A Biobehavioral Perspective

16 May

A biobehavioral  or a diathesis-stress  model of chronic  pain needs to con- sider the factors discussed above and their mutual interrelationships in the explanation  of chronic pain. The existence of a physiological disposition  or diathesis is one important  component.  This predisposition  is related to a re- duced threshold for nociceptive stimulation and can be determined by genetic factors and acquired through early learning experiences. For example, Mogil (1999) showed that large genetic variations in individual pain sensitivity ex- ist. Very impressive evidence for the role of early traumatic experience comes from the work of Anand et al. (1999) who showed that minor noxious experi- ence in neonate rats leads to dramatic alterations (sensitization) in nociceptive processing in the adult organism. A further component  of the biobehavioral model is a response stereotypy of a particular bodily system such as exagger- ated muscular responses of the lower back muscle to stress and pain that is based both on the diathesis and on aversive experiences present at the time of the development of the response. These aversive stimuli may include personal or work stress or problematic occupational conditions and will lead not only to painful responses but also to avoidance behaviors and associated maladaptive cognitive and affective processes. The cognitive evaluation of these external or internal stimuli is of great importance in the pain response as discussed above. The focus of the biobehavioral perspective is thus on the patient and not just on the symptoms or the underlying pathology, and this focus also requires that the treatment of the patients be tailored not only to medical factors but that it incorporates  psychosocial variables that may often be predominant in states of chronic pain.

Memory for Pain

An important maintaining factor in this chronicity process is the development of central neuroplastic changes or pain memories. These pain-related memo- ries may be explicit (open to conscious awareness) or implicit (not conscious such as habits) and may subsequently guide the patient’s experience and be- haviors. For example, pain patients have a tendency to remember preferentially negative and pain-related life events and show a deficit in the retrieval of posi- tive memories. The experience of

the processing of pain. This expanded cortical representation is accompanied by increased sensitivity to both painful and nonpainful  stimuli and may be further enhanced by learning processes or attention to painful stimulation. An even more dramatic  example of a learned memory for pain has been found in phantom limb pain patients (Flor et al. 1995). In upper extremity amputees the magnitude of the phantom limb pain was found to be proportional to the amount of reorganization  in primary somatosensory cortex, namely, the shift of the cortical mouth representation into the area where the amputated  limb was formerly represented.  The brain  obviously maintains  a memory of the former input to the deafferented area and subsequently stimulation stemming from areas adjacent  to the deafferented  zone elicits sensations  and pain in the now absent limb. Phantom  pain and cortical reorganization  are absent in congenital  amputees,  suggesting a major role for learning. Neuroplastic learning-related  changes outlast the time of nociceptive stimulation  and can produce extensive and enduring alterations of nociceptive processing that have to be taken into account in effective treatment planning.

Psychological Treatment of Chronic Pain

Operant Behavioral Treatment

Patients who show high levels of pain behaviors and are incapacitated by their pain should profit from operant behavioral treatment. The goals of this treat- ment are the increase of activity levels and healthy behaviors related to work, leisure time, and family as well as medication reduction and management and the change of the behavior of significant others (cf., Fordyce 1976). The overall goal is to reduce disability by reducing pain and increasing healthy behaviors. Medication is switched from a prn basis to a fixed time schedule, where med- ication is given at certain times of the day to avoid negative reinforcement learning from occurring. Similar principles are applied to the enhancement of activity and the reduction of inactivity and invalidity. This approach has been found to be effective in patients with chronic back pain as well as other pain syndromes. Figure 1 shows data on the treatment of fibromyalgia in an operant protocol (Thieme et al. 2003).

Cognitive-Behavioral Treatment of Chronic Pain

The cognitive-behavioral model of chronic pain emphasizes the role of cog- nitive, affective and behavioral factors in the development and maintenance of chronic pain. The central tenet of cognitive-behavioral treatment  is to re- duce feelings of helplessness and uncontrollability  and to establish a sense of

chronic pain also leads to the development of somatosensory pain memories, for example, an expanded representation of the affected body part in primary somatosensory cortex and other areas related to

A Biobehavioral Perspective

Fig. 1 Changes in pain intensity, number of doctor visits, and number of hospital visits in an operant behavioral compared to a standard medical treatment  for chronic fibromyalgia syndrome. (Based on Thieme et al. 2003)

control over pain in the patients. This is achieved by the modification of pain- eliciting and maintaining behaviors, cognitions, and emotions. The cognitive- behavioral approach teaches patients various techniques to effectively deal with episodes of pain. Pain-related cognitions are changed by cognitive restructur- ing and pain coping strategies such as attention  diversion, use of imagery, or relaxation that increase self-efficacy. Several studies have examined the effi- cacy of cognitive-behavioral pain management, which must be considered as a very effective treatment of chronic pain (e.g., Turk and Okifuji 2002).

