scholarly journals The Role of Purinergic Receptors in Cancer-Induced Bone Pain

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Sarah Falk ◽  
Maria Uldall ◽  
Anne-Marie Heegaard
Keyword(s):  
Inflammatory Pain ◽  
Bone Pain ◽  
Purinergic Receptors ◽  
Sensory Information ◽  
Cellular Mechanisms ◽  
Pain State ◽  
Current Therapies ◽  
Peripheral Site

Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular mechanisms underlying cancer-induced bone pain including the involvement of ATP and the purinergic receptors in the progression of the pain state. In nociception, ATP acts as an extracellular messenger to transmit sensory information both at the peripheral site of tissue damage and in the spinal cord. Several of the purinergic receptors have been shown to be important for the development and maintenance of neuropathic and inflammatory pain, and studies have demonstrated the importance of both peripheral and central mechanisms. We here provide an overview of the current literature on the role of purinergic receptors in cancer-induced bone pain with emphasis on some of the difficulties related to studying this complex pain state.

scholarly journals Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Wang ◽  
Lin Xu ◽  
Jiro Miura ◽  
Mithun Kumar Saha ◽  
Yume Uemura ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Muscle Development ◽  
Branchial Arch ◽  
Precursor Cells ◽  
Cellular Mechanisms ◽  
Pregnant Mice ◽  
Cranial Neural Crest Cells ◽  
Cranial Muscle

The first and second branchiomeric (branchial arch) muscles are craniofacial muscles that derive from branchial arch mesoderm. In mammals, this set of muscles is indispensable for jaw movement and facial expression. Defects during embryonic development that result in congenital partial absence of these muscles can have significant impact on patients’ quality of life. However, the detailed molecular and cellular mechanisms that regulate branchiomeric muscle development remains poorly understood. Herein we investigated the role of retinoic acid (RA) signaling in developing branchiomeric muscles using mice as a model. We administered all-trans RA (25 mg/kg body weight) to Institute of Cancer Research (ICR) pregnant mice by gastric intubation from E8.5 to E10.5. In their embryos at E13.5, we found that muscles derived from the first branchial arch (temporalis, masseter) and second branchial arch (frontalis, orbicularis oculi) were severely affected or undetectable, while other craniofacial muscles were hypoplastic. We detected elevated cell death in the branchial arch mesoderm cells in RA-treated embryos, suggesting that excessive RA signaling reduces the survival of precursor cells of branchiomeric muscles, resulting in the development of hypoplastic craniofacial muscles. In order to uncover the signaling pathway(s) underlying this etiology, we focused on Pitx2, Tbx1, and MyoD1, which are critical for cranial muscle development. Noticeably reduced expression of all these genes was detected in the first and second branchial arch of RA-treated embryos. Moreover, elevated RA signaling resulted in a reduction in Dlx5 and Dlx6 expression in cranial neural crest cells (CNCCs), which disturbed their interactions with branchiomeric mesoderm cells. Altogether, we discovered that embryonic craniofacial muscle defects caused by excessive RA signaling were associated with the downregulation of Pitx2, Tbx1, MyoD1, and Dlx5/6, and reduced survival of cranial myogenic precursor cells.

scholarly journals Use of Animal Models in Understanding Cancer-induced Bone Pain

2015 ◽  
Vol 8s1 ◽  
pp. CGM.S21215 ◽  
Author(s):  
Lauren M. Slosky ◽  
Tally M. Largent-Milnes ◽  
Todd W. Vanderah
Keyword(s):  
Quality Of Life ◽  
Animal Models ◽  
Cancer Pain ◽  
Bone Metastases ◽  
Bone Pain ◽  
Model Choice ◽  
Immunocompetent Host ◽  
The Past ◽  
Pain State

