Access to the PPM Journal and newsletters is FREE for clinicians.
12 Articles in Volume 17, Issue #2
Chronic Pain and Bipolar Disorders: A Bridge Between Depression and Schizophrenia Spectrum
Differences in Pain Management of Peripheral Vascular Disease and Peripheral Artery Disease
Duloxetine and Liver Function Tests
How Well Do You Know Your Patient?
Insurers End Policies Requiring Prior Authorization for Opioid Use Disorder
Letters to the Editor: Initiating Hormones
Managing Opioid Use Disorders and Chronic Pain
Opportunities and Challenges of Pain Management: The Family Physician’s Perspective
Pathways to Recovery From Co-Occurring Chronic Pain and Addiction
Strategies for Weaning Opioids in Patients With an Opioid Use Disorder and Chronic Pain
Treating Multiple Pain Syndromes: A Case Series Using a Functional Medicine Model
Treatment of Chronic Exhaustion and Chronic Fatigue Syndrome

Differences in Pain Management of Peripheral Vascular Disease and Peripheral Artery Disease

When diagnosing peripheral artery disease, a common condition in people with diabetes, leg pain may arise from intermittent claudication and ischemia.

Peripheral vascular disease (PVD) is a term that applies to a variety of vessel-occlusive conditions, which may develop within either the arterial or venous systems. When PVD develops, the condition is often seen concurrently with coronary artery disease, diabetes, and hypertension.1 However, PVD may arise from vasculitides (inflammation of multiple vasculitis) and other venous problems such as chronic venous insufficiency.

According to the American Heart Association, PVD is divided into 2 categories: organic and functional.2 Organic PVD is related to vessel blockage arising from inflammation, fatty infiltrates, or tissue damage. Functional PVD, which is not connected to structural problems within blood-vessel walls, arises from vessel compression or spasm. While PVD and peripheral artery disease (PAD) typically are used interchangeably, PAD has been classified as a subset of organic PVD.3

Diagnosing leg pain as peripheral artery disease in people with diabetes.

PAD is among the most common cardiovascular diseases, affecting more than 12 million men and women.4 As many as 1 in every 20 adults over the age of 50 years, and 1 in every 4 adults over the age of 70 years are likely to develop PAD. In addition to age, the risk of developing this condition rises in individuals who have diabetes, a history of current or past smoking, and the presence of other cardiovascular risk factors such as hypertension.

Development of PAD involves any artery except those supplying the heart directly. The term PAD broadly covers the vascular diseases, in which thromboembolic and atherosclerosis pathophysiologic processes occur, introducing changes to the normal function and structure of the aorta and its visceral arterial branches. Usually, PAD is indicative of a condition involving the main artery that supplies blood to the legs. Lower extremity PAD, or PVD, typically is caused by atherosclerosis due to obstruction of the internal lining of a blood vessel and leads to poor skin, limb, and muscle perfusion.5

PVD, or arteriosclerosis obliterans, is a condition manifesting from insufficient tissue perfusion that results in hardening of the arteries. When muscles fail to get sufficient nutrients and oxygen during exercise, a cramping discomfort referred to as claudication is likely to occur. This symptom may be referred to as intermittent claudication because the pain has a tendency to dissipate with rest. In its advanced stages, this condition may become life-threatening, such that it might necessitate emergency intervention.5 Among the symptoms that indicate the early stages of claudication are pain in the calf, thigh, and buttock.6 With these symptoms, ascertaining the onset of the disorder requires an ankle-arm index, imaging, or segmental blood procedures.6 The choice of procedure is dependent upon the symptoms evident.

Symptomatic PAD occurs in response to an imbalance in the nutrients available to skeletal muscles and an inability to meet the physiological demand for these substances. The normal nutrient balance is naturally lost in PAD once arterial stenosis occurs, leading to insufficient blood flow to the skeletal muscle. When the vessel lumen narrows, there is a pressure gradient that grows across the stenotic lesion, which is proportional to blood viscosity as well as the extent of stenosis. A stenosis that does not result in pressure gradient at rest, might cause a gradient when another stenosis develops during exercise. In a healthy person, a rise in cardiac output, as well as a decrease in regular vascular resistance is adequate to boost blood flow to skeletal muscles, which will recompensate for the increased demand. Nevertheless, an arterial stenosis, that is not apparent at rest, might become evident during exercise if augmented peripheral muscle demands do not match the augmented flow.  

