Clinically, pain is broadly classified into three types according to the different etiologies and mechanisms that cause pain.
(i) injury-derived pain, which is associated with various injurious stimuli acting on injury receptors.
(ii) neurogenic pain, associated with nerve injury or spontaneous dysfunction.
③ sympathetic pain, which is mainly sympathetically mediated and related to the dysfunction and damage of sympathetic nerves. The chronic pain encountered in clinical practice ;
Although most of them are mixed pain of the above three types, they have different clinical manifestations according to their main etiology. Among them, the pain closely related to sympathetic nerve mediated, roughly contains the following several Henan Provincial People’s Hospital Pain Department Ma Songhe
The following aspects.
1 Complex Regional Pain Syndrome (CRPS), which refers to a clinical syndrome characterized by severe intractable and variable pain, malnutrition and dysfunction secondary to accidental injury, medically induced injury or systemic disease. It includes two typical sympathetic pain disorders, namely reflex sympathetic dystrophy (RSD) and causalgia. Although the etiology and mechanism of these painful diseases are different, the clinical manifestations are mostly similar, so they are mostly named as post-injury pain syndrome, burning neuralgia, painful dystrophy, chronic injury edema, post-injury vasomotor disorders, etc.
2 Visceral pain, which originates from thoracic, abdominal, pelvic and other visceral organs, can be transmitted to the center through the vegetative nerves, and is mostly caused by tumors, ischemia or inflammatory lesions. It is characterized by an indefinite location, a wide range of pain, and often associated with involvement pain. The pain caused by the wall layer of thorax, peritoneum, mesentery and diaphragm is transmitted by the somatic nerve, so once the lesion is invaded, a more fixed and definite pain can appear.
3 Peripheral vascular painful diseases, including pain caused by peripheral vascular contraction dysfunction, embolism, sclerosis and other lesions. Most of these diseases have sympathetic dysfunction, and can be diagnosed, prognosed and treated by sympathetic blockade. For example, Raynaud’s disease, red scarring limb pain, cyanosis of the hands and feet, reticular cyanosis, arteriovenous embolism, vasculitis, retinopathy, etc.
In this article, we focus on the diagnosis and treatment of Complex Regional Pain Syndrome (CRPS).
Significance and methods of vegetative nerve function examination
The determination of systemic or local phytonadic function is of great importance for the diagnosis, treatment, determination of efficacy, prevention of complications and prognosis of painful diseases. Since the number of postganglionic neurons in the vegetative nervous system is much higher than that of preganglionic fibers (the ratio is about 2~30:1), the impulse of one preganglionic nerve fiber element can cause a large number of postganglionic cells to discharge. A single nerve can cause a wide range of symptoms with imprecise localization. That is, a small number of preganglionic neurons can control a considerable range of peripheral effector organs. This anatomical connection acts as an amplifier of the responses of peripheral tissues and end-organs. These characteristics determine the complexity of sympathetic pain in clinical practice and the variability of the response to various therapies. In the treatment of painful diseases, the need to fully grasp the functional status of the vegetative nervous system before and after treatment should be emphasized.
Before nerve block: the examination of the function of the vegetative nervous system should be emphasized. It is not difficult to diagnose and determine the treatment guidelines for typical lesions. However, for some lesions, it is not obvious whether they are vegetative or not, or how much vegetative nerve involvement is involved in the process of lesion development. A case of cardiac arrest after SGB has been reported, which was later analyzed as a result of high vagal tone (1).
After nerve block: the examination of vegetative nerve function is even more important. On the basis of determining the effect of the nerve block itself, it plays an important role in identifying the type of pain, deciding the treatment policy, and judging the prognosis. To determine the objective effect of nerve block, it is sometimes necessary to perform extremely delicate examinations. Such as the micro-psychic sweating method, micro-nerve electrode method, etc.
Physiological regulation: In physiological condition, when sympathetic tension is increased, it is usually manifested by bright and prominent eyes, dilated pupils, pale and dry skin, vertical hair phenomenon, rapid heartbeat, elevated blood pressure, free breathing, dry mouth, lack of gastric juice, gastric dilatation, weak constipation, hyper-metabolism, and tendency to be thin; when parasympathetic tension is increased, pupils are narrowed, skin is moist and blue, heartbeat is slow, blood pressure When the parasympathetic tone is increased, the pupils are narrowed, the skin is cyanotic, the heartbeat is slow, the blood pressure is lowered, the breathing is shortness (shortness of breath), salivation, the stomach acid is increased, spasmodic constipation alternates with diarrhea, the metabolism is reduced, and obesity tends to occur. In general, vagal tone is increased during sleep, both parts are high during sexual maturity, and both parts are low in the elderly.
