Introduction to Neurons http://www.macalester.edu/psychology/whathap/UBNRP/neuropathy/Neurons.

html The information on this page will familiarize you with the structure and function of our nerve cells (neurons). There are millions of these cells throughout our body that serve to transfer information about our external world (think temperature, pressure, pain, hot or cold) to our brain. Definitions Dendrite Treelike protrusion from the soma of a neuron; along with the soma, constitutes the receiving zone for messages from other cells. The dendrites, which constitute all the fibers extending out from the neuron except the axon, are best thought of as extensions of the cell body. The dendrites serve to extend the receptive surface of the neuron, as they are literally covered with synapses... both the dendrites and the cell body receive information through synaptic connections from other neurons. Cell Body The cell body contains all the same organelles as other cells in the body, including the mitochondria, smooth and rough endoplasmic reticulum, nucleus,and microtubules Nucleus The nerve cell; the basic unit of a synaptic nervous system. Specialized for the transmission of information. Axon The fiberlike extension of a neuron through which the cell sends information to target cells. The axon has two essential functions in the neuron. One function is to conduct information in the form of the action potential from the neuron cell body to the synaptic terminals in order to trigger synaptic transmission. The other major function is to transport chemical substances from the cell body to the synaptic terminals and backward from the synaptic terminals to the cell body. Synaptic Vesicle The tiny storage organelles (bladders) with an axon where a neurons neurotransmitter is stored; each vesicle contains thousands of copies of the transmitter molecules. Synapse The area of contact between the axon of a presynaptic neuron and the dendrite or soma of a postsynaptic neuron; site of information transfer between nerve cells. Receptor Field A receptor cells region of sensitivity. Schwann Cell Specialized glial cell found in the peripheral nervous system; responsible for the production of myelin. Myelin

Compact wrapping material that surrounds and insulates axons of some neurons; produced by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system.

Image above adapted from Bloom, Nelson, & Lazersons Brain, Mind, and Behavior Lower Image courtesy of U of Miami http://fig.cox.miami.edu/~cmallery/150/neuro/c7.48.8.node.ranvier.jpg All definitions taken from: Bloom, F.E., Lazerson, A., & Nelson, C.A. (2001). Brain, Mind, and Behavior (3rd ed.). U.S.A.: Worth Publishers.

How do Neurons Communicate? (1) Neurons communicate using synaptic neurotransmitters as the basic conveyors of information -neurotransmitter: chemical released by nerve cells at a synapse for the purpose of relaying information (2) The neuron sending the message across the synapse is known as the presynaptic neuron (3) The neuron receiving the message across the synapse is known as the postsynaptic neuron (4) the presynaptic neuron releases its neurotransmitter into the synapse when the action potential has moved down to the end of the axon (5) Synaptic vesicles at the end of the axon receive the message from the action potential to migrate to the outer membrane of the axon terminal. Once migrate, these vesicles fuse temporarily to the membrane and open to release their neurotransmitters into the synapse (6) The released neurotransmitters diffuse in the synaptic gap and bind to the membrane of the postsynaptic neurons (7) If more neurotransmitters are released into the synapse than can bind to the postsynaptic neuron, there are a few mechanisms that clear them from the area: -Sometimes, the excess neurotransmitters are destroyed by an enzyme released into the synapse from the membrane of the postsynaptic neuron -Other times, the presynaptic neuron uses a process known a reuptake, recollecting the excess neurotransmitters and repackaging them into synaptic vesicles Image adapted from Bloom, Nelson, & Lazersons Brain, Mind, and Behavior Types of Synaptic Messages 1. Excitatory, (depolarizing): the presynaptic neuron commands the postsynaptic to fire

