Chronic Neuropathic Pain in Women after Breast Cancer Treatment

Fozia Bokhari, RN, BN; Jo-Ann V. Sawatzky, RN, PhD


Pain Manag Nurs. 2009;10(4):197-205. 

In This Article

The Human Response to Illness Model

According to the American Nurses Association (ANA), an essential feature of the definition for the profession of nursing includes "prevention of illness and injury, alleviation of suffering through the diagnosis and treatment of human response". (ANA, 2007) Consequently, the human response to health and illness is central to nursing science. (Mitchell, Galluci, & Fought, 1991) The Human Response to Health and Illness (HRTI) model is an appropriate theoretic framework to establish a comprehensive understanding of chronic neuropathic PPBT. (Mitchell et al. (1991)) view human responses to health and illness as encompassing four perspectives, including physiologic, pathophysiologic, behavioral, and experiential responses, within the context of influencing personal and environmental factors. Thus, this model provides a holistic and multidimensional framework for gaining insight into chronic neuropathic PPBT. In addition, the HRTI model offers guidance for nursing practice, education, and research.

Physiologic Response

Physiologic regulatory responses are the normal biologic functions of a healthy person. (Mitchell et al., 1991) Acute or "normal" pain perception begins with a painful stimulus and follows two opposing pathways: pain-conduction versus pain-inhibition. (Stillman, 2006) In the pain-conduction pathway, nociceptors send an electrical signal from the stimulus via a wave of depolarization to first-order neurons that terminate in the dorsal horn of the spinal cord to the second-order neurons, which cross over to the opposite side of the spinal cord. This conduction continues up to the thalamus to the third-order neurons which in turn connect to specific areas in the limbic system and cerebral cortex leading to pain perception. (Stillman, 2006) In the opposing pain-inhibition pathway, transmission of pain signals is inhibited through the synapse of short interneurons in the dorsal horn with antinociceptive (i.e., analgesic) neurons that start in the brain stem and travel down to the spinal cord. (Stillman, 2006) Thus, nociceptive enhancement may result from hindrance of inhibitory synaptic connections, whereas nociceptive inhibition arises from disruption of synapses between first- and second-order neurons (Stillman, 2006).

The physiologic response for a woman with breast cancer involves the normal acute pain following surgery and treatment. The "normal" healing time for the body to recover from surgery, radiation, and/or chemotherapy varies from person to person. It follows that the acute pain following these treatments also varies with each individual. However, undertreated acute postoperative pain is a risk factor for chronic neuropathic pain in postsurgical patients. (Kehlet, Jensen, & Woolf, 2006)

Pathophysiologic Response

The pathophysiologic response refers to disordered, abnormal, or undesired biologic function. (Mitchell et al., 1991) The pathophysiologic response to breast cancer treatment occurs when acute pain progresses to chronic neuropathic pain. According to the International Association for the Study of Pain (IASP), chronic pain is defined as pain that lasts 3 months beyond the normal healing time. (Merskey & Bogduk, 1994) The IASP defines neuropathic pain as "pain initiated or caused by a primary lesion or dysfunction of the nervous system". (Merskey & Bogduk, 1994, p. 212) Postsurgical tissue damage, nerve damage, and inflammation can cause nociceptive and neuropathic pain, with the neuropathic pain predominating as healing continues. (Jung et al, 2003)

Chronic PPBT follows the typical pathophysiology of other types of neuropathic pain. A lesion of the somatosensory system is thought to be a common starting point, with peripheral and central mechanisms also playing roles. Peripheral sensitization occurs when neuroma development at the proximal nerve stump causes regenerating unmyelinated sprouts to develop continuous spontaneous activity, abnormal excitability, and an increased sensitivity to chemical, thermal, and mechanical stimuli, thus triggering the pain response. (Truini & Cruccu, 2006) First-order neurons may increase their firing, and inhibitory (i.e., analgesic) pathways may be impaired. (Stillman, 2006) Peripheral sensitization, which is related to up-regulation of sodium channels in first-order neurons, is sometimes followed by central sensitization. In central sensitization, alterations in the nociceptors and ion channels' expression can cause activation of gene transcription, leading to molecular changes. (Truini & Cruccu, 2006) Central sensitization is largely mediated by NMDA receptors. (Gilron, Watson, Cahill, & Moulin, 2006) Prolonged pain or use of neurotoxic drugs may cause second- or third-order neurons to develop pain "memory" and to become centrally sensitized, leading to chronic pain development. (Stillman, 2006)

