CPM
Carboxypeptidase M precursor (EC 3.4.17.12) (CPM)
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The temporal stability (test-retest reliability) of temporal summation of pain (TS) and conditioned pain modulation (CPM) has yet to be established in healthy older adults. The purpose of this study was to compare the temporal stability of TS and CPM in healthy older and younger adults and to investigate factors that might influence TS and CPM stability. In a test-retest study, 40 healthy older adults and 30 healthy younger adults completed two sessions of quantitative sensory testing within a two-week period that included TS of heat pain, TS of mechanical pain, and CPM with pressure pain thresholds and suprathreshold heat pain as test stimuli and a cold water immersion as a conditioning stimulus. Participants also completed self-report measures of situational catastrophizing, anxiety, clinical pain, and physical activity. Absolute and relative stability were examined for each variable. Bivariate correlations examined the associations of age, clinical, behavioral, and psychological variables with the intra-individual stability of TS and CPM. The results revealed moderate to excellent stability for the TS measures and poor to moderate stability for CPM. The results also revealed significant age differences for two of the TS measures and CPM, with younger adults having greater stability compared with older adults. Additionally, the magnitude and stability of psychological factors were correlated with stability of TS. These findings suggest that TS and CPM may be more reliable in younger compared with older adults. Furthermore, psychological states may be an important factor influencing the stability of TS in healthy adults.
Keywords
- Aging
- Anxiety
- Conditioned Pain Modulation
- Pain Catastrophizing
- Reliability
- Temporal Summation of Pain
Conditioned pain modulation (CPM) is a laboratory test resulting in pain inhibition through activation of descending inhibitory mechanisms. Older adults consistently demonstrate reduced CPM compared with younger samples; however, studies of sex differences in younger cohorts have shown mixed results. This study tested for sex differences in CPM within samples of younger and older adults. Participants were 67 younger adults (mean age = 25.4 years) and 50 older adults (66.4 years). Study conditioning paradigms were the cold-pressor test and contact heat pain administered in separate sessions. Pressure pain threshold and ramping suprathreshold heat were the test stimuli across three time points after presentation of the conditioning stimuli (CS). Significant inhibition was observed during both testing sessions. The hypothesis for sex differences across both age cohorts was supported only for ∆PPTh. However, sex differences did not reach significance for either paradigm using ascending suprathreshold heat as the test stimuli. The overall trend was that younger males experienced the strongest CPM and older females the weakest. From a methodological perspective, duration differences were seen in CPM, with inhibition decaying more quickly for PPTh than for suprathreshold heat pain. Furthermore, there were no differences in inhibition induced by cold-pressor test and contact heat pain as CS. Sex differences were similar across both age cohorts with males experiencing greater inhibition than females. Cross-sectional associations were also demonstrated between CPM inhibition and measures of recent pain, further supporting CPM as an experimental model with clinical utility.
Keywords
- Aging
- CPM duration
- Conditioned pain modulation
- Conditioning stimulus
- Sex differences
- Test stimulus
The purpose of this article was to examine age-related changes in conditioned pain modulation (CPM) and temporal summation (TS) of pain using meta-analytic techniques. Five electronic databases were searched for studies, which compared measures of CPM and TS among healthy, chronic pain-free younger, middle-aged, and older adults. Eleven studies were included in the final review for TS and 11 studies were included in the review of CPM. The results suggested a moderate magnitude of difference in TS among younger and middle-aged/older adults, with the older cohorts exhibiting enhanced TS of pain. Considerable variability existed in the magnitude of the effect sizes, which was likely due to the different experimental methodologies used across studies (ie, interstimulus interval, stimulus type, and body location). In regards to CPM, the data revealed a large magnitude of difference between younger and older adults, with younger adults exhibiting more efficient pain inhibition. Differences in CPM between middle-aged and older adults were minimal. The magnitude of pain inhibition during CPM in older adults may depend on the use of concurrent versus nonconcurrent protocols. In summary, the data provided strong quantitative evidence of a general age-related decline in endogenous pain modulatory function as measured by TS and CPM. PERSPECTIVE: This review compared CPM and TS of pain among younger, middle-aged, and older adults. These findings enhance our understanding of the decline in endogenous pain modulatory function associated with normal aging.
