Limb pain may affect all or part of an extremity (for joint pain, see Pain in and Around a Single Joint Pain in and Around a Single Joint Patients may report "joint" pain regardless of whether the cause involves the joint itself or surrounding (periarticular) structures such as tendons and bursae; in both cases, pain in or around... read more and Pain in Multiple Joints Pain in Multiple Joints Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more ). Pain may be constant or intermittent, and unrelated to motion or precipitated by it. Accompanying symptoms and signs often suggest a source.
Etiology of Limb Pain
The most common causes of pain in a limb are also readily apparent by history.
Musculoskeletal injuries and overuse
This discussion covers extra-articular limb pain unrelated to injury or strain. Pain that is in only one joint Pain in and Around a Single Joint Patients may report "joint" pain regardless of whether the cause involves the joint itself or surrounding (periarticular) structures such as tendons and bursae; in both cases, pain in or around... read more or in multiple joints Pain in Multiple Joints Joints may simply be painful (arthralgia) or also inflamed (arthritis). Joint inflammation is usually accompanied by warmth, swelling (due to intra-articular fluid, or effusion), and uncommonly... read more is discussed elsewhere.
There are many causes (see table Some Causes of Nontraumatic Limb Pain Some Causes of Nontraumatic Limb Pain Limb pain may affect all or part of an extremity (for joint pain, see Pain in and Around a Single Joint and Pain in Multiple Joints). Pain may be constant or intermittent, and unrelated to motion... read more 
) but the most common are the following:
Radiculopathy
Uncommon but serious causes that require immediate diagnosis and treatment include
Deep soft-tissue infection
Acute coronary ischemia Overview of Acute Coronary Syndromes (ACS) Acute coronary syndromes result from acute obstruction of a coronary artery. Consequences depend on degree and location of obstruction and range from unstable angina to non–ST-segment elevation... read more (manifesting with only referred arm pain)
Evaluation of Limb Pain
It is important to exclude acute arterial occlusion Acute Peripheral Arterial Occlusion Peripheral arteries may be acutely occluded by a thrombus, an embolus, aortic dissection, or acute compartment syndrome. Acute peripheral arterial occlusion may result from: Rupture and thrombosis... read more 
.
History
History of present illness should address the duration, intensity, location, quality, and temporal pattern of pain. Recent injury, excessive and/or unusual use, and factors that worsen pain (eg, limb movement, walking) and relieve pain (eg, rest, certain positions) should be noted. Any associated neurologic symptoms (eg, numbness, paresthesias) should be identified.
Review of systems should seek symptoms of possible causes, including back or neck pain (radiculopathy), fever (infections such as osteomyelitis Osteomyelitis Osteomyelitis is inflammation and destruction of bone caused by bacteria, mycobacteria, or fungi. Common symptoms are localized bone pain and tenderness with constitutional symptoms (in acute... read more 
, cellulitis Cellulitis Cellulitis is acute bacterial infection of the skin and subcutaneous tissue most often caused by streptococci or staphylococci. Symptoms and signs are pain, warmth, rapidly spreading erythema... read more 
, or deep soft-tissue infection), dyspnea (DVT Deep Venous Thrombosis (DVT) Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more 
with pulmonary embolism Pulmonary Embolism (PE) Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more 
, myocardial infarction Acute Myocardial Infarction (MI) Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery. Symptoms include chest discomfort with or without dyspnea, nausea, and diaphoresis.... read more 
), and chest pain or sweating (myocardial ischemia).
Past medical history should identify known risk factors, including cancer (metastatic bone tumors Metastatic Bone Tumors Any cancer may metastasize to bone, but metastases from carcinomas are the most common, particularly those arising in the following areas: Breast Lung Prostate Kidney read more 
); immunocompromising disorders or drugs (infections); hypercoagulable states (DVT Deep Venous Thrombosis (DVT) Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more ); diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more ; peripheral vascular disease, hypercholesterolemia, and/or hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more 
(acute or chronic ischemia); osteoarthritis Osteoarthritis (OA) Osteoarthritis is a chronic arthropathy characterized by disruption and potential loss of joint cartilage along with other joint changes, including bone hypertrophy (osteophyte formation). Symptoms... read more 
or rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily involves the joints. RA causes damage mediated by cytokines, chemokines, and metalloproteases. Characteristically... read more 
(radiculopathy); and prior injury (complex regional pain syndrome Complex Regional Pain Syndrome (CRPS) Complex regional pain syndrome (CRPS) is chronic neuropathic pain that follows soft-tissue or bone injury (type I) or nerve injury (type II) and lasts longer and is more severe than expected... read more ). Family and social history should address family history of early vascular disease and cigarette smoking (limb or myocardial ischemia) and illicit use of parenteral drugs (infections).
Physical examination
Vital signs are reviewed for fever (suggesting infection) and tachycardia and/or tachypnea (compatible with DVT with pulmonary embolism, myocardial infarction, and infection with sepsis).
The painful limb is inspected for color, edema, and any skin or hair changes, and palpated for pulses, temperature, tenderness, and crepitation (a subtle crackling sensation indicating soft-tissue gas). Strength, sensation and deep tendon reflexes are compared between affected and unaffected sides. Systolic blood pressure (BP) is measured in the ankle of the affected extremity and compared with systolic BP of an arm; the ratio of the two is the ankle-brachial index.
