Managing Pain in Peripheral Arterial Disease: Strategies and Treatments

PAD is a common disease and may remain either asymptomatic or symptomatic. The most frequent early symptom is intermittent claudication, a discomfort in the muscles that occurs with exercise and is relieved by rest. The more severe atherosclerotic blockages, chronic limb-threatening ischemia, can lead to pain at rest, ulcers or gangrene. The consequences of these can be major, including disability and limb loss. It is the association of leg symptoms, particularly intermittent claudication, with impaired walking and quality of life that constitute the burden of PAD. There can be significant reduction in mobility and function from intermittent claudication that can lead to loss of independence. The risk factors and coexisting disease states associated with PAD are extremely important as are the identification of its atypical presentations. These topics will be explored as they relate closely to the mechanisms of disease and provide areas for which management strategies can be targeted.

Strategies for Managing Pain in Peripheral Arterial Disease

Exercise is often limited by leg pain. If the patient has been mainly sedentary due to pain, and the onset of the pain has been within the previous few months, a trial of simple analgesia/NSAIDs, supervised exercise, and best medical therapy is indicated. In many cases, this will be sufficient to relieve pain and increase exercise distance.

Peripheral arterial disease (PAD) is a common condition caused by atherosclerosis, leading to a reduction in blood flow to the lower limbs. Patients often develop painful ischemic rest pain and/or critical limb ischemia. In the majority of patients, exercise and medications are effective in reducing or resolving PAD symptoms. When to take various further interventional approaches often depends on the severity of symptoms, general health, and patient choice.


Several different classes of drugs targeting symptom improvement have been evaluated in the treatment of claudication due to PAD. Agents such as naftidrofuryl, which is not available in some countries, are thought to have vasodilatory properties, but meta-analyses of numerous randomized trials concluded that they are of little benefit. Similarly, in contrast to their clear symptomatic benefit in patients with coronary artery disease, antiplatelet agents have only modest performance in improving claudication and increasing walking distance, a reflection of the multifactorial nature of the disease process in the lower extremities. The exercise and smoking cessation with cilostazol or clopidogrel in patients with PAD (ESPRESS) study showed that a cilostazol-based strategy that includes risk factor modification and exercise counseling can be successful in achieving the highly laudable outcome of smoking cessation.

Treatment of claudication should begin with risk factor modification and exercise therapy. Although not specifically evaluated in clinical trials, in patients with intermittent claudication due to PAD, the management of concomitant risk factors such as hypercholesterolemia, hypertension, and diabetes can delay progression of atherothrombotic disease in other beds, reduce cardiovascular morbidity and mortality, and possibly increase walking time. However, because many patients continue to be limited by leg symptoms, additional medical therapy to improve symptoms and increase functional capacity is often necessary.

Exercise and Physical Therapy

Exercise therapy programs for PAD are an integral part of the treatment plan for patients at all stages of the disease. As with other atherosclerotic diseases, the goals of exercise therapy are to increase function by improving the muscle’s metabolic efficiency, enhance collateral blood flow, and ultimately improve cardiovascular and limb outcomes. Treadmill exercise has been the most widely studied form of exercise training in PAD patients. Both supervised treadmill exercise and home-based treadmill exercise have shown significant improvement in treadmill walking performance compared with controls. In addition to improving function, many forms of exercise training have shown improvement in the way patients feel. Supervised treadmill exercise has been found to improve both physical and social function in PAD patients and improve overall quality of life. Improvement in quality of life is an important treatment goal in patients with intermittent claudication and is an outcome that must be considered when evaluating the impact of any intervention. In general, improvement in treadmill walking performance increases with longer duration exercise programs. A meta-analysis of supervised exercise therapy for claudication demonstrated that programs lasting six months or longer were associated with the greatest improvements in treadmill walking performance. Unfortunately, despite the clear benefits of exercise therapy, PAD patients are among the least active of all patient groups. A recent analysis of NHANES data showed that only 36% of patients with PAD engage in any kind of leisure time physical activity and only 15% engage in regular physical activity, which is most likely insufficient to affect claudication symptoms. This is particularly concerning given the fact that this is the same percentage of PAD patients that qualifies for therapy services under Medicare guidelines.

Lifestyle Modifications

The role of lifestyle in the management of pain is very important. A motivated patient can be very successful at controlling their symptoms. Patients should be encouraged to stop smoking. This is one of the most important factors in both symptom control and disease modification. Nicotine in all forms constricts blood vessels and may have direct toxic effects on the artery walls. Patients should be referred with a view to participation in a local smoking cessation program. Regular exercise may increase the distance that a patient can walk without pain. This may be difficult as the symptoms themselves make exercise painful. Forming an exercise group for patients with intermittent claudication has been shown to be successful. This sort of group setting can provide the necessary support and encouragement, which a patient may not otherwise receive. Patients may have heard conflicting information regarding the role of specific exercises and rest in the management of intermittent claudication. They should be informed that there are no activities which are harmful to the peripheral circulation. It has been shown that people who continue working are likely to walk more before resting than those who retire. This is unlikely to be due to the nature of the employment and is more probably due to the fact that those who retire stop walking to rest at a certain point, whereas those who are working will continue until a specific task is completed. Lastly, patients should be encouraged to optimize the treatment of any other medical conditions and to adopt a healthy lifestyle.