Keywords
- Aging
- conditioned pain modulation
- meta-analysis
- pain modulation
- temporal summation
Increased levels of particulate matter (PM) air pollutants in East Asia have resulted in detrimental health impacts increasing morbidity and mortality. Epidemiological studies suggest a possible relation between the cutaneous exposure of PM and increased oxidative stress and inflammation which lead to skin lesions. The present study utilizes an integrated cell culture model of keratinocytes and fibroblasts to mimic viable skin layers and investigate the possible effects of PM exposure after penetration through corneocytes. The skin perfection is upheld by homeostatic functionality of epidermal cells and the integrity of connective tissues. Exposure to xenobiotics could alter the skin cell homeostasis aggravating premature skin aging. Stimulation of HaCaT keratinocytes by PM collected from Beijing, China (CPM) increased the intracellular ROS levels triggering a cascade of events aggravating inflammatory responses and connective tissue degradation. In HDF fibroblasts, treatment with preconditioned keratinocyte culture media augmented inflammatory responses, cellular differentiation, and connective tissue degradation. Above events were marked by the increased intracellular ROS, inflammatory mediators, pro-inflammatory cytokines, matrix metalloproteinases (MMP)-1 and -2 levels, collagenase, and elastase activity. Fucosterol treatment of keratinocytes dose-dependently attenuated the detrimental effects both in keratinocytes and fibroblasts restoring the conditions near to physiological levels. Further evaluations could be advanced on developing fucosterol, in forms such as rejuvenating cosmeceuticals which could attenuate detrimental responses of CPM exposure.
MeSH Terms
- Air Pollutants
- Cells, Cultured
- Coculture Techniques
- Cytokines
- Fibroblasts
- Humans
- Inflammation
- Keratinocytes
- NF-kappa B
- Oxidative Stress
- Particulate Matter
- Reactive Oxygen Species
- Skin
- Skin Diseases
- Stigmasterol
Keywords
- Fibroblasts
- Fucosterol
- Inflammation
- MMP
- Particulate matter
- Skin aging
Physical activity is associated with the aging workers' ability to work and predicts working beyond retirement age. To better understand physical activity behaviour in this growing population group, we aimed at characterising 24-hour physical activity patterns among aging workers, and to describe the association between occupational category and total, occupational and leisure-time physical activities. We included 878 workers (mean age 62.4 years, SD 1.1, 85% women) from the Finnish Retirement and Aging Study, who wore an accelerometer on their non-dominant wrist for 1 week. We plotted mean hourly activity counts per minute (CPM) for working days and days off. We also compared mean daily CPM between genders and occupations between working days and days off, and work and leisure time by using repeated measures analysis of variance. Activity patterns were different between genders, occupations and types of the day. Women (2580, 95% CI 2540 to 2620) had higher daily mean CPM than men (2110, 95% CI 2020 to 2000). Women in manual occupations were more active than women in non-manual occupations during working days. The differences among men were in the same direction but less pronounced than among women. We found no differences in activity levels between occupations during days off and leisure time on working days. In aging workers, physical activity differs by gender and occupation during working time, but not during leisure time. As low physical activity is associated with increased risk of early exit from employment, physical activity should be promoted at workplaces, especially among men and people in non-manual occupations.
