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Previous studies have demonstrated that migraine is associated with enhanced perception and altered cerebral processing of sensory stimuli. More recently, it has been suggested that this sensory hypersensitivity might reflect a more general enhanced response to aversive emotional stimuli. Using functional magnetic resonance imaging and emotional face stimuli (fearful, happy and sad faces), we compared whole-brain activation between 41 migraine patients without aura in interictal period and 49 healthy controls. Migraine patients showed increased neural activation to fearful faces compared to neutral faces in the right middle frontal gyrus and frontal pole relative to healthy controls. We also found that higher attack frequency in migraine patients was related to increased activation mainly in the right primary somatosensory cortex (corresponding to the face area) to fearful expressions and in the right dorsal striatal regions to happy faces. In both analyses, activation differences remained significant after controlling for anxiety and depressive symptoms. These findings indicate that enhanced response to emotional stimuli might explain the migraine trigger effect of psychosocial stressors that gradually leads to increased somatosensory response to emotional clues and thus contributes to the progression or chronification of migraine.
Learn More >To investigate the prevalence of anxiety, depression and mixed anxiety and depressive disorder (MADD) and factors associated with these conditions in women with chronic pelvic pain (CPP) compared to a pain-free control group. A cross-sectional study was conducted with 100 women with CPP and 100 without CPP. The Hospital Anxiety and Depression Scale (HADS) was used to evaluate the presence of anxiety and depression. Sociodemographic, behavioral and clinical characteristics were investigated. Fisher's exact test was used to compare characteristics between groups. A log-binomial regression model was used, with adjustment for age, skin color, schooling, body mass index and pain. Prevalence ratios (PR), together with their 95% confidence intervals (CI), were calculated to investigate factors associated with anxiety, depression and MADD. The prevalence of anxiety was 66% in the CPP group and 49% in the controls (=0.02). Depression was identified in 63% of the women with CPP and in 38% of the controls (<0.01). MADD was present in 54% of the CPP group and in 28% of the controls (<0.01). In the adjusted analysis, CPP (PR=1.3; 95%CI: 1.1-1.6), physical abuse (PR=1.5; 95%CI: 1.2-1.8) and sexual abuse (PR=1.5; 95%CI: 1.1-1.8) were independently associated with anxiety. Women of 25 to 34 years of age were less likely to have anxiety (PR=0.6; 95%CI: 0.4-0.8). CPP (PR=1.6; 95%CI: 1.2-2.2), physical abuse (PR=1.3; 95%CI: 1.1-1.7) and sexual abuse (PR=1.7; 95%CI: 1.3-2.2) were independently associated with depression. CPP (PR=1.9; 95%CI: 1.3-2.7), smoking (PR=1.5; 95%CI: 1.1-2.1), physical abuse (PR=1.4; 95%CI: 1.1-1.9) and sexual abuse (PR=1.4; 95%CI: 1.1-1.8) were independently associated with MADD. The prevalence of anxiety, depression and MADD was higher in women with CPP compared to the pain-free controls. Factors associated with mental disorders were identified. The independent association between CPP and anxiety, depression and MADD was noteworthy. These findings suggest that systematic management of psychological factors could contribute towards improving the mental health of these women.
Learn More >The annual number of surgical operations performed is increasing throughout the world. With this rise in the number of surgeries performed, so too, the challenge of effectively managing postoperative pain. In Africa, there are scanty data available that make use of multi-center data to characterize the quality of postoperative pain management. In this study using a longitudinal data, we have attempted to characterize the quality of postoperative pain management; among patients scheduled for major elective orthopedic, gynecologic and general surgery.
Learn More >Lumbar spinal stenosis (LSS) is a chronic condition that causes low back pain and neurogenic claudication, often resulting in significant limitation of daily activities. In this open-label randomized controlled pilot study, we assessed the safety and feasibility of 4-week novel integrative inpatient treatments for LSS.
