Limitations of Pharmacotherapy

16 May

Limitations of Pharmacotherapy: Behavioral Approaches to Chronic Pain
Abstract Pharmacotherapy is most appropriate in acute pain, whereas in chronic pain states behavioral approaches or a combination  of behavioral treatment  and pharmacotherapy is more appropriate. In this chapter we first describe the role of learning and memory as well as other psychological factors in the development of chronic pain and emphasize that chronic pain must viewed as the result of a learning process with resulting central neuroplastic changes. We then describe operant behavioral and cognitive-behavioral treatments  as well as biofeedback and relaxation  techniques  and present  innovative  treatment  procedures aimed at altering central pain memories.  We complete the section with a discussion of combined behavioral and pharmacological approaches and an interdisciplinary  view.

Keywords  Operant conditioning in acute and chronic pain · Learning · Memory · Physical training · Cognitive and behavioral therapeutic approaches · Multidisciplinary rehabilitation


Pharmacotherapy of chronic pain has several limitations. First, the drug does not always target the region in the central nervous system where the main effect should be but will occupy all receptors, thus leading to unwanted general and side effects. Second, analgesic medication is as much prone to tolerance and loss of efficacy as other drugs, and especially opioids can themselves induce hyperalgesia over time (Angst and Clark 2006). Third, long-term  analgesic medication can be associated with learning processes that enhance the amount of medication consumed and can drive patients into dependence and lead to cognitive and other neuropsychological deficits (Buntin-Mushock et al. 2005). Moreover, in chronic states of pain the initial cause of the pain is often no longer relevant and other—in many cases central—factors may now be causal for the pain that is experienced. In this chapter we will give an overview of the behavioral and learning-related  factors that contribute  to chronic pain, including their neural correlates, and will then describe behavioral as well as combined behavioral and pharmacological approaches that can address these factors and can overcome some of the limitations of pharmacotherapy.

The Role of Learning Mechanisms and Psychological Factors in Chronic Pain

Operant Learning

A new era in thinking  about  pain began with Fordyce’s (1976) description of the role of operant  factors in chronic  pain. In the operant  formulation, behavioral manifestations  of pain rather  than  pain per se are central. It is suggested that when an individual is exposed to a stimulus that causes tissue damage, the immediate response is withdrawal and attempts  to escape from noxious sensations. This may be accomplished by avoidance of activity believed to cause or exacerbate pain, help seeking to reduce symptoms, and so forth. These behaviors are observable and, consequently, subject to the principles of operant  conditioning,  i.e., they respond  to contingencies  of reward and punishment.

The operant  view proposes that acute “pain behavior” such as limping to protect  a wounded  limb from producing  additional  nociceptive input  may

come under the control of external contingencies of reinforcement  and thus develop into a chronic pain problem. Pain behavior (e.g., complaining, inac- tivity) may be positively reinforced directly, for example, by attention  form

a spouse or healthcare provider. Pain behavior may also be maintained by the escape from noxious stimulation by the use of drugs or rest, or the avoidance

of undesirable activities such as work. In addition, “well behavior” (e.g., ac- tivity, working) may not be sufficiently reinforcing and the more rewarding pain behaviors may therefore  be maintained.  The pain behavior originally elicited by organic factors may come to occur, totally or in part, in response to reinforcing environmental  events. Because of the consequences of specific behavioral responses, it is proposed that pain behaviors may persist long after the initial cause of the pain is resolved or greatly reduced. The operant  con- ditioning model does not concern itself with the initial cause of pain. Rather it considers pain as an internal subjective experience that may be maintained even after an initial physical basis of pain has resolved. Operant conditioning can lead to increased inactivity and invalidity and also plays an important role in the increase of medication levels since the intake of medication—especially on a prn basis when there are high pain levels—may be viewed as a conse- quence of a negative reinforcement process (a negative consequence, the pain, is removed by medication intake). Not only observable pain behaviors but also verbal expressions of pain and physiological variables may come under  the control of the contingencies of reinforcement.

Respondent Learning Mechanisms

Factors contributing to chronicity that have previously been conceptualized in terms of operant learning may also be initiated and maintained by respondent conditioning  (Gentry and  Bernal 1977). In the typical classical condition- ing paradigm, a previously neutral variable (conditioned stimulus, CS), when paired with a biologically significant stimulus (unconditioned stimulus, US) comes to elicit a conditioned  response  (CR) that resembles the response  to the unconditioned stimulus, the unconditioned response (UR). For example, if a certain movement has been associated with pain, just thinking about the movement may already elicit fear and muscle tension (previously elicited by pain) and may then motivate avoidance behaviors. Lethem et al. (1983) have suggested that once an acute pain problem exists, fear of motor activities that the patient expects to result in pain may develop and motivate avoidance of activity. Nonoccurrence  of pain is a powerful reinforcer for reduction  of ac- tivity and thus the original respondent  conditioning  may be followed by an operant learning process whereby the nociceptive stimuli and the associated responses need no longer be present for the avoidance behavior to occur. In acute pain states it may be useful to reduce movement, and consequently avoid- ing pain, to accelerate the healing process. Pain related to sustained  muscle contractions might, however, also be conceptualized as a US in the case where no acute injury was present and sympathetic activation and tension increases might be viewed as URs that may elicit more pain, and conditioning  might proceed in the same fashion as outlined  above. Thus, although the original association between pain and pain-related stimuli results in anxiety regarding