-In this situation, the receiving cell may or may not fire in response to the neurotransmitter; signals coming in must reach a designated threshold before it will fire 2. Inhibitory: the presynaptic neuron commands the postsynaptic neuron NOT to fire

http://www.macalester.edu/psychology/whathap/UBNRP/neuropathy/Neurons.html Diabetic Neuropathy Diabetes Characterized by high blood sugar (hypoglycemia) and the bodys inability to regulate blood sugar levels. There are an estimated 20.8 million people in the U.S. with diabetes mellitus, approximately 7% of the national population. (American Diabetes Association) Image taken from http://apps.uwhealth.org/health/adam/hie/2/8679.htm There are two different types of diabetes: Type I: People are born with a pancreas that cannot produce insulin and therefore require insulin injections to regulate blood sugar levels. This accounts for approximately 5-10% of diabetic cases in the U.S. (American Diabetes Association) Type II: People build a resistance to insulin resulting in high blood sugar levels. Also, the pancreas may become unable to produce enough insulin to regulate blood sugar levels effectively. This is the most common type of diabetes in the U.S. Insulin is a hormone in the body secreted by the pancreas that helps to open cells to allow sugar (glucose) to enter and fuel them. Without enough insulin, the body does not use the molecular energy it intakes from food, causing frequent hunger, thirst, fatigue, blurred vision and other symptoms. Basically, insulin allows our food to fuel our bodys cells. A lack of effective insulin makes it impossible for the cells to extract energy from our food so that we have energy during our daily lives. There is no certain cause of type II diabetes, diets high in sugar and fat, lack of exercise, and a family history of diabetes are related to the development of Type II Diabetes. Type I is usually diagnosed early in life and is caused by a defect in the pancreas that stops it from producing insulin. Diabetes can cause nerve death. Approximately half of people with diabetes have some form of nerve damage. This nerve damage in diabetics is called diabetic neuropathy. Nerves are located throughout our bodies and their principle function is to let the brain know about what is going on in the environment around us andthrough this information, allowing us to control how we use our bodies in our environment. Image from: www.dkimages.com For example, we have nerves that send messages from our fingertips to our brain, informing us of heat changes, smoothness and roughness of surfaces (think sandpaper), pressure, vibration, wetness, and pain. Without these nerves, we lose the ability to gain certain information about our environment (think of holding your finger on a stove burner and not feeling the hot, burning sensation). We also lose the ability to rely on many unconscious bodily functions that rely on the nervous system for information (our heart rate relies upon the nervous system for information, and damage to the nerves that control heart rate can cause the heart to beat at a constant high rate instead of rising and falling in response to varying bodily functions and exercise).

In diabetics, neuropathy is most likely caused by prolonged periods of high blood sugar (glucose) and damage to blood vessels in the circulatory system caused by obesity (damage to the blood vessels lowers the amount of oxygen received by nerves, thus causing them damage or death). Overexposure to high amounts of sugar in the blood has been shown to damage nerve cells, but researchers are still trying to understand how this happens. To examine your risk to developing Diabetes, you may either take a short diabetes risk test or a more interactive and in-depth test at the following sites: Diabetes Risk Test More interactive/in-depth diabetes risk test More information on healthy food choices for diabetics Information about foot care

The Types of Neuropathy There are several different types of neuropathy, each affecting different areas of the body. The most common four types are peripheral neuropathy, autonomic neuropathy, proximal neuropathy, and focal neuropathy. Here are details on these types of neuropathy including symptoms caused by each: Peripheral Neuropathy Peripheral neuropathy is the most common type of neuropathy amongst diabetics. With peripheral neuropathy, the nerves that are damaged are referred to as the peripheral nerves (see image). Its symptoms include tingling, pain, increased sensitivity, numbness, and feelings of weakness in the hands and feet. If untreated, the symptoms may progress up the arms and legs.

