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Mayo Clin Proc. 2010 March; 85(3 Suppl): S42-S50.
PMCID: PMC2844010

Assessment and Treatment of Psychosocial Comorbidities in Patients With Neuropathic Pain


Chronic neuropathic pain is a prevalent problem that eludes cure and adequate treatment. The persistence of intense and aversive symptoms, inadequacy of available treatments, and impact of such pain on all aspects of functioning underscore the important role of several psychosocial factors in causing, maintaining, and amplifying the perception of pain severity, coping adequacy, adaptation, impaired physical function, and emotional distress responses. Moreover, these factors have an influential role in response to treatment recommendations. In this article, we (1) review the prevalence and nature of emotional distress, (2) describe and propose methods for screening and comprehensive psychosocial assessment, and (3) review evidence supporting the potential complementary role of psychosocial treatments of patients with chronic pain. The cognitive-behavioral perspective and treatment approach are emphasized because the greatest amount of evidence supports their benefits. Published results of psychological treatments are modest; however, the same indictment can be placed on currently available pharmacological, medical, and interventional treatments for patients with chronic pain. We note the limited research on the effectiveness of psychological treatment specifically applied to patients with chronic neuropathic pain but suggest that it is reasonable to extrapolate from successful trials in other types of chronic pain. Furthermore, psychological approaches should not be viewed as alternatives but rather should be integrated as part of a comprehensive approach to the treatment of patients with chronic neuropathic pain.

CBT = cognitive-behavioral therapy; SF-MPQ = Short-Form McGill Pain Questionnaire

Chronic neuropathic pain is a prevalent problem that eludes successful treatment. Despite increasing knowledge of the neurophysiologic factors underlying neuropathic pain and advances in pharmacological and invasive treatments, no cure is currently available for most patients. Although newer subclasses of medications (eg, anticonvulsants and antidepressants) and topical and transdermal preparations have expanded clinicians' armamentarium, on average these medications reduce pain severity by 30% to 40%, and often this reduction is achieved in less than 50% of patients treated.1 Even when medications and invasive procedures effectively reduce pain, they often do not produce concomitant improvements in physical and emotional functioning.

There is also a likelihood that available treatments for chronic pain will result in serious complications or adverse effects for a large percentage of patients. For example, premature termination rates from drug trials because of lack of efficacy or adverse events often exceed 30%,1 and more than 40% of patients enrolled in long-term, open-label extensions of clinical trials for opioids terminate participation.2 Furthermore, opioids may be less effective in the setting of neuropathic pain and have risk of misuse and abuse that may exceed 40%.3-5 In some studies, investigators reported that more than 40% of patients with implanted devices for pain control experience adverse events6; up to 67.7% of patients treated with lumbar surgery for back pain reported that their pain was worse after surgery,7 and at least moderate adverse effects have been reported to occur in 30% to 61% of all patients who undergo spinal manipulations.8 These findings do not argue against the use of such treatments but serve as reminders of limitations and possible harmful effects.

The mean duration of pain in patients who seek treatment at chronic pain treatment facilities is approximately 7 years.9 Consequently, all domains of their lives may have been compromised for a substantial amount of time. It is hardly surprising that levels of emotional distress for patients with persistent pain are high. Estimates suggest that at least 1 current psychiatric diagnosis is present in 59% of patients with chronic back pain treated at pain facilities and at least 1 lifetime psychiatric diagnosis is present in 77% of these patients.10 In contrast, community estimates are 15% for at least 1 current psychiatric diagnosis and 29% to 38% for at least 1 lifetime psychiatric diagnosis.11 Other reports suggest that approximately 33% of patients evaluated at tertiary care pain facilities experience anxiety disorders12 and between 40% and 60% of people meet criteria for a depressive disorder.13 Given the information and data on the limited efficacy of treatments available, 1 group raised the question: “Why aren't all patients [with chronic pain] depressed?”14

One must be cautious, however, about relying on diagnostic criteria for psychiatric disorders in patients with neuropathic pain. Many psychiatric diagnoses in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition15 have symptoms that overlap with symptoms of medical conditions. Moreover, somatic symptoms that can be attributed to pain and the medication being taken overlap with clinical depression (eg, sleep disturbance, motor retardation, loss of energy, and change in appetite and weight).

