The journal of pain : official journal of the American Pain Society
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We defined the nature of the pharmacological interaction between ginsenosides and morphine in a nociceptive state and clarified the role of the different types of opioid receptor in the effects of ginsenosides. An intrathecal catheter was placed in male Sprague-Dawley rats. Pain was induced by formalin injection into the hindpaw. Isobolographic analysis was used to evaluate drug interactions. Furthermore, a nonselective opioid receptor antagonist (naloxone), a μ opioid receptor antagonist (CTOP), a δ opioid receptor antagonist (naltrindole), and a κ opioid receptor antagonist (GNTI) were given intrathecally to verify the involvement of the opioid receptors in the antinociceptive effects of ginsenosides. Both ginsenosides and morphine produced antinociceptive effects in the formalin test. Isobolographic analysis revealed a synergistic interaction after intrathecal delivery of the ginsenosides-morphine mix. Intrathecal CTOP, naltrindole, and GNTI reversed the antinociceptive effects of ginsenosides. RT-PCR indicated that opioid receptors' mRNA was detected in spinal cord of naïve rats and the injection of formalin had no effect on the expression of opioid receptors' mRNA. Taken together, our results indicate synergistic antinociception following intrathecal coadministration of a ginsenosides/morphine mix in the formalin test, and that μ, δ, and κ opioid receptors are involved in the antinociceptive mechanism of ginsenosides. ⋯ This article concerns the antinociceptive activity of ginsenosides, which increases antinociception by morphine. Thus, a spinal combination of ginsenosides and morphine may be useful in the management of acute pain as well as facilitated state pain.
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Breast cancer metastasis to bone is frequently accompanied by pain. What remains unclear is why this pain tends to become more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression, sensory nerve fibers that innervate the breast cancer bearing bone undergo a pathological sprouting and reorganization, which in other nonmalignant pathologies has been shown to generate and maintain chronic pain. Injection of human breast cancer cells (MDA-MB-231-BO) into the femoral intramedullary space of female athymic nude mice induces sprouting of calcitonin gene-related peptide (CGRP(+)) sensory nerve fibers. Nearly all CGRP(+) nerve fibers that undergo sprouting also coexpress tropomyosin receptor kinase A (TrkA(+)) and growth-associated protein-43 (GAP43(+)). This ectopic sprouting occurs in periosteal sensory nerve fibers that are in close proximity to breast cancer cells, tumor-associated stromal cells, and remodeled cortical bone. Therapeutic treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. The present data suggest that the breast cancer cells and tumor-associated stromal cells express and release NGF, which drives bone pain and the pathological reorganization of nearby CGRP(+)/TrkA(+)/GAP43(+) sensory nerve fibers. ⋯ Therapies that block breast cancer pain by reducing the tumor-induced pathological sprouting and reorganization of sensory nerve fibers may provide insight into the evolving mechanisms that drive breast cancer pain and lead to more effective therapies for attenuating this chronic pain state.
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A large number of oncology patients with bone metastasis report significant and often unrelieved pain that is associated with reduced quality of life and impaired functional status. Our research team previously assessed the efficacy of a tailored self-care psychoeducational intervention to improve pain management in these patients. Samplewide analyses demonstrated improvements in pain intensity and analgesic prescriptions. However, substantial interindividual variability was observed within the intervention group. In the current paper, hierarchical linear modeling (HLM) was used to determine factors that contributed to variability in pain intensity and analgesic prescription and intake in the sample of patients who participated in the intervention. Specifically, HLM analyses identified demographic, clinical, and psychological characteristics that predicted variation in pain intensity and analgesic prescription and intake at baseline (intercepts) and over the course of the 6-week study (trajectories). Awareness of these predictors may be particularly useful for the identification of patients who would benefit most from this type of intervention. Furthermore, these findings highlight specific aspects of the intervention that may be modified in order to further improve pain management in these patients. ⋯ This paper describes the application of HLM to explain interindividual variability in pain and analgesic outcomes among oncology outpatients with metastatic bone pain who participated in a psychoeducational intervention to improve pain management. Findings identify particularly responsive subgroups, areas for improvement to the intervention, and targets for future intervention.
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Comparative Study Clinical Trial
The relationship between physical activity and brain responses to pain in fibromyalgia.
The relationship between physical activity and central nervous system mechanisms of pain in fibromyalgia (FM) is unknown. This study determined whether physical activity was predictive of brain responses to experimental pain in FM using functional magnetic resonance imaging (fMRI). Thirty-four participants (n = 16 FM; n = 18 Control) completed self-report and accelerometer measures of physical activity and underwent fMRI of painful heat stimuli. In FM patients, positive relationships (P < .005) between physical activity and brain responses to pain were observed in the dorsolateral prefrontal cortex, posterior cingulate cortex, and the posterior insula, regions implicated in pain regulation. Negative relationships (P < .005) were found for the primary sensory and superior parietal cortices, regions implicated in the sensory aspects of pain. Greater physical activity was significantly (P < .05) associated with decreased pain ratings to repeated heat stimuli for FM patients. A similar nonsignificant trend was observed in controls. In addition, brain responses to pain were significantly (P < .005) different between FM patients categorized as low active and those categorized as high active. In controls, positive relationships (P < .005) were observed in the lateral prefrontal, anterior cingulate, and superior temporal cortices and the posterior insula. Our results suggest an association between measures of physical activity and central nervous system processing of pain. ⋯ Our data suggest that brain responses to pain represent a dynamic process where perception and modulation co-occur and that physical activity plays a role in balancing these processes. Physically active FM patients appear to maintain their ability to modulate pain while those who are less active do not.
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Clinical Trial
Pain-related attentional biases: the importance of the personal relevance and ecological validity of stimuli.
The literature regarding pain-related attentional biases is currently marked by considerable inconsistency. The primary aim of the present study was to examine whether 2 stimulus-related factors may be important to the detection of pain-related attentional biases: 1) the personal relevance of stimuli; and 2) their ecological validity. To do this, the present research compared the ability of a word-based dot-probe task (ie, lower ecological validity) and picture-based dot-probe task (ie, higher ecological validity) to detect attentional biases using generally selected (ie, lower personal relevance) and idiosyncratically selected stimuli (ie, higher personal relevance). To do this, the present study used a large sample of chronic pain patients and matched pain-free individuals. Attentional biases were found among both chronic pain patients and pain-free individuals for idiosyncratically selected pictorial stimuli (ie, highest ecological validity and personal relevance) but not for generally selected pictorial stimuli or for pain-related word stimuli, irrespective of whether they were idiosyncratically or generally selected. These biases were found to stem from vigilance for pain-related stimuli. Overall, the findings of the present study suggest that similar pain-related attentional biases can be found among both pain-free individuals and chronic pain patients and that stimulus-related factors may be important to the detection of those biases. ⋯ To date, research examining pain-related attentional biases has yielded inconsistent results. The present study sought to examine 2 stimulus-related factors often identified for their potential to influence the consistency of findings. The findings of this study highlight the importance of considering stimulus-related factors when designing and interpreting pain-related dot-probe research.