Diabetics with peripheral neuropathy typically complain of having intense pains in their feet. The sensations that they experience are described as a feeling of burning in conjunction with stabbing or shooting pain. Sometimes most of a hand or foot will become numb while the areas that are unaffected will become supersensitive causing people to feel great pain at the slightest touch. This sensation of numbness that individuals with diabetic neuropathy feel is often described as feeling as though one is wearing a sock or glove. The danger of this numbness is that oftentimes, it can lead people to overlook what would normally be painful cuts, sores, blisters, or other injuries they have on their feet. When even small injuries to the extremities go unnoticed, infections may develop and spread to the bone, thus requiring amputation. For this reason, it is important for diabetics to pay attention to the sensations, or lack thereof, they experience in their feet and routinely check for foot injuries that could lead to more serious issues. Picture from www.wildirismedicaleducation.com. Autonomic Neuropathy Autonomic neuropathy describes damage to nerves that control various body systems. This includes the nerves that control heart rate, regulate blood pressure, and control the level of sugar in the blood stream. Additionally, autonomic neuropathy can have negative affects on the digestive system, urinary tract, eyes, sex organs, respiration, and sweat glands. Here are details on each system affected: Digestive system o Symptoms of autonomic neuropathy affecting the digestive system include alternating experiences of constipation and diarrhea, indigestion, heartburn, nausea, vomiting, and bloating. The nerves in the intestines may be damaged, causing slow movement of the bowels which leads to constipation. With the digestive problems caused by autonomic neuropathy, ones ability to digest food is slowed by the damage the neuropathy has caused to the stomach. In addition to this problem, the body of a diabetic is impaired in its ability to regulate blood sugar levels, a problem which may lead a diabetic with

autonomic neuropathy to feel hungry even though their stomach is full of slowly digesting food. Such a situation leads to more eating, which overfills the stomach and leads to vomiting. The urinary tract o Autonomic neuropathy can cause bladder control problems which may lead to a number of symptoms, such as feeling the need to urinate when one doesnt need to, having a urinary leak, experiencing an over- or underfrequency of urination, and contracting frequent bladder infections. Urinary bladder infection occurs because nerve damage prevents the bladder from emptying completely, causing a buildup of bacteria. Cardiovascular System (Heart and Blood Vessels) o Neuropathy can occur in the nerves of the heart and blood vessels causing an inability of those organs to regulate blood pressure throughout the body. An individual with this type of autonomic neuropathy may experience sudden drops in blood pressure going to a standing position after sitting or lying down for a period of time. This drop can cause light-headedness, dizziness, and fainting. Conversely, blood pressure may remain consistently high instead of changing throughout daily activity. Typically, blood pressure would be higher during stressful physical activity and lower at rest. Thus, when an individual with autonomic neuropathy quickly changes from a restful sitting position to a standing position, their blood pressure does not increase rapidly enough and they experience the symptoms of dizziness, light-headedness, and fainting. Warning signs of low blood sugar o Typically, when a diabetic has low blood sugar levels (referred to as hypoglycemia) they begin to show warning signs that includesweating, heart palpitations, nervousness, and shakiness. However, a diabetic with autonomic neuropathy may not have the fortune ofshowing thesewarning signs as the body systemthat sends out these warnings may be damaged by the neuropathy. This means that if a diabetic with this form of neuropathy had low blood sugar (hypoglycemic), they might faint without any warning or feeling of being hypoglycemic when in the past (before the autonomic neuropathy started) they had clear warning signs. Sweat Glands o Nerve damage can occur in the sweat glands causing the body to not sweat when it should. Conversely, a person may sweat more than he/she should especially at night or while eating. Both of these conditions hurt the bodys ability to regulate temperature. Eyes o The nerves controlling the opening and closing of the pupils of the eyes may become damaged. This damage makes vision challenging when there is a sudden change in illumination. It also makes driving at night particularly challenging as light levels change rapidly with the flashing of headlights.

