Browse by Audience
Chronic Migraine (CM) is a disabling neurologic condition with a severe impact on functioning and quality of life. Successful therapeutic management of patients with CM is complex, and differences in therapeutic response could be attributable to genetically determined factors, sensitivity to pharmacological treatment, psychosocial and relational factors affecting the patient's compliance and approach on the therapeutic treatment. The aim of this prospective observational study was to explore self-efficacy, coping strategies, psychological distress and headache-related disability in a cohort of 40 patients with CM (mean age: 46.73; standard deviation 13.75) treated with OnabotulinumtoxinA and the relationship between these clinical and psychological aspects and acute medication consumption during OnabotulinumtoxinA prophylactic treatment. Patients presented an overall significant reduction in the Headache Index (HI) ( < 0.001), HI with severe intensity ( = 0.009), and total analgesic consumption ( = 0.003) after the prophylactic treatment. These results are in line with the literature. Despite this, higher nonsteroidal anti-inflammatory drugs consumption was associated with higher psychological distress, higher HI with severe and moderate intensity, and worse quality of life. Conversely, triptans consumption was correlated with HI of mild intensity, and problem-focused coping strategies. To conclude, the psychological profile, and in particular, the psychological distress and specific coping strategies might influence the self-management of acute medication.
Learn More >Fibromyalgia (FM) is a chronic syndrome characterized by widespread musculoskeletal pain, and physical and emotional symptoms. Although its pathophysiology is largely unknown, immune-inflammatory pathways may be involved. We examined serum interleukin (IL)-6, high sensitivity C-reactive protein (hs-CRP), CXCL-8, and IL-10 in 67 female FM patients and 35 healthy women while adjusting for age, body mass index (BMI), and comorbid disorders. We scored the Fibromyalgia Severity Score, Widespread Pain Index (WPI), Symptom Severity Scale (SSS), Hospital Anxiety (HADS-A), and Depression Scale and the Perceived Stress Scale (PSS-10). Clinical rating scales were significantly higher in FM patients than in controls. After adjusting for covariates, IL-6, IL-10, and CXCL-8 were lower in FM than in HC, whereas hs-CRP did not show any difference. Binary regression analyses showed that the diagnosis FM was associated with lowered IL-10, quality of sleep, aerobic activities, and increased HADS-A and comorbidities. Neural networks showed that WPI was best predicted by quality of sleep, PSS-10, HADS-A, and the cytokines, while SSS was best predicted by PSS-10, HADS-A, and IL-10. Lowered levels of cytokines are associated with FM independently from confounders. Lowered IL-6 and IL-10 signaling may play a role in the pathophysiology of FM.
Learn More >The aim of this study was to identify inflammatory mediators of potential clinical relevance in synovial fluid (SF) samples of patients with knee osteoarthritis (OA). Therefore, radiographic OA severity, knee pain and function of 34 OA patients undergoing unicompartmental (UC) and bicompartmental (BC) knee arthroplasty were assessed prior to surgery and SF samples were analyzed for a broad variety of inflammatory mediators, including interleukins (ILs), interferons (IFNs), C-X-C motif ligand chemokines (CXCLs), and growth factors (nerve growth factor; NGF, vascular endothelial growth factor; VEGF, and stem cell growth factor β; SCGF-β) using multiplex assay. Significant differences were observed between the SF levels of different inflammatory markers. When compared to UC OA, significantly higher concentrations of IL-7, IL-8, IL-10, IL-12, IL-13, IFN-γ, VEGF and CXCL1 were detected in BC OA. Correlation analyses revealed significant associations between OA severity and IL-6, IL-8, IFN-γ, SCGF-β, VEGF, CXCL1. Interestingly, increases in both anti- (IL-10, IL-13) and pro-inflammatory (IL-7, IL-12, IFN-γ) cytokines, as well as growth factors (SCGF-β, VEGF), correlated significantly with the level of knee pain. Poorer knee function was associated with higher IL-6, IL-10, IL-12, IL-13, IL-18, βNGF, SCGF-β, VEGF and CXCL9 levels. In conclusion, this study provides an extensive profile of synovial inflammatory mediators in knee OA and identifies cytokines of potential clinical relevance. In fact, five of the mediators examined (IL-10, IL-12, IL-13, SCGF-β, VEGF) significantly correlate with both knee pain and function.
