1. How much time does a neridronate infusion last?
Not more than 2 hours and it is carried out in Day Hospital. Usually it is administered over the course of 4 days with one infusion per day of 100mg of neridronate, given four times. For a total of 400 mg of Neridronate. The first infusion is the longest because it includes, to begin with, a visit by the doctor; a nurse (who will follow the whole treatment) will then have to set the pumping speed according to each patient. This process will not have to be repeated during the other three infusions.
2. Is this treatment for CRPS II as well?
The first study for the treatment was only for CRPS I cases but, after it was approved by Italian HealthCare, it is regularly used also for CRPS II treatment. CRPS 1 and 2 differences are still under discussion because it is not clear and probably, in the future, it will not even be considered.
The real difference is on the stage of the condition in which the patient is: the doctors usually do not treat patients suffering from CRPS stage 4.
3. Where do I get the infusion? Which clinic/hospital?
You would get the infusions in one of the University Hospitals in Verona or in the hospital in Peschiera Del Garda, near Verona.
4. Which are the contraindications and the side effects?
Scientifically Neridronate, differently from the other bisphosphonates, has no side effects. Dr. Adami confirms this along with many other doctors and it is an easy to find information in the Internet.
Some minor side effects (possible low fever and arthralgia immediately after the infusion affect approximately 30% of patients).
It is not indicated in the case of documented hyper-sensibility and renal insufficiency and in women who are pregnant or breastfeeding.
It is rare, but it could cause some redness that disappears within one hour.
If the patient suffers of rheumatism, neridronate could cause some pain, but this will help rheumatisms as well so, in the end, it will give even more benefits to the patient.
5. How many patients have you treated?
In the last 2 years (2016/17) CRPS Treatment Italy has treated 51 patients from all over the world, especially U.S.A. and U.K.
6. Who are the doctors and what are the structures?
The doctors were all part of Professor Adami’s team that completed the first study on the effects of Neridronate on CRPS and allowed the therapy to be the standard procedure for the condition.
Prof. Biasi Domenico, professor at AOUI (Azienda Ospedaliera Universitaria Integrata di Verona)
Dr. Righetti Daniela, Chief of Rheumatology at Pederzoli clinic , Peschiera del Garda (VR)
Dr. Fabrizio Martella – Chief of Polispecialistico
Dr. Gianfranco Pisano, MD MD – Rheumatologist, Physiotherapist and Orthopedic at “Nuova Medicina” Verona
Dr. Giorgio Ghilardi, MD GS CTVS – Surgeon at the University Hospital of Milan;
AOUI Azienda Ospedaliera Universitaria Integrata di Verona http://www.ospedaleuniverona.it
Pederzoli Clinic, Peschiera del Garda (VR) http://www.cdcpederzoli.it
7. Why 4 days instead of 8 days?
Every doctor uses their own experience in their recommendations to patients.
Dr Righetti has always worked with such scheme. Whilst, Dr Biasi, who is doctor and university professor at AOUI, has instead adopted Dr Adami scheme - that is, one infusion per day.
According to him, such scheme is faster and more effective - or aggressive, as you say.
Neridronate is a safe medication. So doing it every other day, or every day is as safe. Mr Claudio suggests that since the first scheme of infusion has not helped in the long run, you can try the more aggressive protocol (one infusion per day).
8. How long will I stay?
The estimated stay is from a week to 10 days.
9. How can I receive Neridronate in the States and have it infused if it is not FDA approved?
FDA has approved Neridronate to treat other conditions. This means it is legal to purchase it and have it mailed to you. In FDA’s website you can read all details about it: https://www.fda.gov/forpatients/other/offlabel/default.htm
10. Do I speak to the doctor before I come over?
Italians do not speak English that well, so we provide an interpreter during your stay that will help you communicate with doctors while you are in Italy; our medical staff will be in constant contact with you and Italian doctors.
11. Neridronate is not FDA approved, so it is not true?
We are in Italy. In Italy there are many people suffering from CRPS but all are cured because they get treated on time. In Italy CRPS is not a problem, this is an objective statement and it can easily be verified.
Italy, according to Bloomberg, in 2017 is the healthiest country in the world and, this, says the article would not be possible if it did not have one of the best Healthcare Systems:
In Italy we have AIFA, which is the Pharmaceutical Agency: http://www.agenziafarmaco.gov.it that is known to be one of the most strict worldwide. AIFA has approved Neridronate Treatment.