Commonly used methods for examining vegetative nerve function
Oculocentric reflex: lie on your back with your eyes closed, use your fingers to lightly press both sides of one of the patient’s eyeballs, and after 3~4 seconds of pressure (with mild pain), count the number of pulses for 15 seconds and calculate the number of pulses for 1 minute, compared with the number of pulses before the examination. Normal people
It can be reduced by 4~12 times after the examination; a reduction of 12 times/min or more is positive, indicating increased vagal tone, and a reduction of
A decrease of 18 to 24 beats/min or more indicates a significant increase in vagal tone. Such patients are particularly prone to syncope and the possibility of cardiac arrest during operation. In addition to a slowed pulse, a reduced pulse force is often seen. Clinically, there may be blackness before the eyes, dizziness, nausea and even vomiting. This is often referred to as vagal tension. Conversely, if the pulse increases instead of decreasing after pressure on the eyeball, it is called an inversion reaction, indicating that the patient has increased sympathetic tone.
Skin striae: The local sympathetic and parasympathetic excitability can be initially determined by observing the local capillary response to stimulation.
<1>White scratching syndrome: white scratching appears within 8~20 seconds when the skin is lightly and quickly scratched with a bamboo stick or nail, lasting for 3~5 minutes. It is due to vasoconstriction caused by neurogenic reflexes. It is more pronounced in the lower extremities. It indicates increased sympathetic excitability.
<2>Red streak syndrome: red streaks appear in 3~5 seconds and last for 8~30 minutes when the skin is scratched with a bamboo stick with slight pressure. If the red stripe is wide and lasts for a long time, it may be due to increased parasympathetic nerve excitability. In severe cases, it appears 1~2 minutes after scratching and lasts 1~12 hours, causing skin elevation and edema at the scratching area, which is caused by vasodilation and serous exudation.
Skin scratching can also occur in normal people, and is only clinically relevant if it lasts too long, or if a reaction occurs regardless of light or heavy scratching.
<3> Prone and standing test The pulse is counted for 1 minute in the prone position, and then for 1 minute after rising. An increase of 10 to 20 pulses from the prone to the standing position is considered to be an increase in sympathetic excitability. A decrease of 10~20 times from the standing to the prone position is considered as increased parasympathetic excitability.
<4>Hair erectile reflex After applying ice or other cold stimuli to the skin of the back of the neck or axilla for a few seconds, the hair erectile muscles contract and the skin follicles bulge in a chicken skin-like appearance. This reflex is innervated by sympathetic nerve segments, and the sympathetic nerve dysfunction can be diagnosed locally according to the response at different sites. For example, C8~T3 innervate the head, face and neck, T4~7 innervate the upper extremities, T8~9 innervate the trunk, and T10~L2 innervate the lower extremities.
<5>Microsweating assay: The moisture of the skin is related to the function of sweat glands. Warm sweating is mainly related to ambient temperature and regulates human body temperature. Neurogenic sweating is mainly controlled by the function of the vegetative nerves. Sweat glands are innervated by the postganglionic fibers of cholinergic sympathetic nerves. By monitoring the neurogenic microsweat secretion of the skin, the sympathetic tension of the organism can be determined in a timely response.
<6>Tiny nerve electrode method: A silicon carbon tiny nerve electrode with a tip diameter of 0.1μ can be inserted into a single nerve cell, and the impulses of sympathetic nerves can be directly elicited and issued in an environment shielded by copper mesh. This is currently the most direct method to determine sympathetic nerve function.
<7>Diagnostic sympathetic block: Selective blockade of sympathetic nerves innervating the lesion site is performed and the effect of the block is observed. If the patient complains of pain relief, the lesion area changes from a sweaty, moist, cool feeling to a comfortable warm feeling with reduced sweating. Then it indicates that the occurrence of the pain is highly associated with sympathetic nerves.
<8>Other ECG R-R interval method, measurement of hormone concentration in blood, etc.
Concept of CRPS
It is generally believed that lesions such as reflex sympathetic dystrophy RSD and causalgia are due to abnormal sympathetic hyperfunction and should respond well to sympathetic blockade. However, we often encounter cases in which sympathetic blockade does not completely prevent the onset of pain even after a complete sympathetic block. In some cases, even after sympathetic blockade, the pain is worse. This phenomenon suggests that although some cases have exactly the same clinical symptoms, the response to sympathetic blockade varies because the pathogenesis is different. Therefore, it has been advocated that in such diseases, those that respond well to sympathetic blockade are called sympathetically maintained pain SMP, and those that do not respond to sympathetic blockade are called sympathetically independent pain SIP, while those that do not respond to sympathetic blockade are called sympathetically independent pain SIP. And for those whose pain worsens after sympathetic blockade is called ABC syndrome (Angry Backfiring C-nociceptor syndrome ABC syndrome) (2,3). Even in the same patient, with different stages of disease development, there can be manifestations of SMP, SIP, and ABC syndrome.
