New Developments in the Understanding and Management of Persistent Pain

Herta Flor PhD


Curr Opin Psychiatry. 2012;25(2):109-113. 

In This Article

Learning, Plasticity and Pain: Implications for Treatment

Learning influences subjective, behavioral, neurophysiological and biochemical aspects of pain that outlast the phase of acute pain and may contribute to the experience of chronic pain. Extinction of learnt pain associations may especially be impaired in chronic pain patients and needs to be the focus of pain management. There are site-specific peripheral and central changes related to pain memory processes that may potentially have to be addressed separately. It is not only the physical stimulus but the learning history that determines the response to noxious stimulation, and thus the learning history must be assessed and included in treatment.

In contrast to the acquisition of a pain-related response, which generalizes easily across stimuli and responses, the extinction or unlearning of a pain response is specific to the stimulus and the response. This means that training a patient to extinguish pain-related responses may be much more difficult than their acquisition. Moreover, extinction involves the learning of an inhibitory process,not just the erasure of anoldmemory trace. Further characteristics of extinction are that the changes in memory fade with the passage of time, whereas acquired emotional memories often become stronger with time. In addition, a change of context can reactivate the extinguished memory, a phenomenon that has been termed renewal. In memory acquisition, generalization of stimuli and responses occurs, in contrast, making the acquired response very resistant to extinction. Finally, stressful events such as a new episode of pain can function like an unconditioned stimulus and can reactivate the extinguished memory (reinstatement). This is problematic in chronic pain patients in whom new stress and pain episodes are likely to occur. For treatment, this means that massed practice in varying contexts during stress and nonstress conditions is necessary. This can be achieved by specific operant-based extinction training, but also by cognitive–behavioral or respondent (biofeedback) approaches.[24•]

The alteration ofmaladaptive brain plasticity is also possible by directly modifying the maladaptive learnt brain response to pain by methods, such as imagery, mirror training or the use of virtual reality, that make use of the fact that the brain processes the perceived rather than the physical reality and could thus reverse maladaptive changes in pain-related memories such as phantom limb pain.[25,26] Stimulation-related procedures were also found to be effective. Noninvasive techniques such as transcranial magnetic stimulation and transcranial direct current stimulation have been applied with good initial results on pain relief.[27••] Brain changes might also be modified by the use of brain computer interfaces that can directly target maladaptive plastic changes.[28] It has also been suggested[29••] that the combination of sensory training and vagus nerve stimulation might be an especially powerful tool to restore normal brain function.

The reversal, as well as prevention, of chronic pain might also be possible by using pharmacological agents that are known to prevent or reverse cortical reorganization, although they are less specific than behavioral interventions. Among these substances, γ-aminobutyric acid agonists, N-methyl-D-aspartate (NMDA) receptor antagonists and anticholinergic substances seem to be the most promising.[30] In the treatment of phobia the effects of exposure therapy related to aversive fear memories could be enhanced by combining the treatment with a partial NMDA receptor agonist (D-cycloserine).[31] NMDA receptor agonists have also been shown to be effective in relieving pain in conjunction with noninvasive brain stimulation (cf.[32•]). As extinction is context-specific, training as many varied behaviors as possible, training in many different environments and the use of stress and pain episodes to train relapse prevention are important parts of this training. Moreover, chronic pain must be prevented as early as possible by pharmacological and psychological interventions in order to keep pain memories from being established.


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