Effect Of CPM Research Articles

Autophagy perturbation upon acute pyrethroid treatment impacts adipogenic commitment of mesenchymal stem cells

Environmental chemical exposure can cause dysregulation in adipogenesis that can result in metabolic syndrome, which includes insulin resistance, type 2 diabetes, cardiovascular disease, as well as excessive body weight. The role of autophagy in adipocyte differentiation is debatable since both positive and negative effects have been reported. Type-I and type-II synthetic pyrethroids α-cypermethrin (CPM) and permethrin (PER), respectively, are reported to increase adipogenesis in vitro and in vivo. However, it is not known how these pyrethroids affect mesenchymal stem cells (MSCs). Thus, this study focused on evaluating the effect of pyrethroids (CPM and PER) pre-treatment (24 h) on MSC commitment and the regulatory role of autophagy in adipogenic lineage commitment. The formation of adipocytes was observed through nile red staining, perilipin expression by immunoflourescence, and adipogenic markers PPARγ, C/EBPα, and FABP4 by western blotting. It was found that the adipogenic differentiation ability of MSCs was significantly increased upon CPM or PER pre-treatment at 100 μM concentration as evident by lipid accumulation and enhanced expression of adipogenic markers. To assess the involvement of autophagy, the expression of p62 and LC3II were evaluated following pre-treatment. Immunoblotting results revealed an increased expression of p62 and LC3II in CPM or PER pretreated MSCs suggesting CPM and PER mediated inhibition of autophagy at 24 h. Further, an increase was observed in adipogenesis upon CPM or PER pre-treatment in combination with chloroquine, while use of rapamycin during pre-treatment abrogated the effect of CPM and PER. Thus, this study concludes that CPM or PER pre-treatment increases the adipogenic differentiation of MSCs. Since chloroquine also demonstrated similar adipogenic response, it further highlights that 24 h pre-treatment with autophagy modulators to inhibit basal autophagy primes MSCs towards adipogenic lineage.

Pain history and experimental pressure pain responses in adolescents: Results from a population-based birth cohort.

Sensitized pain mechanisms are often reported in musculoskeletal pain conditions, but population-based paediatric studies are lacking. We assessed whether adolescents with musculoskeletal pain history had evidence of increased responsiveness to experimental pressure stimuli. Data were from 1496 adolescents of the Generation XXI birth cohort. Pain history was collected using the Luebeck Pain Questionnaire (self-reported at 13, parent-reported at 7 and 10 years). Two case definitions for musculoskeletal pain were considered: (1) cross-sectional-musculoskeletal pain lasting more than 3 months at age 13 and (2) longitudinal-musculoskeletal pain at age 13 with musculoskeletal pain reports at ages 7 and/or 10. Lower limb cuff pressure algometry was used to assess pain detection and tolerance thresholds, conditioned pain modulation effects (CPM, changes in thresholds in the presence on painful conditioning) and temporal summation of pain effects (TSP, changes in pain intensity to 10 phasic painful cuff stimulations). Adolescents with musculoskeletal pain at age 13 plus a history of pain in previous evaluations (longitudinal definition) had lower pain tolerance thresholds compared to the remaining sample (40.2 v. 49.0 kPa, p = 0.02), but showed no differences in pain detection threshold, CPM effect and TSP effect. Pain sensitivity, CPM effects and TSP effects were not significantly different when the current pain only case definition (cross-sectional) was used. Adolescents with current musculoskeletal pain who had a history of pain since childhood had lower tolerance to cuff stimulation. This may suggest long-standing musculoskeletal pain since childhood may contribute to sensitisation, rather than the presence of current pain only. Repeated musculoskeletal pain up to age 13 years may contribute to higher pain sensitivity (particularly lowered pressure pain tolerance) in the general adolescent population. This does not seem to be the case when reported pain experiences are recent or when the outcomes are temporal pain summation or CPM. In this community-based paediatric sample, the vast majority showed no sign of altered pain processing, but a small fraction may reveal some pain sensitization at 13 years of age.

