JBJS | Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Reflex Sympathetic Dystrophy and Pain Dysfunction in the Lower Extremity*†

The Journal of Bone & Joint Surgery, Volume 78, Issue 12

Instructional Course Lecture | December 01, 1996

Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Reflex Sympathetic Dystrophy and Pain Dysfunction in the Lower Extremity*†

THOMAS N. LINDENFELD, M.D.‡, CINCINNATI, OHIO; BERNARD R. BACH JR., M.D.§, CHICAGO, ILLINOIS; EDWARD M. WOJTYS, M.D.¶, ANN ARBOR, MICHIGAN

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An Instructional Course Lecture, The American Academy of Orthopaedic Surgeons.

The Journal of Bone & Joint Surgery. 1996; 78:1936-44

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Introduction

Most orthopaedic surgeons have faced the challenge of managing patients who have marked limitation of motion of the knee. Others have managed patients who have a disability because of sympathetically maintained pain—that is, reflex sympathetic dystrophy. Both of these conditions can be difficult to treat. When sympathetically maintained pain and severe contractures occur together in the knee, the problems of diagnosis and treatment are magnified. Sympathetically maintained pain can be disproportionately severe and associated with periarticular swelling as well as with muscle inhibition^23,47, which may lead to a slow and painful course in physical therapy. The relative lack of progress in rehabilitation of the knee, as well as the sympathetically maintained pain itself, frequently produce anxiety and depression in these patients, which can lead to poor compliance and worsening stiffness. Increasing stiffness in the knee often limits the ability of a patient to walk, kneel, climb, sit, work, or participate in sports activities and leads to additional emotional stress and upset. As the depression worsens, a vicious cycle results. Unless early and appropriate measures are taken to break the cycle, both the patient and the treating physician will be faced with anger, frustration, and ultimately, an unsatisfactory outcome.

Although hand surgeons have long dealt with sympathetically maintained pain the upper extremity¹⁴, the syndrome has not been as well recognized or treated as frequently in the lower extremity^9,15,33,40. However, recent reports^{2,5,10,11,20,23,25} have helped to delineate sympathetically maintained pain in the lower extremity, and we now have a better understanding of the pathophysiology and treatment of the condition. The keystone of treatment for this type of stiff and painful knee is early recognition²⁷. Sympathetically maintained pain, patella infera, and arthrofibrosis may be interrelated, and all are best treated early in their course because they can progress quickly to the point where resolution becomes quite difficult¹⁴. Too often, early signs and symptoms of these processes are not recognized or are ignored, making treatment received later much more complicated^16,35. Early treatment is important because of the difficulty in managing more chronic syndromes and because irreversible changes are more likely to occur when the condition persists untreated. Alterations in collagen crimp patterns and crosslinks result in permanent shortening of the periarticular soft tissues¹⁷. Furthermore, alterations in patellar height and in the mechanics of the tibiofemoral joint can ultimately lead to the breakdown of the articular surface. The pain and dysfunction caused by this chondral degeneration can make sympathetically maintained pain even more difficult to treat and can lead to irreversible and painful conditions such as arthritis within the joint.

Successful management of a patient who has a stiff and painful knee requires an understanding of the basic mechanisms that cause sympathetically maintained pain, arthrofibrosis, and patella infera. This basic understanding can lead to early recognition of this difficult problem, and treatment can be initiated as soon as possible, creating the best chance of success.

*Printed with permission of The American Academy of Orthopaedic Surgeons. This article will appear in Instructional Course Lectures, Volume 46, The American Academy of Orthopaedic Surgeons. Rosemont, Illinois, March 1997.

†No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

‡Cincinnati Sportsmedicine and Orthopaedic Center, Deaconess Hospital, 311 Straight Street. Cincinnati. Ohio 45219.

§Department of Orthopedic Surgery, Sports Medicine Section, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, 1725 West Harrison Street, Suite 1063, Chicago, Illinois 60612.

¶MedSport, Department of Surgery, University of Michigan, P.O. Box 363, Ann Arbor Michigan 48106-0363.

‡Cincinnati Sportsmedicine and Orthopaedic Center, Deaconess Hospital, 311 Straight Street. Cincinnati. Ohio 45219.

§Department of Orthopedic Surgery, Sports Medicine Section, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, 1725 West Harrison Street, Suite 1063, Chicago, Illinois 60612.

¶MedSport, Department of Surgery, University of Michigan, P.O. Box 363, Ann Arbor Michigan 48106-0363.

