The journal of pain : official journal of the American Pain Society
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The zinc finger transcription factor Egr1 is critical for coupling extracellular signals to changes in cellular gene expression. Expression of Egr1, as well as other immediate early genes, is up-regulated in response to a number of noxious stimuli. Activity-dependent activation of Egr1 has been reported in forebrain regions, including the anterior cingulate cortex (ACC), after peripheral injury. However, no study has reported a direct contribution of Egr1 to behavioral nociceptive responses. Here, we use Egr1 knockout mice to show that Egr1 is selectively required for behavioral responses to persistent inflammatory pain. Behavioral responses to peripheral inflammation were significantly reduced in Egr1 knockout mice, whereas responses to acute noxious stimuli were normal. In addition, inflammation triggered an up-regulation of Egr1 expression in the ACC of wild-type mice. Last, synaptic potentiation induced by theta (theta) burst stimulation in the ACC was significantly reduced or blocked in Egr1 knockout mice. Our study suggests that the transcription factor Egr1 plays a selective role in nociceptive behavioral responses to persistent inflammatory pain but not to acute noxious stimuli. ⋯ Chronic pain diminishes the quality of life. Here, we show that the immediate early gene Egr1 plays a role in chronic inflammatory, but not acute, pain. Egr1 knockout mice showed reduced nociceptive behaviors to persistent inflammatory pain and inflammation increased Egr1 expression in the anterior cingulate cortex of wild-type mice.
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Review Case Reports
Ethical challenges in the management of chronic nonmalignant pain: negotiating through the cloud of doubt.
After successful cancer pain initiatives, efforts have been recently made to liberalize the use of opioids for the treatment of chronic nonmalignant pain. However, the goals for this treatment and its place among other available treatments are still unclear. Cancer pain treatment is aimed at patient comfort and is validated by objective disease severity. For chronic nonmalignant pain, however, comfort alone is not an adequate treatment goal, and pain is not usually proportional to objective disease severity. Therefore, confusion about treatment goals and doubts about the reality of nonmalignant pain entangle therapeutic efforts. We present a case history to demonstrate that this lack of proportionality fosters fears about malingering, exaggeration, and psychogenic pain among providers. Doubt concerning the reality of patients' unrelieved chronic nonmalignant pain has allowed concerns about addiction to dominate discussions of treatment. We propose alternate patient-centered principles to guide efforts to relieve chronic nonmalignant pain, including accept all patient pain reports as valid but negotiate treatment goals early in care, avoid harming patients, and incorporate chronic opioids as one part of the treatment plan if they improve the patient's overall health-related quality of life. Although an outright ban on opioid use in chronic nonmalignant pain is no longer ethically acceptable, ensuring that opioids provide overall benefit to patients requires significant time and skill. Patients with chronic nonmalignant pain should be assessed and treated for concurrent psychiatric disorders, but those with disorders are entitled to equivalent efforts at pain relief. The essential question is not whether chronic nonmalignant pain is real or proportional to objective disease severity, but how it should be managed so that the patient's overall quality of life is optimized. ⋯ The management of chronic nonmalignant pain is moving from specialty settings into primary care. Primary care providers need an ethical framework within which to adopt the principles of palliative care to this population.
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Randomized Controlled Trial Comparative Study Clinical Trial
Psychophysical outcomes from a randomized pilot study of manual, electro, and sham acupuncture treatment on experimentally induced thermal pain.
In this pilot study comparing the analgesic effects of three acupuncture modes--manual, electro, and placebo (with Streitberger placebo needles)--in a cohort of healthy subjects, we found that verum acupuncture treatment, but not placebo, lowered pain ratings in response to calibrated noxious thermal stimuli. This finding was mainly the result of highly significant analgesia in 5 of the 11 subjects who completed the 5-session study. Of the 5 responders, 2 responded only to electroacupuncture and 3 only to manual acupuncture, suggesting that acupuncture's analgesic effects on experimental pain may be dependent on both subject and mode. We developed a simple quantitative assessment tool, the Subjective Acupuncture Sensation Scale (SASS), comprised of 9 descriptors and an anxiety measure to study the relationship between the deqi sensation induced by acupuncture and the putative therapeutic effects of acupuncture. The SASS results confirm that the deqi sensation is complex, with all subjects rating multiple descriptors during each mode. We found significant correlations of analgesia with SASS ratings of numbness and soreness, but not with ratings of stabbing, throbbing, tingling, burning, heaviness, fullness, or aching. This suggests that attributes of the deqi sensation may be useful clinical indicators of effective treatment. ⋯ The results of this study indicate the existence of both individual subject and acupuncture mode variability in the analgesic effects of acupuncture. This suggests that switching acupuncture mode may be a treatment option for unresponsive patients.
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Randomized Controlled Trial Clinical Trial
Preparing for pain management: a pilot study to enhance engagement.
A significant proportion of individuals fail to engage in cognitive-behavioral treatments for pain. The aim of this pilot study was to develop and evaluate a Preparation for Pain Management Intervention administered before community-based therapy (CBT) pain management workshops. Participants (N = 78) were randomly assigned to a treatment group receiving a 2-session intervention including assessment and feedback based on the Preparation for Pain Management Profile (PPMP) or to a control group receiving assessment (treatment as usual) and an attention placebo interview in place of the feedback session. The interviews were conducted with both groups before patients were offered participation in pain management workshops. Results demonstrate that participants in the treatment group were significantly more likely to attend workshops than were participants in the control group (P < .01). ⋯ This paper describes a randomized controlled trial assessing a brief motivational intervention aimed at increasing engagement in community-based pain management workshops.