The prevalence estimates of psychiatric comorbidities previously noted raise the question of whether having a chronic medical condition and not specifically pain increases emotional distress. Gore et al16 presented data that directly compared emotional and physical functioning of community samples of people with diabetes mellitus and individuals with diabetic painful neuropathies (Figure). On each measure, people with diabetes reported diminished emotional functioning. Moreover, those with diabetic painful neuropathies identified even greater decrements in functioning and higher levels of emotional distress than the community sample, but more importantly when compared with people with diabetes who did not have diabetic painful neuropathies. These data raise an important question: Are these emotional factors causal or reactive? That is, patients may have a premorbid history of emotional problems, existing psychiatric and psychosocial problems may exacerbate the presence of chronic pain and related symptoms, or psychiatric and psychosocial problems may evolve in response to a chronic, painful condition. Regardless, the rates of emotional distress are high and need to be considered when the physician develops a comprehensive treatment plan in which both physical and psychological symptoms are treated.

Impact of diabetic painful neuropathies (DPNs) on physical and mental health status (N=255). Adapted from J Pain Symptom Manage,16 with permission.

The average age of patients treated at pain facilities is 44 years, and the mean duration of reported pain is 7 years.9 Thus, before pain onset, patients' histories spanned 37 years; detailed exploration of these histories is important in understanding how people respond to their current symptoms. Moreover, people with pain live in a social context in which the significant people in their lives likely have a large influence on their adaptation to chronic pain. These facts, along with the others previously described, underscore the need to attend to psychosocial and behavioral factors, as well as neurophysiological factors, in treating patients with neuropathic pain.

Patients with neuropathic pain and psychological comorbidities create diagnostic dilemmas; such patients require additional treatment consideration to optimize outcomes. Regardless of whether they are causes or effects, psychiatric comorbidities and psychosocial problems can exacerbate and negatively affect the severity of pain, the course of the disease, patients' adaptation, and responses to treatment. Thus, we propose that successful treatment of most patients with chronic neuropathic pain requires an integrated, multimodal approach, rather than individual pharmacological and nonpharmacological therapies.

These observations of the efficacy of available treatments and duration of pain have led to several conclusions: (1) the persistence of pain, even if reduced, will continue in most people; (2) pain, especially persistent pain, will continue to affect all domains of people's lives; (3) psychosocial and behavioral factors will play an important role in the experience, maintenance, and exacerbation of pain; and (4) in the absence of cure, success will depend a great deal on adaptation to symptoms and self-management that complements biomedical interventions. In the remainder of this article, we describe strategies for assessing patients with neuropathic pain and review psychological approaches and interventions that can be used to help patients with chronic neuropathic pain, extrapolating from the chronic pain literature in general.


On the basis of a biopsychosocial perspective, clinicians should assess not only the physical source of the pain through examination and diagnostic tests but also the patient's mood, fears, expectations, coping efforts, and resources; responses of significant others; and the impact of pain on the patient's life. In short, the clinician must evaluate the whole patient, not just the physical symptoms or the site of pain. Regardless of whether a neuroanatomic basis for the pain can be documented or whether psychosocial problems preceded or resulted from the pain, a comprehensive evaluation process will help identify how biomedical, psychosocial, and behavioral factors interact to influence the nature, severity, and persistence of symptoms and disability.

Psychosocial assessment of patients with neuropathic pain does not differ from assessment of patients with chronic pain except that the clinician must ask about the unique characteristics of nerve-related pain. Psychosocial assessment addresses the specific behaviors (responses to the patient's symptoms by significant others, such as family members or coworkers), cognitions (eg, beliefs, attitudes, expectations, interpretation of the meaning, and implications of symptoms), and mood (eg, anxiety and depression), each of which synergistically contributes to the subjective experience of pain. This type of information should be included as the basis for developing a comprehensive treatment plan. The set of questions with the acronym ACT-UP (Activities, Coping, Thinking, Upset [mood], People responses; Table 1) is an efficient method to cover important psychosocial and behavioral areas. Additional questions may follow, depending on patients' responses, and referral for a more comprehensive psychological evaluation may be appropriate.