FDA designed Neridronate as a Breakthrough Therapy for CRPS Treatment. It is the first pharmaceutical to have this designation for this condition.
The Breakthrough Therapy Designation is supported by the clinical study (phase II), that has shown a significantpain reduction and of the symptoms in CRPS.
FDA gave the Fast Track designation in August 2015.
12. For how long have you been doing this? For how long has this treatment been Routine in Italy?
We, of CRPS Treatment Italy, offer our services to people hit by CRPS from over two years. We suggest you to see professor Adami’s reviews: he has studied CRPS for over 15 years and accomplished the objective of brevetting the use of Neridronate that Italian laws eventually approved. In Italy, we can say that all the affected people have a complete remission. This is news that you can surely find on the Internet: it is public and official.
We exhort you once again to go and verify everything I say. We only report official news: because we are not doctors, we are only scientific observers and counselors. We study the problems of the patients and research for the best solutions. On our website you can find them on: https//crps-treatment.com/our-story.html
13. What are the statistics for long-term patients?
The available data shows that, if treated within 1 year from the onset, in 32% of cases, the patient can hope for a complete and permanent remission of the disease. However, of the long-term patients, the 40% experienced a decrease of pain level by 30 – 40 %, 25 % said their pain decreased by 20%. Only the 2% experienced no effect.
14. Why did the FDA not approve the treatment?
From what we understand is about the brevet and commercialization of Ketamine.
There are interests at stake that we cannot know. We do not know why USA did not approve the treatment but, it is certain, the treatment works in India and Italy. This is well documented in the Internet. You can verify this on the Internet.
15. Neridronate is dangerous?
Neridronate, it is recognized, is not dangerous: it is an aminobiphosphonate but, differently from other bisphosphonates, has no side effects. The FDA also acknowledges this.
16. Neridronate causes jaw necrosis?
Neridronate, it is globally known, does not have secondary effects.
In the case in which the patient is under dental surgery and does not declare it, might feel some pain, but this never results in a necrosis.
The Treatment, however, is not recommended if:
Blood test show levels of Creatinine and Calcium
The patient is suffering from a kidney failure
The patient went or is going to go through dental surgery within three months
The patient is pregnant.
17. Can you give me more information on CRPS type 2?
We can only give you official information that you can find on Internet and on our website. CRPS Treatment Italy, though, is the only organization that found clinics and hospitals that treat CRPS 2. So that we do not give you inaccurate information, we exhort you to read all of the studies of Professor Adami. Also go to: https//crps-treatment.com/index.html
18. Is there a clinic in the United States / Australia /etc.. that has this treatment?
Not that we know of. Nobody has ever communicated it to us. In social networks as well, there is no news about such clinic. There only are trials. There is no evidence of concrete results coming from these trials.
Neridronate treatment brings permanent benefits.
We must underline that a small percentage of treated patients (who have been suffering from the disease for many years) have declared that they have not felt any relevant improvement. All of the patients that have been battling with this condition for a few months have a complete remission.
We only bring official data. We are not doctors, but scientific observers and counselors. We study the problems of a patient and offer the best solutions.
WHAT DO YOU NEED
1. Why do you request documents?
The documents we ask for before the treatment are required by the Italian law and by AOUI in order to understand if the patient is eligible.
To better understand your case and giving you more detailed information, Dr Biasi needs to evaluate your medical records.
Doing that we will be able to get back to you with all the suggestions and explanations on costs and even prescriptions if the doctor thinks it is needed.
2. What blood test do I need? What do I have to ask for?
The blood test need to show Creatinine and Calcium levels, which are indicated in most blood tests. If you need to take new ones in order to have them more recent, you can ask for vitamin D levels. The doctor needs to see them so that, in case of need, he can prescribe some integrators to take around a week before the beginning of treatment.
This way we will have a broader idea of your body situation and the efficacy of the treatment in your own case.
3. What airport and which air and how much are the airfares?
The nearest airports (and these are the ones CRPS Treatment Italy suggests) are Valerio Catullo in Verona, or Marco Polo in Venezia.
The flight cost depends on what company you use and is not included in the offer.It usually costs between 500/1000 €.
1. The services we offer are just a honey trap.
The services we offer are a confirmed reality by all the patients that used them.