Many common cancers have a propensity to metastasize to bone. Although malignancies often go undetected in their native tissues, bone metastases produce excruciating pain that severely compromises patient quality of life. Cancer-induced bone pain (CIBP) is poorly managed with existing medications, and its multifaceted etiology remains to be fully elucidated. Novel analgesic targets arise as more is learned about this complex and distinct pain state. Over the past two decades, multiple animal models have been developed to study CIBP's unique pathology and identify therapeutic targets. Here, we review animal models of CIBP and the mechanistic insights gained as these models evolve. Findings from immunocompromised and immunocompetent host systems are discussed separately to highlight the effect of model choice on outcome. Gaining an understanding of the unique neuromolecular profile of cancer pain through the use of appropriate animal models will aid in the development of more effective therapeutics for CIBP.

scholarly journals Convergence of Synapses, Endosomes, and Prions in the Biology of Neurodegenerative Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Gunnar K. Gouras
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Brain Regions ◽  
Neural Function ◽  
Cellular Mechanisms ◽  
Normal Functions ◽  
Age Related ◽  
Cell Propagation

Age-related misfolding and aggregation of disease-linked proteins in selective brain regions is a characteristic of neurodegenerative diseases. Although neuropathological aggregates that characterize these various diseases are found at sites other than synapses, increasing evidence supports the idea that synapses are where the pathogenesis begins. Understanding these diseases is hampered by our lack of knowledge of what the normal functions of these proteins are and how they are affected by aging. Evidence has supported the idea that neurodegenerative disease-linked proteins have a common propensity for prion protein-like cell-to-cell propagation. However, it is not thought that the prion-like quality of these proteins/peptides that allows their cell-to-cell transmission implies a role for human-to-human spread in common age-related neurodegenerative diseases. It will be important to better understand the molecular and cellular mechanisms governing the role of these aggregating proteins in neural function, especially at synapses, how their propagation occurs and how pathogenesis is promoted by aging.

scholarly journals Randomized Double-Blind Trial of Pregabalin Versus Placebo in Conjunction With Palliative Radiotherapy for Cancer-Induced Bone Pain

2016 ◽  
Vol 34 (6) ◽  
pp. 550-556 ◽  
Author(s):  
Marie Fallon ◽  
Peter J. Hoskin ◽  
Lesley A. Colvin ◽  
Susan M. Fleetwood-Walker ◽  
Douglas Adamson ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Bone Pain ◽  
Rating Scale ◽  
Breakthrough Pain ◽  
Pain Interference ◽  
Double Blind ◽  
End Point ◽  
Average Pain

Purpose Cancer-induced bone pain (CIBP) affects one third of patients with cancer. Radiotherapy remains the gold-standard treatment; however, laboratory and clinical work suggest that pregabalin may be useful in treating CIBP. The aim of this study was to examine pregabalin in patients with CIBP receiving radiotherapy. Patients and Methods A multicenter, double-blind randomized trial of pregabalin versus placebo was conducted. Eligible patients were age ≥ 18 years, had radiologically proven bone metastases, were scheduled to receive radiotherapy, and had pain scores ≥ 4 of 10 (on 0-to-10 numeric rating scale). Before radiotherapy, baseline assessments were completed, followed by random assignment. Doses of pregabalin and placebo were increased over 4 weeks. The primary end point was treatment response, defined as a reduction of ≥ 2 points in worst pain by week 4, accompanied by a stable or reduced opioid dose, compared with baseline. Secondary end points assessed average pain, interference of pain with activity, breakthrough pain, mood, quality of life, and adverse events. Results A total of 233 patients were randomly assigned: 117 to placebo and 116 to pregabalin. The most common cancers were prostate (n = 88; 38%), breast (n = 77; 33%), and lung (n = 42; 18%). In the pregabalin arm, 45 patients (38.8%) achieved the primary end point, compared with 47 (40.2%) in the placebo arm (adjusted odds ratio, 1.07; 95% CI, 0.63 to 1.81; P = .816). There were no statistically significant differences in average pain, pain interference, or quality of life between arms. There were differences in mood (P = .031) and breakthrough pain duration (P = .037) between arms. Outcomes were compared at 4 weeks. Conclusion Our findings do not support the role of pregabalin in patients with CIBP receiving radiotherapy. The role of pregabalin in CIBP with a clinical neuropathic pain component is unknown.