Core-shell structured polystyrene microspheres for improving plugging performance of oil-based drilling fluids

To avoid damage to wellbore stability in shale formations from drilling fluid intrusion and pressure transmission, it is important to develop a plugging material that can effectively plug micropores and fractures in shale formations. In this paper, polystyrene microspheres (CPM) with core-shell structure were synthesized by seed emulsion polymerization, and characterized by infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), particle size analysis, TEM observation and contact angle test. The effects of CPM on emulsion stability and emulsion rheological performance were evaluated by electrical stability tests and rheological performance tests, respectively. The plugging performance was evaluated using filter materials with different pore sizes as filter media. The experimental results showed that CPM had good thermal stability with a thermal decomposition temperature up to 374.3 °C. CPM had a core-shell structure with a median value (D50) of 229 nm and a three-phase contact angle of 116.2°. The synergistic effect of CPM and organoclay can significantly improve the stability of emulsions and viscosity at low shear rates. For different pore sizes of filter media, CPM achieved effective plugging of micropores, reducing fluid loss volume to less than 6 mL for different pore sizes of micropore filter membranes and 29.6% for ceramic sand discs. In this paper, a preparation method of plugging material with good plugging performance was given, which provided technical support for the development of plugging agents for Oil-based drilling fluids (OBDFs).

Effect of hip CPM on gross motor function and development of the hip joint: a single-center randomized controlled study on spastic cerebral palsy children with hip dysplasia.

To investigate the effectiveness of hip continuous passive motion (hCPM) on hip development at skeletal maturity and gross motor function for spastic cerebral palsy children with hip dysplasia. Prospective case-control research of hCPM with goal-directed training versus merely goal-directed training. On the basis of goal-directed training, the hCPM group used the hip joint CPM instrument (the external fixator was connected to the power device to make the hip joint carry out continuous passive movement) for 40-60 min, twice a day, and five times a week, and received continuous training for 8 weeks simultaneously. The control group received only goal-directed training for 8 weeks. Functional outcomes pertaining to the affected hip joints were assessed via gross motor function measure (GMFM), migration percentage (MP), acetabular index (AI), and Harris hip functional score (HHS) at the time of enrollment and the end of the intervention. The case-control research included 65 participants (mean age = 46.20 months, SD = 17.09 months; Gross Motor Function Grading System level: III = 41, IV = 24) who were randomly selected to either the hCPM (n = 45) or the control group (n = 20). No differences were found in baseline (acquisition phase) GMFM, MP, AI, or HHS (t = -1.720, P = 0.090; t* = 1.836, P* = 0.071; t# = -1.517, P# = 0.139; t* = -1.310, P* = 0.195; t# = -1.084, P# = 0.097; t = -1.041, P = 0.301). At the 8-week follow-up, GMFM, MP, AI, and HHS significantly improved over baseline in the hCPM group (hCPM group: t = 18.59, 20.172*, 40.291#, 16.820*, 32.900#, 28.081; P < 0.001). Between-group differences at 8-week follow-up times points favored the hCPM group for GMFM (t = -2.637, P = 0.011), MP (t* = 2.615, P* = 0.014; t# = 3.000, P# = 0.006), AI (t* = 2.055, P* = 0.044; t# = 2.223, P# = 0.030), HHS (t = -4.685, P < 0.001) (*: left side; #: right side). Spastic cerebral palsy children with hip dysplasia achieved meaningful functional improvement after 8 weeks of goal-directed training with hCPM therapy.

The effect of air pollution control devices in coal-fired power plants on the removal of condensable and filterable particulate matter.

