Complex regional pain syndrome is one of the intractable neuropathic pain disorders, and the mechanism of its development remains unclear. It is currently believed that the development and maintenance of complex regional pain syndrome is the result of a combination of factors.
Definition
Complex regional pain syndrome used to be considered as an autonomic dysfunction syndrome with terms such as reflex sympathetic disorder, burning pain, post-traumatic pain syndrome, nutritional disorder, neurovascular dysreflexia, post-traumatic neuralgia, sympathetic neuralgia, shoulder-hand syndrome, etc. In 1994, the International Pain Society adopted the term “complex regional pain In 1994, the International Pain Society adopted the term “complex regional pain syndrome” to describe chronic regional pain discomfort associated with altered secretion of sweat and vasoconstriction. Complex regional pain syndrome is defined as “a pain syndrome secondary to an injurious event such as trauma that includes regional pain, altered sensation (e.g., nociceptive hypersensitivity), temperature abnormalities, abnormal sweating, skin color changes, and edema.”
Classification and diagnostic criteria
In 1994, the International Pain Society developed diagnostic criteria for complex regional pain syndromes
There are two types of complex regional pain syndromes.
Complex regional pain syndrome I (reflex sympathetic dystrophy).
(i) With an initial time of injury or cause of activity limitation.
(ii) Persistent pain, sensory abnormalities, or nociceptive hypersensitivity that is disproportionate to any stimulus.
③The painful area shows edema, altered blood flow to the skin, or abnormal secretion of secretion of sweat.
④Exclusion of other conditions that cause the same degree of pain and dysfunction. The diagnosis must meet 2 to 4 criteria.
Complex regional pain syndrome II (burning pain).
①Persistent pain, abnormal sensation or nociceptive hypersensitivity after nerve injury, but not necessarily limited to the area of distribution of the damaged nerve.
(②The painful area has edema, altered skin blood flow, or abnormal secretion of secretion of sweat.
(③ Exclude other conditions that cause the same degree of pain and dysfunction. All criteria must be met for the diagnosis.
The modified International Pain Society criteria by Bruehl et al. will facilitate the validity of the diagnosis of complex regional pain syndrome. Have an initial injurious duration or cause of activity limitation; have at least 1 symptom of each of the following 4: (i) sensory: tactile hypersensitivity. ②Vasomotor: temperature asymmetry, and/or skin color change, and/or skin color asymmetry. ③Sweat secretion/edema: edema, and/or altered sweating, and/or sweating asymmetry. ④Motor/nutritional: decreased motor amplitude, and/or motor kinetic disorders (muscle weakness, tremors, abnormal muscle tone), and/or nutritional alterations (hair, nails, skin).
Presence of at least 1 of 2 or more of the following signs: (i) sensory: pain hypersensitivity (pins and needles), and/or tactile hypersensitivity (light touch). ②Vasomotor: temperature asymmetry, and/or skin color change, and/or skin color asymmetry. ③Sweat secretion/edema: edema, and/or altered sweating, and/or sweating asymmetry. (iv) Motor/nutritional: reduced motor amplitude, and/or motor kinetic disorders (muscle weakness, tremors, abnormal muscle tone), and/or nutritional alterations (hair, nails, skin).
Clinical trials have revealed that the sympathetic nervous system is associated with the maintenance of complex regional pain syndromes, and Roberts describes this pain profile in terms of “sympathetic maintenance pain”, i.e., pain relief by blocking the sympathetic efferent system. In contrast, “sympathetically unrelated pain” is pain that does not respond to sympathetic blockade. In addition, the pain is aggravated by sympathetic blockade, which is called “Angry Backfiring C-nociceptor syndrome”.
