Browse by Audience
Migraine is a complex neurovascular disorder, which causes intense socioeconomic problems worldwide. The pathophysiology of disease is enigmatic; accordingly, therapy is not sufficient. In recent years, migraine research focused on tryptophan, which is metabolized via two main pathways, the serotonin and kynurenine pathways, both of which produce neuroactive molecules that influence pain processing and stress response by disturbing neural and brain hypersensitivity and by interacting with molecules that control vascular and inflammatory actions. Serotonin has a role in trigeminal pain processing, and melatonin, which is another product of this pathway, also has a role in these processes. One of the end products of the kynurenine pathway is kynurenic acid (KYNA), which can decrease the overexpression of migraine-related neuropeptides in experimental conditions. However, the ability of KYNA to cross the blood-brain barrier is minimal, necessitating the development of synthetic analogs with potentially better pharmacokinetic properties to exploit its therapeutic potential. This review summarizes the main translational and clinical findings on tryptophan metabolism and certain neuropeptides, as well as therapeutic options that may be useful in the prevention and treatment of migraine.
Learn More >To assess whether alcohol intake is associated with the onset of migraine attacks up to 2 days after consumption in individuals with episodic migraine (EM).
Learn More >Ehlers-Danlos syndromes are hereditary disorders of connective tissue that are characterized by joint hypermobility, skin hyperextensibility and tissue fragility. The most common subtype is the hypermobile type. In addition to symptoms of small fibre neuropathy (SFN) due to damage to the small peripheral nerve fibres with degeneration of the distal nerve endings, autonomic disorders such as postural tachycardia syndrome are frequently reported features in patients with hypermobile Ehlers-Danlos syndromes (hEDS). To date, the underlying pathophysiological mechanisms are still not completely understood.
Learn More >Along with the development of novel migraine therapies as the monoclonal antibodies against calcitonin gene-related peptide (CGRP) and its receptor, the question arises if the treatment of chronic migraine (CM) and medication overuse headache (MOH) must be reconsidered. Have previous therapeutic approaches, including glucocorticoids, lost their role in the management of this debilitating disorder? In this narrative review, we present an overview of the available treatment options in CM and MOH in light of CGRP antibodies as well as an evaluation of the role of glucocorticoids in withdrawal therapy.
Learn More >The effectiveness of onabotulinumtoxinA (BTX-A) has been established in primary trigeminal neuralgia (TN). However, to the best of our knowledge, the efficacy of BTX-A in secondary TN has not yet been studied.
Learn More >HIV stigma may influence physical activity in people living with HIV (PLWH) and chronic pain. We prospectively examined the relationship between stigma, activity and chronic pain in a convenience sample of PLWH initiating antiretroviral therapy in an inner-city clinic in Johannesburg, South Africa. Participants wore accelerometers to measure daily duration and intensity of activity for 2 weeks. Stigma was assessed with the Revised HIV Stigma Scale. Participants [n = 81, 89% female, age mean (SD) 42 (8)] were active for a median of 7 h daily (IQR 5.2, 9.2), but at very low intensity, equivalent to a slow walk [median (IQR): 0.39 m s (0.33, 0.50)]. Duration and intensity of activity was not associated with stigma, even after controlling for age, self-assessed wealth, pain intensity and willingness to engage in physical activity (p-values > 0.05). As stigma did not associate with greater activity, drivers of sustained activity in South African PLWH remain unclear.
Learn More >Although neuronal Toll-like receptors (TLRs) (e.g., TLR2, TLR3, and TLR7) have been implicated in itch sensation, the roles of keratinocyte TLRs in chronic itch are elusive. Herein, we evaluated the roles of keratinocyte TLR2 and TLR7 in chronic itch under dry skin and psoriasis conditions, which was induced by either acetone-ether-water treatment or 5% imiquimod cream in mice, respectively. We found that TLR2 and TLR7 signaling were significantly upregulated in dry skin and psoriatic skin in mice. Chronic itch and epidermal hyperplasia induced by dry skin or psoriasis were comparably reduced in TLR2 and TLR7 knockout mice. In the dry skin model, the enhanced messenger RNA (mRNA) expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, TNF-α, and IFN-γ were inhibited in TLR2 mice, while CXCL2, IL-31, and IL-6 were inhibited in TLR7 mice. In psoriasis model, the enhanced mRNA expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, and TNF-α were inhibited in TLR2 mice, while CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, and TNF-α were inhibited in TLR7 mice. Incubation with Staphylococcus aureus (S. aureus) peptidoglycan (PGN-SA) (a TLR2 agonist), imiquimod (a TLR7 agonist), and miR142-3p (a putative TLR7 agonist) were sufficient to upregulate the expression of pruritic cytokines or chemokines in cultured keratinocyte HaCaT cells. Finally, pharmacological blockade of C-X-C Motif Chemokine Receptor 1/2 and high mobility group box protein 1 dose-dependently attenuated acute and chronic itch in mice. Together, these results indicate that keratinocyte TLR2 and TLR7 signaling pathways are distinctly involved in the pathogenesis of chronic itch.
Learn More >Low back pain contributes to an increasing global health burden exacerbated by unsustained improvements from current treatments. There is a need to develop, and test interventions to maintain initial improvements from low back pain treatments. One option is to implement a booster intervention. This study aimed to develop and test the feasibility of implementing a booster intervention delivered remotely to supplement the benefits from a complex intervention for chronic low back pain.
Learn More >