Human Brain Imaging Studies of Chronic Pain: Translational Opportunities

Depression is ranked as one of the strongest predictors for low back pain. This association is observed by multiple studies, with odds ratios increasing with intensity of back pain and severity of depression ;. In order to investigate the predictive power of baseline depression on the transition from acute to chronic pain (3 months post-acute back pain), a recent prospective study evaluated the direct and indirect effects of multiple parameters on chronic pain severity and disability . The model only accounted for 26% of the variance in chronic pain. Acute pain intensity did not directly predict pain three months later, and baseline pain beliefs failed to predict chronic pain magnitude. Despite these relatively weak relationships to chronic pain, the authors argued that their findings support the growing literature contending that progression to chronic pain is more dependent on psychosocial and occupational factors than on medical characteristics of the spinal condition. In general, a long series of studies now describe psychosocial and psychological factors in predicting functional and social disability, where the interrelationship between ratings of catastrophizing, pain-related fear of (re-) injury, depression, disability, and pain severity are studied and modeled in combination with demographics in various chronic pain conditions. Although these factors may be associated with pain in certain individuals, attempts to create models of CBP based upon them have been unproductive ;;;; for further details see . It is now being recognized that psychosocial factors constitute “non-negligible risks” for the development of low back pain and cannot account for how or why a patient transitions into the chronic pain state. We have examined cognitive and sensory properties of chronic pain patients, with the simple notion that living with chronic pain may impart a cost in such processing. A long list of cognitive abnormalities has been described in chronic pain patients. The most noteworthy are attentional and memory deficits ;. However, little effort has been placed in differentiating such deficits based on chronic pain type. We reported that, in contrast to matched healthy controls, CBP and complex regional pain syndrome (CRPS) patients are significantly impaired on an emotional decisionmaking task . Moreover, the performance of CBP patients was highly correlated with their verbal report of pain at the time of performing the task. In contrast to CBP, CRPS patients’ performance was not modified when their pain was manipulated using a sympathetic block. The latter implies that the brain mechanisms underlying the two types of chronic pain, or the impact of each condition on the brain, may be distinct and thus also distinctly modulate emotional states. It should be noted that the CRPS patients were tested on a long battery of other cognitive tasks as well, and their performance on these was not different from healthy control subjects. Two important conclusions are drawn from these observations. Firstly, cognitive disruption in chronic pain is specific to the type of test administered, implying impact on unique brain circuitry. Secondly, there are important differences between chronic pain conditions, even on the same cognitive task, suggesting that each condition may underlie unique brain activity/reorganization, which complicates our understanding of these conditions as it demands that we study each and every chronic pain regarding its cognitive and brain signature. More importantly, the implication that distinct chronic pain conditions have unique brain signatures open the possibility that each one of them may be understood in its own right, enabling the development of novel, specific therapies for each. This theme will be repeated several times below, emphasizing that brain-derived parameters repeatedly indicate the specific properties of distinct chronic pain conditions. It should be emphasized that the impact of chronic pain does not only result in deficits. When CBP patients were contrasted to healthy subjects as to gustatory abilities, we were able to show decreased threshold to gustatory detection and increased sensitivity to supra-threshold tastants for all modalities examined . Thus, these CBP patients are generally more sensitive in taste perception. It is possible that this ability is a predisposing factor. In fact, all the brain and cognitive changes we describe here are cross-sectional studies, and thus in all cases the distinction between predisposition and a consequence to chronic pain remains unsettled. More likely, increased taste sensitivity is a result of brain representation/reorganization as a consequence of living with CBP. We ascribe the deficit in emotional decision-making in CBP and CRPS as a consequence of the representation/reorganization of brain activity between the lateral and medial prefrontal cortex. In fact, our observation of activity in medial prefrontal cortex in CRPS was the initial impetus for testing chronic pain patients with the “gambling test.” We also think that the increased taste sensitivity is a direct result of changes in activity/connectivity of the insular cortex in CBP Our earlier observation that insular cortex activity increases in CBP patients in proportion to the number of years they are in chronic pain , and given that parts of the insular cortex are considered primary gustatory cortex, led us to the hypothesis that gestation may be different in CBP Therefore, the cognitive and sensory changes we have observed in chronic pain patients are derived from observations regarding cortical representation and reorganization, and thus these domains are complementary to each other, reinforcing the idea that the brain abnormalities do result in very specific changes in information processing.