Brief Psychosocial Screening: ACT-UP


Generally, a referral for psychological evaluation may be indicated in the following circumstances: (1) when disability greatly exceeds what would be expected on the basis of physical findings alone, (2) when patients make excessive demands on the health care system, (3) when patients persist in seeking medical tests and treatments that are not indicated, (4) when patients display significant emotional distress (eg, depression or anxiety), or (5) when patients display evidence of addictive behaviors or continual non-adherence to the prescribed treatment regimen. Before interventional pain procedures, such as spinal cord stimulation or intrathecal drug administration, are considered, a formal psychological evaluation should be considered. General areas that are covered in a more extensive psychological interview of patients with pain are outlined in Table 2.

Areas Covered in Psychological Interviews


A psychological interview with patients is typically semistructured; however, a structured psychiatric interview17 can be incorporated as a tool to examine psychopathological conditions. A psychological interview needs to extend beyond assessing psychopathologic conditions because its primary purpose is to assess a wide range of psychosocial factors (not just psychopathologic factors) related to a patient's symptoms, maladaptive behaviors, and disability.

When interviewing a patient with chronic pain, the clinician should focus not only on gathering information provided by the patient but also on observing the patient's pain behaviors and the manner in which information is conveyed. When possible, it is valuable to observe how significant others respond to the patient's behavioral presentation to better understand their beliefs and expectations about pain because these factors may influence how significant others respond to the patient and will affect the patient's behaviors. Patients' beliefs about the cause of their symptoms, their symptoms' trajectory, and past or potential beneficial treatments will influence emotional adjustment and adherence to therapeutic interventions. A habitual pattern of maladaptive thoughts may contribute to a sense of hopelessness, dysphoria, and unwillingness to engage in recommended treatments and activities. These reactions, in turn, deactivate the patient and severely limit his or her coping efforts. The clinician should also determine both the patient's and significant others' expectations and goals for treatment and their future. An expectation that pain will be eliminated completely may be unrealistic, and this issue needs to be addressed to prevent discouragement when pain recurs or persists. Helping the patient to set appropriate and realistic goals is important in pain rehabilitation because it requires the patient to attain a more complete understanding of chronic pain that extends beyond the traditional dualistic medical model that rigidly separates mind from body.

To help patients with neuropathic pain better understand the psychosocial aspects of their pain, clinicians should focus patients' attention on their reports of specific thoughts, behaviors, emotions, and physiologic responses that precede, accompany, and follow pain episodes or exacerbations, as well as on the environmental conditions and consequences associated with cognitive, emotional, and behavioral responses in these situations. Clinicians should also attend to the following to establish salient features: the temporal association of these cognitive, affective, and behavioral events; their specificity vs generality across situations; and the frequency of their occurrence. Furthermore, the clinician needs to seek information that will assist in the development of potential alternative responses, appropriate goals for the patient, and possible reinforcers for these alternatives.

Patients with chronic pain are often prescribed a variety of medications not only for their pain but also for the myriad comorbid symptoms that may be part of their diagnosis. The clinician needs to discuss a patient's medications because many pain medications are associated with adverse effects that may mimic emotional distress. For example, clinicians should be familiar with adverse effects that result in fatigue, sleep difficulties, and mood changes to avoid the misdiagnosis of depression. A general understanding of commonly used medications for neuropathic pain is important, and when possible, the goal should be to simplify the regimen by finding a single agent that can positively influence both pain and other symptoms, such as mood and sleep.


In addition to interviews, a number of assessment instruments have been designed to evaluate patients' attitudes, beliefs, and expectations about themselves, their symptoms, and the health care system.18 Easily administered, standardized instruments assess a wide range of behaviors, obtain information about behaviors that may be private (eg, sexual relations) or unobservable (eg, thoughts and emotional arousal), require less clinician time, and contain normative data that allow comparison to reference groups. These instruments should not be viewed as alternatives to interviews, but as complements because they can suggest issues to be addressed in more depth during an interview or by other methods.