Learn More >The neurobiology of persistent pain shares common underlying psychobiology with that of traumatic stress. Modern treatments for traumatic stress often involve bottom-up sensorimotor retraining/exposure therapies, where breath, movement, balance and mindfulness, are used to target underlying psychobiology. Vigorous exercise, in particular Bikram yoga, combines many of these sensorimotor/exposure therapeutic features. However, there is very little research investigating the feasibility and efficacy of such treatments for targeting the underlying psychobiology of persistent pain.
Learn More >In addition to the increased risk for cardiovascular (CV) disease and CV events associated with migraine, patients with migraine can also present with a number of CV risk factors (CVRFs). Existing treatment options can be limited due to contraindications, increased burden associated with monitoring, or patient avoidance of side effects. Safe and effective migraine treatment options are needed for patients with migraine and a history of CV or cerebrovascular disease or with increased risk for CV events. This analysis was designed to evaluate the safety and efficacy of oral lasmiditan, a selective serotonin 5-hydroxytryptamine 1F receptor agonist, in acute treatment of migraine attacks in patients with CVRFs.
Learn More >Animal models of migraine and experimental techniques used to examine trigeminal sensory processing.
Migraine is a common debilitating condition whose main attributes are severe recurrent headaches with accompanying sensitivity to light and sound, nausea and vomiting. Migraine-related pain is a major cause of its accompanying disability and can encumber almost every aspect of daily life.
Learn More >Chemotherapy-induced peripheral neuropathy (CIPN) remains a pressing clinical problem, however our understanding of sexual dimorphism in CIPN remains unclear. Emerging studies indicate a sex-dimorphic role of Toll-like receptor 4 (TLR4) in driving neuropathic pain. In this study we examined the role of TLR9 in CIPN induced by paclitaxel in wild-type and mutant mice of both sexes. Baseline pain sensitivity was not affected in either mutant male or female mice. Intraplantar and intrathecal injection of the TLR9 agonist ODN 1826 induced mechanical allodynia in both sexes of wild-type and knockout mice but failed to do so in mutant mice. Moreover, knockout or C-fiber blockade by resiniferatoxin failed to affect intraplantar ODN 1826-induced mechanical allodynia. Interestingly, the development of paclitaxel-evoked mechanical allodynia was attenuated by TLR9 antagonism or mutation only in male mice. Paclitaxel-induced CIPN caused macrophage infiltration to dorsal root ganglia (DRG) in both sexes, and this infiltration was not affected by mutation. Paclitaxel treatment also upregulated TNF and CXCL1 in macrophage cultures and DRG tissues in both sexes, but these changes were compromised by mutation in male animals. Intraplantar adoptive transfer of paclitaxel-activated macrophages evoked mechanical allodynia in both sexes, which was compromised by mutation or by treatment with TLR9 inhibitor only in male animals. Finally, TLR9 antagonism reduced paclitaxel-induced mechanical allodynia in female nude mice (T cell and B cell deficient). Together, these findings reveal sex-dimorphic macrophage TLR9 signaling in chemotherapy-induced neuropathic pain.Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect in cancer patients undergoing clinical chemotherapy treatment regimens. The role of sex-dimorphism with regards to the mechanisms of CIPN and analgesia against CIPN remains unclear. Previous studies have found that the infiltration of immune cells such as macrophages into dorsal root ganglia (DRG) and their subsequent activation promote CIPN. Interestingly, the contribution of microglia to CIPN appears to be limited. Here, we show that macrophage TLR9 signaling promotes CIPN in male mice only. This study suggests that pathways in macrophages may be sex-dimorphic in CIPN. Our findings provide new insights into the role of macrophage signaling mechanisms underlying sex-dimorphism in CIPN, which may inspire the development of more precise and effective therapies.
Learn More >