MeSH Terms
- Exercise
- Female
- Finland
- Humans
- Leisure Activities
- Longitudinal Studies
- Male
- Middle Aged
- Occupations
- Retirement
- Sex Factors
- Surveys and Questionnaires
Keywords
- accelerometry
- aging worker
- leisure-time physical activity
- occupational physical activity
- occupational status
The personality dimensions of neuroticism and extraversion are strongly associated with emotional experience and affective disorders. Previous studies reported functional magnetic resonance imaging (fMRI) activity correlates of these traits, but no study has used brain-based measures to predict them. Here, using a fully cross-validated approach, we predict novel individuals' neuroticism and extraversion from functional connectivity (FC) data observed as they simply rested during fMRI scanning. We applied a data-driven technique, connectome-based predictive modeling (CPM), to resting-state FC data and neuroticism and extraversion scores (self-reported NEO Five Factor Inventory) from 114 participants of the Nathan Kline Institute Rockland sample. After dividing the whole brain into 268 nodes using a predefined functional atlas, we defined each individual's FC matrix as the set of correlations between the activity timecourses of every pair of nodes. CPM identified networks consisting of functional connections correlated with neuroticism and extraversion scores, and used strength in these networks to predict a left-out individual's scores. CPM predicted neuroticism and extraversion in novel individuals, demonstrating that patterns in resting-state FC reveal trait-level measures of personality. CPM also revealed predictive networks that exhibit some anatomical patterns consistent with past studies and potential new brain areas of interest in personality.
MeSH Terms
- Adult
- Aging
- Artifacts
- Connectome
- Extraversion, Psychological
- Female
- Humans
- Magnetic Resonance Imaging
- Male
- Neural Pathways
- Neuroticism
- Predictive Value of Tests
- Rest
- Sex Characteristics
- Young Adult
Widespread pressure hyperalgesia, facilitated temporal summation of pain (TSP), and impaired conditioned pain modulation (CPM) have been found in knee osteoarthritis (KOA) patients compared with controls and these parameters have further been suggested to be altered in the elderly. This study investigated the influence of age on pressure hyperalgesia, TSP, and CPM in patients with KOA and controls. One hundred thirty-three severe KOA patients and 50 age-matched and sex-matched asymptomatic controls were assessed by cuff algometry and handheld pressure algometry. Pain sensitivity was assessed around the head of the gastrocnemius muscle to identify mild pain detection threshold (MPDT) and pressure tolerance threshold (PTT). TSP was assessed by visual analogue scale scores of the pain evoked by 10 repetitive cuff stimulations. CPM was assessed as the difference in PTT before and during cuff-induced tonic arm pain. Pressure pain thresholds (PPTs) were assessed by handheld algometry at the tibialis anterior muscle. Two subgroups were analyzed in the age range below and above 65 years. Pearson correlations between age and pain parameters were applied. Patients demonstrated reduced MPDT, PTT, and PPT (P<0.01), facilitated TSP (P<0.02), and a trend toward impaired CPM (P=0.06) compared with controls. A negative correlation was found between MPDT, PTT, and PPT and age (P<0.05) but no age-related association was found for TSP and CPM. Pressure hyperalgesia was affected by age whereas dynamic pain mechanisms such as TSP and CPM were unaffected suggesting that these parameters are robust for a larger age range and reliable for long-term follow-up studies.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Analysis of Variance
- Female
- Humans
- Hyperalgesia
- Male
- Middle Aged
- Muscle, Skeletal
- Osteoarthritis, Knee
- Pain Measurement
- Pain Threshold
- Pressure
- Touch
Family history of breast cancer is associated with an increased risk of contralateral breast cancer (CBC) even in the absence of mutations in the breast cancer susceptibility genes BRCA1/2. We compared quality-adjusted survival after contralateral prophylactic mastectomy (CPM) with surveillance only (no CPM) among women with breast cancer incorporating the degree of family history. We created a microsimulation model for women with first-degree, second-degree, and no family history treated for a stage I, II, or III estrogen receptor (ER)-positive or ER-negative breast cancer at the ages of 40, 50, 60, and 70. The model incorporated a 10-year posttreatment period for risk of developing CBC and/or dying of the primary cancer or CBC. For each patient profile, we used 100,000 microsimulation trials to estimate quality-adjusted life expectancy for the clinical strategies CPM and no CPM. CPM showed minimal improvement on quality-adjusted life expectancy among women age 50-60 with no or a unilateral first-degree or second-degree family history (decreasing from 0.31 to -0.06 quality-adjusted life-years (QALYs)) and was unfavorable for most subgroups of women age 70 with stage III breast cancer regardless of degree of family history (range -0.08 to -0.02 QALYs). Sensitivity analysis showed that the highest predicted benefit of CPM assuming 95 % risk reduction in CBC was 0.57 QALYs for a 40-year-old woman with stage I breast cancer who had a first-degree relative with bilateral breast cancer. Women age 40 with stage I breast cancer and a first-degree relative with bilateral breast cancer have a QALY benefit from CPM similar to that reported for BRCA1/2 mutation carriers. For most subgroups of women, CPM has a minimal to no effect on quality-adjusted life expectancy, irrespective of family history of breast cancer.