Self-report measures of pain often ask patients to quantify their pain by providing a single, general rating of pain: “Is your usual level of pain mild, moderate, or severe?” or “Rate your typical pain on a scale from 0 to 10, in which 0 equals no pain and 10 is the worst pain you can imagine.” Several simple methods can be used to evaluate current pain intensity: numerical rating scales, verbal rating scales, and visual analog scales. The numerical rating scales may be the most useful in clinical studies. However, the limitations of these unidimensional measures must be recognized because they are nonlinear across their range and fail to reflect much of the complexity of the pain experience.

Pain Quality

In addition to intensity, pain is known to have different sensory and affective qualities that can be measured to describe more fully an individual's pain experience. Because the efficacy of pain treatments can vary for different pain qualities, these measures can identify treatments that are efficacious for certain types of pain but not for overall pain intensity. For example, the Short-Form McGill Pain Questionnaire (SF-MPQ)19 assesses 15 sensory and affective pain descriptors, and its sensory and affective subscales have demonstrated responsivity to treatment in a number of clinical trials.20,21 Recently, a revised version of the SF-MPQ, the SF-MPQ-2, has been published.22 The major advantage of the SF-MPQ-2 is the addition of descriptors specific to neuropathic pain. In addition, the format has been modified from a 0- to 3-point scale to a 0- to 10-point scale, providing increased opportunities to detect small changes that may occur after treatment and activities.

Pain Modifiers

For most people with neuropathic pain, pain severity varies. Thus, it is useful to ask the patient what he or she thinks amplifies (eg, specific activities, circumstances that contribute to exacerbation of pain, or time of day) and alleviates the pain (eg, medication, rest, temperature, exercise, or distraction).


Diagnosing the cause of emotional distress in people with chronic pain is a challenge because pain-related symptoms, such as fatigue, reduced activity level, decreased libido, appetite change, sleep disturbance, weight gain or loss, and memory and concentration deficits, are also considered “vegetative” symptoms of depressive disorders. Therefore, improvements or deterioration in such symptoms can be a result of changes in pain, emotional distress, or both.

The Beck Depression Inventory23,24 and the Profile of Mood States (which assesses 6 mood states—tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment—and also provides a summary measure of total mood disturbance)25 are standard measures that have well-established reliability and validity in assessing symptoms of depression and emotional distress. These measures have been recommended to assess emotional distress of participants enrolled in clinical trials.26


As noted previously, patients display a broad range of pain behavior responses that communicate to others that they are experiencing pain, distress, and suffering. Although there is no one-to-one relationship between these pain behaviors and self-reports of pain, experience suggests that they are at least modestly correlated. Informally, a health care professional can observe behaviors during an interview and examination. Because the patient knows he or she is being observed in these contexts, it is useful to observe behaviors in the waiting room, while the patient walks to the examination room, during history taking and physical examination, and when the patient exits. Additionally, the clinician should observe a patient's behavior in the presence of significant other(s) and observe the significant other(s)' responses to the behaviors. Variations in these behaviors in different situations should be noted.

Uses of the health care system and analgesic medication can be viewed as pain behaviors. Patients can record in a daily diary the frequency and quantity of medication they take during a specified interval, such as a week. Such information helps identify behavioral patterns in response to pain that the patient may not recall during interviews.

A diary may also help identify the antecedent (eg, anxiety or stress) and consequent events associated with pain intensity and medication use. Examining antecedents is useful for identifying patterns of medication use that may be associated with factors other than pain per se. Similarly, patterns of response to the use of analgesic may be identified, and the possible reinforcing role can be investigated.


Self-report measures have been developed to assess patients' reports of their abilities to engage in a range of functional activities, such as being able to walk up stairs, lift specific weights, and perform activities of daily living. These measures are also designed to evaluate the severity of the pain experienced while these activities are being performed. A number of well-established, psychometrically supported generic (eg, Medical Outcomes Study 36-Item Short-Form Health Survey)27 and pain-specific (eg, Brief Pain Inventory, Interference Scale28 and Multidimensional Pain Inventory Interference Scale29) measures of functional status are available and have been recommended for use in clinical trials.26

In general, disease-specific measures are designed to evaluate specific effects of a disorder that may not be assessed by a generic measure. Generic measures often do not have the sensitivity to measure change resulting from treatment; this is particularly true for an individual patient. In these cases, the disease-specific measures are more sensitive to change. Disease-specific measures may be more sensitive to the effects of treatment on function, but generic measures provide information about physical functioning and treatment benefits that can be compared across different conditions and studies.30


