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1.
Mayo Clin Proc ; 99(5): 782-794, 2024 May.
Article in English | MEDLINE | ID: mdl-38702127

ABSTRACT

The rapidly evolving coaching profession has permeated the health care industry and is gaining ground as a viable solution for addressing physician burnout, turnover, and leadership crises that plague the industry. Although various coach credentialing bodies are established, the profession has no standardized competencies for physician coaching as a specialty practice area, creating a market of aspiring coaches with varying degrees of expertise. To address this gap, we employed a modified Delphi approach to arrive at expert consensus on competencies necessary for coaching physicians and physician leaders. Informed by the National Board of Medical Examiners' practice of rapid blueprinting, a group of 11 expert physician coaches generated an initial list of key thematic areas and specific competencies within them. The competency document was then distributed for agreement rating and comment to over 100 stakeholders involved in physician coaching. Our consensus threshold was defined at 70% agreement, and actual responses ranged from 80.5% to 95.6% agreement. Comments were discussed and addressed by 3 members of the original group, resulting in a final model of 129 specific competencies in the following areas: (1) physician-specific coaching, (2) understanding physician and health care context, culture, and career span, (3) coaching theory and science, (4) diversity, equity, inclusion, and other social dynamics, (5) well-being and burnout, and (6) physician leadership. This consensus on physician coaching competencies represents a critical step toward establishing standards that inform coach education, training, and certification programs, as well as guide the selection of coaches and evaluation of coaching in health care settings.


Subject(s)
Delphi Technique , Mentoring , Humans , Clinical Competence/standards , Consensus , Leadership , Physicians/standards , Physicians/psychology , Professional Competence/standards
2.
Child Adolesc Psychiatr Clin N Am ; 33(1): 17-32, 2024 01.
Article in English | MEDLINE | ID: mdl-37981333

ABSTRACT

Documented disparities have profoundly impacted the training and careers of physicians from socially and historically marginalized groups, including women, people with disabilities, people who identify with racial and ethnic minority groups, and the lesbian, gay, bisexual, transgender, and queer or questioning+ community. Professionalism is a core component of medical training and practice, yet a focus on workforce diversity, equity, and inclusion is often absent. This report aims to encourage the adoption of workforce diversity, equity, and inclusion as a crucial component of professionalism, with an emphasis on the field of psychiatry.


Subject(s)
Professionalism , Psychiatry , Humans , Female , Ethnicity , Minority Groups , Workforce
3.
Psychiatr Clin North Am ; 45(2): 243-258, 2022 06.
Article in English | MEDLINE | ID: mdl-35680240

ABSTRACT

Documented disparities have profoundly impacted the training and careers of physicians from socially and historically marginalized groups, including women, people with disabilities, people who identify with racial and ethnic minority groups, and the lesbian, gay, bisexual, transgender, and queer or questioning+ community. Professionalism is a core component of medical training and practice, yet a focus on workforce diversity, equity, and inclusion is often absent. This report aims to encourage the adoption of workforce diversity, equity, and inclusion as a crucial component of professionalism, with an emphasis on the field of psychiatry.


Subject(s)
Professionalism , Psychiatry , Ethnicity , Female , Humans , Minority Groups , Workforce
4.
BMC Psychiatry ; 22(1): 19, 2022 01 06.
Article in English | MEDLINE | ID: mdl-34991514