http://diabetes.niddk.nih.gov/dm/pubs/neuropathies/ Proximal Neuropathy Proximal neuropathy is more common in type II diabetics and older diabetics. Nerve damage is found in the hips, thighs, buttocks, and legs usually specific to one side of the body. The nerve damage in this situation causes pain and weakness in these areas. Walking may be difficult for individuals with proximal neuropathy, and they may need assistance transitioning from a seated to a standing position. Focal Neuropathy Focal neuropathy describes the incidence of neuropathy that occurs in a specific point in the body rather than a nerve circuit, which is characteristic of peripheral, autonomic, and proximal neuropathies. Focal neuropathy has a sudden onset, and it typically occurs in the head, torso, or legs. In addition to its rapid development, focal neuropathy is characterized by pain, and it is more likely to occur in older rather than younger people. Here are some specific examples of focal neuropathy: Eyes- inability to focus, double vision, aching Paralysis on one side of the face (Bells Palsy) Severe pain - typically in the lower back or pelvis, thigh, chest, stomach, abdominal area, and pain on the shin or inside of the foot.

Suggestions on how to live with diabetic neuropathy: The best advice any individual with diabetes can receive is that it is imperative to try to keep your blood sugar (glucose) levels within your target range. To do this, monitor your blood glucose levels throughout daily life. Decisions regarding what to eat, the amount of physical activity to undertake, and the amount of medications to take (if prescribed) can help you control your blood sugar levels as well. A helpful tool that is useful in keeping tabs on your blood sugar levels is the blood glucose meter. These can help you maintain your blood sugar levels in the range of 90-110 mg/dL. To learn about blood sugar meters, visit the FDA's website: http://www.fda.gov/diabetes/glucose.html Buy a blood sugar meter: http://www.diabetesnet.com/diabetes_technology/blood_glucose_meters.php Getting an A1C test from a doctor at least twice a year is also very helfpul. This test will inform you of your average blood glucose levels during the past two to three months. This will allow you to better understand your blood glucose levels so that, in the future, you can make more informed decisions regarding lifestyle choices. As discussed in the peripheral neuropathy section of this website, foot care is extremely important in self-care for diabetics. The occurrence of neuropathy can lead one to not notice sensations of pain or injury in the feet and allow an infection to develop and spread to the bone. Because of this it is essential for a diabetic to check their feet every day, especially if sensations of numbness have been experienced. Additionally, it is important to be careful with exercise, as autonomic neuropathy may make it difficult to transition between states of low activity to high activity. To complete a symptom checklist that evaluates diabetic neuropathy, click here. Drug Treatment for Pain Associated with Diabetic Neuropathy: Pain is one of the most problematic symptoms of diabetic neuropathy. Gabapentin has been prescribed as an effective drug treatment for pain and sleep loss due to pain in diabetic neuropathy. Additionally, the drugs Amitriptyline and Cymbalta have been found to relieve the pain associated with diabetic neuropathy. (Backonja, 1998) (Max, 1987) Therapeutic Drug-Induced and Cancer-Related Neuropathies Introduction: Therapeutic drug trials and drug legislation cannot anticipate every interaction or side effect a medication may have on the general population, and therefore, these interactions may go unnoticed until they have developed into full-blown difficulties themselves. (Arnold, 1979) Definitions for italicized words can be found in the Glossary. DRUG INDUCED NEUROPATHIES What does it mean to have a drug-induced neuropathy? Drug-induced means that an individuals neuropathy was caused primarily by his/her medication(s). Although these neuropathies only affect 2-4% of individuals who take specific prescription medications, the complex issues of resulting symptoms, drug continuation, and pain treatment proves very frustrating for many individuals. What types of therapeutic drugs may lead to neuropathy? And what types of neuropathy do they lead to? Although many powerful drugs have the potential to create serious side effects like neuropathy, there are around seven main categories of medications that have shown to do so. These are: chemotherapy drugs, antifungal drugs, antibiotics, drugs involved in the treatment of infectious disease, cardiovascular and cholesterol drugs, hypnotics, and psychotherapeutic drugs used to treat addictions. Please see the table provided for examples of such drugs, as well as for more information on what types of neuropathy they may cause. (Critchley, 1979)(Flatters, 2006) Click here to read a short story from a man who developed peripheral neuropathy after getting treatment for colon cancer. What are some symptoms of drug-induced neuropathy? Since most drug-induced neuropathies tend to be peripheral, their side effects are similar to neuropathies not induced by medication. You should consult with your doctor if you have any of the following side effects from a prescribed medication(Leonard, 2005):

