. Today, multiple lead systems are used just as often as the single lead systems. With either quadrapolar or octopolar lead arrays, electrical combinations can be reprogrammed or changed to better locate the area of the spinal cord that controls the painful area.

After a system is implanted, it can be programmed with different or multiple programs to improve the patient's pain relief.  Figures 10 and 11 show the "Pain Doc" that programs multiple programs used with ANS equipment and N'Vision, a hand-held programmer from Medtronic, Inc., that can program both Medtronic's IPG stimulator series and Medtronic's Synchromed Pump 

Figure 10: PainDoc® programmer (Advanced Neuromodulation Systems, Inc. (Plano, TX)	Figure 11: Medtronic's N'Vision hand-held programmer that programs stimulators and pumps (Minneapolis, MN)

Who is a Candidate for Spinal Cord Stimulation?
Spinal cord stimulation (SCS) is a therapy used for the control of neuropathic pain. Pain from surgery or tissue injury will not respond to spinal cord stimulation. These types of pains are called nociceptive pain. SCS can only control pain that comes from damage to the nervous system or that is caused by abnormal processes of this system. This type of pain is called neuropathic pain. Patients with the following disorders are considered candidates for SCS when less conservative therapies have failed: 

• Patients with persistent pain in the legs that radiate from the back (sciatica)
• Patients with persistent upper arm pain
• Patients who have persistent back, buttock, and/or leg(s) pain after back surgery (so-called failed back surgery syndrome)
• Patients who have persistent neck, arm and hand pain after neck surgery (so-called failed neck surgery syndrome)
• Patients with RSD (reflex sympathetic dystrophy), now called CRPS (complex regional pain syndrome), that has failed more conservative therapies
• Patients with peripheral neuropathies such as diabetic neuropathy
• Patients with injury or damage to their nerves that go from the spinal cord to the arms or the legs

According to Medtronic Corporation, Medtronic neurostimulation systems are indicated as an aid in the management of chronic, intractable pain of the trunk and/or limbs - including unilateral or bilateral pain - associated with the following:

• Arachnoiditis or Lumbar Adhesive Arachnoiditis
• Complex Regional Pain Syndrome (CRPS) or Reflex Sympathetic Dystrophy (RSD) or Causalgia
• Degenerative Disk Disease (DDD)/ Herniated Disk pain refractory to conservative and surgical interventions.
• Epidural Fibrosis
• Failed Back Syndrome or Low Back Syndrome or Failed Back
• Multiple Back Operations
• Painful Neuropathies
• Peripheral Causalgia
• Post-Laminectomy Pain
• Radicular Pain Syndrome or Radiculopathies resulting in pain secondary to Failed Back Syndrome or Herniated Disk
• Unsuccessful Disk Surgery

Recently, SCS is being used to treat other painful disorders. There is increasing evidence that SCS can be used to relieve pain and improve blood flow to the upper or lower extremities in patients with peripheral vascular disease. Patients with intractable headaches that start at the back of the head, patients with intractable pain from angina and patients with abdominal pain from pancreatitis are now being treated by electrical stimulation using SCS devices.  If you are one of these patients, please discuss this option with your doctor. 

An SCS Trial for Pain Control
Before implanting a permanent system, most, if not all physicians will perform a test, called a trial, that will tell him or her whether SCS will work for your pain.  Patients must feel stimulation in the area of their pain when the electrodes are placed into the spinal canal over the spinal cord.  For this reason, all trials are performed under local anesthesia.  Your doctor will ask you questions during the trial procedure. Trials may be performed in the following ways:

• Placing a "trial" lead through a needle without an incision: In this case, the lead used for the trial is thrown away before final implant of the system. The surgeon places the lead through a needle without making an incision. Power is generated by an external source that looks like a radio which is connected to the trial lead.  At final permanent implantation, a new electrode lead is placed through an incision into the same area over the spinal cord as the trial lead.  The new and final/permanent lead is totally implanted and connected to the power source.
• Placing a "permanent" lead through a needle with an incision: In this case the lead used is placed through an incision and anchored to the body's tissue under the skin.  The implanted lead is connected under the skin to an electric cable that is tunneled under the skin to an exit place from the skin away from the original incision.  Power is generated by an external source that looks like a radio which is connected to the cable outside of the body.  At final permanent implantation, this implanted lead is connected inside the body to the totally implanted system.
• "On the table" surgical trial:  In this case, the electrode lead array is placed into the epidural space and the patient is asked if he or she feels the electrical sensations within the area of their pain AND if these sensations decrease the pain.  If the patient feels the stimulation in the area of his or her pain and feels that these sensations are pleasurable and decrease his or her pain, the surgeon then implants the final system.