There are numerous possible causes of chronic neuropathic PPBT. Common theories include: injury to the interchostobrachial nerve; damage to axillary nerves and tissue damage due to surgery; aggravation caused by radiation therapy or chemotherapy; and formation of secondary neuromas from surgical scars. (Jung et al., 2003, Selim et al., 2002, Temple and Ketcham, 1985, Vecht et al., 1989, Wallace et al., 1996) In mastectomies, as in other amputations, phantom breast pain sensations have been identified as another source of this form of chronic discomfort. (Jung, Herrmann, Griggs, Oaklander, & Dworkin, 2005) Complete axillary dissections, owing to their invasiveness, as well as retraction compression during the procedure, can also lead to chronic neuropathic PPBT. (Jung et al., 2003) Although the recent advances in minimally invasive surgical techniques, such as sentinel lymph node dissections, and adequate pain control during and after surgery have decreased the incidence of chronic neuropathic PPBT, (Jung et al., 2003, Selim et al., 2002) little is known about the long-term outcomes for chronic neuropathic PPBT.

Behavioral Responses

Behavioral responses refer to directly measurable and observable signs and symptoms. (Mitchell et al., 1991) According to, (McCaffery (2001)) pain is what the patient says it is and is therefore highly subjective. Neuropathic pain is typically characterized by burning, shooting, and electric shock–like sensations in the area around the treatment site. (Polomano & Farrar, 2006) In terms of pain quality, common verbal neuropathic pain descriptors include numbness, pins and needles, burning, and stabbing, (Boureau, Doubrere, & Luu, 1990) as well as throbbing, lancinating, unpredictable, lightning-like, sharp, shooting, scalding, aching, and pruritic. (Davis, 2006)

Because of the subjective nature of pain, self-report tools have been widely used in the literature to measure the characteristics, duration, and location of chronic neuropathic pain response. Pain scales are commonly used to measure pain intensity, and various pain questionnaires are used to measure pain quality and duration.

Although many researchers use the McGill Pain Questionnaire, a number of other tools are currently used to screen for neuropathic pain, including the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), the Neuropathic Pain Questionnaire (NPQ), Douleur Neuropathique en 4 questions (DN4), painDETECT, and ID-Pain. (Bennett et al., 2007) Unfortunately, these pain measures have had limited bedside evaluation and require further testing to determine validity and reliability. (Bennett et al., 2007) On the other hand, the Neuropathic Pain Scale (NPS) is a widely used, reliable, and valid pain quality tool. (Galer and Jensen, 1997, Jensen et al., 2005) The NPS (Jensen et al., 2005) contains two global ratings (intensity and unpleasantness), as well as eight specific ratings for pain location (deep and surface) and pain quality (sharp, hot, dull, cold, sensitive, and itchy). The NPS enables clinicians to accurately assess changes in pain after pain treatment and thus provides the rationale for polypharmacy treatment options, as needed. (Jensen et al., 2005)

Indirect measurement of chronic neuropathic PPBT includes the objective assessment of associated symptoms such as edema, allodynia, and dysesthesia located in the axilla, chest wall, arm, or shoulder of the treatment side. (Selim et al., 2002) Quality of life can also be objectively measured; for example, 40% of women with chronic neuropathic PPBT report increased pain with movement leading to arm restriction and "frozen shoulder" syndrome; greater than 50% report pain with activities of daily life and sleep disturbances. (Selim et al., 2002)

Experiential Responses

The experiential perspective refers to the experience of living with the response to illness. (Mitchell et al., 1991) Therefore, the assessment of this perspective is based on self-reports. To date, no researchers have actually studied the lived experience of chronic neuropathic PPBT survivors. The chronic neuropathic pain literature mentions that this condition is debilitating (Wascher et al., 2004) and therefore of concern, but there is no further elaboration on the experience of living with this syndrome.

Extrapolating from studies on other neuropathic pain conditions does, however, offer some insight into living with chronic pain. For example, individuals suffering from allodynia due to neuropathic pain can experience flare-ups from normal everyday stimuli, such as clothes rubbing against the skin. (Arnstein, 2004) Specific to the breast cancer population, restrictions in what one can wear may have a significant impact on a woman's self-esteem. As well, chronic neuropathic pain often fluctuates, from being relatively stable for weeks or months to episodes of minor or major flare-ups. (Arnstein, 2004) These factors can be very stressful for the individual. Persistent, unremitting stress can generate detrimental long-term effects, increasing an individual's susceptibility to stress-related physical and mental health problems. (Arnstein, 2004) Thus, living with persistent pain can have a negative impact on an individual's overall quality of life. Further research, which focuses on the lived experience of women with PPBT, will provide insight into improving their outcomes.