Epidemiology
The average age of onset of complex regional pain syndrome is 36-46 years, with a predominance of women (60%-81%). The incidence is 44% to 61% in the upper extremities and 39% to 51% in the lower extremities. The causes of complex regional pain syndrome [5]: fractures accounted for 16%-46%, ligament strains or sprains accounted for 10%-29%, postoperative injuries accounted for 3%-24%, contusions and crush injuries accounted for 8%-18%, and unknown causes accounted for 2%-17%. The incidence of complex regional pain syndrome in children and adolescents is low, and the characteristics are different from those of adults [6]: the affected limb is more common in adults than in lower limbs, and in children and adolescents lower limbs > upper limbs (6s1); gender is more common in adults (2.4s1) and predominantly in children and adolescents males (7s1); prognosis is more common in adults with long-term disability, and the majority of children and adolescents recover well.
Clinical manifestations
Sensory system signs and symptoms The main manifestations are unbearable pain and nociceptive hypersensitivity. The majority of patients have pain that is burning, drilling, pins-and-needles, or firing and is localized to deeper tissues. Nociceptive hypersensitivity is often triggered by mechanical stimulation, joint movement and exposure to cold environments, and abnormal pain is triggered by non-invasive tactile stimuli. Sensory deficits are more common. rommel et al. observed decreased sensation to hypothermia and pins and needles in the affected limb in 33% of patients. thimmineur et al. found that 49% of patients with complex regional pain syndrome of the upper limb had trigeminal nerve hyperalgesia.
Autonomic system signs and symptoms The main manifestation is altered vasomotor or sweating function. Most patients present with edema of the affected limb, which can be exacerbated by weight bearing, painful stimuli, temperature changes, and hydrostatic pressure. The temperature difference between the affected limb and the contralateral normal limb is more than 1 °C. 59% of patients have a sweating disorder, of which 94% have increased sweating. The color of the affected skin area may be blue, purple or pale.
Signs and symptoms of motor system and nutritional disorders Motor dysfunction includes weakness, decreased mobility, tremor, abnormal muscle tone, and myoclonus. Muscle strength is often reduced, and Zyluk [9] observed a significant reduction in grip strength in 78% of patients. In the early stages of the disease there is joint exudation and in the later stages there is contracture and fibrosis. 24-60% of patients have tremor. Patients may also present with abnormal muscle tone and myoclonus. Nutritional disorders are often manifested by abnormal reduction or increase in nails and hair, hyperkeratosis, and thinning of the skin of the affected limb.
Myofascial dysfunction Myofascial dysfunction is present in the majority of cases (56% to 60%), especially when the upper extremity is involved, and is associated with the course of the disease.
Assessment criteria
Pain assessment Pain assessment is critical. Most clinical studies have used a single visual analogue score as the primary pain rating criterion. jensen et al. demonstrated that single pain intensity grading was less reliable in chronic patients, whereas three daily assessments over a 4-d period showed good internal consistency and validity. dworkin et al. suggested that patients could self-assess their average pain level on time. forouzanfar et al. compared complex regional Forouzanfar et al. compared single and multiple pain ratings in patients with complex regional pain syndrome and confirmed good correlation and consistency; however, “recall average” pain reflects greater variability in pain intensity.
Skin temperature assessment Schurman et al. used infrared thermal camera measurements to compare the skin temperature of the affected finger with the corresponding finger on the contralateral side and found that a systematic temperature difference (>1°C) between the affected side and the healthy side was observed in only 42% of patients with complex regional pain syndrome type I. They concluded that in a thermal equilibrium environment, the skin temperature of the affected finger is not as high as that of the healthy side. They concluded that a systemic temperature difference may exist in patients with complex regional pain syndrome type I in a thermal equilibrium setting. However, this cannot be used as a diagnostic basis due to lack of specificity.
Motor assessment Active mobility was classified into four categories (normal, impaired, severely impaired, disuse). Electromyography and nerve conduction are also used to test motor function.
Autonomic function assessment Autonomic function can be evaluated by edema grading (5-point scale: no edema, localized edema, localized severe edema, generalized edema, generalized severe edema), skin temperature and color changes, and sweating. Sweating function can be assessed by a sweating test. The quantitative sweating axon reflex test assesses local autonomic function by acetylcholine-induced sweating, while the thermoregulatory sweating test qualitatively assesses local sweating function induced by increased body temperature.