Everyone agrees that our services are essential to face a trip in an unknown country, especially for medical purpose.
24/7 assistance during your whole stay, if you have any need please call us.
Support and assistance in case of loss of Passport;
Support and assistance in case of loss of Luggage;
Support and assistance in case of missing the Plane;
Native speaker interpreter with specific knowledge of medical terms and drugs:
An English-speaking Interpreter will be always available;
Majority of Italians do not speak English, therefore a Bilingual Guide will be at patient service;
Very competent staff who will be with patient throughout the entire stay in Italy;
They will assist the patient during the whole process of treatment;
They will be available for any issue and need for information.
Hotel accommodation for patient and companion (if any) with meals included:
Hotel is very close both to our offices and to the main facilities (stores, Vicenza downtown, and main roads to hospital and US Base);
Hotel Staff can speak English very well;
In case of emergency, Hotel Reception is instructed to call the ambulance and provide interpreting between paramedics and patient;
If needed, phone-calling service is available at the reception Desk.
Transportation (Airport to Hotel and vice versa, Hotel to Hospital and vice versa):
English-speaking driver will be ready at the airport exit room with wheelchair/crutches (if needed) and a board with patient's name on;
Same Driver will provide both pick-up service at airport and driving service at the moment of departure;
Patient will be assigned to one Driver and Interpreter who will take care to drive patient and caregiver to hospital and back to hotel;
Assistance will be provided in reaching local stores to buy anything one might need and do some shopping.
Assistance during treatment at the Clinic:
English-speaking Interpreter will be present throughout the whole time of infusions for each sessions;
Doctor will visit the patient assisted by nurses and Interpreter;
Doctor will prescribe medicine in case of side effects (see: "What is Neridronate?");
At the last infusion, final visit with the doctor and further instructions to follow for the treatment to be more effective;
Second opinion (if needed) by other specialists about your situation or other pathologies;
Recall treatment in case your doctor believes they would be helpful;
Assistance on getting meds prescribed and purchased at the pharmacy.
2. What kind of hotel will I stay in?
The clients are all satisfied of the 4 star Tiepolo Hotel http://www.vicenzatiepolohotel.it/
High-level design and excellent personnel selection; breakfast - lunch and dinner a la carte, wine and water included and fresh fruit every day. The Hotel is near CRPS Treatment’s main office so that the staff can quickly be there in case of need, day and night (all included), for Pharmacy, shopping...
3. I need a special hotel room.
Tiepolo Hotel and CRPS Treatment Italy have signed a convention. Hotel Tiepolo has soundproof rooms with disabled people's access.
4. What if I find the hotel by myself?
It is possible to arrange luxury accommodation in very important touristic locations, but in that case, CRPS Treatment Italy will have to make a different price.
5. Do you have facilities for families to stay during treatment?
You can surely come with your family. Our usual service package includes one caregiver, a third person would cause a price difference but it is possible to be up to five people.
6. If you come to Italy, we will not give you a diagnosis.
To come to Italy we will need a diagnosis signed by your doctor. It is impossible for us to start talking about the treatment without the diagnosis. As for the blood test, we can have it done here, but the patient will need to consider at least three more days of stay.
7. How much does the treatment/program cost in full (including tax)? What is included in the cost, and what is NOT included?
Services are complete of all you may need during your stay and after! Here you can find the details.
Additionally, you can also ask for our CRPS Light Treatment, that is an extra but highly helpful for patients, especially long-tem ones. Our agency is the only one that applies such support treatment.
As for the costs: our costs are ALL inclusive of Italian taxes. We would definitely need to evaluate your case to understand if you are eligibile and if you need some prescritpion to supply on Calcium or else before coming here. Once we have understood your specific case and how can we help you, we can call you to discuss the next steps.
Please feel free to browse our website in full: we have articlesalongside with video testimonials.
8. Can you give me information in English?
We all speak English: all our staff is bilingual Italian-English. Please, check all details in our service section of our CRPS website and Counseling.
9. This Agency is a fraud. It just is a scam, they ask for too much money when all we need is the treatment.
We are not the “middle man”: we offer a complete service. We work to support people who consider coming to Italy to get treated.
We have studied over time and had a wide experience of every case and every need for people that come to Italy.
We are 100% with you with English mother-tongue speaking interpreters. 24/7 everywhere and every time.
The service is all-inclusive.
