Browse by Audience
Atopic dermatitis (atopic eczema) is the most common inflammatory skin disease and has a significant burden on the quality of life of patients, families and caregivers. Its pathogenesis is a complex interplay between genetics and environment, involving impaired skin barrier function, immune dysregulation primarily involving the Th2 inflammatory pathway, itch, and skin microbiome. Restoration of skin barrier integrity with regular emollients and prompt topical anti-inflammatory therapies are mainstays of treatment. Systemic therapy is considered for moderate to severe disease. New understanding of inflammatory pathways and developments in targeted systemic immunotherapies have significantly advanced atopic dermatitis management. Dupilumab is a safe and effective treatment that is now available in Australia. Other promising agents for atopic dermatitis include Janus kinase, interleukin (IL)-13 and IL-31 inhibitors.
Learn More >To improve the treatment of painful Diabetic Peripheral Neuropathy (DPN) and associated co-morbidities, a better understanding of the pathophysiology and risk factors for painful DPN is required. Using harmonised cohorts (N = 1230) we have built models that classify painful versus painless DPN using quality of life (EQ5D), lifestyle (smoking, alcohol consumption), demographics (age, gender), personality and psychology traits (anxiety, depression, personality traits), biochemical (HbA1c) and clinical variables (BMI, hospital stay and trauma at young age) as predictors.
Learn More >Migraine with cranial autonomic symptoms is well described in the literature, but its prevalence in previous studies varies enormously. A precise estimate of the prevalence in a population-based material is important because migraine with cranial autonomic symptoms might represent an endophenotype, in which genetic and pathophysiological features differ from those without cranial autonomic features. The aim of the present study, therefore, was to estimate the prevalence in a big population-based sample using both questionnaire-based diagnosis (N = 12,620) and interview-based diagnosis (N = 302). We validate questionnaire-based diagnosis of migraine with cranial autonomic symptoms and develop the first diagnostic criteria for future research of this possible endophenotype.
Learn More >Ectopic discharge ("ectopia") in damaged afferent axons is a major contributor to chronic neuropathic pain. Clinical opinion discourages surgical resection of nerves proximal to the original injury site for fear of resurgence of ectopia and exacerbated pain. We tested this concept in a well-established animal neuroma model. Teased fiber recordings were made of ectopic spontaneous discharge originating in the experimental nerve-end neuroma and associated dorsal root ganglia (DRGs) in rats that underwent either a single transection (with ligation) of the sciatic nerve, or two consecutive transections separated by 7, 14, 21 or 30 days. Ectopia emerged in afferent A- and C-fibers after a single cut with kinetics anticipated from prior studies. When resection was carried out during the early period of intense A-fiber activity a brief period of resurgence was observed. However, resection of neuromas of more than 14 days was followed by low levels of activity with no indication resurgence. This remained the case in trials out to 60 days after the first cut. Likewise, we saw no indication of resurgent ectopia originating in axotomized DRG neuronal somata and no behavioral reflection of resurgence. In summary, we failed to validate the concern that proximal resection of a problematic nerve would lead to intense resurgent ectopic discharge and pain. As the well-entrenched concept of resurgence is based more on case-reports and anecdote than on solid evidence, it may be justified to relax the stricture against resecting neuromas as a therapeutic strategy, at least within the framework of controlled clinical trials.
Learn More >Prior research has demonstrated the widespread presence of racial disparities in emergency department (ED) care and analgesia. We hypothesized that racial disparities continue to exist in ED analgesic prescribing patterns, time to analgesia, and time to provider in the treatment of headache.
Learn More >Monoclonal antibodies directed against the neuropeptide calcitonin gene-related peptide (CGRP) belong to a new generation of therapeutics that are effective in the prevention of migraine. CGRP, a potent vasodilator, is strongly implicated in the pathophysiology of migraine, but its role remains to be fully elucidated. The hemisected rat head preparation and laser Doppler flowmetry were used to examine the effects on CGRP release from the dura mater and meningeal blood flow of the subcutaneously injected anti-CGRP monoclonal antibody fremanezumab at 30 mg/kg, when compared to an isotype control antibody. Some rats were administered glycerol trinitrate (GTN) intraperitoneally to produce a migraine-like sensitized state. When compared to the control antibody, the fremanezumab injection was followed by reduced basal and capsaicin-evoked CGRP release from day 3 up to 30 days. The difference was enhanced after 4 h of GTN application. The samples from the female rats showed a higher CGRP release compared to that of the males. The increases in meningeal blood flow induced by acrolein (100 µM) and capsaicin (100 nM) were reduced 13-20 days after the fremanezumab injection, and the direct vasoconstrictor effect of high capsaicin (10 µM) was intensified. In conclusion, fremanezumab lowers the CGRP release and lasts up to four weeks, thereby lowering the CGRP-dependent meningeal blood flow. The antibody may not only prevent the released CGRP from binding but may also influence the CGRP release stimulated by noxious agents relevant for the generation of migraine pain.
Learn More >There is a great unmet need for new therapeutics with novel mechanisms of action for patients with Crohn's disease. The ADVANCE and MOTIVATE studies showed that intravenous risankizumab, a selective p19 anti-interleukin (IL)-23 antibody, was efficacious and well tolerated as induction therapy. Here, we report the efficacy and safety of subcutaneous risankizumab as maintenance therapy.
Learn More >Risankizumab, an interleukin (IL)-23 p19 inhibitor, was evaluated for safety and efficacy as induction therapy in patients with moderately to severely active Crohn's disease.
Learn More >Dysfunction of glutamatergic synaptic plasticity in basolateral amygdala (BLA) constitutes a critical pathogenic mechanism underlying the depression-like behaviors induced by chronic pain. Astrocytes serve as an important supporting cell modulating glutamatergic synaptic transmission. Here, we found that peripheral spared nerve injury (SNI) induced astrocyte activation to release IL-6 in BLA. Inhibition of astrocyte activity attenuated SNI-induced IL-6 overexpression and depression-like behaviors. Moreover, SNI enhanced the abundance of DHHC2 in synaptosome and DHHC3 in Golgi apparatus, promoted PSD-95 palmitoylation, and increased the recruitment of GluR1 and NR2B at synapses. Suppression of IL-6 or PSD-95 palmitoylation attenuated the synaptic accumulation of GluR1 and NR2B in BLA and improved depression-like behaviors induced by SNI. Furthermore, IL-6 downstream PI3K increased the expression of DHHC3 in Golgi apparatus and facilitated the interaction of palmitoylated PSD-95 with GluR1 and NR2B at synapses. These findings collectively suggested that SNI activated astrocyte to release IL-6 in BLA, which promoted PSD-95 palmitoylation and enhanced the synaptic trafficking of GluR1 and NR2B, and subsequently mediated the depression-like behaviors induced by nerve injury.
Learn More >The purpose of this review was to systematically assess the effectiveness of 10Hz repetitive transcranial magnetic stimulation (rTMS) in fibromyalgia.
Learn More >