It is easy to see how muscle discomfort, fatigue, and pain manifest as the primary symptoms of PAD. Having this condition will most likely result in blocked arteries. Usually, PAD is an indication that there are atherosclerotic changes elsewhere in the body, which may include the heart, brain, or kidneys. Patients with this condition have an increased risk of mortality, stroke, and myocardial infarction.7 For clinicians, the challenge in making a diagnosis is that most individuals may be asymptomatic.

Making a Differential Diagnosis of Leg Pain

The patient who presents with complaints of pain in the calves after exercising is likely to have advanced PAD. The calf muscles are usually the most common site for claudication, although it can also take place in the buttock or thigh muscles if there is sufficient proximal blockage. During exercise, a buildup of lactic acid may occur because of anaerobic respiration in which the oxygen demand is not fulfilled because of arterial blockage, initiating pain. Normally, this pain would dissipate in less than 5 minutes once the patient discontinues the exercise and returns to rest, only to return again when the patient begins to move again.

Making a differential diagnosis of PAD would require evaluating the leg for both musculoskeletal and neurological factors. The best way to achieve this is by making use of standardized monofilaments to assess light touch sensation.8 It is common for symptoms to be confused with those of spinal stenosis, but this pain most commonly radiates down both legs rather than just affecting 1 leg. In the case of spinal-cord claudication, the pain is localized to a specific muscle group, and upon walking there tends to be a history of recurring numbness, weakness, or heaviness instead of pain.6 In addition, clinicians will want to rule out other conditions with similar complaints of pain, including peripheral neuropathy, systemic vasculitides, and restless leg syndrome.  

Screening based on an ankle-brachial index that is measured by Doppler ultrasonography has proven highly useful in identifying patients who had previously unrecognized PAD since these patients might not have the classic claudication symptoms.9 The ankle-brachial index is a simple test for detecting the presence of PAD by comparing the blood pressure in the ankle to the blood pressure in the arm. This diagnostic test offers a picture of the adequacies of blood flow to the limbs, whereas the benefit of a Doppler ultrasound is gaining an evaluation of the blood flow within the main veins and arteries in the limbs. Another diagnostic procedure, the treadmill test, may be used to assess the severity of symptoms as well as the level of exercise required to elicit physical symptoms, such as pain.10

Some experts have argued that a comprehensive physical examination with particular attention to the auscultation for arterial bruits, pulses, and examination for postural color changes may be almost as helpful as an ankle-brachial index with Doppler ultrasonography.

Primary care physicians such as family physicians and internists may feel comfortable treating patients with mild PAD. However, in cases of more advanced PAD, clinicians are encouraged to consider referring these patients to a vascular expert for assessment and treatment. These same patients may also have had or are in need of consultation with a cardiologist since cardiovascular disease often arises in those with PAD.11

Intermittent Claudication Signals Presence of PVD

Intermittent claudication (IC) is defined as an ache in the legs brought about by exercise and reduced with rest. This is 1 of the most commonly presented signs of PAD, affecting between 1.7% - 7.1% of patients over the age of 55 years.6 IC is a gentle symptom, with just 2% of patients requiring amputation. It is also a powerful marker of growing cardiovascular risk. This means that 20% - 30% of IC patients may not live more than 5 years after an IC diagnosis because of the heightened risk for cardiovascular events.

There are 3 main clinical features typically found in people with IC:

  • Any discomfort totally resolves within 2 to 5 minutes after exercising has been stopped unless a person has walked to a level of severe leg pain
  • The ache is reproducible with the same intensity of exercise daily
  • When walking (or exercise) is resumed, the discomfort tends to reappear after walking about the same distance

When arteries are damaged by atherosclerosis at a particular site, there is a possibility that there is also damage in other locations, such as the brain or heart. If a blood clot is formed in a damaged artery in either of these regions, a narrowed, diseased artery may suddenly close off entirely, causing a stroke or heart attack.  This common occurrence in patients with PAD offers confirmation as to their higher risk for both these conditions. In actual fact, the possibility of dying from a heart attack is much higher in people with PAD compared to those without this condition.8

A significant consideration in the pathophysiology of PAD is the crucial functional impairment that arises in peripheral arteries, in which there is diminished vasomotor function and increased vasoconstriction.12 Increased leukocyte adhesiveness, platelet aggregation, tissue and vascular inflammation, and adverse muscle tissue elements have been noted in those with PAD and likely contribute significantly to the genesis, symptomatology, and progression of the disease.