Total particulate matter (TPM), including condensable and filterable particulate matter (CPM and FPM), is one of the pollutants that need to be controlled in the coal combustion process. In this study, CPM and FPM were sampled from sixteen coal-fired power units and two coal-fired industrial units. The removal effects of air pollution control devices equipped in the units on the migration and emission of particles were investigated by analyzing samples from inlets and outlets of apparatus. The average removal efficiency of TPM by dry-type dust removal equipment, wet flue gas desulfurization devices, and wet-type precipitators reached 98.57 ± 0.90%, 44.89 ± 15.01%, and 28.45 ± 7.78%, respectively. The removal efficiency of dry-type dust removal equipment and wet-type precipitators to TPM is mainly determined by the purification effect of FPM and CPM, respectively, and both types of particles contribute to the removal efficiency of desulfurization systems to total TPM. The concentrations of CPM (12.01 ± 5.64mg/Nm3) and FPM (1.95 ± 0.86mg/Nm3) emitted from ultra-low emission units were the lowest, and CPM is the dominant particle, especially the higher proportion of organic components in CPM.

Anisotropically Hybridized Porous Crystalline Li-S Battery Separators.

Anisotropically hybridized porous crystalline Li-S battery separators based on porous crystalline materials that can meet the multiple functionalities of both anodic and cathodic sides are much desired for Li-S battery yet still challenging in directional design. Here, an anisotropically hybridized separator (CPM) based on an ionic liquid-modified porphyrin-based covalent-organic framework (COF-366-OH-IL) and catalytically active metal-organic framework (Ni3 (HITP)2 ) that can integrate the lithium-polysulfides (LiPSs) adsorption/catalytic conversion and ion-conduction sites together to directionally meet the requirements of electrodes is reported. Remarkably, the-obtained separator exhibits an exceptional high Li+ transference-number (tLi+ =0.8), ultralow polarization-voltage (<30mV), high initial specific-capacity (921.38mAhg-1 at 1C), and stable cycling-performance, much superior to polypropylene and monolayer-modified separators. Moreover, theoretical calculations confirm the anisotropic effect of CPM on the anodic side (e.g., Li+ transfer, LiPSs adsorption, and anode-protection) and cathodic side (e.g., LiPSs adsorption/catalysis). This work might provide a new perspective for separator exploration.

No relevant differences in conditioned pain modulation effects between parallel and sequential test design. A cross-sectional observational study.

BackgroundConditioned pain modulation (CPM) is measured by comparing pain induced by a test stimulus with pain induced by the same test stimulus, either during (parallel design) or after (sequential design) the conditioning stimulus. Whether design, conditioning stimulus intensity and test stimulus selection affect CPM remains unclear.MethodsCPM effects were evaluated in healthy participants (N = 89) at the neck, forearm and lower leg using the cold pressor test as the conditioning stimulus. In three separate experiments, we compared the impact of (1) design (sequential versus parallel), (2) conditioning stimulus intensity (VAS 40/100 versus VAS 60/100), and (3) test stimulus selection (single versus dual, i.e., mechanical and thermal). Statistical analyses of the main effect of design (adjusted for order) and experiment were conducted using linear mixed models with random intercepts.ResultsNo significant differences were identified in absolute CPM data. In relative CPM data, a sequential design resulted in a slightly lower CPM effect compared to a parallel design, and only with a mechanical test stimulus at the neck (−6.1%; 95% CI [−10.1 to −2.1]) and lower leg (−5.9%; 95% CI [−11.7 to −0.1]) but not forearm (−4.5%; 95% CI [−9.0 to 0.1]). Conditioning stimulus intensity and test stimulus selection did not influence the CPM effect nor the difference in CPM effects derived from parallel versus sequential designs.ConclusionsDifferences in CPM effects between protocols were minimal or absent. A parallel design may lead to a minimally higher relative CPM effect when using a mechanical test stimulus. The conditioning stimulus intensities assessed in this study and performing two test stimuli did not substantially influence the differences between designs nor the magnitude of the CPM effect.

