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Common Therapies To Treat Complex Pain Syndrome

Complex Regional Pain Syndrome (CRPS) is a multifactorial and disabling disorder with complex etiology and pathogenesis. The objectives of CRPS therapy should be pain relief, functional restoration and psychological stabilization, but early intervention is best to achieve these objectives. 

Several drugs have been used to reduce pain and improve the functional status of CRPS, despite the lack of scientific evidence to support their use in this scenario. They include anti-inflammatory drugs, analgesics, anaesthetics, anaesthetics, anticonvulsants, antidepressants, oral muscle relaxants, corticosteroids, calcitonin, calcium channel blockers and topical agents. NSAIDs did not show any value in the treatment of CRPS. Glucocorticoids are the only anti-inflammatory drugs for which there is direct clinical evidence in the initial phase of CRPS. Opioids are a second or third line treatment option, but tolerance and long-term toxicity are unresolved issues. The use of tricyclic anticonvulsants and antidepressants has not been well studied for pain management in CRPS. 

In recent years, bisphosphonates have been the most studied pharmacological agents in the treatment of CRPS and there is good evidence to support their use in this condition. Recently, the efficacy of intravenous administration of Neridronate has been reported in a randomized controlled trial. These results were confirmed in the open extension phase of the study, when patients previously enrolled in the placebo group received Neridronate at the same dose, and these results were maintained at one-year follow-up.

The current literature concerning sympathetic blockages and sympathectomy techniques lacks evidence of efficacy. Low evidence was recorded for an anti-free radical cream, dimethyl sulfoxide cream. The same level of efficacy was observed for vitamin C in the prevention of CRPS in patients with a fractured wrist. In conclusion, the best therapeutic approach available at CRPS is multimodal and is based on the use of different classes of drugs, associated with early physiotherapy.

Neridronate at appropriate doses is associated with clinically relevant and persistent benefits in patients with CRPS.


It is clear that Complex Regional Pain Syndrome (CRPS) affects the vascular, nervous, skeletal, and immune systems. Usually, CRPS develops in a peripheral limb after trauma or surgery and is characterized by pain, such as typical burning pain, accompanied by allodynia and hyperalgesia, disproportionate to the inciting event and a variety of autonomic disorders and trophic abnormalities.

The management of CRPS is challenging, partly because of the lack of clinical data on the effectiveness of available therapies and partly because the success of CRPS treatment requires a multidisciplinary approach. The interdisciplinary approach to treating patients with CRPS is the most pragmatic, useful and cost-effective approach available today. Therefore, this approach should be multimodal, including the following interventions: occupational, physical, professional and recreational therapy; psychological/behavioral therapy; drugs; invasive procedures such as nerve blocks, spinal cord stimulation and sympathectomy. 

The goals of therapies in CRPS should be pain relief, functional restoration and psychological stabilization and to achieve these goals, treatments should be performed as soon as possible. Physical and occupational therapy is the cornerstone and first line of treatment for CRPS. Early mobilization is essential and should be encouraged, avoiding the patient’s painful symptoms. The objectives of physical and occupational therapy are to reduce oedema, normalize painful limb sensation through desensitizing therapies and reduce functional damage by avoiding unadaptive positioning of the limb affected by CRPS. In particular, the rehabilitation approach should be adapted to specific body functions and consists of progressive load exercise programs that include passive and regular active exercises to mobilize the joints in order to improve or maintain the amplitude of movement. These interventions are generally used in combination with pain medications.


Therapeutic Approach

It has been seen that the main symptom of CRPS is pain, often associated with limb dysfunction and psychological distress. In all subjects where pain persists, the most common psychological symptoms are they are anxiety, depression, loss of sleep, which is why an interdisciplinary therapeutic approach is always recommended Pain is generally the main symptom of CRPS and is often associated with limb dysfunction and psychological discomfort in order to improve the quality of life of those affected. The foundations on which to build the care system for CRPS are education, pain relief, physical rehabilitation and psychological support responding to objectives of primary importance.