Learn More >Translational research aiming to elucidate mediators and moderators of placebo and nocebo effects is highly relevant. This experimental study tested effects of a brief progressive muscle relaxation (PMR) exercise, designed to alter psychobiological stress parameters, on the magnitude of placebo and nocebo effects in a standardized psychosocial treatment context. In 120 healthy volunteers (60 men, 60 women), pain expectation, pain intensity, and pain unpleasantness in response to individually-calibrated rectal distensions were measured with visual analog scales during a baseline. Participants were then randomized to exercise PMR (relaxation group: = 60) or a simple task (control group: = 60), prior to receiving positive (placebo), negative (nocebo) or neutral suggestions regarding an intravenous administration that was in reality saline in all groups. Identical distensions were repeated (test). State anxiety, salivary cortisol, heart rate, and blood pressure were assessed repeatedly. Data were analyzed using analysis of covariance, planned Bonferroni-corrected group comparisons, as well as exploratory correlational and mediation analyses. Treatment suggestions induced group-specific changes in pain expectation, with significantly expectation in placebo and expectation in nocebo groups. PMR had no discernable effect on pain expectation, state anxiety or cortisol, but led to significantly lower heart rate and systolic blood pressure. Relaxation significantly interacted with positive treatment suggestions, which only induced placebo analgesia in relaxed participants. No effects of negative suggestions were found in planned group comparisons, irrespective of relaxation. Exploratory correlation and mediation analyses revealed that pain expectation was a mediator to explain the association between treatment suggestions and pain-related outcomes. Clearly, visceral pain modulation is complex and involves many cognitive, emotional, and possibly neurobiological factors that remain to be fully understood. Our findings suggest that a brief relaxation exercise may facilitate the induction of placebo analgesia by positive when compared to neutral treatment suggestions. They underscore the contribution of relaxation and stress as psychobiological states within the psychosocial treatment context-factors which clearly deserve more attention in translational studies aiming to maximize positive expectancy effects in clinical settings.
Learn More >Chronic pain is increasingly recognized as a common and disabling problem for people living with HIV (PLWH). In a recent systematic review of psychosocial factors associated with chronic pain in PLWH, it was reported that very few studies to date have examined protective psychological factors that might help mitigate chronic pain for PLWH. The current study examined pain-specific resilience in relation to clinical and experimental pain, as well as pain coping in PLWH and chronic pain. Pain-specific resilience specifically refers to the ability to maintain relatively stable, healthy levels of psychological and physical functioning in the face of ongoing and persistent pain.
Learn More >Gap junctions (GJs), which consist of proteins called connexins, are intercellular channels that allow the passage of ions, second messengers, and small molecules. GJs and connexins are considered as emerging therapeutic targets for various diseases. Previously, we screened numerous compounds using our recently developed iodide yellow fluorescent protein gap junctional intercellular communication (I-YFP GJIC) assay and found that flunarizine (FNZ), used for migraine prophylaxis and as an add-on therapy for epilepsy, inhibits GJIC in LN215 human glioma cells. In this study, we confirmed that FNZ inhibits GJIC using the I-YFP GJIC assay. We demonstrated that FNZ inhibits GJ activities via a mechanism that is independent of calcium channels and dopaminergic D2, histaminergic H1, or 5-HT receptors. In addition, we showed that FNZ significantly increases connexin 43 (Cx43) phosphorylation on the cell surface, but does not alter the total amount of Cx43. The beneficial effects of FNZ on migraines and epilepsy might be related to GJ inhibition.
Learn More >Magnetic resonance imaging (MRI) can provide objective continuous intervertebral disc (IVD) measures in low back pain (LBP) patients. However, there are limited studies comparing quantitative IVD measures of symptomatic and asymptomatic individuals.
Learn More >Neuropathic pain is a debilitating and commonly treatment-refractory condition requiring novel therapeutic options. Accumulating preclinical studies indicate that the potassium channel Slack (K1.1) contributes to the processing of neuropathic pain, and that Slack activators, when injected into mice, ameliorate pain-related hypersensitivity. However, whether Slack activation might reduce neuropathic pain in humans remains elusive. Here, we evaluated the tolerability and analgesic efficacy of loxapine, a first-generation antipsychotic drug and Slack activator, in neuropathic pain patients. We aimed to treat 12 patients with chronic chemotherapy-induced, treatment-refractory neuropathic pain (pain severity ≥ 4 units on an 11-point numerical rating scale) in a monocentric, open label, proof-of-principle study. Patients received loxapine orally as add-on analgesic in a dose-escalating manner (four treatment episodes for 14 days, daily dose: 20, 30, 40, or 60 mg loxapine) depending on tolerability and analgesic efficacy. Patient-reported outcomes of pain intensity and/or relief were recorded daily. After enrolling four patients, this study was prematurely terminated due to adverse events typically occurring with first-generation antipsychotic drugs that were reported by all patients. In two patients receiving loxapine for at least two treatment episodes, a clinically relevant analgesic effect was found at a daily dose of 20-30 mg of loxapine. Another two patients tolerated loxapine only for a few days. Together, our data further support the hypothesis that Slack activation might be a novel strategy for neuropathic pain therapy. However, loxapine is no valid treatment option for painful polyneuropathy due to profound dopamine and histamine receptor-related side effects. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02820519.
Learn More >Reduction in pain following multidisciplinary treatment is most often associated with a reduction in disability. To further elaborate the relationship between pain intensity and disability, the present study investigated three main questions: first, whether multidisciplinary treatment leads to a significant improvement in pain, disability and psychological variables (depression, pain acceptance and catastrophizing). Second, it was examined whether pain reduction may account for significant changes in the psychological variables (pre- to follow-up change scores). Finally, it was analyzed whether the psychological changes mediate the association between reduction in pain and in disability after controlling for age, sex and pain history.
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