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TABLE I EFFECTS OF SYMPATHETIC STIMULATION MEDIATED BY ALPHA AND BETA RECEPTORS

Alpha Receptor	Beta Receptor
Vasoconstriction (skin)	Vasodilation (muscle)
Pilomotor contraction	Bronchial relaxation
Cardiac acceleration	Cardiac acceleration
Intestinal relaxation

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TABLE I EFFECTS OF SYMPATHETIC STIMULATION MEDIATED BY ALPHA AND BETA RECEPTORS

Alpha Receptor	Beta Receptor
Vasoconstriction (skin)	Vasodilation (muscle)
Pilomotor contraction	Bronchial relaxation
Cardiac acceleration	Cardiac acceleration
Intestinal relaxation

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TABLE II PHARMACOLOGICAL TREATMENT FOR SYMPATHETICALLY MAINTAINED PAIN

Drug	Dose	Mechanism of Action	Use	Side Effects
Alpha blockade
Phenoxybenzamine (Dibenzyline; SmithKline Beecham, Philadelphia, Pennsylvania)	10 milligrams every night, may increase to 10 milligrams 3 times a day	Blocks peripheral alpha, receptors, decreases sympathetic tone	Causalgias	Hypotension
Prazosin (Minipress; Pfizer, Parsippany, New Jersey)				Hypotension, tachycardia, decreased sexual function, nasal congestion
Terazosin (Hytrin; Abbott Laboratories, North Chicago, Illinois)				May have fewer side effects than other alpha blockers
Clonidine	Pain relief can be obtained with use of Clonidine patches	Alpha2 agonist, blocks alpha1 transmission both peripherally and centrally		Hypotension
Antidepressants
Trazodone (Desyrel; Apothecon, Princeton, New Jersey)	50 milligrams 3 times a day	Blocks serotonin receptors, activates descending pain inhibitory fibers	Most chronic pain syndromes	Multiple side effects
Tricyclic antidepressants
Desipramine (Norpramin; Marion Merrell Dow, Kansas City, Missouri)	100 to 200 milligrams a day			Myocardial ischemia, urinary retention
Doxepin (Sinequan; Roerig Division, Pfizer, New York, N.Y.)	10 to 25 milligrams 3 times a day
Amitriptyline (Elavil; Stuart Pharmaceuticals, Wilmington, Delaware)	25 milligrams 3 times a day			Orthostatic hypotension
Calcium channel blockers
Nifedipine (Procardia; Pratt Pharmaceuticals, New York, N.Y.)	10 to 30 milligrams 3 times a day	Relaxes smooth muscle, increases peripheral blood flow, decreases discharges from ephaptic scars	Peripheral nerve injury, especially in patients who have decreased blood flow	Headaches, hypotension
Diltiazem (Caredizem; Marion Merrell Dow, Kansas City, Missouri)	30 milligrams 4 times a day, increased to 60 to 90 milligrams 4 times a day
Verapamil (Calan; G. D. Searle, Chicago, Illinois)
Nicardipine (Cardene; Syntex, Palo Alto, California)
Anticonvulsants
Carbamazepine (Tegretol; Basel, Summit, New Jersey)	100 milligrams by mouth twice a day, up to 800 milligrams a day	Suppresses pathological electrical discharges in central nervous system and in peripheral nervous system	Ephapses, burning pain, sharp discharges	Depression of central nervous system, drowsiness, multiple side effects
Clonazepam (Klonopin; Roche Laboratories, Nutley, New Jersey), tricyclic	0.5 milligram twice a day to 3 times a day, may be increased
Gabapentin (Neurontin, Parke-Davis, Morris Plains, New Jersey)
Valproic acid

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TABLE II PHARMACOLOGICAL TREATMENT FOR SYMPATHETICALLY MAINTAINED PAIN

Drug	Dose	Mechanism of Action	Use	Side Effects
Alpha blockade
Phenoxybenzamine (Dibenzyline; SmithKline Beecham, Philadelphia, Pennsylvania)	10 milligrams every night, may increase to 10 milligrams 3 times a day	Blocks peripheral alpha, receptors, decreases sympathetic tone	Causalgias	Hypotension
Prazosin (Minipress; Pfizer, Parsippany, New Jersey)				Hypotension, tachycardia, decreased sexual function, nasal congestion
Terazosin (Hytrin; Abbott Laboratories, North Chicago, Illinois)				May have fewer side effects than other alpha blockers
Clonidine	Pain relief can be obtained with use of Clonidine patches	Alpha2 agonist, blocks alpha1 transmission both peripherally and centrally		Hypotension
Antidepressants
Trazodone (Desyrel; Apothecon, Princeton, New Jersey)	50 milligrams 3 times a day	Blocks serotonin receptors, activates descending pain inhibitory fibers	Most chronic pain syndromes	Multiple side effects
Tricyclic antidepressants
Desipramine (Norpramin; Marion Merrell Dow, Kansas City, Missouri)	100 to 200 milligrams a day			Myocardial ischemia, urinary retention
Doxepin (Sinequan; Roerig Division, Pfizer, New York, N.Y.)	10 to 25 milligrams 3 times a day
Amitriptyline (Elavil; Stuart Pharmaceuticals, Wilmington, Delaware)	25 milligrams 3 times a day			Orthostatic hypotension
Calcium channel blockers
Nifedipine (Procardia; Pratt Pharmaceuticals, New York, N.Y.)	10 to 30 milligrams 3 times a day	Relaxes smooth muscle, increases peripheral blood flow, decreases discharges from ephaptic scars	Peripheral nerve injury, especially in patients who have decreased blood flow	Headaches, hypotension
Diltiazem (Caredizem; Marion Merrell Dow, Kansas City, Missouri)	30 milligrams 4 times a day, increased to 60 to 90 milligrams 4 times a day
Verapamil (Calan; G. D. Searle, Chicago, Illinois)
Nicardipine (Cardene; Syntex, Palo Alto, California)
Anticonvulsants
Carbamazepine (Tegretol; Basel, Summit, New Jersey)	100 milligrams by mouth twice a day, up to 800 milligrams a day	Suppresses pathological electrical discharges in central nervous system and in peripheral nervous system	Ephapses, burning pain, sharp discharges	Depression of central nervous system, drowsiness, multiple side effects
Clonazepam (Klonopin; Roche Laboratories, Nutley, New Jersey), tricyclic	0.5 milligram twice a day to 3 times a day, may be increased
Gabapentin (Neurontin, Parke-Davis, Morris Plains, New Jersey)
Valproic acid