MeSH Terms
- Adult
- Aged
- Biomarkers, Tumor
- Breast Neoplasms
- Clinical Decision-Making
- Female
- Humans
- Life Expectancy
- Markov Chains
- Middle Aged
- Neoplasm Staging
- Patient Outcome Assessment
- Population Surveillance
- Probability
- Prophylactic Mastectomy
- Quality of Life
- Risk Factors
- Tumor Burden
Keywords
- Breast cancer
- Contralateral breast cancer
- Decision analysis
- Prophylactic mastectomy
Most women diagnosed with unilateral breast cancer without BRCA1 or BRCA2 mutations are at low risk of contralateral breast cancer. Contralateral Prophylactic Mastectomy (CPM) decreases the relative risk of contralateral breast cancer, but may not increase life expectancy; yet international uptake is increasing. This study applied protection motivation theory (PMT) to determine factors associated with women's intentions to undergo CPM. Three hundred eighty-eight women previously diagnosed with unilateral breast cancer and of negative or unknown BRCA1 or BRCA2 status were recruited from an advocacy group's research database. Participants completed measures of PMT constructs based on a common hypothetical CPM decision-making scenario. PMT constructs explained 16% of variance in intentions to undergo CPM. Response efficacy (CPM's advantages) and response costs (CPM's disadvantages) were unique individual predictors of intentions. Decision-making appears driven by considerations of the psychological, cosmetic and emotional advantages and disadvantages of CPM. Overestimations of threat to life from contralateral breast cancer and survival benefit from CPM also appear influential factors. Patients require balanced and medically accurate information regarding the pros and cons of CPM, survival rates, and recurrence risks to ensure realistic and informed decision-making.
MeSH Terms
- Adult
- Australia
- Cross-Sectional Studies
- Decision Making
- Female
- Humans
- Intention
- Life Expectancy
- Middle Aged
- Motivation
- Patient Preference
- Prophylactic Mastectomy
- Psychological Theory
- Risk Assessment
- Self Efficacy
- Surveys and Questionnaires
- Unilateral Breast Neoplasms
Public health initiatives world-wide recommend increasing physical activity (PA) to improve health. However, the dose and the intensity of PA producing the most benefit are still debated. Accurate assessment of PA is necessary in order to 1) investigate the dose-response relationship between PA and health, 2) shape the most beneficial public health initiatives and 3) test the effectiveness of such initiatives. Actigraph accelerometer is widely used to objectively assess PA, and the raw data is given in counts per unit time. Count-thresholds for low, moderate and vigorous PA are mostly based on absolute intensity. This leads to largely inadequate PA intensity assessment in a large proportion of the elderly, who due to their declining maximal oxygen uptake (VO2max) cannot reach the moderate/vigorous intensity as defined in absolute terms. To resolve this issue, here we report relative Actigraph intensity-thresholds for the elderly. Submaximal-oxygen-uptake, VO2max and maximal heart rate (HRmax) were measured in 111 70-77 year olds, while wearing an Actigraph-GT3X . Relationship between VO2max percentage (%), counts-per-minute (CPM) and gender (for both the vertical-axis (VA) and vector-magnitude (VM)) and VO2max% and HRmax% was established using a mixed-regression-model. VM-and VA-models were tested against each other to see which model predicts intensity of PA better. VO2max and gender significantly affected number of CPM at different PA intensities (p < 0.05). Therefore, intensity-thresholds were created for both men and women of ranging VO2max values (low, medium, high). VM-model was found to be a better predictor of PA-intensity than VA-model (p < 0.05). Established thresholds for moderate intensity (46-63 % of VO2max) ranged from 669-3367 and 834-4048 CPM and vigorous intensity (64-90 % of VO2max) from 1625-4868 and 2012-5423CPM, for women and men, respectively. Lastly, we used this evidence to derive a formula that predicts customized relative intensity of PA (either VO2max% or HRmax%) using counts-per-minute values as input. Intensity-thresholds depend on VO2max, gender and Actigraph-axis. PA intensity-thresholds that take all these factors into account allow for more accurate relative intensity PA assessment in the elderly and will be useful in future PA research. (ClinicalTrials.gov Identifier: NCT02017847, registered 17. December 2013).