We have had experience in helping who lost the documents or medicines, needed prescriptions, and driving to the pharmacy, even in the middle of the night. We are with the client even if he just wants to go shopping.
The point, for us, is that you can never know what a suffering person may need, especially in a foreign country (a wheel chair, crutches, or even driving a patient to the emergency room). We have it all covered.
Any client is completely ensured.
10. We are too far to have direct contact with local clinics
Our clinics are clearly stated.
The doctors that will execute the infusions are indicated along with their curriculum and are all part of prof. Adami’s school.
It also is possible to interview, even at the phone with our doctors, but only after the signing of the contract. In any case, it would be a great pleasure to exchange opinions directly with the patient’s doctor, to collaborate in the exclusive interest of people who want to try Neridronate in Italy.
We are trying to be present at the events and conferences around the States as well: we were in New York from the 8th to the 12th of December with RSDSA.
We would be happy to have your doctor as a guest along with the patient. Doctor’s trip and stay will be completely covered. He will be able to talk with Professor Domenico Biasi of the University Of Verona Hospital Company. It could be a great study opportunity.
For us of CRPS Treatment and of www.medicaltourismitaly.com would be a true honor to have him with us.
11. They are always there, while we are on the other side of the ocean.
Our Team specialized in CRPS Treatment and has worked for many years with great success. Our mission is to make you feel at home. We are absolutely positive that the treatment will do you nothing but good.
12. CRPS Light.
Our continuous research for pain decrease and control makes this staff a one of a kind in the world! CRPS Light is a lamp that simulates the whole spectrum of sunlight minus the ultraviolet. Absolutely everybody, all of treated patients, noticed huge benefits from the treatment. The light’s rays influence neuropeptides, the neural pain transmitters and is FDA approved.
The treatment would be an extra, so requires an extra payment, but many clients have ordered the light to continue the beneficial treatment.eficial treatment.
1. How do we do the payment?
Once you have the confirmation for treatment, we will send you the instructions on how to do a wire transfer.
2. Do I pay when I arrive?
We can arrange two solutions:
a) You can pay all amount through wire transfer before arriving to Italy;
b) You can pay half amount before arriving and the second half at your arrival.
DIFFERENCE WITH KETAMINE
1. Difference with Ketamine?
Ketamine gives a temporary relief and it has a high possibility of being addictive. Neridronate does not have any major side effects and, by locally suppressing increased bone turnover it seems to interrupt a vicious cycle that causes the chronic symptoms. Ketamine treatment is much more expensive, considering it needs to be repeated.
2. Ketamine is cheaper?
Neridronate is actually the cheapest: considering the price per infusion and the fact that the relief is only temporary, not counting the major side effects, Neridronate is much more advantageous.
This is because these infusions mostly result in permanent benefits and, at least, a huge cut in pain medicines expenses, when not in a complete remission, if done on time.
3. Ketamine is in many American clinics, so it is easy to find?
Yes, that is true. That is probably why it is so hard for Neridronate infusions to be accepted as a treatment in the first place. Anyway, ketamine is easier to find indeed, but, for now, you can get this therapy only in Italy.
4. Ketamine is safe and has no side effects except some cardiopathy during the infusion?
We suggest this treatment after viewing statistics and results, because we are not doctors, we are observers and scientific counselors.
We know, as a fact, that, if caught on time, it leads to complete remission. In any case this treatment leads to permanent benefits.
HIPAA AND PATIENT RIGHTS
What will you do with my personal data?
Personal data and all of the documents are HIPAA certified.
The Health Insurance Portability and Accountability Act (HIPAA) of 1996 mandated changes in federal regulations governing the provision of health benefits, delivery and payment of health care services and security and confidentiality of patient health information. The federal Department of Health and Human Services (DHHS) oversees the implementation of these regulations, including rules regarding patient privacy that were effective April 14, 2003.
We would need a declaration signed by the interested person to do of this data anything that does not fall under the cases you can find here.
Complex Regional Pain Syndrome Fact Sheet
What is complex regional pain syndrome?
Complex regional pain syndrome (CRPS) is a chronic (lasting greater than six months) pain condition that most often affects one limb (arm, leg, hand, or foot) usually after an injury. CRPS is believed to be caused by damage to, or malfunction of, the peripheral and central nervous systems. The central nervous system is composed of the brain and spinal cord; the peripheral nervous system involves nerve signaling from the brain and spinal cord to the rest of the body. CRPS is characterized by prolonged or excessive pain and changes in skin color, temperature, and/or swelling in the affected area.