Effect of continuous passive motion on the early recovery outcomes after total knee arthroplasty

IntroductionContinuous passive motion (CPM) is a frequently used method in the early post-operative rehabilitation of patients after knee surgery. In this study, the effectiveness of the CPM method was evaluated after primary total knee arthroplasty during an early recovery period.MethodsEighty patients undergoing total knee arthroplasty were assigned into two groups. The experimental group received CPM and active exercises, while the control group active exercises only. All subjects were evaluated once before the surgery and at a discharge, in terms of mean active range of motion (AROM), mean Knee Society Score (KSS), and Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC).ResultsThe mean AROM for the experimental group was 82.3° ± 14.3° and 76.1° ± 22.2° for the control. The mean KSS score was 136.4 ± 19.3 points for the experimental group, and 135.7 ± 15.1 for the control. There were no statistical differences between the two groups. The KSS functional score was 66.4 ± 8.1 points for the experimental group compared to 62.2 ± 7.3 points for the control, but there was a statistically significant difference between the groups at discharge from the hospital (p = 0.009). A subjective estimation of the pain level, joint stiffness and function also showed a statistically significant difference between the two groups (38.6 ± 14.3 points for the CPM group and 21.2 ± 15.7 for the control).ConclusionThese findings show that there is no significant effect of CPM in terms of improving clinical measurements. However, there was a significant beneficial effect on the subjective assessment of pain level, joint stiffness, and functional ability.

Study on Rehabilitation Effect of CPM after Total Knee Arthroplasty

Study on Rehabilitation Effect of CPM after Total Knee Arthroplasty

Pre-treatment pain sensitivity is associated with outcome following exercise therapy in patients with knee osteoarthritis - an observational study

Purpose: Exercise therapy in combination with education is recommended as first-line treatment for painful knee osteoarthritis (KOA). In clinical practice, supervised exercise therapy and education demonstrate approx. 25% pain relief following an 8-week treatment program. Studies indicate that some patients with KOA experience larger pain relief compared to others. Assessments of peripheral and central pain mechanisms has been used to predict responders and non-responders to treatment. Studies on surgery and treatment with non-steroid anti-inflammatory drugs in patients with KOA have indicated that patients with higher levels of pain sensitivity might respond less positive. The primary aim of this observational study was to investigative if measures of pre-treatment pain sensitivity was associated with clinical outcomes after supervised exercise therapy and education. Methods: Patients with painful KOA (numeric rating scale [NRS, 0-10] ≥ 3) were included, and examined before and 1-2 weeks after 6-8 weeks of supervised exercise therapy (2 sessions of 1 hour per week) and 2 sessions of patient education. Handheld pressure pain threshold (PPT) was assessed locally at the most painful knee at 4 peripatellar sites (knee) and at two remote sites at the m. tibialis anterior (TA) and the contralateral m. extensor carpi radialis longus (ECRL). Further, computer-controlled cuff algometry at the lower leg with the most intense knee pain was used to assess pain detection threshold (cPDT), pain tolerance threshold (cPTT) and conditioned pain modulation (cCPM). Peak pain intensity within the last 24 hours (NRS, 0-10), PainDetect questionnaire (PDQ, 0-38) and Knee injury and Osteoarthritis Outcome Score (KOOS) were assessed as clinical measures. PDQ assesses the pain phenotype with a score ≤ 12 indicating probably nociceptive pain, 13-18 uncertain pain phenotype and ≥ 19 probably neuropathic pain. KOOS4 was defined as the average score of the subscale scores for Pain, Symptoms, Activity of Daily Living and Quality of Life (0-100 with 0 indicating extreme problems and 100 indicating no problems). Physical performance was assessed using the 40-meter walk test (40MWT). A treatment attendance score (%) was calculated for each patient by dividing the number of sessions attended by the number of sessions scheduled (twice per week). This study was approved by the local ethical committee (N-20190045) and pre-registered at clinicaltrials.org (NCT04123756). All participants gave oral and written informed consent prior to enrollment. Results: This interim analysis reports on the first patients recruited for this observational study. Eleven KOA patients (6 women) with mean peak pain intensity of 6.0 ± 1.5, median pain duration 17.0 months (range: 5-120) and body mass index of 30.3 ± 5.7 were included in this interim analysis. In one subject, follow-up was made by telephone due to the COVID-19 situation, leaving 10 subject for the analysis on changes in pain sensitivity measures. Attendance score was 98.1 ± 18.1% during 7.1 ± 0.7 weeks. Following treatment, improvements were observed in KOOS4 (57.1 ± 10.0 at baseline vs. 65.3 ± 13.1 at follow-up, P < 0.01), and peak pain intensity (6.0 ± 1.5 vs. 3.2 ± 2.3, P < 0.001). No differences were seen for PDQ (7.6 ± 2.6 vs 6.8 ± 3.6, P = 0.77) and 40MWT (27.1 ± 6.6 sec vs. 25.8 ± 5.2 sec, P = 0.29). Further, no changes in any of the pain sensitivity measures were found following treatment (all Ps > 0.15). Pre-treatment cPDT (rs < 0.73, P < 0.05) and cPTT (rs < 0.72, P < 0.05) were associated with post-treatment KOOS4. No significant associations were found between pre-treatment PPT or CPM effects and post-treatment peak pain measures or change in KOOS-4 (P > 0.05). Conclusions: These results indicate that patients with higher pre-treatment pressure pain sensitivity have worse KOOS4 scores following supervised exercise therapy and education.

