Psychologically-based interventions for adults with chronic neuropathic pain: A scoping review.

OBJECTIVE: As psychologically-based interventions have been shown to have clinical utility for adults with chronic pain generally, a similar benefit might be expected in the management of chronic neuropathic pain (NeuP). However, to date this has not been established, with existing systematic reviews on this topic being hampered by the scarcity of Randomised Controlled Trials (RCTs). This review aimed to identify the type of psychologically-based interventions studied for adults with chronic NeuP. It also aimed to assess whether there are enough RCTs to justify undertaking an updated systematic review. METHODS: Seven databases and two clinical trial registries were searched for NeuP and psychologically-based interventions from database inception to December 2021, and the search was updated in February 2023. The search was broadened by reviewing the reference list of included studies and contacting field experts. Predetermined study characteristics were extracted. RESULTS: Of 4682 records screened, 33 (less than 1%) articles met the eligibility criteria. Four broad intervention approaches were observed, including cognitive-behavioural approaches (n = 16), mindfulness/meditation (n = 10), trauma focused therapy (n = 4), and hypnosis (n = 3). Thirteen RCTs were identified, and of these, nine retained 20 participants in each arm at post-treatment. CONCLUSIONS: Cognitive Behavioural Therapy was the most common therapeutic approach identified, whereas mindfulness/meditation was the most frequently used technique. Almost half to two-thirds of the studies reported significant improvements in either pain, disability, or distress, suggesting psychologically-based interventions are potentially beneficial for adults with chronic NeuP. An updated systematic review seems warranted.

Extracellular Vesicles and Bacteriophages: New Directions in Environmental Biocolloid Research.

There is a long-standing appreciation among environmental engineers and scientists regarding the importance of biologically derived colloidal particles and their environmental fate. This interest has been recently renewed in considering bacteriophages and extracellular vesicles, which are each poised to offer engineers unique insights into fundamental aspects of environmental microbiology and novel approaches for engineering applications, including advances in wastewater treatment and sustainable agricultural practices. Challenges persist due to our limited understanding of interactions between these nanoscale particles with unique surface properties and their local environments. This review considers these biological particles through the lens of colloid science with attention given to their environmental impact and surface properties. We discuss methods developed for the study of inert (nonbiological) particle-particle interactions and the potential to use these to advance our understanding of the environmental fate and transport of extracellular vesicles and bacteriophages.

Characterizing the Transport and Surface Affinity of Extracellular Vesicles Isolated from Yeast and Bacteria in Well-Characterized Porous Media.

Extracellular vesicles (EVs) are membrane-bounded, nanosized particles, produced and secreted by all biological cell types. EVs are ubiquitous in the environment, operating in various roles including intercellular communication and plant immune modulation. Despite their ubiquity, the role of EV surface chemistry in determining transport has been minimally investigated. Using the zeta (ζ)-potential as a surrogate for surface charge, this work considers the deposition of EVs from the yeast, Saccharomyces cerevisiae, and two bacterial species, Staphylococcus aureus and Pseudomonas fluorescens, in well-characterized porous medium under various background conditions shown to influence the transport of other environmental colloidal particles: ionic strength and humic acid concentration. The affinity of S. cerevisiae EVs for the porous medium (glass beads) appeared to be sensitive to changes in ionic strength, as predicted by colloid stability (Derjaguin, Landau, Verwey, and Overbeek or DLVO) theory, and humic acid concentration, while P. fluorescens EVs deviated from DLVO predictions, suggesting that mechanisms other than charge stabilization may control the deposition of P. fluorescens. Calculations of attachment efficiency from these deposition studies were used to estimate EV transport using a clean-bed filtration model. Based on these calculations, EVs could be transported through such homogeneous porous media up to 15 m.

Comparative electrokinetic properties of extracellular vesicles produced by yeast and bacteria.

Extracellular vesicles (EVs) are nano-sized, biocolloidal proteoliposomes that have been shown to be produced by all cell types studied to date and are ubiquitous in the environment. Extensive literature on colloidal particles has demonstrated the implications of surface chemistry on transport behavior. Hence, one may anticipate that physicochemical properties of EVs, particularly surface charge-associated properties, may influence EV transport and specificity of interactions with surfaces. Here we compare the surface chemistry of EVs as expressed by zeta potential (calculated from electrophoretic mobility measurements). The zeta potentials of EVs produced by Pseudomonas fluorescens, Staphylococcus aureus, and Saccharomyces cerevisiae were largely unaffected by changes in ionic strength and electrolyte type, but were affected by changes in pH. The addition of humic acid altered the calculated zeta potential of the EVs, especially for those from S. cerevisiae. Differences in zeta potential were compared between EVs and their respective parent cell with no consistent trend emerging; however, significant differences were discovered between the different cell types and their EVs. These findings imply that, while EV surface charge (as estimated from zeta potential) is relatively insensitive to the evaluated environmental conditions, EVs from different organisms can differ regarding which conditions will cause colloidal instability.

Lack of Detectable Direct Effects of Silver and Silver Nanoparticles on Mitochondria in Mouse Hepatocytes.