these stimuli, with time the expectation of pain related to activity may lead to avoidance of adaptive behaviors even if the nociceptive stimuli and the related sympathetic activation are no longer present. Fear of pain and activity may become conditioned  to an expanding number  of situations.  Avoided activi- ties may involve simple motor behaviors, but also work, leisure, and sexual activity. In addition to the avoidance learning, pain may be exacerbated and maintained in these encounters with potentially pain-increasing situations due to the anxiety-related sympathetic activation and muscle tension increases that may occur in anticipation  of pain and also as a consequence of pain. Thus, psychological factors may directly affect nociceptive stimulation and need not be viewed as only reactions to pain. Vlaeyen and Linton (2000) have shown that fear avoidance is a major predictor of chronic pain and disability.

Cognitive Factors in Chronic Pain

Cognitive-behavioral models of chronic pain emphasize that the evaluation of the pain experience by the patient greatly determines the amount of pain that is experienced as well as its negative consequences (Turk et al. 1983). Gen- eral assumptions  that characterize the cognitive-behavioral  perspective are: (1) people are active processors of information  and not passive reactors; (2) thoughts  (e.g., appraisals, expectancies) can elicit or modulate mood, affect physiological processes, influence the environment,  and serve as the impetus for behavior. Conversely, mood, physiology, environmental factors, and behav- ior can influence thought processes; (3) behavior is reciprocally determined by the person and environmental  factors; (4) people can learn more adaptive ways of thinking, feeling, and behaving; and (5) people are capable and should be involved as active agents in change of maladaptive thoughts, feelings, and behaviors.

From the cognitive-behavioral perspective, people suffering from chronic pain are viewed as having negative expectations about their own ability to con- trol certain motor skills such as performing specific physical activities (e.g.,

climbing stairs, lifting objects) that are attributed  to one overwhelming fac- tor, namely, a chronic pain syndrome. Moreover, chronic pain patients tend to believe that they have a limited ability to exert any control over their pain.

Such negative, maladaptive appraisals about the situation and personal efficacy may reinforce the experience of demoralization,  inactivity, and overreaction to nociceptive stimulation. A great deal of research has been directed toward

identifying cognitive factors that contribute to pain and disability. These have consistently demonstrated that patients’ attitudes, beliefs, expectancies about their plight, themselves, their coping resources and the healthcare system affect their reports  of pain, activity, disability, and response to treatment.  A num-

ber of studies have used experimental pain stimuli and demonstrated that the conviction of personal control can ameliorate the experience of experimen-

tally induced nociception.  Moreover, the type of thoughts  employed during exposure to painful stimulation  has been related to pain tolerance and pain intensity ratings. Catastrophic thoughts have been associated with lower pain tolerance and higher ratings of pain intensity. In contrast,  coping thoughts have been related to higher pain tolerance and lower pain intensity ratings. Once beliefs and expectancies (cognitive schemata) about a disease are formed they become stable and are very difficult to modify. Patients tend to avoid ex- periences that could invalidate their beliefs and they guide their behavior in accordance with these beliefs even in situations where the belief is no longer valid (no corrective feedback is received to discredit this belief ). For example, feeling some muscular pain following activity may be caused by lack of mus- cle strength and general deconditioning and not by additional tissue damage. Imaging studies have shown that cognitive factors modify the central process- ing of pain and that attention can increase and distraction can decrease brain activation related to pain.

Pain and Affect

The affective factors associated with pain include many different emotions, but they are primarily negative in quality. Anxiety and depression have received the greatest amount of attention  in chronic pain patients; however, anger has recently received considerable  interest  as an important emotion  in chronic pain patients. Research suggests that from 40% to 50% of chronic pain patients suffer from depression (Bair et al 2003). There have been extensive and fruitless debates concerning the causal relationship  between depression and pain. In the majority of cases, depression appears to be the patients’ reaction to their plight. The presence of depression is closely related to the feelings of loss of control and helplessness often associated with pain. Several investigators have also found a close association between fear of pain and dysfunctional coping. In addition,  high comorbidity  between anxiety disorders and pain seems to be present. Muscular hyperreactivity to stress seems to be closely associated with fear of pain. Anger has been widely observed in individuals with chronic pain. The internalization  of angry feelings seems to be strongly related  to measures  of pain intensity,  perceived interference,  and reported  frequency of pain  behaviors.  Anger and  hostility are closely associated  with pain  in persons with lower back pain. Frustrations related to persistence of symptoms, limited information  on etiology, and repeated treatment  failures along with anger toward employers, the insurance industry, the healthcare system, family members, and themselves, also contribute  to the general dysphoric mood of these patients. The impact of anger and frustration  on exacerbation of pain and treatment  acceptance has not received adequate  attention.  It would be reasonable to expect that the presence of anger may serve as an aggravating factor, associated with increasing autonomic arousal and blocking motivation

and acceptance  of treatments  oriented  toward  rehabilitation  and disability management  rather than cure, which are often the only treatments  available for chronic pain.

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