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Post Breast Therapy Pain Syndrome: A Surgeon's Perspective
Robert A. Wascher, MD, FACS
A variety of postmastectomy/postaxillary dissection pain syndromes (PM/PADPS) have been described in women who have undergone surgical treatment for breast cancer. These include pain in the surgical scar, chest wall and upper arm, as well as shoulder discomfort, and phantom breast tactile sensations and pain. The incidence of chronic pain syndromes following breast cancer treatment has been estimated to occur in 20-25% patients undergoing axillary (armpit) dissection, with or without mastectomy, and appears to correlate with the extent of axillary surgery. Additional factors linked to breast cancer-associated chronic pain syndromes include polyneuropathies caused by chemotherapy and radiation therapy, which may be additive to impairments caused by surgery. As with most chronic pain entities, affected patients frequently experience some degree of debilitation that interferes with their ability to lead productive and comfortable lives. Moreover, the concomitant overlay of stress and anxiety that commonly follows the diagnosis of cancer further adds to the functional impact of unremitting postoperative pain in afflicted patients.
The true etiology of PM/PADPS remains unclear, but is probably multifactorial in nature. The most commonly cited theory of chronic postoperative pain in breast cancer patients is the intentional sacrificing of the intercostobrachial nerves. These sensory nerves exit through the muscles of the chest wall, and provide sensation predominantly to the shoulder and upper arm. Because these nerves usually run through the packet of lymph nodes in the armpit, they are commonly cut by the surgeon in the process of removing the lymph nodes. In most patients, loss of innervation of the upper arm results in numbness of the affected areas. However, many women experience a period of uncomfortable paresthesias in the affected areas for several months. Symptoms described as burning, tingling, itching, or frank lancinating pain, have all been described. In the majority of cases, the brain eventually stops expecting sensory input from the affected area, and the patient is left with a sensation of numbness that is not particularly noticeable. In a small percentage of patients, however, chronic pain results, and the painful symptoms persist. The symptoms may be present almost continually, or they may occur in response to changes in physical activity or temperature. They may also be exacerbated by physical contact with the affected area. Although the loss of intercostobrachial nerve function has been implicated in PM/PADPS, there are at least some studies that appear to show no decrease in the incidence of such chronic pain syndromes when these nerves are preserved during surgery. However, most studies have shown a distinct correlation between the extent of axillary lymph node dissection and the subsequent development of neuropathic pain syndromes involving the upper arm.
Chest wall and surgical scar pain are also part of the constellation of symptoms that can occur in PM/PADPS, and are more likely to be a direct result of extensive surgical removal of breast tissue than axillary lymph node dissection. The sensory nerves that innervate the skin of the chest perforate the chest wall and the substance of the breast, and are often cut or damaged in the course of breast tissue resection. Extensive resections, and mastectomy in particular, disrupt the cutaneous sensory nerves that provide normal sensation to the skin overlying the breast and lateral chest. As with the loss of intercostobrachial nerve function, recovery from mastectomy is marked by numbness in the affected areas in most patients, although some patients will persistently experience unpleasant or frankly painful paresthesias. In some cases, regeneration of the disrupted nerves may occur, generally over a period of months-to-years. Patients, may, therefore, regain at least some sensation in areas previously rendered numb by their surgery. Such peripheral nerve regeneration does not always have a beneficial outcome though, as aberrant connections between regenerating nerves and the uninjured nerves adjacent to the areas of surgical manipulation may result in chronic paresthesias and pain. Formation of neuromas at the cut ends of sensory nerves may also lead to pain and hypersensitivity in the area of surgical trauma. An even more debilitating condition, known as reflex sympathetic dystrophy (RSD), has also been know to occur due to abnormal healing and regeneration of injured nerve fibers. An abnormal interconnection between the regenerating sensory nerves of the skin and the sympathetic nerves that course along blood vessels and other structures can lead to unbearable hypersensitivity in the affected area to touch, movement, or temperature changes. Even the slightest tactile stimulation may result in searing pain in patients with RSD, and is very difficult to treat effectively.