MeSH Terms
- Accelerometry
- Aged
- Aging
- Anaerobic Threshold
- Exercise Tolerance
- Female
- Geriatric Assessment
- Humans
- Kinetocardiography
- Male
- Physical Conditioning, Human
The rate of contralateral prophylactic mastectomy (CPM) is rising rapidly, despite limited evidence about the procedure's relative benefits and harms. The objective of this study is to examine the impact of CPM on life expectancy (LE) and quality-adjusted life expectancy (QALE) in women with sporadic unilateral breast cancer. A Markov model was developed to compare 18 hypothetical cohorts of 45-year-old women with newly diagnosed unilateral, sporadic breast cancer treated with or without CPM. The probability of developing distant metastases by American Joint Committee on Cancer stage and molecular subtype was derived from British Columbia Cancer Agency data. Additional model parameters were identified from the medical literature. Sensitivity analyses were performed to examine the impact of plausible variations in key model parameters on results. CPM improved LE in all cohorts (range 0.06-0.54 years). Stage had more effect on LE than subtype (stage I mean, 0.44 years, stage III mean, 0.11 years). However, after adjusting for quality-of-life, No CPM was favored in all cohorts. Univariate sensitivity analysis demonstrated that the most influential model parameter was the post-CPM health state utility. The preferred strategy shifted from No CPM to CPM when the post-CPM utility exceeded 0.83 (base case value 0.81). PSA indicated that LE gains and QALE decreases were stable in all cohorts. The primary determinant of survival after unilateral breast cancer is stage at diagnosis. Our results suggest that routine CPM would not improve quality-adjusted survival for the majority of women with unilateral sporadic breast cancer.
MeSH Terms
- British Columbia
- Clinical Decision-Making
- Decision Support Techniques
- Female
- Humans
- Incidence
- Life Expectancy
- Markov Chains
- Mastectomy
- Neoplasm Metastasis
- Prognosis
- Quality-Adjusted Life Years
- Risk Assessment
- Sensitivity and Specificity
- Unilateral Breast Neoplasms
Contralateral prophylactic mastectomy (CPM) rates have substantially increased in recent years and may reflect an exaggerated perceived benefit from the procedure. The objective of this study was to evaluate the magnitude of the survival benefit of CPM for women with unilateral breast cancer. We developed a Markov model to simulate survival outcomes after CPM and no CPM among women with stage I or II breast cancer without a BRCA mutation. Probabilities for developing contralateral breast cancer (CBC), dying from CBC, dying from primary breast cancer, and age-specific mortality rates were estimated from published studies. We estimated life expectancy (LE) gain, 20-year overall survival, and disease-free survival with each intervention strategy among cohorts of women defined by age, estrogen receptor (ER) status, and stage of cancer. Predicted LE gain from CPM ranged from 0.13 to 0.59 years for women with stage I breast cancer and 0.08 to 0.29 years for those with stage II breast cancer. Absolute 20-year survival differences ranged from 0.56% to 0.94% for women with stage I breast cancer and 0.36% to 0.61% for women with stage II breast cancer. CPM was more beneficial among younger women, stage I, and ER-negative breast cancer. Sensitivity analyses yielded a maximum 20-year survival difference with CPM of only 1.45%. The absolute 20-year survival benefit from CPM was less than 1% among all age, ER status, and cancer stage groups. Estimates of LE gains and survival differences derived from decision models may provide more realistic expectations of CPM.