Treatments for Peripheral Arterial Disease

Angioplasty is a possible treatment if your peripheral artery disease (PAD) symptoms are disabling or if you are at risk for developing critical limb ischemia. During angioplasty, a balloon-tipped catheter is used to widen the narrowed artery. The catheter is inserted through the skin into a large artery and threaded through the blood vessels to the site of the blockage. The balloon is then inflated to flatten the plaque against the artery wall. This restores blood flow through the artery. There are two types of balloon angioplasty. With traditional balloon angioplasty, the balloon is inserted into the artery at the blockage and is inflated with high pressure. The second type, called low-pressure or atherectomy-assisted angioplasty, also uses a cutting device at the tip of the catheter to remove plaque. This reduces the possibility that plaque will be dislodged and travel through the bloodstream to other sites, a complication of high-pressure angioplasty.

Angioplasty and Stenting

Pain and symptom control is important for patients with limb ischemia and angioplasty and stenting can do much to help patients maintain or improve their quality of life. With the advanced state of illness of many patients with critical limb ischemia, maintenance of limb viability and relief of ischemic pain are paramount and PAD patients at the end of life, though described as a “forgotten tribe”, can benefit greatly from the introduction of palliative care services.

Palliative care, a growing subspecialty of care for persons with serious illness, provides an additional layer of support to patients, their families, and their caregivers. This type of care is focused on providing relief from the symptoms and stress of the illness. The goal is to improve the quality of life in patients facing serious, complex illness. This can be done through pain management and by controlling symptoms. Patients with peripheral arterial disease (PAD) and its associated symptoms can benefit from palliative care, though the mainstays of medical and invasive therapies to reduce symptoms related to PAD should not be overlooked or overshadowed.

Bypass Surgery

The term bypass surgery is also derived from its origin in coronary revascularization, the process by which alternative routes of blood supply are created in the heart to ‘bypass’ narrowed arteries and restore blood flow. Similarly, in PAD surgical bypass involves grafting a blood vessel from another part of the body, or a synthetic substitute, to create a new route for blood flow around the site of the blockage. This is done while under a general anesthetic and is the most extensive of the invasive methods used to treat PAD but has the highest long-term success rates. Bypass is frequently done on an inpatient basis and may require a hospital stay of up to a week. The use of anesthetic and invasive surgery will make the patient unsuitable if they are high-risk for surgical intervention. This method is also unsuitable if the patient has a generalized narrowing of the arteries, rather than specific sites of blockage, unless they do not respond to an extended period of supervised exercise. Bypass surgery is symptomatic relief and has shown to improve quality of life but also has a risk of morbidity and mortality, estimated to be between 4-9% and 1.2-3% during the operation. The risk depends on the health and age of the patient, what their current life expectancy is and what other medical conditions they may have.


There is no doubt that a person facing amputation of a limb is likely to have a similar emotional response to the patient with critical leg ischemia. However, there has been little study of the psychological and emotional response to amputation, nor of the effect of amputation on the family of the patient. A small study has recently been completed at the University of Newcastle, UK, examining the ability of pain-relief medication and lumbar sympathectomy to improve blood flow in the remaining leg of patients who were about to have an amputation. This was a pilot study which had a vast inclusion and exclusion criteria, embracing all forms of PAD, but it was halted early due to lack of patient recruitment so no meaningful conclusions can be drawn. These patients can only be in the very bottom end of intermittent claudication group where the neurotransmitter treatment is not yet recommended.

It is possible that a severe blockage in the leg arteries could cause such damage to the tissues that the condition cannot be improved. What is more, pain at rest and the threat of gangrene may mean that amputation is considered the best way to stop the pain, even though the patient has no life-threatening condition. What should he do?


Pain is the most common reason for people with peripheral arterial disease (PAD) to seek medical attention. Managing pain in PAD can be challenging because there are three main types of leg pain in people with PAD: intermittent claudication, severe pain at rest, and pain on walking in the absence of classical intermittent claudication. At this time, there are few effective therapies for intermittent claudication. Supervised exercise therapy and lower extremity revascularization to treat intermittent claudication are generally aimed at improving limb function and rarely change the primary subjective symptom limited walking distance. Cilostazol is the only medication approved by the United States Food and Drug Administration specifically for intermittent claudication. The PDE-3 enzyme inhibitors have been subject to numerous research trials showing improvements in primary and secondary intermittent claudication endpoints. However, most of this has been anecdotal and more investigation needs to be done to see if this class of medication truly improves limb function above just increasing pain free walking time. Overall, there is little data for the direct treatment of intermittent claudication and most general efforts should be focused on control of cardiovascular risk factors and antiplatelet therapy to prevent myocardial infarction, stroke, or cardiovascular-related death. This may seem overly simplistic when first considering management of patients with leg symptoms from PAD, but when claudication is not a terminal disease and patients with this being their only symptom are at risk for all-cause mortality similar to those with known cardiovascular disease.

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