ABSTRACT

BACKGROUND: Global health crises, such as the COVID-19 pandemic, confront healthcare workers (HCW) with increased exposure to potentially morally distressing events. The pandemic has provided an opportunity to explore the links between moral distress, moral resilience, and emergence of mental health symptoms in HCWs. METHODS: A total of 962 Canadian healthcare workers (88.4% female, 44.6 + 12.8 years old) completed an online survey during the first COVID-19 wave in Canada (between April 3rd and September 3rd, 2020). Respondents completed a series of validated scales assessing moral distress, perceived stress, anxiety, and depression symptoms, and moral resilience. Respondents were grouped based on exposure to patients who tested positive for COVID-19. In addition to descriptive statistics and analyses of covariance, multiple linear regression was used to evaluate if moral resilience moderates the association between exposure to morally distressing events and moral distress. Factors associated with moral resilience were also assessed. FINDINGS: Respondents working with patients with COVID-19 showed significantly more severe moral distress, anxiety, and depression symptoms (F > 5.5, p < .020), and a higher proportion screened positive for mental disorders (Chi-squared > 9.1, p = .002), compared to healthcare workers who were not. Moral resilience moderated the relationship between exposure to potentially morally distressing events and moral distress (p < .001); compared to those with higher moral resilience, the subgroup with the lowest moral resilience had a steeper cross-sectional worsening in moral distress as the frequency of potentially morally distressing events increased. Moral resilience also correlated with lower stress, anxiety, and depression symptoms (r > .27, p < .001). Factors independently associated with stronger moral resilience included: being male, older age, no mental disorder diagnosis, sleeping more, and higher support from employers and colleagues (B [0.02, |-0.26|]. INTERPRETATION: Elevated moral distress and mental health symptoms in healthcare workers facing a global crisis such as the COVID-19 pandemic call for the development of interventions promoting moral resilience as a protective measure against moral adversities.


Subject(s)
COVID-19 , Pandemics , Adult , Aged , Anxiety/epidemiology , Canada , Cross-Sectional Studies , Depression/epidemiology , Female , Health Personnel , Humans , Male , Mental Health , Middle Aged , Morals , SARS-CoV-2
5.
Front Physiol ; 12: 750696, 2021.
Article in English | MEDLINE | ID: mdl-34721074

ABSTRACT

Acid-Sensing Ion Channels (ASICs) are proton-gated sodium-selective cation channels that have emerged as metabolic and pain sensors in peripheral sensory neurons and contribute to neurotransmission in the CNS. These channels and their related degenerin/epithelial sodium channel (DEG/ENaC) family are often characterized by their sensitivity to amiloride inhibition. However, amiloride can also cause paradoxical potentiation of ASIC currents under certain conditions. Here we characterized and investigated the determinants of paradoxical potentiation by amiloride on ASIC3 channels. While inhibiting currents induced by acidic pH, amiloride potentiated sustained currents at neutral pH activation. These effects were accompanied by alterations in gating properties including (1) an alkaline shift of pH-dependent activation, (2) inhibition of pH-dependent steady-state desensitization (SSD), (3) prolongation of desensitization kinetics, and (4) speeding of recovery from desensitization. Interestingly, extracellular Ca2+ was required for paradoxical potentiation and it diminishes the amiloride-induced inhibition of SSD. Site-directed mutagenesis within the extracellular non-proton ligand-sensing domain (E79A, E423A) demonstrated that these residues were critical in mediating the amiloride-induced inhibition of SSD. However, disruption of the purported amiloride binding site (G445C) within the channel pore blunted both the inhibition and potentiation of amiloride. Together, our results suggest that the myriad of modulatory and blocking effects of amiloride are the result of a complex competitive interaction between amiloride, Ca2+, and protons at probably more than one site in the channel.

6.
Phys Rev E ; 104(2-1): 024127, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34525655

ABSTRACT

We study Nielsen complexity and Fubini-Study complexity for the transverse XY spin chain and establish their nonanalyticity at the critical lines. We obtain the scaling behavior of both complexities near quantum phase transitions in the thermodynamic limit, as a function of the system parameters. The scaling of the Nielsen complexity with the system size is also established, close to criticality. We also obtain analytic expressions for the Fubini-Study complexity in some special cases for this model, while a numerical analysis in more generic situations is carried out. Our study clearly demonstrates the differences in the two notions of complexity in the transverse XY model.