As with most chronic pain syndromes, there appear to be powerful psycho-emotional factors that play a role in the development of PM/PADPS. Chronic pain syndromes are thought to arise following a physical injury that causes damage to sensory nerves. That is to say, despite the psycho-emotional components that appear to play a key role, chronic pain syndromes follow a physical injury that results in acute physical pain. However, many studies of chronic pain syndromes have shown an inconsistent relationship between matched sites and degrees of surgical trauma and the subsequent incidence of chronic postoperative pain syndromes. Patients who appear to have undergone identical surgical procedures do not all develop chronic pain syndromes (in fact, most do not). Certainly, individual differences in healing may account, at least in part, for such findings. At the same time, it has been shown that severe and chronic pain can, in many patients, result in the remodeling of parts of the brain that are tasked with processing painful stimuli. For reasons that are still not entirely clear, one part of the brain, the limbic system, can become hypersensitized to painful stimuli, resulting in a sort of a feedback loop between injured sensory nerves and the emotional pain centers of the brain. Additionally, neural pain receptor networks within the spinal cord are also thought to play a role in the perpetuation of painful sensations from the operative site. For these reasons, many psychotropic and neurotropic drugs, including antidepressants and neurontin, can reduce the severity of chronic pain syndromes. One should not mistake this linkage between the physical trauma of surgery and the brain's processing of the resulting stimuli as implying that PM/PADPS are merely a manifestation of chronic depression or some other behavioral or mental illness (though almost all patients with chronic pain syndromes experience depression, and for understandable reasons). Patients afflicted with these and other chronic pain syndromes unquestionably experience real, debilitating and often severe pain.
Ideally, prevention is the best cure. There have been several studies that have identified a reduced incidence of PM/PADPS following axillary sentinel lymph node biopsy in place of full axillary dissection. Certainly, this minimally invasive approach to axillary lymph node sampling results in a much lower likelihood of injury to the intercostobrachial nerves, as well as to the sensory nerves innervating the skin of the lateral chest wall and axilla. At the present time, the American College of Surgeons Oncology Group is sponsoring two multicenter clinical trials that address the role of axillary dissection and SLN biopsy. The first trial (Z0010) seeks to understand the significance of micrometastatic disease in the SLN and bone marrow. In this trial, patients who do not have SLN or bone marrow metastases by standard histopathological criteria are observed closely, and do not undergo axillary dissection. A central laboratory also checks the SLN(s) and bone marrow for evidence of micrometastatic disease, although the patients and surgeons do not receive the results of this analysis until the end of the trial. Patients in the Z0010 trial can elect to participate in the second trial (Z0011) if their SLNs are found to have metastatic tumor by standard histopathological criteria. The Z0011 trial randomizes patients with a positive SLNs into one of two treatment arms: radiation alone versus axillary dissection plus radiation. Thus, the clinical importance of complete axillary dissection, with or without a positive SLN, should be revealed by these two studies. A third trial, sponsored by the NSABP, has similar study goals. Although it will be at least 5 years before the results of these studies will be available, they should answer at least two important questions. First, do patients who have no tumor involvement of their SLNs do any worse if their remaining axillary lymph nodes are left intact? Secondly, in those patients who have spread of cancer cells to the SLN, does the act of leaving behind the remaining axillary lymph nodes impact on patient prognosis? These are crucial questions in view of the contradictory findings of previous studies on the impact of complete axillary lymph node dissection on patient outcome.
In conjunction with the development of minimally invasive techniques for surgically staging the axillary lymph nodes, breast-conserving treatment of the primary breast tumor has gained considerable popularity among both patients and surgeons over the past decade. Following NSABP clinical trials showing no difference in patient outcomes (i.e., local recurrence and overall survival) between patients undergoing modified radical mastectomy (MRM) and those undergoing lumpectomy with radiation therapy, the majority of early stage breast cancer cases are now treated by removal of the primary tumor, and not by mastectomy. Reducing the extent of surgical trauma to nerve-bearing tissues should reduce-though not entirely eliminate-the incidence of postoperative chronic pain syndromes. There will, of course, continue to be patients who will be counseled to undergo MRM by their physicians, or who will, themselves, choose to have the entire breast removed. Patients with extensive lobular carcinoma, inflammatory carcinoma, multifocal disease, and patients with very large tumors are all likely to receive recommendations in favor of mastectomy. Some patients who are eligible for breast-conserving therapy may also choose, for a variety of reasons, to undergo mastectomy instead.
Once PM/PADPS has become established in a patient, a variety of treatments are available. Few of them will entirely eliminate the discomfort or pain, but many will ameliorate symptoms to a considerable extent. As a cancer surgeon, my repertoire of treatment options is somewhat limited, and does not encompass the entire spectrum of therapy currently available. The rare patient who fails my attempts at providing relief is usually referred to professional pain management experts, including anesthesiologists and physical medicine/rehabilitation physicians. Often, mobility-related causes of chronic postmastectomy/postaxillary dissection pain can be improved after consultation with physical therapists and occupational therapists.