For this reason the International Pain Society has proposed the concept of Complex Regional Pain yndrome CRPS (CRPS). That is, pathological pain caused by local injury, which usually persists beyond the predictable healing process of the trauma, often causing significant motor hypofunction, manifests itself over time in a progressive and diverse syndrome (4). Of course, in CRPS, the traditional RSD and burning pain are also included. CRPS is usually divided into 2 types. RSD belongs to CRPS type I, which is called the possibility of nerve damage, but it is not possible to determine exactly what nerve is damaged. Burning pain, on the other hand, belongs to CRPS type II, where there is often more obvious and definite nerve damage.
Clinical features of CRPS.
<1>Site Mostly in the upper or lower extremities, but also in the trunk and head and face.CRPS type I has characteristic pathologic changes at the site of damage as well as at its distal end, and the central end of the injury site is generally normal. In some patients, the pathological changes progress from the site of injury to the central side, and in CRPS type II, the pathological changes are usually only peripheral to the site of nerve damage and produce sensory disturbances.
<2>Symptoms Clinical manifestations are varied, and pain is an important symptom of this type of disease. These pains include spontaneous pain and evoked pain. Evoked pain can be broadly divided into allodynia (pain hypersensitivity) and hyperalgesia (pain hypersensitivity). It is important to note that there are a number of patients who have a history of severe and unusual pain for several years or even a decade, but have no other typical manifestations other than pain.
a. Pain The acute phase, which occurs days or weeks or sometimes months after the injury, is characterized by sudden spontaneous pain that lasts for about several weeks. The nature of the pain is varied, not always burning pain, there are also many patients without spontaneous pain, but as physical activity pain. It is often accompanied by unusual pain or nociceptive hypersensitivity. Most cases usually present with mechanical, thermal, mental, or emotional stimuli that induce unusual pain, and some patients often present with nociceptive hypersensitivity. In some cases, 3-6 months or more after the injury, the pain can still be persistent and spread to the surrounding area. Sensory and nociceptive hypersensitivity is aggravated, especially tactile and temperature sensation.
b. Nutritional disorders In and around the injury site accompanied by vasomotor nerve dysfunction, swelling occurs. Sometimes, although the puffiness is not obvious, there is often a complaint of swelling. The skin color begins to accompany sweating and mostly appears moist and flushed. The skin temperature may appear hot or cold indefinitely, and in later stages it tends to decrease, showing ischemic changes. With the progressive development of the disease, the growth rate of hair and nails changes from faster to slower, and the skin gradually becomes thin and the nails curl and lose their luster.
c. Motor function Decreased grip strength and reduced fine-motor function can occur at an early stage. The joints become stiff due to disuse atrophy of the muscles as a result of the reduced range of motion. Subcutaneous tissue atrophy often occurs after 6 months or more of disease duration, resulting in thinning and shiny skin and increased or decreased sweating of the affected skin. This is accompanied by hypertrophy of the myofascia, joint contracture, and osteoporosis, which are generally thought to be due to poor blood flow and disuse atrophy. x-ray examination may show osteoporosis.
CRSP diagnostic criteria.
① A longer or recent history of injury, history of disease.
② Persistent burning-like pain or unusual pain or pain hypersensitivity.
③ There is vasomotor and sweating dysfunction, nutritional changes such as muscle atrophy or failure, limb edema or dryness, and hypersensitivity to cold and other stimuli.
(iv) Diagnostic sympathetic block test is mostly positive.
CRPS treatment
Once diagnosed with CRPS, methods of pain relief should be sought as early as possible, along with adequate and aggressive rehabilitation treatment.
<1>Preventive treatment. It is important to treat the injured surface well and to start adequate analgesia early in the injury. In other words, the pain should be controlled in the acute phase and prevented from progressing to chronicity. Combining this with psychiatric treatment is generally considered to yield better results.
<2>Nerve block treatment
Sympathetic nerve blocks are the mainstay. Commonly used nerve blocks include: SGB, thoracic sympathetic block, lumbar sympathetic block, and intravenous local nerve block. Epidural block, subarachnoid block and local pain point block can also be used as appropriate. When the effect of local anesthetic block is not obvious, sympathetic nerve block with salbutamol has also been tried.
In principle, repeated use of local anesthetics, especially when the pain gradually decreases with repeated blocks, should be performed continuously. When the pain symptoms do not improve after local anesthetic block or when the temporary improvement is followed by a gradual decrease in effect, nerve destruction or sympathectomy with nerve-destroying drugs should be considered. When sympathetic nerve trunk and ganglion blocks are performed, the principle of using a single drug with local anesthetics should be emphasized. As in the case of SGB, which is widely used clinically, there are often authors who use very complex formulations of anti-inflammatory and analgesic solutions for SGB. this is both unnecessary and prone to increased complications, and is not consistent with the therapeutic mechanism of SGB.