Biofeedback and Relaxation

Biofeedback refers to the modification  of a normally  nonconscious  bodily process (e.g., skin temperature, muscle tension) by making the bodily process perceptible  to the patient.  The respective physiological signal is measured and amplified and  fed back to the patients  by the use of a computer  that translates variations in bodily processes into visual, auditory, or tactile signals. Seeing or hearing one’s blood pressure  or muscle tension enables a person to self-regulate it. The most common type of biofeedback for chronic pain is muscle tension or electromyographic  (EMG) biofeedback, which was found to be effective for several chronic musculoskeletal pain syndromes (e.g., Flor et al. 1992; see Fig. 2). For migraine  headache, temperature, blood flow of the temporal artery, or slow cortical potentials have been fed back with good

Fig. 2 Changes in pain intensity  after treatment  with biofeedback, pseudo therapy,  and a standard medical treatment for chronic back pain

results. Similar positive data are available for Raynaud’s disease with respect to temperature feedback. Another respondent  method uses various types of relaxation training  among which progressive muscle relaxation seems to be especially suited for the treatment of chronic musculoskeletal pain.

Innovative Treatment of Chronic Pain: Changing Pain Memories

The discussion in the preceding sections suggests that the alteration  of so- matosensory  pain memories might be an influential method to reduce both chronic musculoskeletal and neuropathic pain. This could be achieved by alter- ing the peripheral input that enters the brain region that coded a pain memory, e.g., by using EMG or temperature biofeedback or by employing a sensory sim- ulation protocol that provides relevant correlated sensory input to the respec- tive brain region. It would also be possible to directly alter the brain response to pain by providing feedback of event-related potential components  or EEG rhythms  or even blood oxygenation  level-dependent  changes in functional magnetic resonance imaging (fMRI). Most of these methods have not yet been tested in a systematic manner and their effects on cortical reorganization  are so far unknown. Alternatively, pharmacological interventions  could be used that prevent or reverse the establishment of central memory traces.

In phantom limb pain, it was assumed that the pain is maintained by cortical alterations fed by peripheral random input. In this case the provision of corre- lated input into the amputation zone might be an effective method to influence phantom limb pain. fMRI was used to investigate the effects of prosthesis use on phantom  limb pain and cortical reorganization.  Patients who systemati- cally used a myoelectric prosthesis that provides sensory and visual as well as motor feedback to the brain showed much less phantom limb pain and cortical reorganization than patients who used either a cosmetic or no prosthesis. The relationship between phantom  limb pain and use of a myoelectric prosthesis was entirely mediated by cortical reorganization (Lotze et al. 1999). When cor- tical reorganization was controlled for, phantom limb pain and prosthesis use were no longer associated. This suggests that sensory input to the brain region that formerly represented  the now absent limb may be beneficial in reducing phantom  limb pain. These studies were performed in chronic phantom  limb pain patients. An early fitting and training with a myoelectric prosthesis would probably be of great value not only in the rehabilitation  of amputees but also in preventing or reversing phantom limb pain.

These assumptions were further confirmed in an intervention study where the patients received feedback on sensory discrimination of the residual limb. Eight electrodes were attached to the residual limb and provided high-intensity

nonpainful electric stimulation of varying intensity and location that led to the experience of intense phantoms  (Flor et al. 2001). The patients were trained to discriminate the location or the frequency of the stimulation (in alternating

trials) and received feedback on the correct responses. The training was con- ducted for 90 min per day and was spread over a period of 2 weeks (10 days of training). Compared to a medically treated control group (receiving an equal

amount of attention) the trained patients showed significantly better discrimi- nation ability on the stump. They also experienced a more than 60% reduction of phantom limb pain and a significant reversal of cortical reorganization with a shift of the mouth  representation back to its original location. The alter-

ations in discrimination ability, pain, and cortical reorganization  were highly significantly correlated.