7.
J Environ Manage ; 289: 112243, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-33827001

ABSTRACT

Safety of sanitation workers remains an often-ignored aspect in Fecal Sludge Management. While shifting workers from manual to mechanical means of de-sludging remains a priority, this paper highlights that there are a number of safety issues, including exposure to sludge, faced by sanitation workers, even in a mechanised context, where de-sludging trucks are utilised to provide de-sludging services. Based on a detailed analysis of observation of stakeholders and extensive process documentation (of de-sludging process), and expert interviews, the study identified three key safety concerns: inhalation of harmful gases, contact with sludge, and physical injury, and determined the underlying cause for the same, using a systems thinking approach. These causes are varied including behaviours and practices by households such as non-compliance of septic tank construction to design standards, irregular cleaning, improper disposal of inappropriate items in toilets; inappropriate or inadequate design of decanting stations, tools and equipment, and inadequate awareness and knowledge among all stakeholders. Using the hierarchy of controls framework, a set of measures are described to increase the safety of workers. These proposed interventions go beyond the provision of Personal Protective Equipment (PPE), and range from behaviour change campaigns, improvements in decanting stations, better access to appropriately designed tools. The study highlights the need to place emphasis on eliminating, substituting and controlling the hazards as necessary steps for PPE to be relevant. Finally, the paper places the issue of occupational safety within the larger context of the informal nature of de-sludging occupation and the overall vulnerability of workers. It posits that this makes safety more complicated to address as several factors need to be taken into account, and actions are required by multiple sets of actors.


Subject(s)
Occupational Health , Cities , Feces , Humans , Sanitation , Sewage
8.
BMJ Open ; 10(12): e043805, 2020 12 12.
Article in English | MEDLINE | ID: mdl-33310814

ABSTRACT

INTRODUCTION: The negative impacts of COVID-19 have rippled through every facet of society. Understanding the multidimensional impacts of this pandemic is crucial to identify the most critical needs and to inform targeted interventions. This population survey study aimed to investigate the acute phase of the COVID-19 outbreak in terms of perceived threats and concerns, occupational and financial impacts, social impacts and stress between 3 April and 15 May 2020. METHODS: 6040 participants are included in this report. A multivariate linear regression model was used to identify factors associated with stress changes (as measured by the Cohen's Perceived Stress Scale (PSS)) relative to pre-outbreak retrospective estimates. RESULTS: On average, PSS scores increased from low stress levels before the outbreak to moderate stress levels during the outbreak (p<0.001). The independent factors associated with stress worsening were: having a mental disorder, female sex, having underage children, heavier alcohol consumption, working with the general public, shorter sleep duration, younger age, less time elapsed since the start of the outbreak, lower stress before the outbreak, worse symptoms that could be linked to COVID-19, lower coping skills, worse obsessive-compulsive symptoms related to germs and contamination, personalities loading on extraversion, conscientiousness and neuroticism, left wing political views, worse family relationships and spending less time exercising and doing artistic activities. CONCLUSION: Cross-sectional analyses showed a significant increase from low to moderate stress during the COVID-19 outbreak. Identified modifiable factors associated with increased stress may be informative for intervention development. TRIAL REGISTRATION NUMBER: NCT04369690; Results.


Subject(s)
COVID-19/psychology , Employment/statistics & numerical data , Income/statistics & numerical data , Social Isolation , Stress, Psychological/epidemiology , Adaptation, Psychological , Adult , Aged , COVID-19/economics , Canada/epidemiology , Cross-Sectional Studies , Female , Humans , Linear Models , Male , Mental Disorders/epidemiology , Middle Aged , Multivariate Analysis , Pandemics/economics , Prospective Studies , Risk Factors , Surveys and Questionnaires
11.
Neuroscience ; 386: 166-174, 2018 08 21.
Article in English | MEDLINE | ID: mdl-29964154