Please discuss with your doctor what type of trial he or she performs or whether he or she will give you options.

Implantation of Leads
Using fluoroscopy, a real-time x-ray machine, the doctor implants the lead(s) into the epidural space of the spinal column (the space that surrounds the spinal cord outside of the fluid chamber in which the spinal cord sits). The lead(s) is implanted either through the skin via an epidural needle (for percutaneous leads) or directly and surgically through a mini laminotomy operation (for paddle leads).

If the doctor is implanting percutaneous leads, he or she makes an incision over the low back area (for control of back and leg pain) or over the upper back and neck area (for pain in the arms). The doctor places an epidural needle through the incision into the epidural space and advances and steers the lead over the spinal cord until it reaches the area of the spinal cord that, when electrically stimulated, produces a comfortable tingling sensation (paresthesia) that covers the patient's painful area. To locate this area, the doctor moves the lead and turns it on and off while the patient provides feedback about stimulation coverage. Because the patient participates in this operation and directs the surgeon to the correct area of the spinal cord, the procedure must be performed with local anesthesia.

If performing a mini laminotomy to implant the lead, the doctor makes the incision either slightly below or above the spinal cord segment that needs to be stimulated. He or she enters the epidural space directly through the hole in the bone and places a paddle lead array over the area to stimulate the spinal cord. The target area for stimulation usually has been located before this procedure during a spinal cord stimulation trial with percutaneous leads.

Indications for Dual Lead Arrays
Single lead arrays generally are successful for electrical stimulation of pain of either one lower or one upper extremity. Although single lead arrays have been used successfully to produce paresthesia in both extremities when the lead is placed exactly over the midline of the spinal cord, dual (2) lead arrays (either 2 quadrapolar or 4 electrode array, or dual octopolar or 8 electrode array) placed parallel to each other on either side of the midline of the spinal cord frequently work better. With these dual quadrapolar or dual octopolar leads, patients with low back pain and pain in both legs can have their pain relieved. The placement of two, three, or even four leads, sending electricity over different areas of the spinal cord, also is indicated in patients whose pain is located over multiple body areas.

Does Spinal Cord Stimulation Work?
Numerous studies show that SCS works. The take home message of most of these reports is that 6 out of 10 patients successfully trialed and implanted still get good pain control with their spinal cord stimulators two years after implantation (a 60% efficacy rate).

The FDA has cleared spinal cord stimulation as a therapy for failed back surgery syndrome, arachnoiditis, complex regional pain syndromes, and peripheral neuropathies. The FDA has not cleared SCS as a therapy for degenerative disk disease, herniated disks, peripheral vascular disease, and intractable angina; however, some doctors use SCS to treat the pain associated with these conditions.

 Implantable Drug Delivery Systems
Endorphins in the body act as the body's natural pain relievers, or keys that lock or bind with endorphin receptors involved with pain perception, which increases pain tolerance. To access these locks and keys, doctors use implantable drug delivery systems to place opioid medications (sometimes called narcotics) directly around the spinal cord (into the intrathecal space). Doctors use these systems with or without other non-opioid medications to relieve both cancer and non-cancer pain.

Spinally Delivered Pain Medications for Patients with Terminal Illnesses
In the U.S. and elsewhere, untreated cancer pain remain  an enormous problem. Studies show that 70% of all patients dying from cancer will experience pain late in their disease and some studies show that less than 50% of patients with terminal cancer pain respond to conservative therapies, such as oral morphine. Some studies also show that many patients who are dying from their disease will die suffering from their intractable, untreated pain if all they are given are oral opioids and non-opioid medications. Clearly, these patients can benefit from more advanced implantable therapies when oral medications fail to control pain adequately.

Cancer patients in whom oral or transdermal (drug patch) delivery of opioids are not working or are working with too many side effects warrant a trial of an implantable drug delivery system that delivers medications spinally. Most doctors agree that if the patient is going to live more than three months, then the patient should have a drug delivery system totally implanted. If the patient is going to live less than three months, then most doctors feel that spinally administered pain medications should be given through an implanted catheter and an external pump.