Treatment
Treatment of complex regional pain syndrome is difficult because the mechanism of pain is not well understood. Close collaboration between multidisciplinary physicians (e.g., psychologists, internists, oncologists, neurologists, and pain medication consultants) can help improve outcomes. The guidelines center on 3 dominant components: rehabilitation, pain management, and psychotherapy.
Rehabilitation/physiotherapy Rehabilitation is the cornerstone of treatment for complex regional pain syndromes. Physical therapy, pain management, and psychotherapy will facilitate the process of rehabilitation.
① Adequate analgesia, encouragement and education of the patient about the disease process.
②Increase patient flexibility: start with light active range of motion requiring stretching, strengthening and postural correction, trigger point injections, electrical stimulation and muscle relaxants if necessary. Control of swelling requires elevation of the affected area, retrograde massage, and use of a Jobst compression pump.
(iii) Functional exercise: including weight bearing, friction skills, isometric strengthening, aerobic exercise and postural normalization.
Psychotherapy The International Pain Society recently stated that patients with complex regional pain syndrome with a pain duration greater than 2 months should receive psychological evaluation to identify and treat psychological disorders such as anxiety, depression, or personality changes. Psychological counseling, behavior modification, biofeedback, relaxation therapy, group therapy, and self-hypnosis may improve the patient’s motivation and ability to deal with things.
Pain management
Medication Studies have proven that corticosteroid therapy is effective in the early stages of complex regional pain syndrome. Subcutaneous injection or transnasal spray of calcitonin is beneficial in the early stages of complex regional pain syndrome. Regional blocks with alpha1 antagonists have been reported to be effective in patients with sympathetic maintenance pain.
Minimally invasive techniques interfering with sympathetic nervous system and adrenergic receptor function such as sympathetic blocks, venous regional blocks and somatic nerve blocks are advocated as treatment for patients with complex regional pain syndrome with sympathetic maintenance pain. Nerve blocks are primarily for pain relief to facilitate physical therapy and functional recovery. A retrospective study showed that prophylactic planetary ganglion blocks in patients with previous complex regional pain syndrome reduced the prevalence of complex regional pain syndrome from 72% to 10% after reoperation of the affected limb.
Invasive techniques If the patient’s recovery or pain relief is not satisfactory, further invasive treatment is required. If the patient responds to sympathetic blockade, epidural placement is required to provide long-term somatic or sympathetic blockade. Epidural use of colistin and ketamine has been reported to be effective in patients with complex regional pain syndrome.
(i) Intrathecal medication: Studies have shown that the choice of intrathecal medication for patients with significant abnormalities in muscle tone, unresponsive to nerve stimulation, chronically ill or requiring palliative care can provide significant pain relief and promote recovery.
②Nerve stimulation: It is the last option for the treatment of complex regional pain syndrome. Bilateral spinal nerve stimulation for complex regional pain syndrome type I and peripheral nerve stimulation for complex regional pain syndrome type II can produce long-term pain relief and improved quality of life.
(iii) Sympathectomy: Patients with complex regional pain syndrome for whom conventional complex regional pain syndrome treatments are ineffective may be considered for surgery or experimental treatment. Radiofrequency and nerve disruption surgery should be considered first for patients with sympathetic maintenance pain.
Experimental treatment
Stimulation of the deep brain and motor cortex may be considered as an experimental treatment. Brain stimulation includes stimulation of the hypothalamic sensory nuclei and/or the periventricular gray matter or periaqueductal gray matter. The literature shows that in patients with intractable neuropathic pain treated with deep brain stimulation, 30-40% of patients have good pain control. Recent promising advances in brain stimulation techniques for the treatment of neuropathic pain have been reported by Nguyen et al. In a group of cases, 75% of patients with central pain and 75% of patients with neurofacial pain experienced significant pain relief with chronic stimulation of the motor cortex. Epidural stimulation of the motor cortex for central pain has the advantage of being safer, simpler and less invasive than deep brain stimulation.