Tingling (pins and needles) Numbness Difficulty telling the difference between rough and smooth surfaces Difficulty feeling hot things Difficulty feeling cold things A greater than normal sense of touch (the glove effect) Burning pain or discomfort without cold Burning pain or discomfort with cold Difficulty identifying objects in your hand Involuntary leg or hand movements Jaw pain Eyelids drooping Throat discomfort Ear pain Tingling in mouth Difficulty with speech Burning or discomfort of your eyes Loss of any vision Feeling shock/pain down back or in extremities/limbs Problems with breathing

How do these drugs potentially cause neuropathy? The ways in which these drugs cause neuropathy is, for the most part, still being studied. However, research has found evidence that appears promising. One is that, most often, the individual has an underlying cause that makes them more susceptible to getting neuropathy. These causes can be from, for example, cancer (read more about this below) or other disabling ailments (such a rheumatoid arthritis, diabetes, or alcoholism), or they can be from a predisposition in ones genetic makeup or genetic malfunction. The drugs that are used in treatments continue where the ailments left off. For example, sometimes giving penicillin injections to a person who is unknowingly allergic to penicillin may result in a type of nerve damage called brachial plexus neuropathy in a case such as this, it was not necessarily the drug that caused the neuropathy, but instead, the patients genetic predisposition to have an allergenic response to the drug that causes such adverse side effects. (Argov, 1979) In addition, the very ways in which these prescription medications function can lead to neuropathy. There are six ways in which therapeutic drugs have been thought to cause neuropathy and the various symptoms that come with it (most notably pain and numbness). Demyelination (Argov,1979) Many of our nerve cells, called neurons, have axons (which help transmit brain messages) that are coated in a white substance called myelin (as a whole, it is called a myelin sheath). Myelin is made up mostly of fat and protein, and it serves as an insulator to our neurons to help electrical signals move faster and more efficiently between our brains and our bodies. The chemicals in some therapeutic drugs (like chemotherapies) often destroy our myelin sheaths. Damage to our myelin disrupts the important messaging system our brain has with our bodies, and a variety of symptoms, including neuropathy, can result. In this instance, numbness is a major side effect since the loss of myelin inhibits a neurons ability to communicate sensory information about changes in the environment. Axonal Degeneration (Argov,1979) Similar to demyelination, axonal degeneration also involves our neurons. An axon is the part of the neuron that carries electrical information from, and sometimes to, a neurons cell body. Usually, most neurons only have one axon; however, most axons have many branches, allowing extensive communication between certain neurons. The drugs that we have been talking about often kill cells indiscriminately, as they kill both necessary and unhealthy cells. In the case of neuropathy, some medicines may result in the death of the axons, which in turn leads to the breakdown of the myelin sheath and the break down of the cells composing the axon, called Schwann cells. The reverse is also true Schwann cell damage and demyelination may expose an axon, resulting in either extreme pain and/or nerve death. Schwann Cell Damage (Argov,1979) Schwann cells are a type of cell that make up the axon of a neuron. They are cells responsible for the formation of the protective myelin sheath. As you may have guessed by now, when either the axon itself or the myelin surrounding it is

