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Crps Pain

Complex Regional Pain Syndrome (CRPS), also known as Reflex Sympathetic Dystrophy (RSD), usually touches middle-aged people, but has been reported to occur in younger individuals.

There are two types of CRPS. CRPS I is a chronic nervous disorder that occurs in one end (e.g., arm, leg, hand, foot) after a minor injury. CRPS II is caused by a direct nerve injury.

Commonly, the complex regional pain syndrome, despite its difficulty in diagnosis, is identified as a disease caused by damage to the sympathetic nervous system, in this case in the nerves that control blood vessels and sweat glands, is responsible for the appearance of symptoms of CRPS. Car accidents, penetrating wounds, crushing injuries, surgeries, infections and fractures are examples of severe traumas that can cause direct nerve injuries and lead to the development of CRPS. Nerves damaged by CRPS can lose their ability to regulate blood flow, sensation and temperature in the affected areas. This can cause chronic pain and other problems in local tissues.

An alternative theory that CRPS is caused by an inappropriate immune response is highlighted by the appearance of redness, heat and swelling in the affected areas. These signs are associated with inflammation, a characteristic component of an immune response.

Signs and symptoms of CRPS may worsen over time or resolve spontaneously. CRPS pain is the main symptom: it is an intense, continuous and burning pain that usually occurs at the extremities. Often, CRPS pain can begin at the point of a traumatic injury, but it can spread across an entire limb. 

The CRPS pain can be caused by stimuli that are usually not painful, such as lightly touch the skin with a feather (allodynia). In addition, a normally painful stimulus can cause disproportionately severe irritation and pain (hyperalgesia).

Allodynia and hyperalgesia of complex regional pain syndrome are indicators of central sensitization. In this condition, CRPS pain appears to be caused by local tissue lesions and inflammations activate the peripheral nervous system (PNS), which sends signals to the central nervous system (CNS). The excitability of neurons within the central nervous system increases, causing normal inputs from the central nervous system to produce abnormal responses. Low-threshold sensory fibers activated by a light touch excite spinal cord neurons that normally respond to more painful stimuli.


What are the other factors that are added to CRPS pain?

In addition to pain, patients with complex regional pain syndrome may also experience:

– Changes in skin color (e.g., spots, purple, pale, red)

– Changes in the structure of the skin (e.g., shinier, thinner, thinner, thicker)

– Changes in skin temperature (e.g. the affected area is warmer or colder than the surrounding tissues)

– Increased skin sensitivity

– Changes in hair and nail growth patterns

– Muscle atrophy

– Rigidity and swelling in the affected joints

– Reduced range of motion at the affected limb

– Depression and anxiety, as the pain and other consequences of CRPS can be severe and long-term.

Many experts believe that CRPS progresses in three stages, although this progression has not been confirmed in clinical studies.

These steps include:

Phase 1 (1-3 months)

Variations in skin temperature, alternating between hot and cold

Faster growth of nails and hair

Muscle spasms

Joint pain

Severe burning and painful pain that worsens with the slightest touch or breeze.

Skin becomes velvety, purple, pale or red; thin and shiny; swollen.


Phase 2 (3-6 months)

Continuous changes in the skin

Nails break and break more easily

Pain worsens

Hair growth slows down

Rigid joints and weak muscles


Phase 3

Irreversible changes can be seen

Limited movement in the limbs due to narrowing of muscles and tendons

(contracture) Muscle waste

Pain in the entire limb

Diagnosis and treatment of CRPS


To diagnose complex regional pain syndrome, other conditions must be excluded. The doctor will make a medical history and perform a physical examination that includes the assessment of the patient’s pain, range of motion and sensory function.

Early diagnosis of CRPS is important and a decisive factor for its recognition can be precisely the recognition of  CRPS pain that affects those affected. In fact, CRPS pain is a distinctive feature of this disease because it is abnormal and out of proportion to the severity of the lesions that appear to be the cause. Although the progression of the disease cannot be stopped, it can be slowed down and the patient’s quality of life can be improved with an appropriate treatment programme aimed primarily at relieving CRPS pain.

In recent years it has been noted that since there is no cure for CRPS pain, treatment focuses on slowing down the progression of the disease and managing CRPS pain and other symptoms.