MeSH Terms
- Adult
- Breast Neoplasms
- Decision Support Techniques
- Disease-Free Survival
- Female
- Humans
- Life Expectancy
- Markov Chains
- Mastectomy
- Middle Aged
- Neoplasm Staging
- Predictive Value of Tests
- Secondary Prevention
- United States
It is well-documented that neonates can experience pain after injury. However, the contribution of individual populations of sensory neurons to neonatal pain is not clearly understood. Here we characterized the functional response properties and neurochemical phenotypes of single primary afferents after injection of carrageenan into the hairy hindpaw skin using a neonatal ex vivo recording preparation. During normal development, we found that individual afferent response properties are generally unaltered. However, at the time period in which some sensory neurons switch their neurotrophic factor responsiveness, we observe a functional switch in slowly conducting, broad spiking fibers ("C"-fiber nociceptors) from mechanically sensitive and thermally insensitive (CM) to polymodal (CPM). Cutaneous inflammation induced prior to this switch (postnatal day 7) specifically altered mechanical and heat responsiveness, and heat thresholds in fast conducting, broad spiking ("A"-fiber) afferents. Furthermore, hairy skin inflammation at P7 transiently delayed the functional shift from CM to CPM. Conversely, induction of cutaneous inflammation after the functional switch (at P14) caused an increase in mechanical and thermal responsiveness exclusively in the CM and CPM neurons. Immunocytochemical analysis showed that inflammation at either time point induced TRPV1 expression in normally non-TRPV1 expressing CPMs. Realtime PCR and western blotting analyses revealed that specific receptors/channels involved in sensory transduction were differentially altered in the DRGs depending on whether inflammation was induced prior to or after the functional changes in afferent prevalence. These data suggest that the mechanisms of neonatal pain development may be generated by different afferent subtypes and receptors/channels in an age-related manner.
MeSH Terms
- Acid Sensing Ion Channels
- Age Factors
- Aging
- Animals
- Animals, Newborn
- Carrageenan
- Disease Models, Animal
- Ganglia, Spinal
- Gene Expression Regulation, Developmental
- Glycoproteins
- Inflammation
- Male
- Mice
- Nerve Fibers, Myelinated
- Nerve Fibers, Unmyelinated
- Nociceptors
- Receptors, Purinergic P2X3
- Skin
- TRPC Cation Channels
- TRPV Cation Channels
Conditioned pain modulation (CPM) refers to the diminution of perceived pain intensity for a test stimulus following application of a conditioning stimulus to a remote area of the body, and is thought to reflect the descending inhibition of nociceptive signals. Studying CPM in children may inform interventions to enhance central pain inhibition within a developmental framework. We assessed CPM in 133 healthy children (mean age = 13 years; 52.6% girls) and tested the effects of sex and age. Participants were exposed to 4 trials of a pressure test stimulus before, during, and after the application of a cold water conditioning stimulus. CPM was documented by a reduction in pressure pain ratings during cold water administration. Older children (12-17 years) exhibited greater CPM than younger children (8-11 years). No sex differences in CPM were found. Lower heart rate variability at baseline and after pain induction was associated with less CPM, controlling for child age. The findings of greater CPM in the older age cohort suggest a developmental improvement in central pain inhibitory mechanisms. The results highlight the need to examine developmental and contributory factors in central pain inhibitory mechanisms in children to guide effective, age appropriate pain interventions. In this healthy sample, younger children exhibited less CPM than did older adolescents, suggesting a developmental improvement in CPM. Cardiac vagal tone was associated with CPM across age. The current findings may inform the development of targeted, developmentally appropriate pain interventions for children.
MeSH Terms
- Adolescent
- Aging
- Catastrophization
- Child
- Conditioning, Psychological
- Female
- Heart Rate
- Humans
- Male
- Pain
- Pain Measurement
- Pain Threshold
- Physical Stimulation
- Sex Characteristics