ABSTRACT

Chronic muscle pain is acutely worsened by exercise. Acid sensing ion channels (ASIC) are heteromeric channels expressed in muscle sensory neurons that detect decreases in pH. We have previously shown ASIC3 is important in activity-induced hyperalgesia. However, ASICs form heteromers with ASIC1a being a key component in sensory neurons. Therefore, we studied the role of ASIC1a in mice using behavioral pharmacology and genetic deletion in a model of activity-induced hyperalgesia. We found ASIC1a-/- mice developed mechanical hyperalgesia similar to wild-type mice, but antagonism of ASIC1a, with psalmotoxin, prevented development of mechanical hyperalgesia in wild-type mice, but not in ASIC1a-/- mice. To explain this discrepancy, we then performed electrophysiology studies of ASICs and examined the effects of psalmotoxin on ASIC heteromers. We expressed ASIC1a, 2 and 3 heteromers or ASIC1 and 3 heteromers in CHO cells, and examined the effects of psalmotoxin on pH sensitivity. Psalmotoxin significantly altered the properties of ASIC hetomeric channels. Specifically, in ASIC1a/2/3 heteromers, psalmotoxin slowed the kinetics of desensitization, slowed the recovery from desensitization, and inhibited pH-dependent steady-state desensitization, but had no effect on pH-evoked current amplitudes. We found a different pattern in ASIC1a/3 heteromers. There was a significant leftward shift in the pH dose response of steady-state desensitization and decrease in pH-evoked current amplitudes. These results suggest that blockade of ASIC1a modulates the kinetics of heteromeric ASICs to prevent development of activity-induced hyperalgesia. These data suggest ASIC1a is a key subunit in heteromeric ASICs and may be a pharmacological target for treatment of musculoskeletal pain.


Subject(s)
Acid Sensing Ion Channel Blockers/pharmacokinetics , Acid Sensing Ion Channels/physiology , Muscle Fatigue/physiology , Pain/metabolism , Peptides/pharmacokinetics , Spider Venoms/pharmacokinetics , Acid Sensing Ion Channel Blockers/therapeutic use , Animals , Female , Kinetics , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle Fatigue/drug effects , Pain/prevention & control , Peptides/therapeutic use , Spider Venoms/therapeutic use
12.
Wiley Interdiscip Rev RNA ; 7(6): 811-823, 2016 11.
Article in English | MEDLINE | ID: mdl-27485475

ABSTRACT

Fusion transcripts (i.e., chimeric RNAs) resulting from gene fusions have been used successfully for cancer diagnosis, prognosis, and therapeutic applications. In addition, many fusion transcripts are found in normal human cell lines and tissues, with some data supporting their role in normal physiology. Besides chromosomal rearrangement, intergenic splicing can generate them. Global identification of fusion transcripts becomes possible with the help of next generation sequencing technology like RNA-Seq. In the past decade, major advancements have been made for chimeric RNA discovery due to the development of advanced sequencing platform and software packages. However, current software tools behave differently in terms of specificity, sensitivity, time, and computational memory usage. Recent benchmarking studies showed that none of the tools are inclusive. The development of high performance (accurate and fast), and user-friendly fusion detection tool/pipeline is still an open quest. In this article, we review the existing software packages for fusion detection. We explain the methods of the tools, and discuss various factors that affect fusion detection. We summarize conclusions drawn from several comparative studies, and then discuss some of the pitfalls of these studies. We also describe the limitations of current tools, and suggest directions for future development. WIREs RNA 2016, 7:811-823. doi: 10.1002/wrna.1382 For further resources related to this article, please visit the WIREs website.


Subject(s)
Gene Expression Profiling , Gene Fusion , High-Throughput Nucleotide Sequencing/methods , Animals , Computer Simulation , Humans , Software
13.
Can J Psychiatry ; 61(8): 480-8, 2016 08.
Article in English | MEDLINE | ID: mdl-27310227