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Fig. 1 A diagram showing the decision-making process in the diagnosis and treatment of sympathetically maintained pain.

Sympathetic Nervous System Dysfunction

Most clinicians recognize the full-blown syndrome of reflex sympathetic dystrophy, which is characterized by a stiff, swollen extremity and pain that is out of proportion to the underlying mechanical problems. Pain that is out of proportion to the inciting cause is the hallmark of the condition. The extremity usually shows changes in color, temperature (vasomotor changes), and sweating (sudomotor changes). Frequently, however, sympathetic dysfunction presents in a more subtle and limited way¹⁸. Only a localized area of the extremity may be painful, and there may be no changes in color or sweating. Unfortunately, even these milder forms of sympathetic dysfunction may be associated with substantial functional limitations. If not recognized, mild sympathetic dysfunction can progress to full-blown reflex sympathetic dystrophy. Recognition and treatment of sympathetic nervous system dysfunction in its earliest stages can prevent the pain and limited function from becoming worse.

Terminology

The terminology of sympathetic nervous system dysfunction has been confusing. Reflex sympathetic dystrophy, major and minor causalgia, reflex algodystrophy, mimo-causalgia (a causalgia-like syndrome without documented nerve injury³⁷), and many other terms have been used to describe different clinical manifestations of sympathetic nervous system dysfunction^23,36. The major reason for the many and often confusing terms is that the root cause of sympathetic nervous system dysfunction and its true pathophysiology have yet to be completely understood¹⁸. Recent work^{4-6,12,20,26,43,45,51} in this area has improved the understanding of sympathetic dysfunction and has led to simplified terminology.

Sympathetic nervous system dysfunction is often part of a pain dysfunction syndrome. A pain dysfunction syndrome is a group of symptoms that are manifested by pain that appears to be excessive and non-anatomical and does not seem to match the underlying physical findings³. The dysfunction may be physical (swelling, stiffness, atrophy, weakness, or the inability to function) or mental (the patient may be withdrawn or depressed).

The three primary components of a pain dysfunction syndrome are a local trigger—that is, a painful organic condition—such as patellofemoral pain, a fracture, or a nerve injury; psychological factors (a personality disorder or particular social circumstances, perhaps reinforced by underlying secondary gain); and systemic factors (a generalized condition that causes or exacerbates pain, such as a peripheral neuropathy or arteritis). These three primary components of the pain dysfunction syndrome are not related to sympathetic nervous system dysfunction. Therefore, they are known as sympathetically independent pain.

A secondary component of the pain dysfunction syndrome is sympathetic nervous system dysfunction. It is secondary because it is initiated by an injury of non-sympathetic tissues. Examples include the development of reflex sympathetic dystrophy after traumatic injury of a limb and the development of shoulder-hand syndrome after myocardial infarction. This pain is, by definition, relieved by sympathetic blockade. In 1986, Roberts termed this type of pain sympathetically maintained pain⁴². The terminology allows all painful sympathetic nervous system dysfunctions to be grouped under one heading, eliminating the need to describe these conditions by their confusing and often overlapping clinical signs and symptoms.

More recently, the International Association for the Study of Pain revised the taxonomy for disorders of the sympathetic system²⁴. These disorders are now referred to as a complex regional pain syndrome. A complex regional pain syndrome is present when regional pain and sensory changes occur after a noxious event. The pain is associated with other findings of a sympathetic disorder, such as changes in skin color and temperature and abnormal swelling and sudomotor activity. These changes are greater than would be expected to result from the initiating noxious event. Complex regional pain syndrome is further categorized into type I and type II. Type I describes an area of sympathetic dysfunction that does not follow the course of a peripheral nerve. After a noxious event, ongoing pain and hyperalgesia develop. At some time in the course of the syndrome, typical sympathetic nervous system dysfunction—that is, edema and sudomotor or surface blood-flow changes—is noted. Classic reflex sympathetic dystrophy fits into this category. Type-II complex regional pain syndrome has a similar constellation of clinical signs and symptoms; however, it is associated with a known nerve injury. The syndromes that were previously termed major and minor causalgia fit best into this category. Although it seems logical, this terminology is too new for us to judge its ultimate utility for describing the patterns of sympathetic nervous system dysfunction.

