Browse by Audience
Sickle cell disease (SCD) is the most common inherited blood disorder in both Jamaica and the United States and is characterized by poor quality of life and debilitating complications, with the hallmark symptom being pain caused by acute and chronic conditions. Individuals with SCD often experience stigma due to their disease status, opioid use, and race. This study sought to understand the influence of perceived stigma and demographic/clinical characteristics on quality of life in adults with SCD in Jamaica (n = 50) and the United States (n = 50). Participants completed interviewer-administered surveys including demographic/clinical characteristics; the Measure of Sickle Cell Stigma (MoSCS); and the Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me). A set of general linear models for each country was built to examine the influence of explanatory variables on the quality of life outcomes. Overall, stigma scores were low for both countries, with the exception of the MoSCS disclosure concerns and expected discrimination subscales, where scores averaged medium and high, respectively. In both countries, being employed was associated with better quality of life; and reports of stigma (internalized stigma and expected discrimination) was associated with worse quality of life. These findings have several implications for healthcare providers caring for individuals with SCD, policy makers, and researchers. Specifically, findings can be used to advocate for improved access to mental health care for individuals with SCD and inform stigma reduction intervention approaches in SCD.
Learn More >Bone marrow lesions (BML) represent areas of deteriorated bone structure and metabolism characterized by pronounced water-equivalent signaling within the trabecular bone on Magnetic Resonance Imaging (MRI). BML are associated with repair mechanisms subsequent to various clinical conditions associated with inflammatory and non-inflammatory injury to the bone. There is no approved treatment for this condition. Bisphosphonates are known to improve bone stability in osteoporosis and other bone disorders and have been used off-label to treat BML. A randomized, triple-blind, placebo-controlled Phase III trial was conducted to assess efficacy and safety of single dose Zoledronic acid (ZOL) 5mg i.v. with Vitamin D 1000 IU/d as opposed to placebo with Vitamin D 1000 IU/d in 48 patients (randomized 2:1) with BML. Primary efficacy endpoint was reduction of edema volume six weeks after treatment as assessed by MRI. Following treatment, mean BML volume decreased by 64.53(±41.92)% in patients receiving Zoledronic acid and increased by 14.43(±150.46)% in the placebo group (p=0.007). A decrease in BML volume was observed in 76.5% of patients receiving ZOL and in 50% of the patients receiving placebo. Pain level (VAS) and all categories of the Pain Disability Index (PDI) improved with ZOL vs placebo after 6 weeks but reconciled after six additional weeks of follow-up. Six SAE occurred in five patients, none of which were classified as related to the study drug. No cases of osteonecrosis or fractures occurred. Therefore single-dose Zoledronic acid 5mg i.v. together with Vitamin D may enhance resolution of bone marrow lesions over 6 weeks along with reduction of pain as compared to Vitamin D supplementation only. This article is protected by copyright. All rights reserved.
Learn More >Ocular discomfort and eye pain are frequently reported by patients with dry eye disease (DED), and their management remains a real therapeutic challenge for the Ophthalmologist. In DED patients, injury at the level of each structure of the ocular surface can determine variable symptoms, ranging from mild ocular discomfort up to an intolerable pain evoked by innocuous stimuli. In refractory cases, the persistence of this harmful signal is able to evoke a mechanism of maladaptive plasticity of the nervous system that leads to increased pain responsiveness. Peripheral and, subsequently, central sensitization cause nociceptor hyperexcitability and persistent pain perception that can culminate in the paradoxical situation of perceiving eye pain even in the absence of ocular surface abnormalities. Effective therapeutic strategies of these cases are challenging, and new options are desirable. Recently, a theoretical novel therapeutic approach concerns enkephalins thanks to the evidence that eye pain sensations are modulated by endogenous opioid peptides (enkephalins, endorphins and dynorphins). In this regard, new topical agents open up a new theoretical scenario in the treatment of ocular discomfort and eye pain in the setting of DED, such as, for example, a multimolecular complex based on proteins and glycosaminoglycans also containing opiorphin that may assist the physiological pain-relieving mechanism of the eye.
Learn More >The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide. Deacetylasperulosidic acid (DAA) has anti-atopic activity in the three main cell types associated with AD: keratinocytes, mast cells, and eosinophils. Our study investigated the anti-atopic activity of DAA in 2,4-dinitrochlorobenzene-induced NC/Nga mice. DAA alleviated the symptoms of AD, including infiltration of inflammatory cells (mast cells and eosinophils), epidermal thickness, ear thickness, and scratching behavior. Furthermore, DAA reduced serum IgE, histamine, and IgG1/IgG2a ratio and modulated the levels of AD-related cytokines and chemokines, namely interleukin (IL)-1β, IL-4, IL-6, IL-9, IL-10, IL-12, tumor necrosis factor-α, interferon-γ, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation the normal T cell expressed and secreted in the serum. DAA restored immune balance by regulating gene expression and secretion of Th1-, Th2-, Th9-, Th17-, and Th22-mediated inflammatory factors in the dorsal skin and splenocytes and restored skin barrier function by increasing the expression of the pro-filaggrin gene and barrier-related proteins filaggrin, involucrin, and loricrin. These results suggest DAA as a potential therapeutic agent that can alleviate the symptoms of AD by reducing pruritus, modulating immune imbalance, and restoring skin barrier function.