ABSTRACT

OBJECTIVES: The Mental Health Experiences Scale is a measure of perceived stigma, the perception of negative attitudes and behaviours by people with mental disorders. A recent Canadian survey (Canadian Community Health Survey-Mental Health) included this scale, providing an opportunity to describe perceived stigma in relation to diagnosis for the first time in the Canadian general population. METHODS: The survey interview began with an assessment of whether respondents had utilised services for an "emotional or mental health problem" in the preceding 12 months. The subset reporting service utilisation were asked whether others "held negative opinions" about them or "treated them unfairly" for reasons related to their mental health. The analysis reported here used frequencies, means, cross-tabulation, and logistic regression, all incorporating recommended replicate sampling weights and bootstrap variance estimation procedures. RESULTS: Stigma was perceived by 24.4% of respondents accessing mental health services. The frequency was higher among younger respondents (<55 years), those who were not working, those reporting only fair or poor mental health, and the subset who reported having received a diagnosis of a mental disorder. Sex and education level were not associated with perceived stigma. People with schizophrenia reported stigmatization only slightly more frequently than those with mood and anxiety disorders. CONCLUSIONS: Stigmatization is a common, but not universal, experience among Canadians using services for mental health reasons. Stigmatization was a problem for a sizeable minority of respondents with mood, anxiety, and substance use disorders as well as bipolar and psychotic disorders.


Subject(s)
Mental Disorders , Mental Health Services/statistics & numerical data , Prejudice/statistics & numerical data , Social Stigma , Adult , Canada/epidemiology , Female , Humans , Male , Mental Disorders/epidemiology , Mental Disorders/psychology , Mental Disorders/therapy , Middle Aged
14.
PLoS One ; 9(4): e93797, 2014.
Article in English | MEDLINE | ID: mdl-24699665

ABSTRACT

Acid-sensing ion channels (ASICs) are Na+ channels activated by changes in pH within the peripheral and central nervous systems. Several different isoforms of ASICs combine to form trimeric channels, and their properties are determined by their subunit composition. ASIC2 subunits are widely expressed throughout the brain, where they heteromultimerize with their partnering subunit, ASIC1a. However, ASIC2 contributes little to the pH sensitivity of the channels, and so its function is not well understood. We found that ASIC2 increased cell surface levels of the channel when it is coexpressed with ASIC1a, and genetic deletion of ASIC2 reduced acid-evoked current amplitude in mouse hippocampal neurons. Additionally, ASIC2a interacted with the neuronal synaptic scaffolding protein PSD-95, and PSD-95 reduced cell surface expression and current amplitude in ASICs that contain ASIC2a. Overexpression of PSD-95 also reduced acid-evoked current amplitude in hippocampal neurons. This result was dependent upon ASIC2 since the effect of PSD-95 was abolished in ASIC2-/- neurons. These results lend support to an emerging role of ASIC2 in the targeting of ASICs to surface membranes, and allows for interaction with PSD-95 to regulate these processes.


Subject(s)
Acid Sensing Ion Channels/metabolism , Cell Membrane/metabolism , Guanylate Kinases/metabolism , Membrane Proteins/metabolism , Neurons/metabolism , Protein Subunits/metabolism , Acid Sensing Ion Channels/genetics , Animals , CHO Cells , Cricetulus , Disks Large Homolog 4 Protein , Hippocampus/metabolism , Mice , Protein Subunits/genetics
15.
Anesthesiology ; 119(5): 1186-97, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23732174

ABSTRACT

BACKGROUND: Understanding the mechanisms underlying deep tissue pain in the postoperative period is critical to improve therapies. Using the in vitro plantar flexor digitorum brevis muscle-nerve preparation and patch clamp recordings from cultured dorsal root ganglia neurons innervating incised and unincised muscle, the authors investigated responses to various pH changes. METHODS: Incision including the plantar flexor digitorum brevis muscle or sham operation was made in the rat hind paw. On postoperative day 1, in vitro single-fiber recording was undertaken. On the basis of previous studies, the authors recorded from at least 40 fibers per group. Also DiI-labeled dorsal root ganglia innervating muscle from rats undergoing incision and a sham operation were cultured and tested for acid responses, using whole cell patch clamp recordings. RESULTS: The prevalence of responsive group IV afferents to lactic acid pH 6.5 in the incision group (15 of 67; 22.3%) was greater than that in the control group (2 of 35; 5.7%; P=0.022). In dorsal root ganglia neurons innervating muscle, incision increased mean current amplitudes of acid-evoked currents; the acid-sensing ion channel blocker, amiloride 300 µM, inhibited more than 75% of the acid-evoked current, whereas, the transient receptor vanilloid receptor 1 blocker (AMG9810 1 µM) did not cause significant inhibition. CONCLUSION: The authors' experiments demonstrated that incision increases the responses of flexor digitorum brevis muscle afferent fibers to weak acid solutions, and increased acid-evoked currents in dorsal root ganglia innervating muscle. The authors' data suggest that up-regulation of acid-sensing ion channels might underlie this increased chemosensitivity caused by surgery.