Sympathetic Nervous System

The sympathetic nervous system is the larger of the two divisions of the autonomic nervous system^19,22. Although the sympathetic system is relatively primitive, it has connections to the neocortex of the brain and its function may be modified by many higher autonomic centers (the hypothalamus, the thalamus, and even the cerebral cortex). Although there are some afferent (peripheral-to-central) fibers, the sympathetic nervous system is mostly an efferent (central-to-peripheral) system. The two main ganglionic trunks are the cervical and lumbar trunks. However, there are many other ganglia throughout the paraspinal area, which form complex interconnections within the sympathetic nervous system and between it and the brain. The complexity of this system makes it difficult to disable the sympathetic system completely in any one anatomical region.

Preganglionic fibers arise from the cell bodies in the gray matter of the spine. They exit the spinal cord in the ventral roots of the spinal nerves, and either they re-enter the spinal cord through the white rami communicans at the same or an adjacent level or they connect to a peripheral sympathetic ganglion. Postganglionic fibers may re-enter the corresponding spinal nerve through the gray rami communicans to innervate viscera or to travel with blood vessels. They also may move to a higher or lower level and may cross the mid-line at multiple points.

The sympathetic nervous system innervates many peripheral structures and affects many bodily functions (Table I). The easiest way to remember the potential of a stimulated sympathetic nervous system is to recall that it prepares one for "fight or flight." The sympathetic nervous system has both alpha and beta receptors. Either of these receptors can be excitatory or inhibitory at the end organ. When stimulated, an alpha receptor tends to cause skin vasoconstriction, pilomotor contraction, cardiac acceleration, and intestinal relaxation. Stimulation of a beta receptor causes muscle vasodilation, bronchial relaxation, and cardiac acceleration.

Pathophysiology

The confusion and complexity of the clinical terminology of sympathetic nervous system dysfunction are largely due to an incomplete understanding of its actions¹⁴. The following theories of the pathophysiology of these disorders have the most clinical and basic science support.

It has long been believed that sensitization of peripheral mechanoreceptors and nociceptors can be a cause of sympathetically maintained pain^6,43. The findings of recent studies^{12,13,27,28,45} suggest that there is a sympathetic-afferent coupling at sensory nerve endings, mediated through sensitive alpha adrenergic receptors. Norepinephrine that is released from sympathetic terminals, as a result of increased sympathetic tone, can stimulate the peripheral sensory nerves of the afferent spinothalamic tract, which transmit intense pain and temperature signals to the neocortex.

Another mechanism may involve the formation of artificial synapses (ephapses) after nerve injury²⁶. Ephapses can simply shunt impulses from efferent (sympathetic) to afferent (sensory) fibers.

Additionally, direct injury of a nerve may allow for an epileptic-type discharge of electrical energy in the area of the injured nerve⁵⁰. This may either directly stimulate sensory nerves or allow for excessive neurotransmitter release, which in turn can stimulate pain fibers.

Finally, deafferentation may affect sympathetic output⁵¹. Simply stated, deafferentation is a substantial decrease in afferent signals to the spinal cord and to other neurological centers. Constant and normal sensory input is thought to suppress sympathetic activity; this is known as the gate theory. When an extremity becomes painful, it is used less. In the case of sympathetically maintained pain, skin sensitivity causes the patient to minimize contact, which eventually results in decreased afferent activity. This decreased afferent activity limits the normal inhibition of the sympathetic system, allowing increased sympathetic discharge. Such a mechanism can explain the positive clinical results seen with massage and desensitization of a body part affected by sympathetically maintained pain.

Diagnosis

History

Sympathetically maintained pain is initiated by a noxious event. It may be surprising to those who do not treat this condition routinely that the inciting event may be a very small or even a trivial injury that normally would be expected to resolve quickly without any adverse sequelae³⁴. A simple ankle sprain, a minor injury of a branch of the saphenous nerve, or a mild sprain of a collateral ligament during knee arthroscopy can initiate a pain dysfunction syndrome. If a patient has an unusual amount of pain immediately postoperatively or post-injury and healing does not progress as expected, sympathetic dysfunction should be suspected.