Learn More >In migraineurs, coloured lenses were found to reduce the visual stress caused by an aversive pattern known to trigger migraines by 70%, but do such patterns also produce a low-level anxiety/fear response? Is this response lessened by colour? We sought to investigate this in a study comprising a broad screening component followed by a dot-probe experiment to elicit attentional biases (AB) to aversive patterns. Undergraduate psychology students completed headache and visual discomfort (VD) questionnaires ( = 358), thereby forming a subject pool from which 13 migraineurs with high visual discomfort and 13 no-headache controls with low visual discomfort, matched on age and sex, completed a dot-probe experiment. Paired stimuli were presented for 500 ms: aversive achromatic 3 cpd square wave gratings vs control, scrambled patterns. These conditions were repeated using the colour that was most comfortable for each participant. VD was greater in the more severe headache groups. On all measures, the migraineurs were more anxious than the controls, and a positive relationship was found between VD and trait anxiety. The 3 cpd gratings elicited an aversive AB in the migraine group which was somewhat reduced by the use of colour, and this was not seen in the controls. The results suggest a new role for colour in reducing visual stress via anxiety/fear reduction.
Learn More >Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitously and marketed for the treatment of epilepsy, migraine, bipolar disorder and neuropathic pain. Apart from this, VPA has potential therapeutic applications in other central nervous system (CNS) disorders and in various cancer types. Since the discovery of its anticonvulsant activity, substantial efforts have been made to develop structural analogues and derivatives in an attempt to increase potency and decrease adverse side effects, the most significant being teratogenicity and hepatotoxicity. Most of these compounds have shown reduced toxicity with improved potency. The simple structure of VPA offers a great advantage to its modification. This review briefly discusses the pharmacology and molecular targets of VPA. The article then elaborates on the structural modifications in VPA including amide-derivatives, acid and cyclic analogues, urea derivatives and pro-drugs, and compares their pharmacological profile with that of the parent molecule. The current challenges for the clinical use of these derivatives are also discussed. The review is expected to provide necessary knowledgebase for the further development of VPA-derived compounds.
Learn More >Increasing pressures exist to reduce or discontinue opioid use among patients currently on long-term opioid therapy (LTOT). It is essential to understand the potential effects of opioid reduction.
Learn More >This study sought to determine whether cannabidiol (CBD) or a CBD derivative, CBD monovalinate monohemisuccinate (CBD-val-HS), could attenuate the development of oxycodone reward while retaining its analgesic effects. To determine the effect on oxycodone reward, animals were enrolled in the conditioned place preference paradigm and received either saline or oxycodone (3.0 mg/kg) in combination with either CBD or CBD-val-HS utilizing three sets of drug-/no drug-conditioning trials. To determine if the doses of CBD or CBD-val-HS that blocked opioid reward would affect nociceptive processes, animals were enrolled in the hot plate and abdominal writhing assays when administered alone or in combination with a subanalgesic (1.0 mg/kg) or analgesic (3.0 mg/kg) dose of oxycodone. Results from condition place preference demonstrated CBD was not able attenuate oxycodone place preference while CBD-val-HS attenuated these rewarding effects at 8.0 mg/kg and was void of rewarding or aversive properties. In contrast to CBD, CBD-val-HS alone produced analgesic effects in both nociceptive assays but was most effective compared with oxycodone against thermal nociception. Of interest, there was a differential interaction of CBD and CBD-val-HS×oxycodone across the two nociceptive assays producing subadditive responses on the hot plate assay, whereas additive responses were observed in the abdominal writhing assay. These findings suggest CBD-val-HS alone, a nonrewarding analgesic compound, could be useful in pain management and addiction treatment settings.
Learn More >Prdm12 is a conserved epigenetic transcriptional regulator that displays restricted expression in nociceptors of the developing peripheral nervous system. In mice, Prdm12 is required for the development of the entire nociceptive lineage. In humans, PRDM12 mutations cause congenital insensitivity to pain, likely because of the loss of nociceptors. Prdm12 expression is maintained in mature nociceptors suggesting a yet-to-be explored functional role in adults. Using Prdm12 inducible conditional knockout mouse models, we report that in adult nociceptors Prdm12 is no longer required for cell survival but continues to play a role in the transcriptional control of a network of genes, many of them encoding ion channels and receptors. We found that disruption of Prdm12 alters the excitability of dorsal root ganglion neurons in culture. Phenotypically, we observed that mice lacking Prdm12 exhibit normal responses to thermal and mechanical nociceptive stimuli but a reduced response to capsaicin and hypersensitivity to formalin-induced inflammatory pain. Together, our data indicate that Prdm12 regulates pain-related behavior in a complex way by modulating gene expression in adult nociceptors and controlling their excitability. The results encourage further studies to assess the potential of Prdm12 as a target for analgesic development.
Learn More >