Remember, spinal drug delivery is a last resort therapy. Before having a trial for spinally delivered pain medications, all patients with non-malignant pain should have tried oral or transdermally administered pain medications, including all of the long-acting opioid medications available, such as methadone, OxyContin, Levodromiran Duragesic patches, or the long-acting morphine preparations such as Oramorph, MSContin, Kadian, and Avinza.

If opioids alone do not relieve a patient's pain, then the patient probably will need other medication added to his or her spinally delivered pain medication, such as the local anesthetic bupivacaine or the pain medication clonidine.

Who is a Candidate for Spinal Drug Delivery?
Because spinal drug delivery delivers drugs directly to the spinal canal and mostly to the intrathecal space (the space containing cerebrospinal fluid around the spinal cord), the medication "bubbles" up all along the spinal cord, bathing receptors processing pain from the whole body. Patients with both nociceptive and neuropathic pains that may be cancer related or non-cancer related (nonmalignant pain) that have failed to respond to more conservative therapies may respond to this form of therapy. Patients with failed back surgery syndrome, patients with CRPS or RSD, patients with intractable abdominal pains, and patients with failed neck surgery syndrome might receive benefit from this form of therapy.

Trial of Spinally Delivered Pain Medications
If oral and transdermal pain medications (including a trial of all of the long-acting medications mentioned above) fail or there are too many side effects with oral or transdermal administration, the patient might be a candidate for a trial of spinally delivered pain medications. To be considered a candidate, a patient should have none of the following contraindications:

• Intolerance to the medications that will be used in the trial
• Localized infection in the areas where the surgery will be performed
• An infection in the blood stream
• Blood that will not clot (This is an absolute contraindication in patients with non-malignant pain but not in patients who are dying)

When confronted with these possible contraindications in the dying patient, doctors must weigh the risks of this procedure with the benefits and discuss these risks and benefits with the patient and his or her family. A trial is considered successful if the patient has a subjective 50% reduction in pain, a reduction in oral or transdermal pain medications, and an improvement in function observed by the family or pain team. Patients who are dying from their disease, however, may not show an improvement in function because the disease itself, and not the pain, may be contributing to the decrease in function. In this group, pain control might not improve function but might improve quality of life.

Trials for spinally administered analgesic (pain relieving) medications can be performed either epidurally (the space outside of the fluid-filled balloon containing the spinal cord) or intrathecally (the space within the fluid-filled balloon containing the spinal cord) in the following ways:

• "Single shot" of medication within the epidural or intrathecal space.
• Multiple "single shots" over a period of several days.
• Continuous infusion of medication via a trial catheter or tube placed within the epidural space or intrathecal space. The medication is delivered through an external pump.
• Continuous infusion of medication via a permanent catheter or tube placed within the epidural space or intrathecal space through an incision. The catheter is connected to a temporary catheter extension which is tunneled outside of the body away from the incision. The medication is delivered through an external pump.

Trials are performed according to the preferences of your doctor. You should discuss whether your physician will give you an option for a trial.

Preventing Withdrawal Symptoms
To prevent acute withdrawal symptoms during the trial for spinally delivered pain medication, patients should be given 50% of the orally or transdermally administered dose of pain medication as an equivalent dose of spinally delivered medication during the first day of the trial, and they should be allowed to continue the remaining 50% of their systemic dose. Each subsequent day, the oral dose should be decreased by 20%, and the spinally delivered dose should be increased by 20%.

Types of Implantable Drug Delivery Systems
The first implantable drug delivery system approved for spinally delivered pain medication was the Infusaid Model #400 pump—a pump that is no longer in production. This pump was a non-programmable, fixed, constant flow pump. Today, FDA-approved constant flow pumps include the Codman Model 3000 pump (Figure 12) and the Medtronic Isomed pump (Figure 13).

Figure 12 Codman Model 3000 Constant Flow Pumps (Codman Division of Johnson & Johnson; Randolph, MA)

Figure 13 Medtronic Isomed Constant Flow Pump (Medtronic, Minneapolis, MN)

In the U.S., other companies are developing new constant flow pumps, but they are not yet approved by the FDA. Examples include the AccuRx^® pump (Figure 14), developed by Advanced Neuromodulation Systems of Plano, Texas, which is currently in clinical trials in the U.S. but is already approved for use in Europe and the Archimedes constant flow pump made by Codman, a Johnson and Johnson company, also available in Europe.