Signs and Symptoms

Sympathetically maintained pain has a variable presentation⁴⁰. In the classic case, within the first six weeks or so after injury the sympathetic overreaction causes a swollen, immobile, and painful limb. The pain is in a non-anatomical distribution—that is, it does not follow the distribution of a single peripheral nerve, and it often is described as burning in nature. There is usually an increase in sweating, and often there are color changes (ranging from blue to dusky red) in the extremity. Frequently, there is allodynia, which is pain that is produced by a non-noxious stimulus such as the light touch of a bedsheet. There also may be hyperpathia, which is an overreaction to a painful stimulus. These factors help to explain why forcing joint motion during physical therapy is not productive. Late in the course of the disease, there are trophic changes: dystrophic, smooth, shiny skin; osteoporosis; fast-growing and brittle nails; hypertrichosis; and muscular and subcutaneous atrophy. Patients who have chronic sympathetically maintained pain may also have extra-articular swelling and joint contractures.

One of the earliest and most helpful signs of early sympathetic dysfunction is intolerance to cold²⁸. Frequently, patients tell the physical therapist that they cannot stand an ice pack or they cannot tolerate winter weather.

Pain that is located specifically in the distribution of the saphenous nerve may represent a saphenous neuralgia, which is really a forme fruste of sympathetically maintained pain⁴¹. This dysfunction previously was termed minor causalgia. With the increasing prevalence of meniscal repair, the saphenous nerve is at risk more frequently. Direct injury of this nerve during an operation can cause saphenous neuritis. This diagnosis can be made when a history of burning pain along the medial side of the knee is noted or when percussing the origin of the nerve at the adductor canal elicits a sensation of burning pain.

Diffuse pain and skin sensitivity about the joint after a major operation are also early signs of sympathetically maintained pain. Although the clinician who treats musculoskeletal conditions about the knee should be able to recognize the early signs of this disorder, it is helpful for other health-care providers to suspect and report signs as well. In the weeks between follow-up visits, early sympathetically maintained pain can develop and progress quickly into a severe and less treatable condition. Frequently, the patient does not progress as expected with physical therapy and may become intolerant of joint manipulation or of the application of wraps or braces. Therapists should refer such patients immediately to the physician for evaluation and treatment.

It should be remembered that sympathetically maintained pain follows a non-anatomical distribution. The pain may not involve an entire extremity or even a large part of the extremity. For example, a forty-two-year-old female mail carrier was first seen by us after she had missed almost six months of work. She had had an excision of a Morton neuroma, but a two-centimeter area of pain had developed postoperatively on the plantar aspect of the foot, in the area of the old incision. The neuroma appeared to have been adequately excised, but multiple attemps to treat the pain had been unsuccessful. When she was questioned, the patient reported that she had skin sensitivity and intolerance to cold in this discrete area of the foot. A series of lumbar sympathetic blocks were performed, and the pain completely resolved. Within ten days after the initiation of treatment, the patient had returned to work full time and she had had no recurrence of symptoms.

Diagnostic Studies

Technetium-99m bone-scanning is a very sensitive but not very specific diagnostic tool. Holden and Mackinnon reported that twenty-two of twenty-three patients who had reflex sympathetic dystrophy in the hands had a positive bone scan²¹. Because of its lack of specificity, we do not recommend bone-scanning for the diagnosis of reflex sympathetic dystrophy. Bone-scanning may be helpful, however, for finding an occult lesion in a patient who has sympathetically maintained pain that is resistant to treatment.

Sympathetic blockade is the best method for the diagnosis of sympathetically maintained pain⁴². If a complete sympathetic blockade does not relieve the pain, the disorder most likely is not sympathetically maintained pain. In our clinical experience, on occasion a patient with sympathetically maintained pain has had incomplete pain relief even with complete sympathetic blockade. The reason for this remains unclear.

There are a variety of ways to achieve a sympathetic blockade, the easiest of which is intravenous administration of an alpha blocker such as phentolamine^1,4. This creates a complete sympathetic blockade so the pain relief should correlate closely with the degree of sympathetically maintained pain. The disadvantage of this method is that the blockade is of short duration and, as a result, does not help in the treatment of the condition.

There are several methods for spinal sympathetic blockade³². To be effective, they must deliver the anesthetic agent to the appropriate area, as documented by an increase of 2 to 3 degrees Celsius in the skin temperature of the involved extremity. Simple visual-analog pain scales should be used to measure the amount of pain relief achieved with the blockade. Our experience in the management of several hundred patients has led us to believe that a decrease in pain of at least 50 per cent must be documented in order for the physician to be confident of a diagnosis of sympathetically maintained pain.

Differential spinal blockade is achieved with use of a simple spinal puncture. This commonly used technique depends on the principle that myelin slows the rate of penetration of an anesthetic agent. Because motor fibers are the most heavily myelinated, sensory fibers are less myelinated, and sympathetic fibers are the least, a low concentration of an anesthetic agent (0.25 per cent lidocaine), placed in the subarachnoid space, penetrates mainly unmyelinated sympathetic fibers. The advantage of this method is that it is a simple, commonly used way to provide a complete sympathetic blockade. Unfortunately, this method rarely achieves a purely sympathetic blockade. Most often, there is some blockade of the sensory system. Therefore, pain relief may be partially due to sensory blockade rather than entirely due to sympathetic blockade. This makes it difficult to establish a clear diagnosis of sympathetically maintained pain.