GROWTH RESPONSE, BODY TEMPERATURE AND BLOOD CONSTITUENTS OF PULLET CHICKS FED CASSAVA PEEL MEAL SUPPLEMENTED WITH CASHEW NUT REJECT MEAL

A 3 x 4 factorial experiment was conducted with four hundred and thirty-two, 7day old Yaafa brown pullet chicks in which the birds were divided into 12 treatment groups with 3 replications of 12 birds each. The diets consisted of 3 levels of cassava peel meal-CPM (0%, 10% and 20%) with each supplemented with 4 levels of cashew nut reject meal-CNM (0%, 10%, 20% and 30%). The study was conducted for 56 days. 20% CPM inclusion in the diets increased (P &lt; 0.05) the bird’s body temperature and significantly (P &lt; 0.05) decreased the weight gain across treatments. Significant (P &lt; 0.05) declines were also seen in the final weight from 0% to 20% CPM inclusion levels 0% CPM inclusion gave the highest (P &lt; 0.05) weight gain 9.56 with the best (P &lt; 0.05) feed/gain ration of 3.62. The cost of 1kg feed consumed (#) and 1kg feed consumed/weight gain #/g) were significantly (P &lt; 0.05) influenced by CPM inclusion in the diets. The lowest values of #38.09 and #4.00, respectively, were recorded in 0% CPM inclusion. The effect in the platelet. However, the effect of CNM inclusion on the performance and cost benefits, showed that the body temperature marginally increased (P &gt; 0.05). Significant (P &lt; 0.05) differences were observed in feed intake, percentage mortality, cost of 1kg feed consumed and cost of 1kg feed consumed/weight gain with CNM inclusion. The 30% CNM inclusion level had the lowest feed intake of 33.91g/bird and the best feed/gain of 3.86. The blood parameters recorded fluctuating values with CNM inclusion. Significant (P &lt; 0.05) differences were observed only in the packed cell volume and the total protein. In the interaction, the highest final weight, weight gain and the best feed/gain were observed in diets 3 (0%CPM and 20%CNM). The lowest body temperature (P &lt; 0.05) of 37.9oC was recorded in diet 1 (0%CPM and 0%CNM) while the highest value of 41.0oC was recorded in diets 9 (20%CPM and 0%CNM) and 10 (20%CPM and 10%CNM). The results showed that the blood parameters were not affected by the protein quality of the diets as CNM inclusion levels masked the deleterious effect of CPM in the diets. It was therefore concluded that the supplementation of CPM diets with CNM enhanced the utilization of the diets by ensuring normal growth response body temperature and blood constitutions.