CRPS is divided into two types: CRPS-I and CRPS-II. Individuals without a confirmed nerve injury are classified as having CRPS-I (previously known as reflex sympathetic dystrophy syndrome). CRPS-II (previously known as causalgia) is when there is an associated, confirmed nerve injury. As some research has identified evidence of nerve injury in CRPS-I, it is unclear if this disorders will always be divided into two types. Nonetheless, the treatment is similar.
CRPS symptoms vary in severity and duration, although some cases are mild and eventually go away. In more severe cases, individuals may not recover and may have long-term disability.
Who can get CRPS?
Although it is more common in women, CRPS can occur in anyone at any age, with a peak at age 40. CRPS is rare in the elderly. Very few children under age 10 and almost no children under age 5 are affected.
What are the symptoms of CRPS?
The key symptom is prolonged severe pain that may be constant. It has been described as “burning,” “pins and needles” sensation, or as if someone were squeezing the affected limb. The pain may spread to the entire arm or leg, even though the injury might have only involved a finger or toe. In rare cases, pain can sometimes even travel to the opposite extremity. There is often increased sensitivity in the affected area, known as allodynia, in which normal contact with the skin is experienced as very painful.
People with CRPS also experience changes in skin temperature, skin color, or swelling of the affected limb. This is due to abnormal microcirculation caused by damage to the nerves controlling blood flow and temperature. As a result, an affected arm or leg may feel warmer or cooler compared to the opposite limb. The skin on the affected limb may change color, becoming blotchy, blue, purple, pale, or red.
Other common features of CRPS include:
changes in skin texture on the affected area; it may appear shiny and thin
abnormal sweating pattern in the affected area or surrounding areas
changes in nail and hair growth patterns
stiffness in affected joints
problems coordinating muscle movement, with decreased ability to move the affected body part
abnormal movement in the affected limb, most often fixed abnormal posture (called dystonia) but also tremors in or jerking of the limb.
What causes CRPS?
It is unclear why some individuals develop CRPS while others with similar trauma do not. In more than 90 percent of cases, the condition is triggered by a clear history of trauma or injury. The most common triggers are fractures, sprains/strains, soft tissue injury (such as burns, cuts, or bruises), limb immobilization (such as being in a cast), surgery, or even minor medical procedures such as needle stick. CRPS represents an abnormal response that magnifies the effects of the injury. Some people respond excessively to a trigger that causes no problem for other people, such as what is observed in people who have food allergies.
Peripheral nerve abnormalities found in individuals with CRPS usually involve the small unmyelinated and thinly myelinated sensory nerve fibers (axons) that carry pain messages and signals to blood vessels. (Myelin is a mixture of proteins and fat-like substances that surround and insulate some nerve fibers.) Because small fibers in the nerves communicate with blood vessels, injuries to the fibers may trigger the many different symptoms of CRPS. Molecules secreted from the ends of hyperactive small nerve fibers are thought to contribute to inflammation and blood vessel abnormalities. These peripheral nerve abnormalities in turn trigger damage in the spinal cord and brain.
Blood vessels in the affected limb may dilate (open wider) or leak fluid into the surrounding tissue, causing red, swollen skin. The dilation and constriction of small blood vessels is controlled by small nerve fiber axons as well as chemical messengers in the blood. The underlying muscles and deeper tissues can become starved of oxygen and nutrients, which causes muscle and joint pain as well as damage. The blood vessels may over-constrict (clamp down), causing old, white, or bluish skin.
CRPS also affects the immune system. High levels of inflammatory chemicals (cytokines) have been found in the tissues of people with CRPS. These contribute to the redness, swelling, and warmth reported by many patients. CRPS is more common in individuals with other inflammatory and autoimmune conditions such as asthma.
Limited data suggest that CRPS also may be influenced by genetics. Rare family clusters of CRPS have been reported. Familial CRPS may be more severe with earlier onset, greater dystonia, and more than one limb being affected.
Occasionally CRPS develops without any known injury. In these cases, an infection, a blood vessel problem, or entrapment of the nerves may have caused an internal injury. A physician will perform a thorough examination in order to identify a cause.