Figure 14 AccuRx® Constant Flow Pump (Advanced Neuromodulation Systems, Inc.; Plano, TX)

Medtronic's Synchromed system is the only totally programmable pump that is approved in the U.S. and Europe. Rate and, therefore, dose of drug, are externally programmable (Figure 15).

Figure 15. Synchromed® Programmable Pump (Medtronic, Inc.; Minneapolis, MN)

Besides increasing or decreasing the rate of continuous delivery of the drug, the Synchromed (c) system can be programmed to deliver a single dose of the drug, a dose of the drug at a specific time, or what doctors call "a complex continuous delivery" of the drug, which is a flat rate of the drug over time interrupted by increases in the rate at certain times of the day.

Trial for Spinally Administered Opioids
Before implanting a spinal catheter or using spinally administered opioids or other spinal pain medications, patients should go through a trial for efficacy (i.e., does it work?) or toxicity (i.e., is it safe?). Depending on the practice of the doctor who will treat with spinal pain drugs, a trial may be performed by injecting the drug directly into the thecal sac (fluid-filled sac surrounding the spinal cord) and observing the patient's response, by injecting into the epidural space around the thecal sac, or by implanting a catheter into the thecal sac or into the epidural space and delivering the drug using an external pump. A positive response is usually defined as a 50% or better decrease in pain and an observed improvement in function.

Implant Procedure
After an appropriate trial or test of spinal pain relieving drugs is performed and determined positive for pain control and negative for too many side effects, a permanent system is implanted. With an implantable drug delivery system, a pump and catheter is implanted while the patient is under local anesthesia, spinal anesthesia, or general anesthesia. To implant the system, the doctor makes an incision in the back and then places an epidural needle into the spinal canal. Once the needle enters the epidural space and cerebrospinal fluid (CSF) comes out of the needle, the doctor advances the spinal catheter (small tube) under x-ray guidance until the tip of the catheter is in the proper location. After the catheter is placed, the doctor advances it in the body, tunnels it under the skin, and connects it to the pump, which is placed in a pocket created under the skin.

Drugs Commonly Used with Implantable Drug Delivery Systems
Morphine is the gold standard of drugs for spinal pain. More is known about spinal morphine than any other spinal pain drug. In the U.S., only morphine has been approved by the FDA as a drug for spinal pain; however, doctors can use their judgment and prescribe other opioid pain medications when patients cannot tolerate morphine. While some patients cannot tolerate morphine, they might tolerate other drugs, such as Dilaudid, Demerol, methadone, fentanyl, and sufentanil.

Additionally, some patients might tolerate a drug during a trial, but they might not tolerate the drug over time, and some patients might develop side effects to the pump therapy. These side effects include the following:

• Nausea and vomiting
• Urinary retention (difficulty in voiding urine)
• Generalized pruritus (itching)
• Constipation
• Over-sedation
• Confusion
• Polyarthralgia (pain in multiple joints)
• Amennorhea (loss of female periods)
• Peripheral edema (water retention in the body)
• Sexual dysfunction (includes sexual interest, enjoyment or performance)
• Malfunction of the system
• Development of what is called a tip granuloma or the development of a fibrous mass at the tip of the catheter that could cause serious damage to the spinal cord

Doctors may attempt to manage these problems with other medications or by revising the catheter system with another surgical procedure. If these other medications cannot manage the side effects, then doctors might change the spinally delivered pain medications. The appropriate dose of opioids for spinal use is highly individualized and depends on the patient's age, the type of pain, and the drug dosage needed for pain control before the system was implanted.

Other Drugs Used in an Implantable Drug Delivery System
Because many patients develop a tolerance to their spinally delivered pain medications or develop pain that does not respond to opioids, many patients require non-opioid pain medication, such as bupivacaine, a local anesthetic drug, and clonidine, an antihypertensive drug with pain relieving properties, or other drugs being used experimentally such as ketamine, an anesthetic; midazolam (Versed), a valium-like drug; and Ziconotide, a sea snail toxin.