damaged by certain drug effects, the Schwann cells will inevitably be damaged or killed as well, leading to some of the many symptoms that occur within neuropathy. A quick recap: Nerve axons are very sensitive. The myelin sheathes that cover axons are important not only for making communication between neurons fast and efficient, but also for protecting these highly sensitive areas. Numbness occurs when myelin is temporarily or permanently destroyed. Temporary demyelination makes a cell less efficient and less responsive to changes in the environment until the axons Schwann cells regenerate new myelin. On the other hand, permanent demyelination, which often occurs in axonal degeneration, leaves the highly sensitive axon completely exposed, and, in the case of Schwann cell damage, the axon is unable to regenerate myelin, resulting in permanent numbness and high pain sensitivity. In any case, if a nerve axon dies, the communication network that that nerve cell is a part of becomes completely disrupted, since there is no axon to relay messages from the body to the brain. The process of axonal degeneration is extremely painful, but ending result is a permanent numbness. Vitamin Deficiencies (Argov,1979) Some drugs affect the body by disturbing its balance (referred to as homeostasis). One way it does this is by affecting vitamin and nutrient levels, causing vitamin deficiencies. The vitamin most often found in insufficient levels after treatments used in cancer and infectious diseases was vitamin B (B1 and B12 to be specific). A deficiency in vitamin B1 has been shown to cause Wernickes encephalopathy, which results in an impaired sensory perception, as well as weakness and pain in the limbs. Insufficient levels of vitamin B12 have been shown to cause not only peripheral neuropathy, but also memory loss. However, exactly how the drugs discussed distress vitamin B levels in such profound ways is still unknown. Channelopathy (Saio, 2006) (Bennett, 2006) Ion channels determine how neurons communicate with one another, and channelopathies are diseases caused by disturbed functions of ion channels. It has been shown that when certain drug therapies, most notably the ones for AIDS, are introduced to the body, they often negatively affect a cells mitochondria, which are responsible for sending out specific proteins to specific places. When mitochondria are impaired, cellular communication becomes abnormal (calcium and sodium receptors on the ion channels are blocked), and we feel very painful peripheral neuropathy. Accumulation of Neurotoxic Effects in the Dorsal Root Ganglion Neurons Dorsal root ganglion neurons lie vertically along the length of the spine. Their axons relay sensory information from the peripheral nervous system (in our bodies) to the central nervous system (in our heads and spinal chord). As mentioned previously, many therapeutic medications can prove to be damaging to nerve cells (neurotoxic), especially chemotherapy drugs. The toxic chemicals from these medications can build up over time in these dorsal root ganglion neurons, eventually leading to damage or cell death. When this happens, sensory information coming from the body to the brain does not get relayed correctly, resulting in the numbness and/or pain experienced in neuropathies. (Fullerton, 1969) Photo courtesy of www.myelitis.org CANCER- RELATED NEUROPATHIES

How can neuropathies be cancer-related? (Eade, 1975)(Benson, 1979) As mentioned, neuropathies can be indirectly related to cancer if the patient is taking a medication that may cause some nerve damage. However, neuropathy can also be directly caused by cancer. It is unknown why many blood cancers, like leukemia, sometimes cause neuropathy; however, it is better understood why cancers that either develop into solid tumors or have a great affect on bone often cause neuropathy. Cancers that develop into tumors, for example, may cause neuropathy by cancer cells themselves taking over, damaging, or killing a nerve cell, or more likely, by cancer tumors developing on or around main nerves, thus compressing the nerve as the tumor grows, causing symptoms of pain and numbness. Bone cancers work differently and more indirectly. Since these cancers slowly degrade bone tissue, they have a grave and often quicker impact on our vertebrae bones, which protect our spinal cord. When such a bone or bones weaken, there occurs what is called a vertebral collapse, in which the spinal cord gets compressed. Although not directly due to interaction with cancer, such compression has a profound and excruciating effect on our nerves. Neuropathies resulting from these types of cancers are almost always irreversible. What are some examples of cancers in which a patient would be more prone to developing neuropathy? (Eade, 1975)(Benson, 1979) Two examples of cancers often linked to neuropathies are lymphomas and multiple myeloma. Lymphomas (which are cancers involving lymphocytes, the white blood cells in the vertebrae immune system) affect the nervous system in the first way mentioned above as lymphatic tumors begin to crowd the space of surrounding neurons, the individual may begin to experience slight neuropathy. Multiple myeloma, in contrast, works like the latter type of possible cancer-nerve interactions. It is a bone cancer that not only is known for leading to spinal compression-induced neuropathies, but also, to peripheral neuropathies caused by the infiltration of amyloid, a type of protein found in excess in many neurological disorders. Click here to read a short story from a woman who has multiple myeloma and peripheral neuropathy. What are some symptoms of cancer-related neuropathies? You should consult with your oncologist if you have any of the following (same probable symptoms as those involved in drug-induced neuropathies)(Leonard, 2005): Tingling (pins and needles) Numbness Difficulty telling the difference between rough and smooth surfaces Difficulty feeling hot things Difficulty feeling cold things A greater than normal sense of touch (the glove effect) Burning pain or discomfort without cold Burning pain or discomfort with cold Difficulty identifying objects in your hand Involuntary leg or hand movements Jaw pain Eyelids drooping Throat discomfort Ear pain Tingling in mouth Difficulty with speech Burning or discomfort of your eyes Loss of any vision Feeling shock/pain down back or in extremities/limbs Problems with breathing