Subject(s)
Ganglia, Spinal/physiology , Muscle, Skeletal/innervation , Muscle, Skeletal/physiology , Nerve Fibers/physiology , Neurons, Afferent/physiology , Animals , Electrophysiological Phenomena , Foot Injuries/pathology , Ganglia, Spinal/cytology , Hydrogen-Ion Concentration , Lactic Acid/pharmacology , Male , Neural Conduction/drug effects , Neurons, Efferent/physiology , Pain Measurement/drug effects , Patch-Clamp Techniques , Physical Stimulation , Rats , Rats, Sprague-Dawley
16.
FASEB J ; 27(2): 793-802, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23109675

ABSTRACT

Acid-sensing ion channels (ASICs) are expressed in skeletal muscle afferents, in which they sense extracellular acidosis and other metabolites released during ischemia and exercise. ASICs are formed as homotrimers or heterotrimers of several isoforms (ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3), with each channel displaying distinct properties. To dissect the ASIC composition in muscle afferents, we used whole-cell patch-clamp recordings to study the properties of acid-evoked currents (amplitude, pH sensitivity, the kinetics of desensitization and recovery from desensitization, and pharmacological modulation) in isolated, labeled mouse muscle afferents from wild-type (C57BL/6J) and specific ASIC(-/-) mice. We found that ASIC-like currents in wild-type muscle afferents displayed fast desensitization, indicating that they are carried by heteromeric channels. Currents from ASIC1a(-/-) muscle afferents were less pH-sensitive and displayed faster recovery, currents from ASIC2(-/-) mice showed diminished potentiation by zinc, and currents from ASIC3(-/-) mice displayed slower desensitization than those from wild-type mice. Finally, ASIC-like currents were absent from triple-null mice lacking ASIC1a, ASIC2a, and ASIC3. We conclude that ASIC1a, ASIC2a, and ASIC3 heteromers are the principle channels in skeletal muscle afferents. These results will help us understand the role of ASICs in exercise physiology and provide a molecular target for potential drug therapies to treat muscle pain.


Subject(s)
Acid Sensing Ion Channels/chemistry , Acid Sensing Ion Channels/metabolism , Muscle, Skeletal/innervation , Muscle, Skeletal/metabolism , Neurons, Afferent/metabolism , Acid Sensing Ion Channels/deficiency , Acid Sensing Ion Channels/genetics , Animals , Electrophysiological Phenomena , Ganglia, Spinal/metabolism , Hydrogen-Ion Concentration , Mice , Mice, Inbred C57BL , Mice, Knockout , Patch-Clamp Techniques , Protein Structure, Quaternary , Protein Subunits , Sensory Receptor Cells/metabolism
17.
Am J Physiol Cell Physiol ; 304(1): C89-101, 2013 Jan 01.
Article in English | MEDLINE | ID: mdl-23135698

ABSTRACT

Acid-sensing ion channels (ASICs) are sodium channels gated by extracellular protons. ASIC1a channels possess intersubunit Cl(-)-binding sites in the extracellular domain, which are highly conserved between ASIC subunits. We previously found that anions modulate ASIC1a gating via these sites. Here we investigated the effect of anion substitution on native ASICs in rat sensory neurons and heterologously expressed ASIC2a and ASIC3 channels by whole cell patch clamp. Similar to ASIC1a, anions modulated the kinetics of desensitization of other ASIC channels. However, unlike ASIC1a, anions also modulated the pH dependence of activation. Moreover, the order of efficacy of different anions to modulate ASIC2a and -3 was very different from that of ASIC1a. More surprising, mutations of conserved residues that form an intersubunit Cl(-)-binding site in ASIC1a only partially abrogated the effects of anion modulation of ASIC2a and had no effect on anion modulation of ASIC3. The effects of anions on native ASICs in rat dorsal root ganglion neurons mimicked those in heterologously expressed ASIC1a/3 heteromeric channels. Our data show that anions modulate a variety of ASIC properties and are dependent on the subunit composition, and the mechanism of modulation for ASIC2a and -3 is distinct from that of ASIC1a. We speculate that modulation of ASIC gating by Cl(-) is a novel mechanism to sense shifts in extracellular fluid composition.