Although not a pain reliever, Baclofen, a drug that decreases spinal spasticity, is used in patients with spinal cord injuries, multiple sclerosis, cerebral palsy, and brain injury. This drug is approved as an antispasticity drug by the FDA for spinal use.

When are SCS and Implantable Drug Delivery Systems Used and Why do Doctors Choose One Over the Other?
Spinal cord stimulation systems and implantable drug delivery systems are effective tools used to fight chronic pain. Although both are implantable pain therapies, they usually are used for different reasons; however, some patients might benefit from either one. SCS is used for neuropathic pain (pain from damage to the nervous system) and not the pain that comes from tissue injury or inflammation, so-called nociceptive pain. Nociceptive pain responds best to opioids, and, therefore, implantable drug delivery systems will work for this type of pain and SCS might not.

If patients with neuropathic pain do not get pain relief with oral opioids or transdermal fentanyl, they probably will not get pain relief with an implantable drug delivery system. Because some patients with neuropathic pain will find relief, all patients who have failed systemic therapies, if appropriate, should get a trial of spinally delivered pain medications. If these medications fail, patients might respond to one of the experimental agents mentioned previously that do work when given intrathecally.

Summary
Untreated chronic pain is costly to society and the individuals suffering from it. When treating chronic pain, health care providers should focus not only on the neurobiologic mechanisms of the process, but also on the psychosocial aspects of the disease. Implantable technologies, although more costly and invasive than oral medications, are helpful and should be used when more conservative and less costly therapies have failed to relieve pain and suffering.

Spinal cord stimulation systems relieve neuropathic pain but not nociceptive pain. Implantable drug delivery systems use opioids, such as morphine, fentanyl, sufentanil, methadone, Dilaudid or Demerol, and/or non-opioid pain medications, such as clonidine or bupivacaine, and can provide pain relief in patients with nociceptive or neuropathic pain syndromes.

Glossary of Terms for Implantable Therapy for Pain Control: Spinal Cord Stimulation and Implantable Drug Delivery Systems