In many cases, CRPS results from a variety of causes. In such instances, treatments are directed at all of the contributing factors.
How is CRPS diagnosed?
Currently there is no specific test that can confirm CRPS. Its diagnosis is based on a person’s medical history, and signs and symptoms that match the definition. Since other conditions can cause similar symptoms, careful examination is important. As most people improve gradually over time, the diagnosis may be more difficult later in the course of the disorder.
Testing also may be used to help rule out other conditions, such as arthritis, Lyme disease, generalized muscle diseases, a clotted vein, or small fiber polyneuropathies, because these require different treatment. The distinguishing feature of CRPS is that of an injury to the affected area. Such individuals should be carefully assessed so that an alternative treatable disorder is not overlooked.
Magnetic resonance imaging or triple-phase bone scans may be requested to help confirm a diagnosis. While CRPS is often associated with excess bone resorption, a process in which certain cells break down the bone and release calcium into the blood, this finding may be observed in other illnesses as well.
What is the prognosis?
The outcome of CRPS is highly variable. Younger persons, children, and teenagers tend to have better outcomes. While older people can have good outcomes, there are some individuals who experience severe pain and disability despite treatment. Anecdotal evidence suggests early treatment, particularly rehabilitation, is helpful in limiting the disorder, a concept that has not yet been proven in clinical studies. More research is needed to understand the causes of CRPS, how it progresses, and the role of early treatment.
How is CRPS treated?
The following therapies are often used:
Rehabilitation and physical therapy. An exercise program to keep the painful limb or body part moving can improve blood flow and lessen the circulatory symptoms. Additionally, exercise can help improve the affected limb’s flexibility, strength, and function. Rehabilitating the affected limb also can help to prevent or reverse the secondary brain changes that are associated with chronic pain. Occupational therapy can help the individual learn new ways to work and perform daily tasks.
Psychotherapy. CRPS and other painful and disabling conditions often are associated with profound psychological symptoms for affected individuals and their families. People with CRPS may develop depression, anxiety, or post-traumatic stress disorder, all of which heighten the perception of pain and make rehabilitation efforts more difficult. Treating these secondary conditions is important for helping people cope and recover from CRPS.
Medications. Several different classes of medication have been reported to be effective for CRPS, particularly when used early in the course of the disease. However, no drug is approved by the U.S. Food and Drug Administration specifically for CRPS, and no single drug or combination of drugs is guaranteed to be effective in every person. Drugs to treat CRPS include:
bisphosphonates, such as high dose alendronate or intravenous pamidronate
non-steroidal anti-inflammatory drugs to treat moderate pain, including over-the-counter aspirin, ibuprofen, and naproxen
corticosteroids that treat inflammation/swelling and edema, such as prednisolone and methylprednisolone (used mostly in the early stages of CRPS)
drugs initially developed to treat seizures or depression but now shown to be effective for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, nortriptyline, and duloxetine
botulinum toxin injections
opioids such as oxycodone, morphine, hydrocodone, and fentanyl. These drugs must be prescribed and monitored under close supervision of a physician, as these drugs may be addictive.
N-methyl-D-aspartate (NMDA) receptor antagonists such as dextromethorphan and ketamine, and
topical local anesthetic creams and patches such as lidocaine.
All drugs or combination of drugs can have various side effects such as drowsiness, dizziness, increased heartbeat, and impaired memory. Inform a healthcare professional of any changes once drug therapy begins.
Sympathetic nerve block. Some individuals report temporary pain relief from sympathetic nerve blocks, but there is no published evidence of long-term benefit. Sympathetic blocks involve injecting an anesthetic next to the spine to directly block the activity of sympathetic nerves and improve blood flow.
Surgical sympathectomy. The use of this operation that destroys some of the nerves is controversial. Some experts think it is unwarranted and makes CRPS worse, whereas others report a favorable outcome. Sympathectomy should be used only in individuals whose pain is dramatically relieved (although temporarily) by sympathetic nerve blocks.
Spinal cord stimulation. Placing stimulating electrodes through a needle into the spine near the spinal cord provides a tingling sensation in the painful area. Electrodes may be placed temporarily for a few days in order to assess whether stimulation is likely to be helpful. Minor surgery is required to implant all the parts of the stimulator, battery, and electrodes under the skin on the torso. Once implanted, the stimulator can be turned on and off, and adjusted using an external controller. Approximately 25 percent of individuals develop equipment problems that may require additional surgeries.