Distraction by a cognitive task has a higher impact on electrophysiological measures compared with conditioned pain modulation

BackgroundConditioned pain modulation (CPM) evaluates the effect of a painful conditioning stimulus (CS) on a painful test stimulus (TS). Using painful cutaneous electrical stimulation (PCES) as TS and painful cold water as CS, the pain relief was paralleled by a decrease in evoked potentials (PCES-EPs). We now aimed to compare the effect of CPM with cognitive distraction on PCES-induced pain and PCES-EP amplitudes.MethodsPCES was performed using surface electrodes inducing a painful sensation of 60 (NRS 0–100) on one hand. In a crossover design healthy subjects (included: n = 38, analyzed: n = 23) immersed the contralateral hand into 10 °C cold water (CS) for CPM evaluation and performed the 1-back task for cognitive distraction. Before and during the CS and 1-back task, respectively, subjects rated the pain intensity of PCES and simultaneously cortical evoked potentials were recorded.ResultsBoth CPM and cognitive distraction significantly reduced PCES-EP amplitudes (CPM: 27.6 ± 12.0 μV to 20.2 ± 9.5 μV, cognitive distraction: 30.3 ± 14.2 µV to 13.6 ± 5.2 μV, p < 0.001) and PCES-induced pain (on a 0–100 numerical rating scale: CPM: 58 ± 4 to 41.1 ± 12.3, cognitive distraction: 58.3 ± 4.4 to 38.0 ± 13.0, p < 0.001), though the changes in pain intensity and PCES-amplitude did not correlate. The changes of the PCES-EP amplitudes during cognitive distraction were more pronounced than during CPM (p = 0.001).ConclusionsCPM and cognitive distraction reduced the PCES-induced pain to a similar extent. The more pronounced decrease of PCES-EP amplitudes after distraction by a cognitive task implies that both conditions might not represent the general pain modulatory capacity of individuals, but may underlie different neuronal mechanisms with the final common pathway of perceived pain reduction.

Individual variability and sex differences in conditioned pain modulation and the impact of resilience, and conditioning stimulus pain unpleasantness and salience.

Distinct pain experiences are shaped both by personal attributes and characteristics of noxious stimuli. An Individual's capacity for endogenous pain inhibition (reflected by conditioned pain modulation [CPM]), their resilience, and the pain unpleasantness and salience of painful stimuli can impact their pain perception. Here, we aimed to determine how individual variability in CPM relates to sex and resilience as personal attributes, and pain unpleasantness and salience of the CPM conditioning stimulus (CS). We evaluated CPM in 106 healthy participants (51 female and 55 male) based on the change in test stimulus pain applied concurrently with a painful CS, both delivered by painful heat. The CS reduced test stimulus pain in only half of the participants (CPM subgroup), but did not do so for the other half (no-CPM subgroup), many who exhibited pain facilitation. A regression model explained CPM effects after accounting for sex, resilience, CS pain unpleasantness and salience. In the CPM subgroup regression model, the CPM effect was positively related to CS pain unpleasantness, while the CPM effect was not related to any variable in the no-CPM subgroup model. Correlation analyses revealed that the CPM effect was anticorrelated with resilience in males with no-CPM. The CPM effect was correlated with CS pain unpleasantness in males with CPM and in females with no-CPM. The CPM effect and CS salience were correlated in the whole group more strongly than in the subgroups. These data reveal that the complexity of contributors to CPM variability include both personal attributes and attributes of the CS.

The Effect of Stress on Repeated Painful Stimuli with and Without Painful Conditioning.

Stress and pain have been interrelated in clinical widespread pain conditions. Studies indicate that acute experimental stress in healthy volunteers has a negative effect on the descending inhibitory pain control system and thus the ability to inhibit one painful stimulus with another (conditioned pain modulation [CPM]) although without effect on general pain sensitivity. CPM effects can be assessed immediately after the stress induction, whereas some physiological stress responses (e.g., cortisol release) are delayed and longer lasting. It is unclear whether CPM may relate to stress-induced increases in cortisol. Twenty-five healthy men had CPM effects measured over a period of 10 minutes. Pain detection thresholds (PDTs) were assessed by repeated test stimuli with cuff algometry on one leg, with and without painful cuff pressure conditioning on the contralateral leg. CPM effects, assessed as the increase in PDT during conditioning stimulation compared with without, were measured before and after experimental stress and a control condition (Montreal Imaging Stress Task [MIST]). Saliva cortisol levels and self-perceived stress were collected. Participants reported the MIST to be more stressful compared with the MIST control, but cortisol levels did not change significantly from baseline. In all sessions, PDT increased during conditioning (P = 0.001), although the MIST compared with the MIST control had no significant effect on PDT or CPM effects. A negative correlation between changes in cortisol and conditioned PDT was found when applying the MIST (P < 0.03). No significant effect of stress was found on CPM compared with a matched control condition. Individual changes in experimental stress and in conditioned pain sensitivity may be linked with cortisol.