My own approach to patients with chronic postoperative pain syndromes following breast cancer surgery begins even before surgery. That is to say, I am careful to explain the possible array of postoperative sensations, symptoms and complications that the patient might experience following surgery. In my experience, patients who have a realistic expectation of potential surgical outcomes are far better able to cope with complications of surgery than patients who are unsuspecting when problems develop. The early postoperative period, which I define as 4-6 weeks after surgery, is a time when the patient is likely to experience a variety of physical and emotional sensations, most of them unpleasant. In most cases, such unpleasant sensations will gradually subside with the passage of time. Providing the patient with empathetic support, and the liberal prescribing of pain medication, go a long way towards aiding the patient's recovery during this phase of their treatment. Based upon the known mechanisms of pain consolidation and reinforcement that occur in the central nervous system of most patients who develop chronic pain syndrome, I attempt to maximize preemptive pain relief approaches. Prior to making an incision, I use a generous amount of local anesthetic even in patients undergoing surgery under a general anesthetic. Although data on preemptive anesthesia is very contradictory, with many studies showing no effect on long-term postoperative pain levels, it does certainly improve early postoperative patient comfort, and reduces the amount of narcotics necessary to provide excellent analgesia. However, I do not skimp on the pain medications either, although one must always be alert to the significant potential side effects inherent in the use of narcotic pain medications.
Patients who develop chronic pain in their scar, breast, chest wall, shoulder, or arm can be helped in several ways. Anti-inflammatory agents (e.g., ibuprofen, naproxen, and other NSAIDs), low doses of antidepressant medications (e.g., Elavil, Pamelor, and the SSRI-class of drugs, including Zoloft) can often be very helpful, although these agents must be taken consistently for several weeks to attain the greatest benefit. Unfortunately, narcotics are relatively ineffective against establish chronic neuropathic pain, and the risk of narcotic dependency is very high when used in this setting. Topical counterirritants, such as capsaicin and mentholated creams, are useful in some cases, although their overall efficacy has been rather poor in most studies. Scar neuromas can often be diagnosed-and simultaneously treated-in patients with localized scar pain by injection of local anesthetics and corticosteroids into the painful site. If the pain completely resolves following one or more injections, then a localized nerve regeneration abnormality, such as scar neuroma, can then be considered to be the cause. Frequently, serial injections over the course of weeks-to-months will dramatically improve the patient's symptoms, and sometimes on a very long-term basis. In those patients who experience only temporary-but complete-relief following such injections, I offer to excise the painful area of the scar along with the offending neuroma. In many cases, this provides excellent and permanent relief to the patient. In those patients who receive no appreciable relief of their pain following local scar injections, surgical removal of all or part of the scar is unlikely to be effective (though I will occasionally agree to do so for a patient who has exhausted all other options, and who understands that success is not likely). Patients with longstanding and severe chronic postoperative pain syndromes, and patients with RSD in particular, present a very difficult dilemma for both patient and physician. Many such patients eventually become dependent on ever-increasing doses of narcotics to control their symptoms, and occasionally with tragic results. For patients with these very refractory and debilitating chronic pain syndromes, a combination of interventions may provide at least some relief from symptoms. In addition to the approaches that I have already described, thoracic sympathectomy may provide relief, although there are some significant risks involved with such procedures. Intermittent or continuous injections of anesthetic and/or corticosteroids into the space around the spinal cord may also be effective. Recently, implantable spinal cord nerve stimulators have been evaluated for use in various chronic pain syndromes, and may also hold promise. Other adjunctive modalities that are often beneficial include guided imagery training and biofeedback. I also occasionally recommend concomitant consultation with a psychologist or psychiatrist who has expertise in treating patients with chronic pain syndromes. One should not interpret this recommendation as the physician questioning a patient's mental health status, or the implication that the patient's suffering is all in her head. However, I cannot overemphasize the powerful psycho-emotional component involved in the limbic reinforcement pathways of patients suffering from chronic pain syndromes. For many patients, even a partial reduction in the severity of their neuropathic pain symptoms with medications, when combined with behavioral therapy, can make an enormous difference on their overall level of comfort and function.
Postmastectomy/postaxillary dissection pain syndromes, as with other well-studied post traumatic chronic pain syndromes, are complex and often difficult to treat conditions. The cause of such syndromes is likely multifactorial, and involves both a physical injury to the patient's nervous system and the subsequent development of loop-feedback circuits in regions of the central nervous system that convey and process painful stimuli, and assign emotional associations to such stimuli. Prevention is the ideal approach, although there are currently no approaches that have been shown to effectively prevent all cases of chronic postoperative pain syndromes. However, several recent studies suggest that the use of minimally invasive surgical approaches in the management of the primary tumor and axillary lymph nodes may be associated with a significantly reduced incidence of chronic pain syndrome in patients with breast cancer.
Once established, most patients with chronic postoperative pain can be effectively managed using a multidisciplinary and multimodal approach. The selective use of anti-inflammatory, psychotropic, neurotropic, behavioral and, in some cases, surgical treatments will ameliorate symptoms in the majority of afflicted patients, allowing patients to return to a fuller and more comfortable life. The more severe and refractory forms of PM/PADPS, including RSD, are extremely challenging, and often do not respond very well to most of the treatments described herein. Additional research into the mechanisms behind such refractory syndromes is, therefore, needed before more effective treatments can be devised.
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