Other types of neural stimulation. Neurostimulation can be delivered at other locations along the pain pathway, not only at the spinal cord. These include near injured nerves (peripheral nerve stimulators), outside the membranes of the brain (motor cortex stimulation with dural electrodes), and within the parts of the brain that control pain (deep brain stimulation). A recent option involves the use of magnetic currents applied externally to the brain (known as repetitive Transcranial Magnetic Stimulation, or rTMS). A similar method that uses transcranial direct electrical stimulation is also being investigated. These stimulation methods have the advantage of being non-invasive, with the disadvantage that repeated treatment sessions are needed.
Intrathecal drug pumps. These devices pump pain-relieving medications directly into the fluid that bathes the spinal cord, typically opioids, local anesthetic agents, clonidine, and baclofen. The advantage is that pain-signaling targets in the spinal cord can be reached using doses far lower than those required for oral administration, which decreases side effects and increases drug effectiveness. There are no studies that show benefit specifically for CRPS.
Emerging treatments for CRPS include:
Intravenous immunoglobulin (IVIG). Researchers in Great Britain report low-dose IVIG reduced pain intensity in a small trial of 13 patients with CRPS for 6 to 30 months who did not respond well to other treatments. Those who received IVIG had a greater decrease in pain scores than those receiving saline during the following 14 days after infusion.
Ketamine. Investigators are using low doses of ketamine—a strong anesthetic—given intravenously for several days to either reduce substantially or eliminate the chronic pain of CRPS. In certain clinical settings, ketamine has been shown to be useful in treating pain that does not respond well to other treatments.
Graded Motor imagery. Several studies have demonstrated the benefits of graded motor imagery therapy for CRPS pain. Individuals do mental exercises including identifying left and right painful body parts while looking into a mirror and visualizing moving those painful body parts without actually moving them.
Several alternative therapies have been used to treat other painful conditions. Options include behavior modification, acupuncture, relaxation techniques (such as biofeedback, progressive muscle relaxation, and guided motion therapy), and chiropractic treatment.
What research is currently being done on CRPS?
The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The NINDS is part of the National Institutes of Health (NIH), the leading supporter of biomedical research in the world.
NINDS-supported scientists are studying new approaches to treat CRPS and to intervene more aggressively to limit the symptoms and disability associated with the syndrome. Other NIH institutes also support research on CRPS and other painful conditions.
Previous research has shown that CRPS-related inflammation is caused by the body’s own immune response. Researchers hope to better understand how CRPS develops by studying immune system activation and peripheral nerve signaling using an animal model of the disorder. The animal model was developed to mimic certain CRPS-like features following fracture or limb surgery, by activating certain molecules involved in the immune system process.
Limb trauma, such as a fracture, followed by immobilization in a cast, is the most common cause of CRPS. By studying an animal model, researchers hope to better understand the neuroinflammatory basis of CRPS in order to identify the relevant inflammatory signaling pathways that lead to the development of post-traumatic CRPS. They also will examine inflammatory effects of cast immobilization and exercise on the development of pain behaviors and CRPS symptoms.
Peripheral nerve injury and subsequent regeneration often lead to a variety of sensory changes. Researchers hope to identify specific cellular and molecular changes in sensory neurons following peripheral nerve injury to better understand the processes that underlie neuroplasticity (the brain’s ability to reorganize or form new nerve connections and pathways following injury or death of nerve cells). Identifying these mechanisms could provide targets for new drug therapies that could improve recovery following regeneration.
Children and adolescents with CRPS generally have a better prognosis than adults, which may provide insights into mechanisms that can prevent chronic pain. Scientists are studying children with CRPS given that their brains are more adaptable through a mechanism known as neuroplasticity. Scientists hope to use these discoveries in order to develop more effective therapies for CRPS.
NINDS-funded scientists continue to investigate how inflammation and the release of adenosine triphosphate (ATP) may induce abnormal connections and signaling between sympathetic and sensory nerve cells in chronic pain conditions such as CRPS. (ATP is a molecule involved with energy production within cells that can also act as a neurotransmitter. Neurotransmitters are chemicals used by nervous system cells to communicate with one another.) A better understanding of changes in nerve connections following peripheral nerve injury may offer greater insight to pain and lead to new treatments.