1. amennorhea:  the absence of a female's periods. Menses stop. Has multiple causes.
2. angina:  pain coming from the heart when the heart muscle does not get enough blood. Usually from clogged blood vessels to heart muscle. Felt by the patient as chest pain, jaw and arm pain. Can be silent.
3.  arachnoiditis:  the arachnoid or pia arachnoid is the filmy covering of the spinal cord and brain.  If inflamed, the resultant disorder is called arachnoiditis.
4. biologic:  having to do with the nature of plants and animals.
5.  cerebrospinal:  fluid that surrounds the spinal cord and brain.
6. constant flow pump:  this type of pump has a reservoir, is refillable, but its rate is fixed at the factory that made it.  Because the rate is fixed, to increase or decrease the dose of a drug, the concentration of the drug within the pump has to be changed.
7. constipation:  the inability to pass stools or uncharacteristically hard stools.  This is an often complication or side-effect of opioids or narcotics.  Occurs more often in the elderly.
8.  CRPS:  complex regional pain syndrome.  The newer term for RSD, having the same signs and symptoms.
9. degenerative disk disease (DDD):  This is not a true disease but an aging process whereby the natural water content of the disks (which act like shock absorbers of the spine) dries up. The outer fibers of the disk are surrounded in inner gel-like substance—with DDD, the water of the gel and the outer fibers dry up.  The outer fibers may crack and the gel escapes causing a herniated or protruding disk.
10. drug patch:  a patch that is placed on the skin and adheres to the skin.  The drug within the patch leaves the patch, enters the skin and from the skin enters the blood stream. This is a transdermal system.
11. dual (2) lead arrays:  this pertains to 2 quadropolar or 2 octopolar leads placed millimeters apart to stimulate both arms or both legs and sometimes the back.
12. electrodes: pertaining to spinal cord stimulation, electrodes send electrical information as an electrical field over the spinal cord.  Usually a programmed positive and a programmed negative electrode need to be activated to produce an electrical field.
13.  endorphins:  the body's own natural pain relieving like substances
14. epidural space:  a space within the bony canal of the spine and skull that surrounds the fluid filled sac that surrounds the brain and spinal cord.  It contains nerves, fat, blood vessels and lymph vessels.
15. external pump:  these pumps "pump" medications into the body either into the blood stream or into the spinal canal via tubes or catheters placed through the skin into blood vessels or the spinal canal.
16.  failed back surgery syndrome:  pertains to persistent pre-surgical pain after back surgery
17. failed neck surgery syndrome:  pertains to persistent pre-surgical pain after neck surgery
18. FDA:  The US Food and Drug Administration.  That government agency that is responsible for ensuring that any new devices or new drugs are safe to be implanted in humans or to be used in humans.
19. gate control theory:  a theory of pain and modulation of that pain that states painful information in small nerve fibers and touch, vibratory or cold sensations in large fibers converge from the periphery of the body at the spinal cord. Touch, cold, and vibration sensations then block painful sensations. This theory also states that pain is modulated by information from the brain such as fear, memory of pain, cultural expectations, etc.
20. herniated disks: The outer fibers of the vertebral disk (body's natural shock absorber) are surrounded in inner gel like substance. With DDD (degenerative disk disease), the water of the gel and the outer fibers dry up.  The outer fibers may crack and the gel escapes causing a herniated or protruding disk.
21. implantable drug delivery systems:  systems that are placed within the body that use a pump to deliver medication. These pumps deliver the drug to the spinal canal by way of implanted tubes (catheters).  Pumps are refillable and some are programmable. Some pumps are not programmable, delivering only one rate of delivery.
22. implantable:  pertains to placing a foreign body, here a spinal cord stimulator or implantable drug delivery system, permanently within the body.
23. incision:   surgical cut through the skin performed by a surgeon
24.  intolerance:  pertains to a therapy that produces too many unwanted side effects.
25. intractable:  resistant to therapy
26. intrathecal:  the fluid filled space surrounding the spinal cord. Contains the spinal cord and cerebrospinal fluid.
27.  IPG:  an implantable pulse generator that has a battery and electronics that generate electricity to be sent to electrodes on a spinal cord stimulator lead.  IPGs can be reprogrammed through the skin with programmers which send signals to the IPG to create programmed changes.
28. laminotomy:  a surgically created small hole in the bony covering, the lamina, of the spinal canal
29. last resort therapy:  See the pain treatment continuum, Figure 1. Therapy reserved when all less invasive and less costly therapies have failed.
30. lead(s): pertaining to spinal cord stimulation, this is a catheter (a very small thin tube) that contains electodes and wires in some configuration that allows electricity to flow from the power generator to the spinal cord from the electrodes within the lead. Leads are percutaneous or surgical and contain one, two, four, or eight electrodes.
31. local anesthesia:  anesthesia, in general terms, is a drug induced "freedom from pain." It is used to prevent the feeling of pain due to surgery or painful procedures. Anesthesia is general where the patient cannot feel pain because he or she is rendered "asleep" and unaware of the pain, or local where the area that is going to be operated upon or where the procedure is to be performed is rendered "numb" to the pain. It is rendered numb by local anesthetics such as lidocaine, bupivacaine, etc..
32. long-acting:  here it pertains to drugs whose action last longer than 3 to 4 hours.  Long-acting medications may last 6, 8, 12, or even 24 hours and longer.
33. nervous system:  the system in the body containing the brain, the spinal cord, and peripheral nerves that control movement, senses, and body functions.