In the case of atherosclerosis, various sections of an arterial tree are affected to different degrees. This phenomenon is most likely caused by an intricate interplay of local environmental and genetic vascular conditions.13

Certainly, inquiring about pain is an essential factor in assessing and treating PAD, given its role as the main force for expressing physical dysfunction. According to Andrew Taylor Still, father of osteopathic medicine, pain is a useful warning signal as well as a sign that some part(s) of the human machine is not working in union with nature.

Particular osteopathic concepts that are related to the biology of pain, central to which is a basic osteopathic belief that movement is always necessary to human life and to the expression of spirit and mind.  Everything that a person does, whether playing, running, talking or seeing, requires movement. The neuro-musculoskeletal system is thus viewed as the basic machinery of life. The other systems, encompassing all organs, exist to maintain and serve the basic machine by maintaining the appropriate supply of nutrients and disposal of waste to achieve the balance of homeostasis.

Therapeutic Strategies to Manage PAD

The treatment of PAD focuses on risk-factor modification, limb viability, cardiovascular event reduction, and symptom improvement. Patients who present with a more advanced level of disease, such as critical limb ischemia (CLI), acute limb ischemia (ALI), and severely limiting symptoms of PAD, require revascularization.

Prior to making any treatment decisions, however, an accurate diagnosis should be confirmed with a detailed history and noninvasive and physical studies (duplex ultrasound and ankle-brachial index). After obtaining the suitable angiographic images, selecting the right vascular access enhances a successful process. Most peripheral vascular interventions may be performed from diverse access sites, such as brachial artery or common femoral artery.14 However, certain interventions require specific access points to accomplish a successful result; among these are angioplasty, which is usually considered to be effective in managing localized blockages. The characteristic of the angioplasty intervention—that is, its minimal invasiveness as compared to open surgery—makes it access-point specific. Proficiency and knowledge of the different access sites require the most considerable skills in peripheral vascular intervention.


With rapid advances in endovascular revascularization expertise and technology, many patients with PAD are well managed using this therapeutic approach.15 Since patients with PAD face an increased likelihood of experiencing cardiovascular events, secondary management is mandatory to improve their long-term prognosis. Even as there has been slight progress in the medication therapy of PAD, exercise and risk factor minimization are necessary to keep the disease progression under control in over 2/3 of patients. When revascularization is required, doctors have made efforts to develop ways to open obstructed arteries with balloons and to bypass obstructions with grafts.  

Charles Dotter first described angioplasty for the treatment of PVD in 1964. However, this application has evolved considerably. The application of angioplasty has proven not only to be durable but effective, paving the way for a technological revolution that has led to the use of percutaneous catheter techniques in more clinical situations. However, even as peripheral angioplasty and coronary angioplastyJess procedures are similar, there are considerable differences in the interventional treatments and tools used to manage each of these conditions.

The success of this intervention, as with most surgical procedures, will be influenced by the physician’s level of training, years of experience, the technique to be employed, and the type of lesion to be treated. Before undertaking an angioplasty, an arteriogram is performed to determine the location of any blockages. Then, a catheter is threaded through the artery until the blockage is reached. The final step is to inflate a tiny balloon, which compresses the plaque, opening the artery and restoring blood flow. Success rates vary from up to 90% improvement in iliac arteries to 65% in the popliteal and femoral arteries.16 However, almost 1/3 of such blockages typically recur within 5 years.

A Role for Medications

Generally, medications have been only marginally effective in reducing symptoms of PAD. The practice of prescribing low-dose aspirin therapy of between 81 and 325 mg daily is important to lower the risk of stroke and heart attack in patients who have atherosclerosis. Patients with CLI warrant comprehensive management, encompassing multidisciplinary care that involves rehabilitation, optimal revascularization, and strategies for pain relief, pressure relief, wound care, management of infection, and modification of atherosclerotic risk factors.

