The Role of Expectation in the Measurement and Management of Pain
Martin Koltzenburg
UCL Institute of Neurology and UCL Institute of Child Health
London, UK
Currently, much research is directed towards understanding the cellular and molecular properties of peripheral nociceptors and spinal cord processes, the primary gateway of the pain pathway. However, cognitive factors and learning processes are thought to play a dominant role in the development of persistent chronic pain (Flor and Turk, 2005).
Expectancy and conditioning are crucial factors influencing clinically relevant features of pain. This includes both pain relieving and pain aggravating manifestations such as the placebo analgesic effect (Hoffman et al., 2005) or catastrophizing, a potent cognitive error that greatly influences pain and disability (Sullivan et al., 2001). Whereas much work has improved our understanding of the sensory-discriminative substrates of cortical pain processing (Apkarian et al., 2005) the neural mechanisms underlying the generation of expectations of pain relief and pain aggravation as crucial motivational goals in humans have remained largely elusive. Using a Pavolvian conditioning paradigm we have recently shown that this can be described in a conceptual framework of opponent appetitive-aversive processes. Consistent with contemporary reward-learning theories, pain relief is reflected by activity in amygdala and midbrain which is mirrored by opposite painful aversion in the lateral orbitofronal and anterior cingulated cortex (Seymour et al., 2005). Interestingly, the acquisition of the novel conditioned pain memory appears to non-declarative as the majority of subjects were unable to report a relationship between cue and change in pain intensity. Previous work established that both reward-related learning (O'Doherty et al., 2003) and aversive prediction (Seymour et al., 2004) are activating the ventral striatum in the human brain and we could show that the opposing appetitive-aversive learning activities were co-expressed in the ventral striatum and anterior insula (Seymour et al., 2005). These areas therefore are the neural substrate by which conditioning cues or prior experiences acquire salience in experimental pain studies in humans. However, the neuropharmacological basis of this important neural network in healthy humans is still incompletely understood and it is entirely unknown whether these neural processes are altered in patients with chronic pain and if so how. One may surmise that patients who have endured persistent chronic pain will “lose” their expectations that interventions will provide pain relief and thus may develop a reduced ability to activate their reward-like brain circuitry (Hoffman et al., 2005). This idea is consistent with frequent clinical observations that many chronic pain patients, particularly those with chronic neuropathic pain, become resistant to pain relieving interventions. The loss of reward-like appreciation may also be related to the finding that chronic pain patients who use narcotic drugs generally do not appear to develop an addiction (Schug et al., 1992). It is currently unclear how the processes involving non-declarative memory acquisition of painful stimuli differ from those that employ explicit memory mechanism. Emerging evidence suggests that they differ in their neural areas of activation and that interact. For example, the conditioned response to a pain relieving treatment can be cancelled by verbal instructions to the contrary (Montgomery and Kirsch, 1997). Recent studies have shown that manipulations of explicit expectations can powerfully modulate the perception of pain. Expectations of decreased pain reduced both the subjective experience of pain and activation of pain-related brain regions, such as the primary somatosensory, insular and anterior cingulate cortex (Koyama et al., 2005).
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