Epidural sympathetic blockade has virtually all of the same strengths and weaknesses as spinal blockade. However, it has one added strength—it may be administered continuously for several days.

Paravertebral blockade is the best method of spinal blockade for sympathetically maintained pain. With this method, a local anesthetic is delivered to the sympathetic chain in the paravertebral area. The advantage is that the anesthetic agent is delivered outside of the spinal column to the sympathetic ganglia, avoiding any blockade of the sensory or motor nerves. It may be done on an outpatient basis, and long-lasting anesthetic agents may be used. The disadvantage of this technique is that a skilled anesthesiologist is required to administer the anesthetic effectively.

Treatment

The treatment of sympathetically maintained pain of the lower extremity involves three separate areas: lumbar sympathetic blockade, through either blocks or operative interruption; pharmacological treatment for both sympathetic and non-sympathetic symptoms; and physical therapy (Fig. 1).

When sympathetically maintained pain is diagnosed in the early stages, repeated long-lasting paravertebral blocks can be an effective treatment³¹, as demonstrated in our patient who had postoperative pain in the foot. The results of paravertebral blocks should be monitored closely to assess their effect. The blocks may provide sympathetic pain relief for much longer than the duration of the pharmacological effect of the anesthetic agent. Our clinical experience indicates that the more complete and long-lasting the pain relief from a lumbar sympathetic block, the better the prognosis for recovery. Blocks may be used as frequently as every other day for two weeks to achieve a long-lasting effect.

Pharmacological Therapy

Several drugs are useful in the treatment of sympathetically maintained pain³⁸, although they cannot be expected to take the place of early diagnosis and appropriate treatment with sympathetic blockade. In fact, they are used more commonly to control the symptoms associated with the chronic stages of this condition (Table II).

Although not universally accepted as an effective treatment, orally administered corticosteroids may interrupt or reverse early sympathetically maintained pain^17,44. If used in the first week or two after injury, an orally administered steroid medication, tapered over three, four, or five days, can be effective in relieving symptoms. We have had good results after administering commercially available drugs such as Medrol Dosepak (methylprednisolone) to patients in our clinic who had early sympathetically maintained pain. Non-steroidal anti-inflammatory medications may have some benefit for patients who have sympathetically maintained pain¹¹, as these drugs are cyclooxgenase inhibitors and interfere with the production of prostanoids. They can, therefore, minimize inflammation facilitated by prostaglandins and decrease peripheral pain secondary to injury. They also may block spinal prostanoids, which facilitate transmission of substance P receptors and glutamate pain fiber in the spinal cord.

Some oral medications for sympathetically maintained pain are safe and can be administered relatively easily by the practicing orthopaedist. However, other medications can be more difficult and dangerous to use. Multiple side effects and drug interactions may occur, and these probably are best monitored by a physician who is experienced in the use of the medication.

The use of narcotics and benzodiazepines, such as Valium (diazepam), Librium (chlordiazepoxide), and Xanax (alprazolam), is not recommended for the treatment of sympathetically maintained pain. These medications tend to lead to drug dependence, depression, and increased pain¹⁴. Frequently, however, patients who have sympathetically maintained pain have already been managed with these drugs and, if they have become dependent on them, management is complicated. In order to prevent such abuse, it is best to insist early in the course of treatment that the patient obtain all drugs from one source. If physicians who previously managed a patient are informed that the patient is under the care of a new physician, the problem of multiple prescriptions for addictive drugs can be decreased.

Lumbar sympathectomy is used generally as a procedure of last resort^{7,39,46,48,49} if anesthetic sympathetic blockade has provided good short-term but not good long-term relief. Although many patients have good early relief with lumbar sympathectomy, the symptoms of sympathetically maintained pain tend to recur^39,48 and, after five years, many patients have a return to the pretreatment condition^8,22. Thus, lumbar sympathectomy may be most helpful for patients who have a limited life expectancy. Sympathectomy for multiple extremities is not tolerated well because of problems with thermal regulation and control of the bowel, the bladder, or ejaculation. For an effective lumbar sympathectomy, a complete ganglionectomy from at least the tenth thoracic vertebra to the fourth lumbar vertebra should be done.

One difficult area in the management of these patients is the differentiation of sympathetically independent pain from the sympathetically maintained pain. Painful stimuli not only initiate sympathetically maintained pain but also help to maintain it. It is important that the orthopaedist not miss the potentially painful lesion hidden in the morass of signs and symptoms of reflex sympathetic dystrophy. A work-up for potentially painful lesions should be complete in order to provide the best prognosis for the patient. A painful chronic infection, a neuroma, an undiagnosed meniscal tear or chondral lesion, and a myriad of other conditions can provide a painful somatic focus for recurrent flare-ups of sympathetically maintained pain, even with use of adequate repeated sympathetic blockade. If an operation is needed to correct a painful area, epidural anesthesia should be used and then maintained continuously for three to four days postoperatively to decrease the potential for a flare-up of the sympathetically maintained pain¹¹.