34. neuropathic pain:  pain that comes from damage to the nervous system or comes from abnormal pain processing mechanisms.  It is very different from nociceptive pain and may be somewhat resistant to opioid (narcotic) pain relievers.
35. neuropathy:  means abnormality or pathology of a nerve
36. nociceptive pain:  pain that activates "nociceptors" or anatomical nerve endings or nerve bodies to send normal pain sensations to the spinal cord and the brain.  Examples include: pain of injury, stomach aches, pain of surgery, etc.  This type of pain usually responds to opioids (narcotic) pain medications.
37. nonmalignant pain:  pain from disorders that don't lead to death
38. octopolar: pertaining to spinal cord stimulation, it means a lead with 8 electrodes
39. opioid:  pertaining to a class of drugs that are pain relievers by acting at the body's own pain relieving receptors.  Also called narcotics.  An example of an opioid is morphine.
40. pancreatitis:  the pancreas is an organ in the abdomen that controls both digestion of food and blood sugar by producing insulin that controls the body's blood sugar.  Inflammation of the pancreas is called pancreatitis.  It is a painful disorder that causes upper abdominal pain that usually radiates from the front of the belly to the back.
41. paresthesia:  tingling sensations experienced by a patient in different areas of the body.  Pertaining to spinal cord stimulation, paresthesia is induced by electrical currents over the spinal cord.  Electrical currents over different parts of the spinal cord create paresthesia in different areas of the body felt by the patient.  For spinal cord stimulation to be successful, the patient must feel paresthesia in the area of his or her pain (concordant paresthesia).
42. percutaneous:  pertains to entering the skin with a needle.
43. peripheral vascular disease:  pertains to disorders of blood vessels within arms and legs.  The end result of these disorders is decreased blood flow to the arm or leg, pain, and sometimes ulcers.
44. polyarthralgia:  pain in multiple joints.
45. programmed:  programming is electrically changing the configuration of active electrodes.  It is always done for the trial and may be done after the placement of a final system.  The object of programming for spinal cord stimulation is to get electrical tingles into the area of the patient's pain and to preserved longevity of the battery.
46. pruritus:  itching of the skin.
47. quadrapolar: pertaining to spinal cord stimulation, it means a lead with 4 electrodes.
48. radio-frequency (RF) systems:  pertaining to spinal cord stimulation, this system has an external power generating source that sends electricity to an implanted receiver like a radio.  The signal gets from the external generator to the implanted receiver through the skin via an antennae worn over the implanted generator.
49. receptors:  the body's own natural chemicals and many drugs act at microscopic molecules produced by the body.  These protein molecules act as receptors for these body's drugs or drugs that come from the outside.  They act like a "lock" waiting for the drug ("key") to start a reaction.
50. retention:  pertains here to the difficulty in starting a stream of urine when going to the bathroom
51. RSD:  reflex sympathetic dystrophy.  An older term, now no longer in general use, that is a constellation of signs (what the doctor sees) and symptoms (what the patient complains of).  It is a painful disorder that causes any or all of the following signs and symptoms: swelling of an arm or leg, undue sweating of the extremity, color changes to the extremity, temperature changes to the extremity, sensitivity and pain to touch, increased pain responses to painful stimuli, etc. This disorder can be caused by abnormal pain processing mechanisms of the nervous system.
52. sciatica:  pertains to pain that comes from spinal nerves of the back and the pain that radiates from the low back down one or both legs.
53. spasticity:  means that muscles are in a state of increased contraction resulting in tightness or rigidity. May be due to a muscle disorder or a nervous system malfunction.
54. spinal cord:  that part of the nervous system within the body that controls information from the peripheral parts of the body to the brain and from the brain to peripheral parts.  It is much like a central train terminal with tracks coming from many different directions going to many different locations.  It controls all senses and movements of the body.
55. syndrome:  a constellation of signs (what the doctor sees) and symptoms (what the patient complains of) that other people share.  It is most often given a name.
56. three months to the end of life rule:  this rule applies to whether one should use an implanted pump system or an external pump system in patients who are in pain and dying from their disease such as cancer.  It is felt to be more gentle to use an external pump and implanted catheter in those patients who might not live for more than 3 months.  This rule does not apply to patients with non-malignant pain problems.
57.  tip granuloma:  pertains to a growth of proteins around the tip of an intrathecally placed catheter.  If the growth is over the spinal cord it can compress the spinal cord leading to neurologic disorders.
58. tolerance:  a body's reaction to a drug that is given for a rather long time whereby it takes a greater dose of the drug to achieve the desired effect of the drug.
59. transdermal:  a drug delivery system whereby the drug leaves a patch, enters the skin, builds up in the skin, and then enters the blood stream
60. trial:  a test.  May be done over short or longer times. As it pertains to spinal cord stimulation and implantable drug delivery, a lead is placed over the spinal cord or a catheter is implanted within the spinal fluid sac (implantable drug delivery) and the patient, over a period of time defined by the doctor, is given the chance to tell the doctor whether the therapy works before implanting a final system.
61. withdrawal symptoms:  unwanted symptoms that appear when a certain drug is suddenly stopped or an antagonist drug is given.  Here it pertains to opioid or narcotic withdrawal which is a flu-like syndrome that causes runny nose, muscle aches, stomach ache, diarrhea, shaking chills and high blood pressure.