The journal of pain : official journal of the American Pain Society
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The aim of this study was to investigate the relevance of the basal ganglia (BG) in pathogenesis of migraine by assessing the abnormal volume and resting-state networks of the BG in migraine patients without aura (MWoA). The volume of the subsets in the BG was compared between 40 MWoA and 40 age- and gender-matched healthy controls. The resting-state functional connectivity of BG subsets with abnormal volume was also investigated. Reduced volume in the left caudate and the right nucleus accumbens (NAc) was detected in the migraine group compared with healthy controls; meanwhile, increased functional connectivity between the BG and several brain regions within nociceptive and somatosensory processing pathways was observed. Correlation analysis revealed significant correlations between the volume of the bilateral caudate and right NAc and disease duration. In addition, an increased monthly frequency of migraine attack was associated with increased functional connectivity between the bilateral caudate and left insula, and longer disease duration was correlated with increased functional connectivity between the right NAc and bilateral anterior cingulate cortex. Our results revealed abnormal volume of BG and dysfunctional dynamics during interictal resting state within pain pathways of the BG in MWoA, which validated the association between the BG and migraine. ⋯ Our findings revealed the presence of reduced volume in NAc and caudate of the BG and interictal dysfunctional dynamics within BG networks in MWoA. The abnormal structure and function within the pain-related pathways of the BG were possibly associated with impaired pain processing and modulatory processes in MWoA.
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Comparative Study
Are psychological predictors of chronic postsurgical pain dependent on the surgical model? A comparison of total knee arthroplasty and breast surgery for cancer.
Anxiety, depression, and catastrophizing are generally considered to be predictive of chronic postoperative pain, but this may not be the case after all types of surgery, raising the possibility that the results depend on the surgical model. We assessed the predictive value of these factors for chronic postsurgical pain in 2 different surgical models: total knee arthroplasty for osteoarthritis (89 patients, 65% women, age = 69 ± 9 years, baseline pain intensity = 4.7 ± 2.1) and breast surgery for cancer (100 patients, 100% women, age = 55 ± 12 years, no preoperative pain). Data were collected before surgery, then 2 days and 3 months after surgery. Anxiety, depression, and catastrophizing were measured with the Spielberger State-Trait Anxiety Inventory, Beck Depression Inventory, and Pain Catastrophizing Scale, respectively. Pain was assessed with the Brief Pain Inventory. Neuropathic pain was detected with the DN4 questionnaire. Multivariate logistic regression analyses for the total knee arthroplasty and breast surgery models considered together indicated that the presence of clinically meaningful chronic pain at 3 months (pain intensity ≥3/10) was predicted independently by age (P = .04), pain intensity on day 2 (P = .009), and state anxiety (P = .001). Linear regression models also showed that pain magnification, one of the dimensions of catastrophizing, independently predicted chronic pain intensity (P = .04). These results were not affected by the surgical model or by the neuropathic characteristics of the pain. Thus, state anxiety and pain magnification seem to constitute psychological risk factors for chronic postsurgical pain relevant in all surgical models. ⋯ This prospective study performed in patients with total knee arthroplasty or breast surgery for cancer shows that state anxiety, amplification of pain, and acute postoperative pain independently predict postsurgical pain at 3 months and that this does not depend on the surgical model.
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Back pain is common and many people experience long-term problems, yet little is known about what prognostic factors predict long-term outcomes. This study's objective was to determine which factors predict short- and long-term outcomes in primary care consulters with low back pain (LBP). Analysis was carried out on 488 patients who had consulted their physician about LBP. Patients were followed up at 6 months and 5 years. Clinically significant LBP at follow-up was defined as a score of 2, 3, or 4 on the Chronic Pain Grade, indicating substantial pain and disability. Cox regression was used to estimate relative risks (RRs) with 95% confidence intervals (CIs) on 32 potential predictive factors, organized into domains (demographic, physical, psychological, and occupational). Baseline pain intensity conferred a 12% increase in risk (RR = 1.12, 95% CI = 1.03-1.20), and patients' belief that their LBP would persist conferred a 4% increase in risk (RR = 1.04, 95% CI = 1.01-1.07) for poor outcome at 6 months. Outcome at 5 years was best predicted by a model with the same factors as in the 6-month model: pain intensity increased risk by 9% (RR = 1.09, 95% CI = .997-1.20), and a belief that their LBP would persist increased risk by 6% (RR = 1.06, 95% CI = 1.03-1.09). Both predictors have the potential to be targets for clinical intervention. ⋯ Few studies have investigated factors that predict long-term back pain. This study has shown that pain intensity experienced during a period of primary care consultation, and patients' perception about whether their back pain will persist, were significant predictors of poor outcome at 6 months and at 5 years.
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The rostroventromedial medulla (RVM) is an important area of the endogenous pain-regulating system, in which 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) are 2 main transmitters involved in pain modulation. However, whether 5-HT and GABA are colocalized is poorly understood. By using glutamate decarboxylase 67-green fluorescence protein (GAD67-GFP) knock-in mouse, we confirmed the colocalization of 5-HT and GABA in the RVM, with a main distribution in the raphe magnus nucleus and paragigantocellular reticular nucleus. Interestingly, more than half (51.6%) of the 5-HT/GABA-immunoreactive (ir) neurons expressed neurokinin-1 receptors (NK-1R) and one-third (30.1%) of the 5-HT/GABA/NK-1R-ir neurons projected to the spinal cord, suggesting that substance P (SP) should regulate the activity of 5-HT/GABA-ir spinal cord-projecting neurons. By combining retrograde and anterograde tracing methods, we observed that the cuneiform nucleus, dorsal raphe nucleus, and lateral periaqueductal gray are the main origin nuclei for the SP-ir fibers and terminals in the RVM. Finally, after formalin injection into the mice hind paw, 29.2% SP-ir RVM-projecting neurons from supra-RVM nuclei and 33.1% NK-1R-ir spinal cord-projecting neurons in the RVM were activated. The present study provides potent morphological evidence that 5-HT and GABA are coexistent in RVM-spinal cord-projecting neurons that are also regulated by SPergic projections. ⋯ The results will greatly enhance our understanding for the modulation of nociceptive information in the descending pain-regulating system.
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In pain clinical trials, the rescue analgesic medication such as patient-controlled analgesia morphine is often made available for patients for breakthrough pain. The patient-controlled analgesia morphine usage decreases the study agent's effect on pain relative to placebo and introduces greater variability in attainment of pain scores. For assessment of analgesic efficacy, the isolated statistical analysis of pain score or morphine consumption as a surrogate marker for pain not only loses statistical efficiency but also may incur increased false-positive findings because of multiple testing. The aim of this article is to review the research to date for choices of statistical tests for pain or morphine consumption outcome, with a focus on systematically evaluating a means for collective analgesic assessment of pain and morphine consumption using an integrated outcome. A case example is illustrated for data visualization, statistical comparison, and effect size estimation using the new endpoint. Some implications for clinical practice and further research are discussed. ⋯ This article provides statistical evidence to conclude that an integrated outcome of pain score and morphine consumption provides an efficient means for integrated analgesic assessment.