Are there any treatments for drug-induced or cancer-related neuropathies? There is no specific treatment or cure for these types of neuropathies. This is a complex issue because the course of drug treatments for and the progression of cancer in affected individuals varies. This variation is due to the amount of time and dosage of medication that nerves were exposed to or the amount of damage caused by direct and indirect involvement of cancer cells. There is current research about how to control the pain and discomfort that comes with neuropathy, and in some trials, there is work being done on how to reverse and prevent such debilitating effects. These include, but are not limited to: the selective targeting of ion channels to manage the neuropathic pain state using a new drug called gabapentin (Xaio, 2007) anti-inflammatory assistance to nerves (glucocorticoids) (Ravits, 1998)

the removal, treatment, and return of blood plasma to a patient (intravenous immune globin and plasmapheresis) (Ravits, 1998) work with acetyl-L-carnitine, which has been shown to prevent the development of peripheral neuropathy that often comes as a side effect of the well-known cancer drug, Taxol (see previous chart ) (Flatters, 2006)

Why are issues surrounding drug-induced and cancer-caused neuropathies so complex? In many cases, therapeutic drugs that can cause neuropathy are often combating diseases that prove to be more life-threatening, such as cancer. In the drug treatment many cancer patients undergo, neuropathy remains a serious dose-limiting side effect if the treatment is causing neurological discomfort. If the resulting neuropathy is too painful for the patient, his/her doctors might have to lower doses or stop treatment. This can be a very difficult decision, as lowering the doses may allow the cancer to regenerate, but stopping treatment does not guarantee the reduction of pain due to the damage that has already been done. (Flatters, 2006)

Diagnostic Tests and Treatments Though some neuropathies slowly diminish on their own, most require medical attention. The first steps of any treatment involve identifying the underlying neuropathy. This can prove to be difficult since there are many types of neuropathy, which may or may not occur in conjunction with one another. It is also difficult to determine the cause of a neuropathy, since there may be more than one. In any scenario, the goals in treatment include controlling symptoms, removing the cause (if possible), and helping the patient gain maximum independence and self-care ability. Diagnostic tests are often preceded by a detailed-medical history to try to determine the cause and stage of the given neuropathy. Tests that are often used to diagnose neuropathy include but are not limited to: EMG where an electrode is inserted through the skin into the muscle; provides information about the ability of a given muscle to respond when the nerves are stimulated Nerve conduction tests where electrodes are placed on the skin to determine the speed on nerve impulses Nerve biopsies when a small piece of nerve tissue is removed for observation Blood tests Skin, pressure, prick, and reflex tests used to test the degree of sensitivity in the periphery (most notably the feet and hands) See the following website for further/more detailed information regarding these tests:

http://www.nlm.nih.gov/medlineplus/ency/article/003928.htm (pictures are also from this site) Treatment often consists of a mixture of physical therapy, occupational therapy, and pain medications we recommend you talk to your doctor for further information regarding your own neuropathy and needs. Links to Support Groups, More Information www.neuropathy.org www.neurologychannel.com