In addition to aspirin therapy, there are a few drugs that may be useful in managing a patient with PAD. Pentoxifylline causes red blood cells to become more flexible.15 In theory, this medication would enable blood to slip past arterial blockages. However, in practical terms, pentoxifylline is more likely to delay the onset of claudication, permitting patients to walk slightly further before requiring a rest; essentially, it postpones symptoms. As such, this medication offers slightly better outcomes.15 Verapamil is a calcium-channel blocker used widely to treat hypertension in patients who have intermittent claudication.

Antiplatelet agents, such as aspirin or clopidogrel, are indicated in patients to enhance event-free survival, even though these drugs do not provide symptom relief. Nevertheless, following revascularization, antiplatelet agents enhance stent or graft patency rates. Antiplatelet therapy must be started preoperatively and carried on as adjuvant pharmacotherapy following a surgical or an endovascular procedure.17 Unless contraindicated, this therapy would have to be continued indefinitely.

Among the alternative therapies, garlic has also been reported to help, though improvements are very modest and data are sparse.18 A variety of modalities from traditional Chinese medicine may be beneficial in managing PAD, including acupuncture, Qi Gong, and Tai Chi.19 One study was conducted to examine lower-extremity perfusion following needle stimulation for 20 minutes, with positive results.19

Osteopathic Manipulative Therapy  

The use of osteopathic manipulative therapy (OMT) aims to address the cause(s) of pain and related symptoms, an approach originated by Andrew Taylor Still. OMT remains true to its holistic perspective in respecting the unity and interdependence of the organ systems in an effort to prevent, diagnose, and treat PAD. While the focus of OMT may be directed primarily to the musculoskeletal system, psychological, physical, emotional, and social aspects of the patient’s condition are also considered in devising an individualized care plan.20 Manual techniques may be introduced to impact bone, muscle, tendon, and joints and to stimulate the body’s own healing powers.20

In a small case-control study of OMT in 30 patients with PAD, the researchers applied a form of OMT, at the practitioner’s discretion, to manage any somatic dysfunctional complaints.3 Treatment was administered for 30 minutes every 2 weeks for 2 months, followed by 1 month without treatment, then treatment was restarted and provided every 3 weeks over 3 months. Commonly employed techniques included strain-counterstrain, muscle energy, myofascial release, soft tissue manipulation, and other osteopathic manual medication therapies.3 Assessments were composed of ABI and brachial artery flow-mediated vasodilation. At 6 months, the OMT cohort showed a statistically significant increase in improved ABI, quality-of-life scores, and time to claudication pain. Additionally, blood levels of serum and soluble intercellular adhesion molecules also decreased significantly.3

The ultimate goal of OMT treatment is to ensure a balance between the sympathetic and parasympathetic nervous systems in order to improve somatic function. A vascular-flow improvement is shown in different manual medicine therapies, possibly mediated in part by the release of nitric oxide.20

Traditional Medical Approaches

In comparison to the lofty goals of OMT, the aim of more conservative treatments for patients with IC is to lessen symptoms by increasing comfort and walking distance. Effective strategies often used to extend walking distance include pharmacotherapy and exercise therapy. Several pharmacological approaches that are known to increase walking distances in patients who have IC include cilostazol, antiplatelet agents, pentoxifylline and lipid-lowering agents.15 Patients with IC respond well to a structured walking program that tends to reduce pain and maximize walking distances. In addition, a regular walking program is known to lower blood pressure and triglycerides, improve glucose tolerance, raise high-density lipoprotein cholesterol and, most significantly, improve survival.21

Smoking represents a key risk factor for critical limb ischemia (CLI). In the general population, smoking tends to increase the risk of this condition 2 to 6 fold. Smokers with CLI have a greater risk of amputation and higher rates of mortality and morbidity. Therefore, it behooves clinicians to work with patients who smoke to find a suitable method to help them stop if they want to improve their quality (and length) of life.


Researchers are still seeking new methods to treat PAD, such as gene therapy. As with other chronic diseases, prevention will always remain the only foolproof method to avoid pain and the undesirable side effects of treatment. The basics of a wholesome lifestyle—eating a balanced and heart-healthy diet, avoiding tobacco use, exercising regularly, and maintaining a steady weight—are some of the basics that even pain practitioners need to promote.

Last updated on: March 17, 2017

Join The Conversation

Register or Log-in to Join the Conversation
close X