Psychological treatments of chronic pain can generally be separated into theoretically based approaches and specific techniques. The most common theoretical approaches are operant conditioning and cognitive-behavioral therapy (CBT), whereas the most frequently used psychological techniques include supportive counseling, cognitive therapy, hypnosis, relaxation, biofeedback, and meditation (Table 3). Because the theoretically based approaches, especially CBT, which incorporates behavioral principles of operant conditioning, have been better researched than the specific techniques, we focus on them. Furthermore, the various psychological techniques can be used within a CBT perspective that incorporates the behavioral principles of operant conditioning.

Psychological Perspectives and Treatments

Operant Conditioning

Operant conditioning is based on the principles of reinforcement, with the emphasis on modifying responses to maladaptive behaviors and, in the case of chronic pain, behaviors that consist of overt expressions of pain, distress, and suffering.31 From this behavioral perspective, pain is conceptualized as a subjective experience that can never be observed directly. All that can be known about patients' pain is inferred from the connection among observable behaviors, such as limping, moaning, and ambulating in a guarded fashion; pain behaviors; and self-reports of pain. These observable behaviors elicit responses from others and clinicians, responses that can serve to reinforce and thereby maintain the behaviors. Conversely, failure to positively reward the behaviors can extinguish them. Thus, the operant conditioning perspective suggests that treatment is focused on changing the contingencies of reinforcement provided by external agents in response to behaviors indicating the presence of pain.

Cognitive-Behavioral Therapy

Treatments based on operant conditioning within the CBT perspective do not focus on eliminating pain but rather on improving physical and emotional functioning despite pain. A range of behavioral and cognitive techniques is used to accomplish these primary objectives. Although CBT evolved from an operant conditioning model, emphasis is also placed on the role of patients' attitudes, beliefs, and expectations.32 Thus, targets of treatment are both responses from the environment, as in operant conditioning, and internal cognitive processes of patients, which are thought to influence their symptom perception and responses. Cognitive-behavioral therapy emphasizes using both behavioral and cognitive techniques (eg, relaxation and problem solving) to help patients shift from being passive, reactive, and helpless in the face of pain to being active and resourceful in coping with their symptoms and their lives despite aversive symptoms. Furthermore, CBT emphasizes teaching patients to reconceptualize their thoughts about the meaning of their pain, replacing their more typical feelings of hopelessness, helplessness, and passivity. The expectation is that patients will gain mastery over their pain, improve their mood, increase activity, and reduce disability.

Distinguishing the cognitive-behavioral perspective from cognitive-behavioral techniques is important.33 The cognitive-behavioral perspective is predicated on the assumption that people believe they are unable to function because of their pain and that they are helpless to improve their situation. Treatment goals focus on helping people with pain to realize that they can manage their problems and learn new skills so they can respond more adaptively after treatment is terminated.

The CBT approach typically combines stress management, problem solving, goal setting, pacing of activities, and relaxation. These skills can be integrated within a rehabilitation approach. Cognitive-behavioral techniques are woven into the fabric of treatment in an effort to enhance patients' sense of self-control. Biofeedback and hypnosis can be incorporated into CBT to facilitate and expand the set of self-management strategies available to a patient to modulate pain perceptions.


The first reported clinical trial of behavioral treatment of chronic pain was published by Fordyce et al34 in 1968, although anecdotal reports about various psychological approaches date back hundreds of years. Since that initial publication, investigators have reported a large number of clinical trials evaluating the efficacy of various psychological treatment approaches and modalities, including CBT, biofeedback, and hypnosis, for a range of chronic pain diagnoses.35,36 These studies focused primarily on patients with musculoskeletal disorders or heterogeneous samples of chronic pain; the percentage of patients with neuropathic pain was unspecified.

The effectiveness of psychosocial treatments in patients with neuropathic pain conditions is limited to 3 small preliminary studies,37-39 each of which reports significant patient benefits with CBT and hypnosis. In one study, hypnosis, but not relaxation, significantly improved pain and physical functioning for up to 3 months after treatment.