Development of a new bed-side-test assessing conditioned pain modulation: a test-retest reliability study.

Background and aims Conditioned pain modulation (CPM) is of considerable interest within pain research. Often CPM testing is conducted in experimental settings using complicated instrumentation, thus challenging the implementation in clinical settings. Being able to assess CPM in a fast and reliable way in clinical settings could lead to a new diagnostic tool allowing improved profiling of pain patients. Methods A test-retest reliability study and a methodological development study were conducted based on different populations. The reliability study included 22 healthy subjects, mean age 23.6 years (SD: 2.4) and the methodological study included 29 healthy subjects, mean age 21.5 years (SD: 1.6). As painful phasic test stimulus, a 6-10 kg handheld, spring-based pressure algometer was applied perpendicularly to the muscle belly of the tibialis anterior muscle for 10 s and as painful tonic conditioning stimulus, 1-2 standard clamps, inducing a force of 1.3 kg, were applied extra-segmentally at the ipsilateral earlobe for 60-120 s. Four different test protocols were evaluated, of which one protocol was investigated for reliability. Test protocol 1 used a 6 kg pressure algometer as painful phasic test stimulus and a single clamp applied for 60 s as painful tonic conditioning stimulus. Test protocol 2 used a 10 kg pressure algometer as painful phasic test stimulus, and two clamps applied for 60 s as painful tonic conditioning stimulus. Test protocol 3 used a 10 kg pressure algometer as painful phasic test stimulus and a single clamp applied for 120 s as painful tonic conditioning stimulus. Test protocol 4 used a 6 kg pressure algometer as painful phasic test stimulus and a single clamp applied for 120 s as painful tonic conditioning stimulus. Results None of the stimuli caused any adverse events, e.g. bruises. In the reliability study (test protocol (1), non-significant CPM effects of 0.3 (SD: 1.6) and 0.2 (SD: 1.0) were observed in session 1 and 2, respectively. The intra-class correlations were 0.67 and 0.72 (p = < 0.01) and limits of agreement (LoA) ranged from -2.76 to 3.31. Non-significant CPM effects of 0.2 (SD: 1.0), -0.1 (SD: 1.1), and 0.0 (SD: 1.2) were observed for test protocol 2, 3, and 4, respectively). Conclusions The bedside test developed for investigating CPM was feasible and easy to use in healthy volunteers. No significant CPM effects were measured and a large variation in CPM effect ranging from -0.14 to 0.32 was observed. Intra-class correlation (ICC) values for the pressure algometer were interpreted as "good relative reliability" (test protocol 1), and LoA revealed a somewhat low absolute reliability. Implications The pressure algometer provided reproducible measurements and was useful for inducing phasic test stimuli. Since no significant CPM effects were detected, no recommendations for the bedside test can yet be made. Further examinations will have to establish if the "one size fits all" application of both test and conditioning stimuli is useful. Future bedside studies involving patient populations are warranted to determine the usefulness of the method.