Sympathetic nerve blocks performed clinically exert their therapeutic effects mainly through mechanisms such as blocking their mediated pain and dilating the blood vessels in their innervated areas. In most of the indications for sympathetic nerve block, the sympathetic nerve trunk or node to be blocked does not have inflammatory lesions, and the purpose of drug injection there is only to temporarily or permanently block the nerve conduction function, so as to release the vasospasm and pain in the area it innervates. Therefore, from the therapeutic principle, there is a fundamental difference between spinal nerve root, trunk and local nerve blocks with inflammatory lesions, and the same formula should not be used uniformly for all nerve blocks.
<3>Transdermal electrical stimulation (TENS)
Can activate the body’s own endogenous opioid peptides involved in analgesia, but also stimulate the thick fiber nerves at the site of pain and analgesia through the mechanism of the gate doctrine. It has a positive effect on altering sensory impulse transmission to the central nervous system, reducing chronic pain and terminating its secondary physiological/pathological response. There has been experience of complete cure of post-herpetic neuralgia of the first branch of the trigeminal nerve and intractable postoperative stabbing pain relying solely on HAN`S treatment.
<4>Medication
a. Antidepressants Commonly used are tri(tetra)cyclic antidepressants such as amytalin, promethazine, doxorubicin and meptyline. In the past, they were mostly used to improve the mental depression of chronic pain, but later they were found to have a unique analgesic effect and were widely used in the treatment of chronic pain. The antidepressant and analgesic effects are mainly produced by inhibiting 5-hydroxytryptamine and norepinephrine reuptake at synaptic sites and affecting the amount of central transmitters (5). In chronic long-term use, the analgesic effect is also related to changes in the activity of substance P, promethazine like peptide, and γ-aminobutyric acid. Generally, adults take 25 mg/day and the elderly take 10 mg/day before bedtime. If the effect is not obvious and there is no side effect, it can be increased by 10~25mg every few days, after reaching 150mg/day, it should be maintained for 1~2 weeks. If there is no side effect, it can be used up to 300mg/day or less. When dry mouth occurs, it indicates that the dosage is sufficient. Close attention should be paid to its complications (anticholinergic, quinidine like effects).
b. Antispasmodics Representative drugs are carbamazepine, sodium phenytoin, sodium valproate. Effective for nerve shock-like pain. More widely used abroad is gabapentin (gabapentin), which can significantly relieve neuralgia caused by diabetes or herpes zoster. The principle of action of this class of drugs is not fully understood. It is thought to be related to the inhibition of abnormal firing or hyperexcitability of damaged neurons. Long-term application of these drugs can produce abnormalities in the liver, kidney, gastrointestinal tract and hematopoietic system, so it is generally recommended to apply or alternate with close monitoring.
c. Anti-arrhythmic drugs Damage to peripheral nerves will lead to increased spontaneous excitability, which is the main cause of increased central sensitivity and the occurrence of chronic intractable pain (6). Virally infected nerve tissue is prone to persistent excitation of nerve fibers due to hypersensitivity of Na channels. Analgesia is achieved by blocking the action of Na channels and inhibiting the excitability of the nerve tissue. Commonly used with slow heart rhythm. 50~200mg three times a day is not recommended for bradycardia, AV block and severe cardiac, hepatic and renal insufficiency.
d. Lidocaine The principle of action is basically the same as that of slow heart rhythm. 100~300mg/1~2 hours of sedation, often with certain efficacy.
e, ketamine NMDA receptor antagonist (7), can inhibit sensory fiber hyperexcitability. Trial method: 0.3mg/kg, after the first half amount of static injection, the remaining amount in 20 minutes of static drip. If the effect is not satisfactory, it can be increased to 0.6mg/kg for 2~3 weeks as a course of treatment. When side effects such as nightmares or nausea appear, use haloperidol or mizoram to counteract.
f. Sympathetic nerve blocking drugs Some studies have shown that sympathetic pain is related to the activation of alpha-adrenergic receptors at the damaged site. Depletion of norepinephrine in sympathetic nerve endings can effectively counteract SMP (8). Phentolamine, 5 mg/dose, 1 to 2 times/day is commonly used.
g. Others Non-steroidal anti-inflammatory analgesics, neurotoxicity, prostaglandin preparations, hormones, morphine-like drugs, etc.
<5>Psychological aspects of treatment
Acute pain in the process of progressing to chronicity, with the emergence of dysfunction, the increase of psychosocial burden, resulting in the bottom of QOL. The role of psychological factors in the whole treatment process cannot be ignored (9). Some psycho-psychological aspects of treatment such as cognitive therapy, relaxation therapy, biofeedback therapy, hypnosis, etc. should be appropriately intervened.