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Migraine is a debilitating neurologic disease. People who experience migraine can have substantial disability, impaired functioning and a decreased quality of life (QoL). Expert recommendations suggest that people with frequent migraine attacks or severe impairment related to attacks may benefit from preventive treatment. Despite these recommendations and the existence of evidence-based guidelines for the use of preventive medication, many people who are candidates for preventive therapies do not receive them. Thus, there is still a substantial unmet need for preventive migraine treatment. Calcitonin gene-related peptide (CGRP) has a demonstrated role in the pathophysiology of migraine. Galcanezumab-gnlm (galcanezumab) is a humanized monoclonal antibody that binds to the CGRP ligand and prevents binding to its receptor. It is administered as a once-monthly subcutaneous injection. The aim of this review is to present a comprehensive overview of the existing short- and long-term efficacy and safety data for galcanezumab in patients with migraine. Data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2 and REGAIN studies show that galcanezumab treatment for 3 or 6 months results in overall reduction in mean monthly migraine headache days in patients with episodic (EVOLVE-1 and EVOLVE-2) and chronic (REGAIN) migraine. Greater proportions of patients with episodic migraine receiving galcanezumab versus placebo demonstrated a ≥ 50%, ≥ 75% and 100% response to therapy and reported a lower level of disability and an improvement in functioning and QoL. Similarly, when compared with placebo, greater proportions of patients with chronic migraine treated with galcanezumab demonstrated a ≥ 50% and ≥ 75% response and reported improved functioning. A 12-month open-label study demonstrated the continued efficacy of galcanezumab for up to 12 months. In all studies galcanezumab was well tolerated. In conclusion, data from pivotal studies show that galcanezumab may fulfill an unmet need in the treatment of patients with migraine who require preventive therapy.
Learn More >Oxaliplatin is a platinum-based antineoplastic drug commonly used for treating colorectal, gastric, and pancreatic cancer. However, it frequently causes peripheral neuropathy as dose-limiting toxicity and is lacking a strategy for prevention. Alogliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, is an oral antidiabetic drug. Previous studies have shown that DPP-4 inhibitors have pleiotropic effects, including neuroprotection. In this study, we investigated the effects of alogliptin on oxaliplatin-induced peripheral neuropathy using in vitro and in vivo models. In PC12 cells, alogliptin attenuated neurite disorders induced by oxaliplatin and cisplatin. The repeated injection of oxaliplatin caused mechanical allodynia and axonal degeneration of the sciatic nerve in rats. These neuropathies were ameliorated by co-administration of alogliptin. Moreover, alogliptin did not attenuate tumor cytotoxicity of oxaliplatin in the cultured colon, gastric, or pancreatic cancer cell lines and tumor-bearing mice. These findings suggest that alogliptin may be beneficial for preventing oxaliplatin-induced peripheral neuropathy.
Learn More >Up to 90% of people with neurological deficits following whiplash injury report chronic symptoms. A recent unique study of neck-specific exercise showed positive results (post-intervention at 12 weeks), regarding arm pain and neurological deficits in people with chronic whiplash associated disorders (WAD). This 1-year follow-up of that randomised controlled study with assessor blinding aimed to examine whether neck-specific exercise with (NSEB) or without (NSE) a behavioural approach has long-term benefits over physical activity prescription (PPA) regarding arm pain and neurological deficits (n = 171). Interventions were: NSE, NSEB, or PPA. Follow-up of arm pain, paraesthesia bothersomeness (questionnaires) and clinical neurological tests were performed after 3, 6 and 12 months and analysed with Linear Mixed Models and General Estimating Equations. The NSE and/or NSEB groups reported significantly less pain and paraesthesia bothersomeness as well as higher odds of normal key muscle arm strength and of normal upper limb neural tension over the year (all p < 0.03), compared with PPA. In conclusion, results suggest that neck-specific exercise with or without a behavioural approach may have persisting long term benefits over PPA regarding arm pain and clinical signs associated with neurological deficits in chronic WAD.
Learn More >This study aimed to understand long-term changes of the osteoarthritic temporomandibular joint (TMJ) condyle using computed tomography (CT) and to verify its correlation with clinical characteristics of temporomandibular disorders. Eighty-nine patients (152 joints; 76 female, 13 male) who had taken follow-up CTs (mean follow-up period: 644.58 ± 325.71 days) at least once in addition to their initial evaluation were selected. Cross-sectional demographic and clinical data and longitudinal CT images were collected. Data were analyzed by analysis of variance and logistic regression. Overall destructive change index (number of TMJ condyle sections in which destructive change was observed) decreased from 1.56 to 0.66. Improvement was seen in 93 joints (61.2%) and 27 joints (17.8%) worsened. In the pain positive group, both initial and final destructive change index were significantly higher compared to the pain negative group (p = 0.04). Occlusal stabilization splint therapy and nonsteroidal anti-inflammatory drug administration showed a significant effect on improving the prognosis of TMJ osteoarthritis (p = 0.015 and 0.011). In conclusion, TMJ osteoarthritis showed long-term improvement in the majority of cases. TMJ osteoarthritis accompanied by pain showed unfavorable prognosis with additional bone destruction. Occlusal stabilization splint and nonsteroidal anti-inflammatory drug administration were beneficial on the prognosis of TMJ osteoarthritis.