In a related study asynchronous tactile stimulation of the mouth and hand

region was used over a period of several weeks. This training was based on the idea that synchronous stimulation leads to fusion and asynchronous stimula- tion leads to a separation  of cortical representation zones. In this case it was postulated that input from the mouth representation that would now activate the region that formerly represented the now-amputated hand and arm would be eliminated and with it the phantom  phenomena  that would be projected to the amputated limb. This intervention also showed a reduction in phantom limb pain and cortical reorganization (Huse et al. 2001).

Moseley (2004) used a tripartite program for patients with complex regional pain syndrome (CRPS). This program contained a hand laterality recognition

task (recognizing a pictured hand to be left or right), imagined movements of

the affected hand, and mirror  therapy (adoption  of the hand posture shown on a picture with both hands in a mirror box while watching the reflection of the unaffected hand). After a 2-week treatment, pain scores were significantly reduced (see Fig. 3). McCabe et al. (2003) also found a reduction in pain ratings during and after mirrored visual feedback of movement of the unaffected limb in complex regional pain syndrome. These studies suggest that modification of input into the affected brain region may alter pain sensation.

Interdisciplinary Treatment Of Chronic Pain

Psychological treatment of chronic pain is usually performed in an interdisci- plinary setting that includes medical interventions, physiotherapy, and social measures that are often combined  to a multimodal  approach.  The problem with multimodal approaches is that some parts of the treatments may counter- act each other and that it is difficult to assess the contribution of the individual components. Rather than combining an array of diverse intervention strategies, it might be more fruitful to aim for a differential indication of various treat- ment components  based on pain-related  characteristics  of the patients.  For example, Turk et al. (1998) found that persons characterized by high levels of dysfunction responded better to an interdisciplinary pain treatment program

Fig. 3 Mean (circles) and standard  error of the mean (vertical bars) for Neuropathic  Pain Scale (NPS) scores for the motor imagery program (MIP) group (filled circles) and control group (open circles) during the experimental period (weeks 0–12) and after cross-over of the control group (weeks 12–24). MIP consisted of 2 weeks each of recognition  of hand laterality (recognition),  imagined hand  movements  (imagined),  and mirror  movements (mirror).  Horizontal bars indicate significance (p<0.05) on post hoc Scheffé tests. (From Moseley 2004)

for fibromyalgia syndrome that those who were interpersonally distressed. An- other important aspect of psychological pain management  is motivating the patients for a psychological approach. This is often difficult since they may be concerned that the referral to a mental health professional implies that their pain is “not real,” they are exaggerating, the pain they feel is really “all in their head,” or their pain is a psychological and therefore not a physical problem. Furthermore,  many pain sufferers fear that a referral for psychological inter- vention implies that they can no longer be helped by the traditional healthcare system and that they are being abandoned as “hopeless cases.” They may view the referral as requiring that they prove that they do have legitimate reasons for their reported symptoms. These people usually believe that psychological assessment is not relevant to their problem, when they know that there must be a known physical basis for their symptoms. The patient may believe that cure of the disease or elimination of the symptoms or physical limitations is all that is required or why they are being referred to a psychologist or psychiatrist. This requires  a motivational  phase prior  to treatment  that  familiarizes the patients with the multidimensional view of chronic pain and motivates them to view a psychological approach  as a chance to alter their attitude  toward their pain and a first step toward improvement.  Interesting new perspectives focus on the combination  of behavioral and pharmacological interventions. For example, Dinse et al. (2003) have shown that the effects of sensory dis- crimination  training can be enhanced or reduced if the training is combined with amphetamine  or an N -methyl-d-aspartate (NMDA) receptor antagonist. Likewise, Ressler et al. (2004) showed that the effects of exposure therapy for aversive fear memories could be enhanced by combining the treatment  with a partial  NMDA receptor  agonist. We are currently  testing if the combina- tion of behavior therapy with a cannabinoid  treatment  is more effective than behavioral treatment alone in the extinction of pain memories.


This chapter focused on the role of learning mechanisms and psychological factors in the development and maintenance of chronic pain. Different psycho- logical treatments  of chronic pain were discussed with a focus on innovative treatments  of chronic pain designed to change pain memories. Future work should investigate the combination  of behavioral and pharmacological inter- ventions.  We closed this chapter  with an overview of the interdisciplinary treatment of chronic pain.

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