Investigators who conducted meta-analyses and systematic reviews involving adult patients with chronic pain arrived at somewhat similar conclusions: as a group, psychological treatments have modest benefits on improving pain and physical and emotional functioning. However, evidence is inadequate for long-term efficacy and somewhat contradictory for effects on vocationally relevant outcomes.35,36,40

Mechanisms involved in successful psychological treatments have received some attention. For example, Turner et al41 found that mediators of improvement in pain and activity 1 year after CBT were cognitive variables, including patients' perceptions of control, disability, self-efficacy, harm, catastrophizing, and rumination. The investigators also found factors that predicted therapeutic change, including the number of pain sites, depression, somatization, rumination, catastrophizing, and stress that existed before treatment. Such data confirm the need to address the psychosocial and physical aspects of the chronic pain experience. Addressing both the psychosocial and the physical aspects is more likely to obtain positive and enduring results even in the absence of cure.

Although only modestly efficacious, psychosocial treatments typically have been used as an adjunctive modality with the most recalcitrant problems. The modest reduction in pain severity obtained with psychological interventions and comprehensive rehabilitation studies is comparable to that observed with more traditional pharmacological and procedural treatment modalities.1 Evidence for the efficacy of psychological treatments on physical functioning is stronger than for pharmacological and invasive treatment.9 These observations suggest that none of the most commonly prescribed treatment regimens, by themselves, are sufficient to eliminate pain and substantially affect physical and emotional functioning in most patients with chronic pain, which is hardly surprising given the complexity of chronic pain. A more realistic approach will likely be one that combines pharmacological, physical, and psychological components, tailoring them according to individual patients' needs.


For the person experiencing chronic pain, the quest for relief often remains elusive, leading to feelings of helplessness, hopelessness, demoralization, and depression. People who experience chronic pain must confront not only the stress created by pain but also a cascade of ongoing stressors that may compromise all aspects of their lives. Living with chronic pain requires considerable emotional resilience; chronic pain tends to deplete emotional reserve and taxes not only the person experiencing pain but also the capacity of significant others to provide support.

A large body of evidence demonstrates that psychological factors can interfere with or hinder a person's ability to cope with the pain experience. As a result, psychological assessment and intervention have become standard in chronic pain treatment. Psychological treatments focus on the emotional distress and maladaptive behaviors that accompany chronic pain; they also provide patients with cognitive and behavioral self-management strategies that may reduce their perceptions of pain and related disability and enhance their self-efficacy. Psychological principles have played a major role in understanding and treating people with pain; mental health care professionals have an important function in interdisciplinary pain rehabilitation programs.

Although psychological approaches and techniques have been found to be helpful for a number of individuals, these treatments have not proven to be beneficial for some people. Investigators are just beginning to explore different aspects of CBT to answer the question, “What works for whom?”42,43 Few available data are consistent in identifying the characteristics of people who would most likely benefit from any of the pain treatment methods described, although some studies suggest that tailored treatments are associated with more improved symptoms compared with standard treatment.44-47 For example, Thieme et al46 found that patients with high levels of pain behaviors responded better to operant behavioral therapy than to CBT; conversely, patients with low levels of pain behavior responded better to CBT than to operant behavioral therapy. Additional studies are needed to determine what treatments delivered in what ways are most effective for people with what set of characteristics with the fewest iatrogenic complications and adverse events. Answers to this complex question will permit more clinical and cost-effective ways to treat people with chronic pain.1

None of the treatments described are successful in completely eliminating pain; consequently, most people have to adapt to the presence of chronic pain and learn self-management in the face of persistent pain and its accompanying symptoms. On the basis of the demonstrated effects of psychological treatment of diverse chronic pain disorders and the preliminary results reported for neuropathic pain, we recommend that psychological approaches be considered as complementary, not alternative, to medical treatment of neuropathic pain. The techniques and modalities described can be readily integrated into more comprehensive rehabilitation programs as useful complements to physical therapy, medication management, and rehabilitation. Patients can use psychological approaches and techniques as active personal interventions in their routine self-management and pain flare-ups. They convey a sense of hopefulness as an antidote to the more common feelings of helplessness and dependency. Thus, we recommend that psychological treatment, in particular CBT, be considered as a part of a comprehensive treatment for patients with chronic neuropathic pain.


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