Recovery in some patients does not take place at all, despite appropriate early treatment. In these cases it is good practice for doctors to support patients by providing them with clear diagnosis, correct information and preparation about the disease, helping to set realistic goals and, where possible, involving civil society, the patient’s partner and/or other family members.


Primary Care

The curative treatment of CRPS changes in a variety of clinical settings, whether acute or chronic CRPS.

In general, unilateral pain in the limbs of patients has many potential causes. In order to have a better certainty of the diagnosis of CRPS, it is good practice to consider the following factors that occur at the same time in the patient: – intensity of pain – limb dysfunction – anguish.

In some cases CRPS are diagnosed as “mild” for those with few signs of severe pain, disability, anguish and where conventional or neuropathic drugs adequately manage the intensity of pain.

Patients with high levels of pain, disability or distress should be directed for specialist counselling and active rehabilitation as soon as possible.



There are cases where the diagnosis of suspected CRPS is postponed and confirmation is expected, especially with regard to CRPS II whose cause of nerve damage (in this case major nerve) needs to be investigated and clarified in the knowledge that CRPS can be triggered by nerve damage but not exclusively by it. In cases where pain treatment is unsuccessful, the patient should be referred to a pain specialist (in the community or in another organisation, including foreign ones) and above all it is important that the family doctor does not rely on non-pain specialists to manage the patient’s persistent pain, even in cases where the patient has mild and moderate pain but in conjunction with other symptoms of CRPS such as anxiety or disability. In these cases the patient should be referred to a multidisciplinary pain clinic.


How to behave in cases of persistent pain after trauma or surgery

Following trauma or surgery, when the patient has been discharged from the trauma or surgical team, the family doctor should consider sending the patient to an orthopaedic specialist, surgeon or trauma service in order to take into account the definitive exclusion of the current pathology.


Occupational therapy and physiotherapy

It is quite common and good practice for the results obtained to resort to physiotherapy rehabilitation with physiotherapists and occupational therapists for patients with CRPS.

Usually occupational therapists and physiotherapists provide rehabilitation to those who are affected by CRPS in different contexts, such as:

-Outpatient rehabilitation: in the community or in hospital facilities

-Stationary rehabilitation: multidisciplinary stationary rehabilitation is described in the section on stationary rehabilitation.


Rehabilitation Medicine

There are countries where, in addition to pharmacological treatment and physiotherapy, it is also possible to follow a rehabilitation medicine programme for all those affected by CRPS defined as “pain management programmes”.

These are multidisciplinary programmes, usually carried out in an outpatient group and solemnly linked to pain medicine departments.



It should be borne in mind that the development of CRPS should not be seen as evidence of sub-optimal surgical management, and that health professionals involved in the rehabilitation of patients with CRPS should be aware of the basic principles of CRPS therapy.

In addition, it is important to reassure patients about full or partial recovery in at least 85% of cases, although ongoing motor dysfunction with limb disabilities may be a common factor.

The patient should also be told that CRPS is a recognised but not easily diagnosed condition and that physiotherapy-supported therapy should be initiated immediately when CRPS is suspected. Another useful factor is the temporary discomfort of the limb in a safe position that can relieve pain and lead to its gentle mobilisation. While excessive loosening is contraindicated in cases where it aggravates pain. It is a good idea for the orthopaedic team to begin treatment early with simple analgesic drugs. These may include codeine, dihydrocodeine, tramadol, nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol.

These drugs do not affect the pain of CRPS but reduce the ongoing pain and pain associated with trauma.

Other drugs considered useful for neuropathic pain are tricycle, antidepressants and anticonvulsants, but the family doctor or pain specialist is usually in the best position to arrange the follow-up required for the drug.

Physiotherapy and occupational therapy, multidisciplinary pain management programs, spinal cord specialist stimulation and rehabilitation programmes.