Learn More >Pain persists in a moderate number of patients following hip or knee replacement surgery. Persistent pain may subsequently lead to the prolonged consumption of analgesics after surgery and expose patients to the adverse drug events of opioids and NSAIDs, especially in older patients and patients with comorbidities. This study aimed to identify risk factors for the increased use of opioids and other analgesics 1 year after surgery and focused on comorbidities and surgery-related factors.
Learn More >Omiganan is an indolicidin analogue with antimicrobial properties that could be beneficial for patients with atopic dermatitis. This randomized, double-blind, placebo-controlled phase II trial explored efficacy, pharmacodynamics and safety of topical omiganan once daily in 36 patients with mild to moderate AD. Patients were randomized to apply topical omiganan 1%, omiganan 2.5% or vehicle gel to one target lesion once daily for 28 consecutive days. Small but significant improvements of the local oSCORAD index and morning itch were observed in the omiganan 2.5% group compared to the vehicle gel group (-18.5%; 95%CI=-32.9,-1.0; p=0.04 and -8.2; 95%CI=-16.3,-0.2; p=0.05 respectively). A shift from lesional to non-lesional skin microbiota was observed in both omiganan treatment groups, in contrast to the vehicle group. In conclusion, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis and small but statistically significant improvement of clinical scores were detected. Our findings warrant further exploration in future clinical trials.
Learn More >Although pain is a prevalent nonmotor symptom in Parkinson's disease (PD), it is undertreated, in part because of our limited understanding of the underlying mechanisms. Considering that the basal ganglia are implicated in pain sensation, and that their synaptic outputs are controlled by the subthalamic nucleus (STN), we hypothesized that the STN might play a critical role in parkinsonian pain hypersensitivity. To test this hypothesis, we established a unilateral parkinsonian mouse model with moderate lesions of dopaminergic neurons in the substantia nigra. The mice displayed pain hypersensitivity and neuronal hyperactivity in the ipsilesional STN and in central pain-processing nuclei. Optogenetic inhibition of STN neurons reversed pain hypersensitivity phenotypes in parkinsonian mice, while hyperactivity in the STN was sufficient to induce pain hypersensitivity in control mice. We further demonstrated that the STN differentially regulates thermal and mechanical pain thresholds through its projections to the substantia nigra pars reticulata (SNr) and the internal segment of the globus pallidus (GPi)/ventral pallidum (VP), respectively. Interestingly, optogenetic inhibition of STN-GPi/STN-VP and STN-SNr projections differentially elevated mechanical and thermal pain thresholds in parkinsonian mice. In summary, our results support the hypothesis that the STN and its divergent projections play critical roles in modulating pain processing under both physiological and parkinsonian conditions, and suggest that inhibition of individual STN projections may be a therapeutic strategy to relieve distinct pain phenotypes in PD.
Learn More >Mindfulness meditation can alleviate acute and chronic pain. It has been proposed that mindfulness meditation reduces pain by uncoupling sensory and affective pain dimensions. However, studies to date have reported mixed results, possibly due to a diversity of styles of and expertise in mindfulness meditation. Furthermore, the interrelations between mindfulness meditation and pain catastrophizing during acute pain remain little known.
Learn More >Genetic and environmental factors are thought to contribute to cluster headache, and cluster headache can affect multiple members of a family. A thorough understanding of its inheritance is critical to understanding the pathogenesis of this debilitating disease.
Learn More >Visceral hypersensitivity of the lower gastrointestinal tract, defined as an increased response to colorectal distension, frequently prompts episodes of debilitating abdominal pain in Irritable Bowel Syndrome (IBS). Although the pathophysiology of IBS is not yet fully elucidated, it is well known that stress is a major risk factor for development and acts as a trigger of pain sensation. Stress modulates both immune responses as well as the gut microbiota and vice versa. Additionally, either microbes themselves or through involvement of the immune system, activate or sensitize afferent nociceptors. In this paper, we review current knowledge on the influence of stress along the gut-brain-microbiota axis and exemplify relevant neuro-immune crosstalk mechanisms in visceral hypersensitivity, working towards understanding how gut microbiota-neuro-immune cross-talk contributes to visceral pain sensation in IBS patients.
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