Pediatric Hemoglobinopathies

2011 ◽  
Vol 29 (1) ◽  
pp. 353-377
Author(s):  
Tonya A. Schneidereith
Keyword(s):  
Genetic Disorders ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Nucleotide Polymorphisms ◽  
Chromosome 11 ◽  
Current Therapies ◽  
Genetic Mechanisms ◽  
State Of The Science

The β-chain hemoglobinopathies affect the β-globin gene on chromosome 11 and comprise some of the most prevalent genetic disorders in humans, including sickle cell disease (SCD) and β-thalassemia. The mutations associated with these diseases cause various symptoms and degrees of severity. Extensive research has sought to identify physiologic and genetic factors responsible for these variations, including the role of fetal hemoglobin (HbF) and its importance in the alleviation of symptoms. This chapter on the genomics of hemoglobinopathies addresses the interests of both the researcher and the caregiver. The pathophysiology of SCD and thalassemia are reviewed, as well as the state of the science on the regulation of HbF, including newly identified quantitative trait loci (QTLs), single nucleotide polymorphisms (SNPs), and suggested genetic mechanisms. Studies on the current therapies of hemoglobinopathies, both pharmacologic and non-pharmacologic, are also reviewed. Research reviews relevant to the care of children include physical and psychological sequelae, genetic counseling, and effects on learning. With a thorough understanding of the normal physiology of hemoglobin, the pathophysiology of SCD and the thalassemias, and the associated physical and psychological sequela, nurses can improve the quality of life for children and families living with these diseases.

scholarly journals Liposomal Nanosystems in Rheumatoid Arthritis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 454
Author(s):  
Margarida Ferreira-Silva ◽  
Catarina Faria-Silva ◽  
Pedro Viana Baptista ◽  
Eduarda Fernandes ◽  
Alexandra Ramos Fernandes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Importance ◽  
Delivery Systems ◽  
Therapeutic Drug ◽  
Market Authorization ◽  
Current Therapies ◽  
Socioeconomic Burden

Rheumatoid arthritis (RA) is an autoimmune disease that affects the joints and results in reduced patient quality of life due to its chronic nature and several comorbidities. RA is also associated with a high socioeconomic burden. Currently, several available therapies minimize symptoms and prevent disease progression. However, more effective treatments are needed due to current therapies’ severe side-effects, especially under long-term use. Drug delivery systems have demonstrated their clinical importance—with several nanocarriers present in the market—due to their capacity to improve therapeutic drug index, for instance, by enabling passive or active targeting. The first to achieve market authorization were liposomes that still represent a considerable part of approved delivery systems. In this manuscript, we review the role of liposomes in RA treatment, address preclinical studies and clinical trials, and discuss factors that could hamper a successful clinical translation. We also suggest some alterations that could potentially improve their progression to the market.

Cognitive Health Counseling 40+

2013 ◽  
Vol 21 (1) ◽  
pp. 24-33 ◽  
Author(s):  
Anne Eschen ◽  
Franzisca Zehnder ◽  
Mike Martin
Keyword(s):  
Outcome Variable ◽  
Pilot Phase ◽  
Subjective Memory ◽  
Cognitive Health ◽  
Health Counseling ◽  
Agents Of Change ◽  
Main Outcome Variable ◽  
Further Development

This article introduces Cognitive Health Counseling 40+ (CH.CO40+), an individualized intervention that is conceptually based on the orchestration model of quality-of-life management ( Martin & Kliegel, 2010 ) and aims at improving satisfaction with cognitive health in adults aged 40 years and older. We describe the theoretically deduced characteristics of CH.CO40+, its target group, its multifactorial nature, its individualization, the application of subjective and objective measures, the role of participants as agents of change, and the rationale for choosing participants’ satisfaction with their cognitive health as main outcome variable. A pilot phase with 15 middle-aged and six older adults suggests that CH.CO40+ attracts, and may be particularly suitable for, subjective memory complainers. Implications of the pilot data for the further development of the intervention are discussed.

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