(292) Age differences in endogenous pain modulation: A systematic review

Over the last decade, a growing body of research has examined age differences in endogenous pain modulation with the dynamic quantitative sensory tests: conditioned pain modulation (CPM; pain inhibition) and temporal summation of pain (TS; pain facilitation). Studies generally indicate reduced CPM and enhanced TS in older compared to younger adults, with some mixed results. The purpose of this study was to examine age differences in CPM and TS using meta-analytic techniques. Depending on the data presented in studies, effect sizes (ES) were calculated either 1) between age groups for TS and CPM scores or 2) within age groups for each measure (i.e., magnitude of CPM and TS for younger adults vs. magnitude of CPM and TS for older adults). Data was extracted from 7 studies for CPM and 10 studies for TS. For CPM, the between-group average effect size indicated more efficient CPM for younger compared to older adults (ES=0.88). Within group effect sizes indicated large CPM effects for younger adults (ES=0.82) and virtually no CPM effect for older adults (ES=0.03). For TS, the average magnitude of age differences was small (ES=0.32), with older adults exhibiting larger TS. Within group effect sizes indicated moderate TS effects for younger (ES=0.62) and older adults (ES=0.72). These effect size trends remained the same regardless of stimuli used for the TS protocols. Average effect sizes for each stimulus type and inter-pulse-interval (above vs. below 3-sec IPI) will be presented. Additionally, weighted effects sizes for CPM and TS will be presented. This systematic review found large age differences in CPM and smaller age differences for TS, which may depend on protocol parameters.

Chemo-somatosensory evoked potentials: A sensitive tool to assess conditioned pain modulation?

Background: Chemo-somatosensory evoked potentials (CSSEPs) elicited by chemical stimulation (CO2 gas) of the nasal mucosa have been shown to be sensitive enough to pick up even weak analgesic effects. With the present study we wanted to investigate whether CSSEPs are also a sensitive tool to capture endogenous pain inhibitory mechanisms elicited by conditioned pain modulation (CPM; where a first conditioning stimulus reduces the sensitivity for a second test stimulus) with a conditioning stimulus of rather low noxious load.Methods: Seventeen healthy participants were tested for CPM effects (conditioning stimulus: tonic heat pain with intensities around the pain threshold induced via a thermode; test stimulus: chemonasal stimulation (73% and 78% CO2)) on CSSEPs and on self-report ratings.Results: We found significant CPM effects in the CSSEPS, with reduced amplitudes and prolonged latencies at several electroencephalogram (EEG) recording positions when using the lower CO2 concentration (73% CO2). In contrast to the visible inhibitory effects on the CSSEPs, subjective ratings of the test stimulus did not reflect CPM action.Discussion: The experimental pain model using CO2 stimuli to elicit CSSEPs proved to be sensitive enough to capture weak CPM effects elicited by a conditioning stimulus of rather low noxious load. The usage of such mild noxious conditioning stimuli—in contrast to stimuli of higher noxious load (e.g., cold pressor test)—has the advantage that the activation of other types of pain inhibitory mechanisms in parallel (like attentional distraction, stress-induced analgesia) can be avoided.

Cecropia pachystachya: a species with expressive in vivo topical anti-inflammatory and in vitro antioxidant effects.

Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, β-carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms.

Anti‐Inflammatory, Antinociceptive and Cytotoxic Effects of the Methanol Extract of Cecropia pachystachya Trécul

Cecropia pachystachya is widely used in the traditional medicine as anti-inflammatory, antitusive, expectorant, antiasthmatic and hypoglycemic. It is also commercially available to treat skin cancer. To validate some of the popular uses of this species, its methanol leaves extract (CPM) was tested for anti-inflammatory, antinociceptive and cytotoxic effects. The anti-inflammatory activity was evaluated by croton oil-induced ear edema test. When used orally, the anti-inflammatory effect of CPM at 300 mg/kg was similar to that of indomethacin with 53% inhibition of the ear edema. Also, results on topical treatment were similar to that of dexamethasone with 83% inhibition of the edema. To evaluate the antinociceptive activity, acetic acid-induced writhing and formalin-induced pain tests were employed. CPM (100 and 300 mg/kg) reduced the number of writhing by 61% and 67%, respectively. In both doses, the activity was comparable to the reference drug, indomethacin. The oral administration of CPM was ineffective in the first phase of formalin test but exhibited great effects on the second phase decreasing the licking time by 85% at 300 mg/kg. The cytotoxic potential of CPM was also investigated against HL60, HL60.bcl2 and Jurkat tumor cell lines and showed an inhibition of more than 50% of cell proliferation. The flavones orientin and isoorientin were detected in CPM.

The Effect of CPM in Total Knee Replacement in Rheumatoid Arthritis

The Effect of CPM in Total Knee Replacement in Rheumatoid Arthritis