Red flags
Sudden, severe pain
Signs of acute limb ischemia (eg, coolness, pallor, pulse deficits, delayed capillary refill)
Dyspnea, chest pain, and/or sweating
Signs of systemic toxicity (eg, delirium, tachycardia, shock, pallor)
Crepitation, tenseness, foul discharge, bullae, necrosis
Risk factors for deep venous thrombosis
Neurologic deficits
Interpretation of findings
It can be helpful to categorize patients by acuity of symptoms and then further narrow the differential diagnosis based on presence or absence of findings of
Ischemia
Inflammation
Neurologic abnormalities
Sudden, severe pain suggests acute ischemia or acute radiculopathy (eg, due to sudden disc herniation). Acute ischemia causes generalized limb pain and manifests with weak or absent pulse, delayed capillary refill (≥ 2 seconds or, with unilateral symptoms, longer than the opposite side), coolness, and pallor; ankle-brachial index is typically < 0.3. Such vascular signs are absent with radiculopathy, in which pain instead follows a dermatomal distribution and is often accompanied by back or neck pain and diminished deep tendon reflexes. However, in both cases, weakness may be present. Acute ischemia due to massive venous thrombosis (phlegmasia cerulea dolens) usually causes edema, which is not present in ischemia due to arterial occlusion.
In subacute pain (ie, of 1 to a few days' duration), redness and tenderness, often accompanied by swelling, and/or warmth, suggest an inflammatory cause. If these findings are focal or circumscribed, cellulitis is likely. Generalized, circumferential swelling is more suggestive of DVT or, much less commonly, deep tissue infection. Patients with a deep tissue infection typically appear quite ill and may have blisters, necrosis, or crepitation. Findings in DVT vary widely; swelling and warmth may be minimal or absent. Neurologic findings of weakness, paresthesias, and/or sensory abnormalities suggest radiculopathy or plexopathy. If neurologic findings follow a dermatomal pattern, radiculopathy is more likely.
Chronic pain can be difficult to diagnose. If neurologic findings are present, causes include radiculopathy (dermatomal distribution), plexopathy (plexus distribution), neuropathy (stocking-glove distribution), and complex regional pain syndrome (variable distribution). Complex regional pain syndrome should be suspected if vasomotor changes (eg, pallor, mottling, coolness) are present, particularly in those with previous injury to the affected extremity. Myofascial pain syndrome causes no neurovascular abnormalities and classically manifests with a palpably tense band of muscle in the area of pain, and pain may be reproduced by pressure on a trigger point near but not overlying the area of pain. In patients with essentially no clinical findings, cancer and osteomyelitis should be considered, particularly in those with risk factors.
Intermittent pain occurring consistently with a given degree of exertion (eg, whenever walking > 3 blocks) and relieved with a few minutes of rest suggests peripheral arterial disease Peripheral Arterial Disease Peripheral arterial disease (PAD) is atherosclerosis of the extremities (virtually always lower) causing ischemia. Mild PAD may be asymptomatic or cause intermittent claudication; severe PAD... read more 
. Such patients typically have an ankle-brachial blood pressure (BP) index of ≤ 0.9; an index ≤ 0.4 indicates severe disease. However, arterial stiffness can produce falsely negative ankle-brachial index values. Because the toe arteries are less susceptible to stiffening, the toe-brachial BP index can be measured instead in patients with suspected peripheral arterial disease and in whom the ankle arteries are likely not compressible (eg, with advanced diabetes or aging). Patients with exertional symptoms and normal or borderline ankle-brachial BP index (> 0.9 but < 1.40) should have repeat ankle-brachial BP index measurement after exercise on a treadmill. Patients with peripheral arterial disease may have chronic skin changes (eg, atrophy, hair loss, pale color, ulceration).
Testing
Cellulitis, myofascial pain, painful polyneuropathy, and complex regional pain syndrome can often be diagnosed clinically. Testing (see table Some Causes of Nontraumatic Limb Pain Some Causes of Nontraumatic Limb Pain Limb pain may affect all or part of an extremity (for joint pain, see Pain in and Around a Single Joint and Pain in Multiple Joints). Pain may be constant or intermittent, and unrelated to motion... read more ) is usually necessary for other suspected causes of pain.
Treatment of Limb Pain
Primary treatment is directed at the cause. Analgesics can help relieve pain.
Key Points
Acute limb ischemia should be considered in patients with sudden, severe pain.
Presence or absence of findings of ischemia, inflammation, and neurologic abnormalities plus the acuity of onset help narrow the differential diagnosis.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
nicotine |
COMMIT, NICORETTE, NICOTROL |
albuterol |
PROVENTIL-HFA, VENTOLIN-HFA |
dobutamine |
No US brand name |
epinephrine |
ADRENALIN |
isoproterenol |
ISUPREL |
norepinephrine |
LEVOPHED |
theophylline |
ELIXOPHYLLIN |
terazosin |
No US brand name |
doxazosin |
CARDURA |
phenoxybenzamine |
DIBENZYLINE |
clonidine |
CATAPRES |
methyldopa |
No US brand name |
levodopa |
INBRIJA |
furosemide |
LASIX |
quinidine |
No US brand name |
vincristine |
MARQIBO KIT |
minoxidil |
ROGAINE |
estrogens |
PREMARIN |
fludrocortisone |
No US brand name |
diltiazem |
CARDIZEM, CARTIA XT |
digoxin |
LANOXIN |
amiodarone |
NEXTERONE |
midodrine |
ORVATEN |
indomethacin |
INDOCIN |
droxidopa |
NORTHERA |
propranolol |
INDERAL |
pyridostigmine |
MESTINON |
octreotide |
SANDOSTATIN |