The most effective treatment options for CRPS pain include:

Pharmacotherapy – Some medications may help mitigate the symptoms of CRPS such as CRPS pain. Pain medications such as bisphosphonates, in particular Neridronate, which is, to this day, the only treatment to ever be linked to a total remission of the CRPS symptoms. Non-steroidal anti-inflammatory drugs (NSAIDs and other analgesics can relieve pain. Corticosteroids, drugs to inhibit bone loss, membrane stabilizing drugs and antidepressants can also be effective. A randomised controlled clinical trial found that intravenous magnesium significantly improved pain, impairment and quality of life and was well tolerated in CRPS type I patients.

Physical and occupational therapy – These therapies should be initiated as soon as possible. Some exercises may help preserve the range of motion and function of joints and muscles in CRPS patients.


Intrathecal Pump Implants – Implanted pain pumps can be extremely useful for long term pain control. A study examining the effectiveness of intrathecal therapy in people suffering from cancer pain showed a reduction in pain in patients.


Peripheral nerve stimulation – This method involves placing tiny electrodes close to the affected nerves. The electrodes release a small electrical current that inhibits pain transmission and provides pain relief.


Sympathetic nerve blocks – A small fine needle is inserted through the skin to block the sympathetic nerves responsible for excessive pain. Procedures that affect the face and upper extremities include Starry Ganglion block and brachial plexus nerve block. For the lower limbs, sympathetic lumbar nerve blocks are commonly performed.


Infusion Techniques – A small catheter is inserted through a needle into the epidural space or directly next to the affected nerves. Local anaesthetic and other drugs are administered through the catheter for prolonged periods. Pain relief can be substantial and lasting when the nerves are continuously blocked with an infusion. Biofeedback – This therapy teaches awareness of processes normally considered involuntary within the body, such as blood pressure, temperature and heart rate, allowing some degree of conscious control of these processes. Biofeedback can influence and improve pain levels and promote relaxation.


Support Groups – Living with CRPS pain can be difficult. Support groups can help CRPS patients deal with the difficulties and discomforts of life with their chronic condition.

The prognosis of complex regional pain syndrome is variable. However, the outcome is generally improved with early detection and treatment. Sometimes, if the condition is captured in the first phase, it is possible to restore the range of motion and even remission. Without early diagnosis and treatment, tissue changes will become irreversible. Patients living with CRPS pain and other painful conditions should consult their physician as soon as possible, who will refer them to a specialist. 

In the last two decades, bisphosphonate use appears to be a convincing evidence based therapeutic strategy, with five randomised controlled trials (RCTs) all showing good results in controlling CRPS pain, local inflammation and functional disability. These treatments have seen an improvement in the quality of life of patients, and a decrease in the intensity of CRPS pain.

Today, biphosphonates are a well-established group of substances for the treatment of metabolic bone diseases, including Paget’s disease, cancer associated hypercalcemia, osteolytic metastases of various cancers and post-menopausal osteoporosis and glucocorticoid-induced glucocorticoid. Selective targeting of bone tissue results from strong affinity with hydroxyapatite.

The efficacy of bisphosphonates – neridronate in treating CRPS pain can also be explained by pharmacodynamics, according to which bone tissue maintains its strength through the incorporation of inorganic components, in particular hydroxyapatite, however fluorapatite and other calcium salts in the organic intercellular substance. Since the organic components of the bone are mainly composed of collagen fibers the bone substance is subject to constant reconstruction, so the osteoclasts, multi-core, between the mobile giant cells. Bisphosphonates interfere with the cycle of bone degradation that occurs during osteoblasts and inhibit the formation of osteoclasts from progenitor cells in the bone marrow and their differentiation and binding to the bone surface. 

Biphosphonates are indicated for metabolic bone diseases associated with increased activity of osteoclasts, effectiveness that has been found through excellent results in the treatment of CRPS through the administration of neridronate, a drug belonging to the family of bisphosphonates precisely. Therefore, it is likely that the action carried out by neridronate on bone resorption and bone turnover will bring significant benefits in the treatment of bone diseases and an inhibition of bone metastases and especially a decrease in bone pain.


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