Subject(s)
Acid Sensing Ion Channels/physiology , Acid Sensing Ion Channels/chemistry , Acid Sensing Ion Channels/genetics , Animals , Binding Sites/physiology , CHO Cells , Cricetinae , Ganglia, Spinal/chemistry , Ganglia, Spinal/physiology , Mice , Mutagenesis/physiology , Primary Cell Culture , Protein Subunits/genetics , Protein Subunits/metabolism , Protein Subunits/physiology , Rats , Sensory Receptor Cells/cytology , Sensory Receptor Cells/physiology
18.
PLoS One ; 7(4): e35225, 2012.
Article in English | MEDLINE | ID: mdl-22506072

ABSTRACT

Three observations have suggested that acid-sensing ion channels (ASICs) might be mammalian cutaneous mechanoreceptors; they are structurally related to Caenorhabditis elegans mechanoreceptors, they are localized in specialized cutaneous mechanosensory structures, and mechanical displacement generates an ASIC-dependent depolarization in some neurons. However, previous studies of mice bearing a single disrupted ASIC gene showed only subtle or no alterations in cutaneous mechanosensitivity. Because functional redundancy of ASIC subunits might explain limited phenotypic alterations, we hypothesized that disrupting multiple ASIC genes would markedly impair cutaneous mechanosensation. We found the opposite. In behavioral studies, mice with simultaneous disruptions of ASIC1a, -2 and -3 genes (triple-knockouts, TKOs) showed increased paw withdrawal frequencies when mechanically stimulated with von Frey filaments. Moreover, in single-fiber nerve recordings of cutaneous afferents, mechanical stimulation generated enhanced activity in A-mechanonociceptors of ASIC TKOs compared to wild-type mice. Responses of all other fiber types did not differ between the two genotypes. These data indicate that ASIC subunits influence cutaneous mechanosensitivity. However, it is unlikely that ASICs directly transduce mechanical stimuli. We speculate that physical and/or functional association of ASICs with other components of the mechanosensory transduction apparatus contributes to normal cutaneous mechanosensation.


Subject(s)
Behavior, Animal/physiology , Mechanoreceptors/physiology , Mechanotransduction, Cellular/physiology , Nerve Tissue Proteins/genetics , Sodium Channels/genetics , Acid Sensing Ion Channels , Acids/metabolism , Animals , Female , Male , Mechanoreceptors/metabolism , Mechanotransduction, Cellular/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Stress, Mechanical
19.
Pain Res Treat ; 2012: 817347, 2012.
Article in English | MEDLINE | ID: mdl-22191025

ABSTRACT

Repeated intramuscular acid injections produce long-lasting mechanical hyperalgesia that depends on activation of ASICs. The present study investigated if pH-activated currents in sensory neurons innervating muscle were altered in response to repeated acid injections, and if blockade of ASICs reverses existing hyperalgesia. In muscle sensory neurons, the mean acid-evoked current amplitudes and the biophysical properties of the ASIC-like currents were unchanged following acidic saline injections when compared to neutral pH saline injections or uninjected controls. Moreover, increased mechanical sensitivity of the muscle and paw after the second acid injection was unaffected by local blockade of ASICs (A-317567) in the muscle. As a control, electron microscopic analysis showed that the tibial nerve was undamaged after acid injections. Our previous studies demonstrated that ASICs are important in the development of hyperalgesia to repeated acid injections. However, the current data suggest that ASICs are not involved in maintaining hyperalgesia to repeated intramuscular acid injections.

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