Glossary Acetyl-Carnitine (abbreviated ALCAR) Treatments with ALCAR have been shown to reverse mitochondrial damage in many kinds of cells, including neurons. This is potentially beneficial for drug-induced neuropathies that damage mitochondria which upsets the regulation of calcium in and out of ion channels. By targeting mitochondria in this way, researchers hope that the neuropathy resulting from mitochondrial damage can either be significantly reduced or perhaps one day prevented. Amyloid

An insoluble fibrous protein that, for unknown reasons, is in excess in many diseases and disorders, such as Alzheimers, diabetes, and multiple myeloma. Distal In relation to neuropathies, nerves that are the furthest away from the central nervous system are the ones that are being affected. Gabapentin The common name for this medication is called Neurotonin. It is often used to treat epileptic seizures, as well as neuropathies of all kinds, most notably diabetic and chemo-related. Although this drug makes use of a neurotransmitter called GABA, the actual way it helps neuropathic pain is unknown. It is generally well-tolerated (few side effects), easily titrated, has few drug interactions, and doesnt require laboratory monitoring. However, it is very expensive, which is a limiting factor for some patients. Glucocorticoids They are a class of steroid hormones. They have an excitatory effect on the nervous system, and they reduce inflammation by suppressing certain immune system cells, an effect which helps reduce the pain that often occurs in sensorimotor neuropathy. Intravenous Immune Globin (abbreviated IGIV) IGIV is a sterilized solution obtained from pooled human blood. It contains the antibodies that protect against infectious agents that cause various disease. Ion An atom or molecule that has lost one or more of its electrons, making it negatively or positively charged. Mitochondria Membrane-enclosed organelles that are found in most eukaryotic cells. They generate and supply cellular energy and are also involved in a range of other processes like cell signaling and cell growth.

Motor Neuropathy In this neuropathy, the neurons that control movement/actions are affected.

Peripheral Neuropathy This is the most common neuropathy (synonymous with sensorimotor neuropathy). It is an umbrella term covering sensory and motor neuropathies. The most common places to experience peripheral neuropathy are the hands and feet, and the most common complaints associated with it are numbness, tingling, or painful burning.

Images taken from apps.uwhealth.org/health/adam/hie/2/8679.htm

Plasmapheresis

It is a therapeutic plasma exchange using a blood purification procedure used to treat several autoimmune diseases. It removes antibodies from the bloodstream, thereby preventing them from attacking their targets, which in neuropathy, is often the neurons themselves. Polyneuropathy A neurological disorder that occurs when many peripheral nerves in the body malfunction simultaneously. Sensorimotor Neuropathy Pain, tingling, or other neuropathic symptoms are felt in a mixture of sensory and motor neurons in the periphery. This term is synonymous with peripheral neuropathy. Sensory Neuropathy In this neuropathy, the neurons that detect sensations (like pain, pressure, temperature, etc) are affected. Subacute Myeloptic Neuropathy (SMON) It is a severe type of neuropathy (notably caused by an antibacterial medication called Choloroquine) dealing with inflammation, compression, and/or shriveling of the spinal cord. Vitamin B1 Also known as thiamin, this vitamin helps fuel the body by converting blood sugar into energy. It essential in maintaining the health of the nervous system, cardiovascular function, and muscular function. Vitamin B12 This vitamins primary function is to form red blood cells and maintain a healthy nervous system. B12 metabolizes the fatty acids essential to maintaining the myelin sheath on an axon. If prolonged deficiency happens, anemia and/or degeneration and demyelination of nerves can occur, and sometimes this damage is irreversible. Wernickes Encephalopathy A disorder caused by vitamin B1 deficiency. It is characterized by incoordination of muscle movement, paralysis of eye muscles (extraocular muscles), confusion, and loss of short-term memory. Cancer/DrugIntroduction Induced Treatments Sources to Neurons Neuropathy

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Diabetic Neuropathy