Physical Therapy anal Exercise

Physical therapy is an important part of the management of patients who have sympathetically maintained pain^13,29,30. Recovery from the muscle dysfunction, swelling, and joint stiffness requires appropriate exercise. Therapists must understand that a patient who has sympathetically maintained pain cannot be managed with normal postoperative care.

These patients have a pain response to normally non-painful stimuli (allodynia), such as light touch, and an excessive response to any stimulus that is painful (hyperpathia). These stimuli are encountered normally during physical therapy. When excessive pain is created, sympathetically maintained pain may worsen. The therapist must have the patient progress slowly with strengthening and range-of-motion exercises and not force the pace too vigorously. Intolerance to cold obviates the use of cold packs and, in fact, moist heat is more effective for reducing pain and stiffness. Possibly the most important element for successful rehabilitation is the avoidance of personality confrontations. These patients are frequently withdrawn, depressed, angry, and unwilling to cooperate with therapy because of the pain and dysfunction¹⁶. It has been our experience that when sympathetically maintained pain is treated successfully, the behavior of the patient may return to normal. Therefore, the personality defects should be assumed to be a part of the disease and not an integral part of the patient. The therapist must learn to ignore some of the unpleasant aspects of the personality of the patient that are created by this disease and focus patiently on muscle-strengthening and range-of-motion exercises.

In order to lessen pain during therapy, active and active-assisted range-of-motion exercises should be encouraged and passive-motion exercises should be discouraged. Transcutaneous electrical nerve stimulation may be helpful to control the pain. Swelling should be controlled with massage instead of ice. It is important for the therapist to listen to the patient, who knows what is working and what is not. Frequently, exercises that are appropriate for a patient who has sympathetically maintained pain differ from those of the typical physical therapy routines.

Overview

Sympathetically maintained pain may affect the lower extremity more commonly than is currently recognized. When a patient is having unusual trouble with pain or stiffness in relation to the inciting injury, a diagnosis of sympathetically maintained pain should be considered. Because this condition frequently does not manifest all of its possible symptoms, the clinician should be aware that other findings such as intolerance to cold or allodynia may be the only clinical signs of sympathetically maintained pain. The key to successful management is early diagnosis and treatment. Lumbar sympathetic blockade can both confirm a diagnosis of sympathetically maintained pain and provide an appropriate early treatment. Many other medications can be useful for treating the symptoms. The help of a practitioner who is experienced in the use of multiple-drug therapy may be necessary. The patient who has sympathetically maintained pain presents a true clinical challenge. The patience, concern, and skill of the surgeon, anesthesiologist, physical therapist, and other health-care professionals, working as a team, are necessary for a successful outcome.

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AbuRahma, A. F.; Robinson, P. A.; Powell, M.; Bastug, D.; and |and |Boland, J. P.: Sympathectomy for reflex sympathetic dystrophy: factors affecting outcome. Ann. Vasc. Surg.,8: 372-379, 1994.8372 1994 [PubMed][CrossRef]

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Fig. 1 A diagram showing the decision-making process in the diagnosis and treatment of sympathetically maintained pain.

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TABLE I EFFECTS OF SYMPATHETIC STIMULATION MEDIATED BY ALPHA AND BETA RECEPTORS

Alpha Receptor	Beta Receptor
Vasoconstriction (skin)	Vasodilation (muscle)
Pilomotor contraction	Bronchial relaxation
Cardiac acceleration	Cardiac acceleration
Intestinal relaxation

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TABLE I EFFECTS OF SYMPATHETIC STIMULATION MEDIATED BY ALPHA AND BETA RECEPTORS

Alpha Receptor	Beta Receptor
Vasoconstriction (skin)	Vasodilation (muscle)
Pilomotor contraction	Bronchial relaxation
Cardiac acceleration	Cardiac acceleration
Intestinal relaxation

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TABLE II PHARMACOLOGICAL TREATMENT FOR SYMPATHETICALLY MAINTAINED PAIN

