Pain Forum最新文献

Many hyperalgesic states and the development of tolerance to morphine converge at the cellular level through the activation of the N-methyl-D-aspartic acid (NMDA) receptor and common signal transduction events including the activation of protein kinase C. Some commonly used opioids and their derivatives possess NMDA receptor antagonist activity. In preclinical models, the behavioral consequences of this activity, as illustrated by the dextro isomer of methadone, are antihyperalgesic effects and the attenuation of morphine tolerance. These observations suggest that the combination of an opioid plus NMDA receptor antagonist activity should be of particular value in pain states where the potency of the opioid has been reduced as a result of hyperalgesia and/or opioid tolerance. One strategy for the development of these observations includes evaluation of these established opioids and their derivatives in clinical studies directed at improving the therapeutic window of the opioid.

In addition to their use in pain management in terminal cancer patients, therapeutic opioids have been found to be potent inducers of apoptosis in several types of human cancer cells, resulting in the inhibition of tumor growth. However, these growth-inhibitory effects appear not to involve conventional opioid receptor types or signal transduction pathways that mediate their central nervous system (CNS) actions, suggesting the existence of multiple binding sites. This offers the potential of designing opioid drugs targeted toward tumor tissues. While these findings suggest a new therapeutic approach for the treatment of several cancers, they indicate a need for more research on the apoptotic effects of chronic opioid use in neuronal cells. A greater understanding of the comparative effects of opioid drugs in the CNS and peripheral tissues could result in the design of better treatment protocols for their use in the control of cancer pain and growth.

Geissen Robinson, and Riley present a stimulating conceptual model of coping with chronic pain in which the authors argue that maladaptive beliefs and coping are primary determinants of adjustment and influence adaptive beliefs and coping through their influence on perceptions of control. We discuss some aspects of the model that require further refinement. First, the assessments of beliefs, appraisals, and coping need to be independent of outcome, obviating the use of “adaptive” and “maladaptive” in conceptual models. Unqualified statements about the universal adaptiveness, or maladaptiveness, of appraisal and coping strategies are likely to be unusual, since some strategies may result in higher emotional adjustment but not physical adjustment or vice versa. Second, beliefs, appraisals, and coping are distinct conceptual dimensions. Conceptual models that delineate relevant dimensions of these constructs rather than unify these partially independent constructs will likely have greater utility. Third, broadening the conceptualization of pain appraisal to include the individual's interpretation of the meaning of the pain is likely to provide expanded understanding of the pain coping process. Fourth, factors active in the individual's environment, particularly social relationships, need to be integrated into any comprehensive model of coping with chronic pain. And fifth, the bidirectional relationships between beliefs, appraisals, and coping need to be integrated into conceptual models. These processes are interrelated and feed back to one another as the individual struggles to cope with the challenges and threat posed by pain. The inherent complexity of coping with pain requires conceptualizations that address its transactional nature and methodologies that capture this dynamic process. Our comments direct future investigators to address when coping works, in what way it works, and for whom it works.