Personal Risk Factors

According to, (Mitchell et al (1991)) personal risk factors influence the individual's vulnerability to the unhealthy states of a human response. Although there are numerous nonmodifiable and modifiable factors that affect one's vulnerability to chronic neuropathic pain, age and weight appear to be the two key risk factors that have been associated with the development of PPBT.

Although the research evidence related to the impact of age on PPBT is inconclusive, younger age has been strongly implicated in the development of chronic pain after breast cancer surgeries. (Gulluoglu et al., 2006, Hack et al., 1999, Macdonald et al., 2005, Poleshuck et al., 2006, Smith et al., 1999, Tasmuth et al., 1995) However, several others have reported no association between these two variables. (Carpenter et al., 1999, Ivens et al., 1992, Kroner et al., 1989) Younger age has also been correlated with chronic pain after cardiac surgery, as well as inguinal herniorrhaphy. (Bruce et al., 2003, Poobalan et al., 2001) It is contended that younger patients are more sensitive to nerve damage, are less likely to tolerate pain, and have increased anxiety leading to more reports of pain; (Bruce et al., 2003, Poobalan et al., 2001) younger women tend to perceive greater emotional distress than older women. (Hack et al., 1999)

Weight is changeable and consequently it is a modifiable person risk factor. Increased body mass index [BMI] (i.e., weight-to-height ratio) has been linked to chronic neuropathic pain development after surgery. (Bruce et al., 2003, Hack et al., 1999, Poobalan et al., 2001, Smith et al., 1999) A higher BMI may make it difficult to distinguish and identify the nerves near the surgical site, thus increasing the susceptibility to nerve damage. (Bruce et al., 2003, Poobalan et al., 2003) However, in their follow-up study of women with PMPS, (MacDonald et al. (2005)) did find that the association with BMI decreased over time after the surgery. Further research is required to resolve these controversies.

Environmental Factors

Environmental factors interact with all four perspectives of the HRTI model, as well as the personal factors. (Mitchell et al., 1991) Like personal risk factors, environmental factors affect individual susceptibility to developing an unhealthy human response to illness. Specific to PPBT, possible environmental influences include social support, socioeconomic status, interventions, such as the type of surgery, pain management, and the availability of specialized pain treatment clinics, and nonsurgical treatment options, such as radiation and chemotherapy.

Although there has been no research specific to women with chronic neuropathic PPBT, there is general acceptance that social support and socioeconomic status are determinants of our health. It follows that a good social support system would enhance the emotional and physical health of women with PPBT. A higher socioeconomic status can provide financial stability for living and medical expenses and generally a better quality of life. In a study that looked at anxiety and support for women with breast cancer, it was found that women living in deprived areas reported a greater degree of anxiety regarding money, other health problems, and family problems than women in more affluent areas. (Macleod, Ross, Fallowfield, & Watt, 2004)

Interventions, which include the type of surgery, the skill of the surgeon performing a mastectomy or lumpectomy, and the invasiveness of the surgery, are environmental factors that play a role in the development of PPBT. Not only women who have had mastectomies, but also those who have had lumpectomies develop chronic neuropathic pain. (Carpenter et al., 1998, Tasmuth et al., 1995, Tasmuth et al., 1996) As well, PPBT may develop in women who have undergone breast reconstruction, augmentation, and reduction. (Wallace et al., 1996) Thus, while the degree of invasiveness of the surgery does appear to play a role in the development of chronic neuropathic PPBT, the fact that it also occurs in women undergoing less invasive procedures is an indication that there are other factors at play.

Increased pain in the acute postoperative period has also been linked in chronic neuropathic pain development. (Poleshuck et al., 2006, Tasmuth et al., 1995) Therefore, effective pain management and access to specialized pain treatment clinics can help alleviate suffering for these women. Finally, the choice of nonsurgical treatment options can also affect the susceptibility to chronic neuropathic PPBT. For example, although several studies have found an association between chronic neuropathic PPBT and radiation therapy, (Poleshuck et al., 2006, Schierle and Winograd, 2004, Tasmuth et al., 1999) others have not. (Hack et al., 1999, Kroner et al., 1989) As well, certain chemotherapy drugs, such as cisplatin and paclitaxel, are known to be neurotoxic and therefore can cause painful neuropathies. (Dellon, Swier, Maloney, Livengood, & Werter, 2004) Thus, environmental factors are an important consideration in the assessment and management of women with chronic neuropathic PPBT.


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