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Acute itch is elicited by histamine, as well as non-histaminergic itch mediators including chloroquine, BAM8-22 and SLIGRL. When injected intradermally, histamine binds to histamine H1 and H4 receptors that activate TRPV1 to depolarize pruriceptors. Chloroquine, BAM-822, and SLIGRL respectively bind to Mas-related G-protein-coupled receptors MrgprA3, MrgprC11, and MrgprC11/PAR2 that in turn activate TRPA1. In this study we tested if histamine, chloroquine, BAM8-22 and SLIGRL elicit thermal hyperalgesia and mechanical allodynia in adult male mice. We measured the latency of hindpaw withdrawal from a noxious heat stimulus, and the threshold for hindpaw withdrawal from a von Frey mechanical stimulus. Intraplantar injection of histamine resulted in significant thermal hyperalgesia (p<0.01) and mechanical allodynia (p<0.0001) ipsilaterally that persisted for 1 hr. Pretreatment with the TRPV1 antagonist AMG-517 (10 or 20 μg), but not the TRPA1 antagonist HC-030031 (50 or 100 μg), significantly attenuated the magnitude and time course of thermal hyperalgesia and mechanical allodynia elicited by histamine (p<0.0001 for both), indicating that these effects are mediated by TRPV1. In contrast, pretreatment with the TRPA1 antagonist significantly reduced thermal hyperalgesia and mechanical allodynia elicited by chloroquine (p<0.001 and, p<0.0001, respectively), BAM-822 (p<0.01, p<0.001, respectively) and SLGRL (p<0.05, p<0.001, respectively), indicating that effects elicited by these non-histaminergic itch mediators require TRPA1. TRPV1 and TRPA1 channel inhibitors thus may have potential use in reducing hyperalgesia and allodynia associated with histaminergic and non-histaminergic itch, respectively.
Learn More >Functional bowel disorders (FBDs) are the most common gastrointestinal problems managed by physicians. We aimed to assess the burden of chronic symptomatic FBDs on ambulatory care delivery in the United States and evaluate patterns of treatment.
Learn More >Accumulating evidence has established a firm role for synaptic plasticity in the pathogenesis of neuropathic pain. Recent advances have highlighted the importance of dendritic spine remodeling in driving synaptic plasticity within the CNS. Identifying the molecular players underlying neuropathic pain induced structural and functional maladaptation is therefore critical to understanding its pathophysiology. This process of dynamic reorganization happens in unique phases that have diverse pathologic underpinnings in the initiation and maintenance of neuropathic pain. Recent evidence suggests that pharmacological targeting of specific proteins during distinct phases of neuropathic pain development produces enhanced antinociception. These findings outline a potential new paradigm for targeted treatment and the development of novel therapies for neuropathic pain. We present a concise review of the role of dendritic spines in neuropathic pain and outline the potential for modulation of spine dynamics by targeting two proteins, srGAP3 and Rac1, critically involved in the regulation of the actin cytoskeleton.
Learn More >Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms.
Learn More >Breast cancer continues to be the most commonly diagnosed cancer among Canadian women, with as many as 25-60% of women suffering from chronic neuropathic pain (CNP) as a pervasive consequence of treatment. While pharmacological interventions have shown limited efficacy for the management of CNP to date, psychological interventions, such as mindfulness-based stress reduction (MBSR), may be a promising alterative for improving pain-related problems. The purpose of this study was to use brain imaging methods to investigate this potential.
Learn More >Dexamethasone is a drug used to prolong the postoperative analgesia in children after peripheral nerve blockade, although the dose usually used (0.2 mg/kg) has not been studied yet. This study is a monocentric, prospective, randomised, placebo-controlled, double-blinded study in a university hospital in France. The primary objective of the study is to evaluate the efficacy of 0.2 mg/kg intravenous dexamethasone on early postoperative pain in children aged 6-15 years, who require a lower limb peripheral nerve block following general anaesthesia.
Learn More >Mindfulness has been shown to be beneficial for chronic pain. The underlying mechanisms of the mindfulness-pain link, however, are yet to be established. Particularly, the effects of mindfulness on pain modulation, which is shown to be dysfunctional among chronic pain patients, barely has been tested. This study investigated whether a short mindful attention training based on Langerian mindfulness mitigates reductions in pain modulation.
Learn More >The purpose of the present systematic review is to provide a current understanding of the mechanism of action and the evidence available to support clinical decision-making. The focus is to summarize randomized controlled trials (RCTs) and nonrandomized or observational studies of spinal cord stimulation in chronic pain to understand clinical effectiveness and the mechanism of action.
Learn More >New daily persistent headache (NDPH) is a subset of chronic headache where the pain is continuous from onset. Phenotypically it has chronic migraine or chronic tension type features. NDPH is considered to be highly refractory. Occipital nerve stimulation (ONS) has been used for treatment of refractory chronic migraine but there are no specific reports of its use for NDPH with migrainous features.
Learn More >We aimed at evaluating the differential involvement of large myelinated Aβ-fibers, small myelinated Aδ- and unmyelinated C-fibers in patients with diabetic polyneuropathy and how they contribute to neuropathic pain.
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