Drug	Dose	Mechanism of Action	Use	Side Effects
Alpha blockade
Phenoxybenzamine (Dibenzyline; SmithKline Beecham, Philadelphia, Pennsylvania)	10 milligrams every night, may increase to 10 milligrams 3 times a day	Blocks peripheral alpha, receptors, decreases sympathetic tone	Causalgias	Hypotension
Prazosin (Minipress; Pfizer, Parsippany, New Jersey)				Hypotension, tachycardia, decreased sexual function, nasal congestion
Terazosin (Hytrin; Abbott Laboratories, North Chicago, Illinois)				May have fewer side effects than other alpha blockers
Clonidine	Pain relief can be obtained with use of Clonidine patches	Alpha2 agonist, blocks alpha1 transmission both peripherally and centrally		Hypotension
Antidepressants
Trazodone (Desyrel; Apothecon, Princeton, New Jersey)	50 milligrams 3 times a day	Blocks serotonin receptors, activates descending pain inhibitory fibers	Most chronic pain syndromes	Multiple side effects
Tricyclic antidepressants
Desipramine (Norpramin; Marion Merrell Dow, Kansas City, Missouri)	100 to 200 milligrams a day			Myocardial ischemia, urinary retention
Doxepin (Sinequan; Roerig Division, Pfizer, New York, N.Y.)	10 to 25 milligrams 3 times a day
Amitriptyline (Elavil; Stuart Pharmaceuticals, Wilmington, Delaware)	25 milligrams 3 times a day			Orthostatic hypotension
Calcium channel blockers
Nifedipine (Procardia; Pratt Pharmaceuticals, New York, N.Y.)	10 to 30 milligrams 3 times a day	Relaxes smooth muscle, increases peripheral blood flow, decreases discharges from ephaptic scars	Peripheral nerve injury, especially in patients who have decreased blood flow	Headaches, hypotension
Diltiazem (Caredizem; Marion Merrell Dow, Kansas City, Missouri)	30 milligrams 4 times a day, increased to 60 to 90 milligrams 4 times a day
Verapamil (Calan; G. D. Searle, Chicago, Illinois)
Nicardipine (Cardene; Syntex, Palo Alto, California)
Anticonvulsants
Carbamazepine (Tegretol; Basel, Summit, New Jersey)	100 milligrams by mouth twice a day, up to 800 milligrams a day	Suppresses pathological electrical discharges in central nervous system and in peripheral nervous system	Ephapses, burning pain, sharp discharges	Depression of central nervous system, drowsiness, multiple side effects
Clonazepam (Klonopin; Roche Laboratories, Nutley, New Jersey), tricyclic	0.5 milligram twice a day to 3 times a day, may be increased
Gabapentin (Neurontin, Parke-Davis, Morris Plains, New Jersey)
Valproic acid

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TABLE II PHARMACOLOGICAL TREATMENT FOR SYMPATHETICALLY MAINTAINED PAIN

Drug	Dose	Mechanism of Action	Use	Side Effects
Alpha blockade
Phenoxybenzamine (Dibenzyline; SmithKline Beecham, Philadelphia, Pennsylvania)	10 milligrams every night, may increase to 10 milligrams 3 times a day	Blocks peripheral alpha, receptors, decreases sympathetic tone	Causalgias	Hypotension
Prazosin (Minipress; Pfizer, Parsippany, New Jersey)				Hypotension, tachycardia, decreased sexual function, nasal congestion
Terazosin (Hytrin; Abbott Laboratories, North Chicago, Illinois)				May have fewer side effects than other alpha blockers
Clonidine	Pain relief can be obtained with use of Clonidine patches	Alpha2 agonist, blocks alpha1 transmission both peripherally and centrally		Hypotension
Antidepressants
Trazodone (Desyrel; Apothecon, Princeton, New Jersey)	50 milligrams 3 times a day	Blocks serotonin receptors, activates descending pain inhibitory fibers	Most chronic pain syndromes	Multiple side effects
Tricyclic antidepressants
Desipramine (Norpramin; Marion Merrell Dow, Kansas City, Missouri)	100 to 200 milligrams a day			Myocardial ischemia, urinary retention
Doxepin (Sinequan; Roerig Division, Pfizer, New York, N.Y.)	10 to 25 milligrams 3 times a day
Amitriptyline (Elavil; Stuart Pharmaceuticals, Wilmington, Delaware)	25 milligrams 3 times a day			Orthostatic hypotension
Calcium channel blockers
Nifedipine (Procardia; Pratt Pharmaceuticals, New York, N.Y.)	10 to 30 milligrams 3 times a day	Relaxes smooth muscle, increases peripheral blood flow, decreases discharges from ephaptic scars	Peripheral nerve injury, especially in patients who have decreased blood flow	Headaches, hypotension
Diltiazem (Caredizem; Marion Merrell Dow, Kansas City, Missouri)	30 milligrams 4 times a day, increased to 60 to 90 milligrams 4 times a day
Verapamil (Calan; G. D. Searle, Chicago, Illinois)
Nicardipine (Cardene; Syntex, Palo Alto, California)
Anticonvulsants
Carbamazepine (Tegretol; Basel, Summit, New Jersey)	100 milligrams by mouth twice a day, up to 800 milligrams a day	Suppresses pathological electrical discharges in central nervous system and in peripheral nervous system	Ephapses, burning pain, sharp discharges	Depression of central nervous system, drowsiness, multiple side effects
Clonazepam (Klonopin; Roche Laboratories, Nutley, New Jersey), tricyclic	0.5 milligram twice a day to 3 times a day, may be increased
Gabapentin (Neurontin, Parke-Davis, Morris Plains, New Jersey)
Valproic acid