Silver nanoparticles (AgNPs) are well-proven antimicrobial nanomaterials, yet little is elucidated regarding the mechanism underlying cytotoxicity induced by these nanoparticles. Here, we tested the hypothesis that mitochondria are primary intracellular targets of two AgNPs and silver ions in mouse hepatocytes (AML12) cultured in glucose- and galactose-based media. AML12 cells were more sensitive to mitochondrial uncoupling when grown with galactose rather than glucose. However, 24 h treatments with 15 nm AgNPs and 6 nm GA-AgNPs (5 and 10 µg/mL) and AgNO3 (1 and 3 µg/mL), concentrations that resulted in either 10 or 30% cytotoxicity, failed to cause more toxicity to AML12 cells grown on galactose than glucose. Furthermore, colocalization analysis and subcellular Ag quantification did not show any enrichment of silver content in mitochondria in either medium. Finally, the effects of the same exposures on mitochondrial respiration were mild or undetectable, a result inconsistent with mitochondrial toxicity causing cell death. Our results suggest that neither ionic Ag nor the AgNPs that we tested specifically target mitochondria and are inconsistent with mitochondrial dysfunction being the primary cause of cell death after Ag exposure under these conditions.

Implementation of Early Intervention Protocol in Australia for 'High Risk' Injured Workers is Associated with Fewer Lost Work Days Over 2 Years Than Usual (Stepped) Care.

Purpose To evaluate whether a protocol for early intervention addressing the psychosocial risk factors for delayed return to work in workers with soft tissue injuries would achieve better long-term outcomes than usual (stepped) care. Methods The study used a controlled, non-randomised prospective design to compare two case management approaches. For the intervention condition, workers screened within 1-3 weeks of injury as being at high risk of delayed returned to work by the Örebro Musculoskeletal Pain Screening Questionnaire-short version (ÖMPSQ-SF) were offered psychological assessment and a comprehensive protocol to address the identified obstacles for return to work. Similarly identified injured workers in the control condition were managed under usual (stepped) care arrangements. Results At 2-year follow-up, the mean lost work days for the Intervention group was less than half that of the usual care group, their claim costs were 30% lower, as was the growth trajectory of their costs after 11 months. Conclusions The findings supported the hypothesis that brief psychological risk factor screening, combined with a protocol for active collaboration between key stakeholders to address identified psychological and workplace factors for delayed return to work, can achieve better return on investment than usual (stepped) care.

Correction to: Implementation of Early Intervention Protocol in Australia for 'High Risk' Injured Workers is Associated with Fewer Lost Work Days Over 2 Years Than Usual (Stepped) Care.

The original version of this article unfortunately contained a spelling error in one of the co-authors's names. The family name of the co-author was incorrectly displayed as "James McCauley" instead of "James McAuley. The original article has been corrected.

Predicting Return to Work in a Heterogeneous Sample of Recently Injured Workers Using the Brief ÖMPSQ-SF.

Purpose (1) to examine the ability of the Örebro Musculoskeletal Pain Screening Questionnaire-short version (ÖMPSQ-SF) to predict time to return to pre-injury work duties (PID) following a work-related soft tissue injury (regardless of body location); and (2) to examine the appropriateness of 50/100 as a suitable cut-off score for case identification. Methods Injured workers (IW) from six public hospitals in Sydney, Australia, who had taken medically-sanctioned time off work due to their injury, were recruited by insurance case managers within 5-15 days of their injury. Eligible participants (N = 213 in total) were administered the ÖMPSQ-SF over the telephone by the case manager. For objective (1) Cox proportional hazards regression analysis was used to predict days to return to PID using the ÖMPSQ-SF. For objective (2) receiver operator characteristic (ROC) analysis was used to determine the ÖMPSQ-SF total score that optimises sensitivity and specificity in detecting whether or not participants had returned to PID within 2-7 weeks. Results The total ÖMPSQ-SF score significantly predicted number of days to return to PID, such that for every 1-point increase in the total ÖMPSQ-SF score the predicted chance of returning to work reduced by 4% (i.e., hazard ratio = 0.96), p < 0.001. Sensitivity and specificity for the ROC analysis comparing ÖMPSQ-SF total score to return to PID within 2-7 weeks suggested 48 as the optimal cut off (sensitivity = 0.65, specificity = 0.79). Conclusion The results provide strong support for the use of the ÖMPSQ-SF in an applied setting for identifying those IW likely to have delayed RTW when administered within 15 days of the injury. While a score of 48/100 was the optimal cut point for sensitivity and specificity, pragmatically, 50/100 should be acceptable as a cut-off in future studies of this type.

The pain course: a randomised controlled trial comparing a remote-delivered chronic pain management program when provided in online and workbook formats.

This study compared a remote-delivered pain management program, the Pain Course, when delivered in online and workbook formats. Participants (n = 178) were randomised into 2 groups: (1) an Internet Group (n = 84) who were provided with secure accounts to the program in an online format; or (2) a Workbook Group (n = 94) who were mailed workbook versions of the program. The content of both programs was identical and comprised 5 core lessons, which participants were encouraged to work through over an 8-week period, according to a prescribed timetable. All participants were provided with weekly contact with a clinical psychologist through email and telephone throughout the program. The overall findings suggest that the workbook format was no less effective or acceptable than the validated online format. Significant improvements (avg. improvement; Internet Group vs Workbook Group) in levels of disability (PDI: 16% vs 24%; RMDQ: 12% vs 15%), anxiety (GAD-7: 36% vs 26%), and depression (PHQ-9: 36% vs 36%) were observed in both groups immediately posttreatment. Further improvements were observed in disability levels to 3-month follow-up, and improvements across the other primary outcomes were maintained until 12-month follow-up. High treatment completion rates and levels of satisfaction were reported in both groups, and both groups required a similarly small amount of clinician contact per participant (M = 74.85 minutes; SD = 41.03). These results highlight the public health potential of remote-delivered pain management programs, delivered in either workbook or online formats, as methods of increasing access to pain management.

Threat and fear of pain induces attentional bias to pain words: An eye-tracking study.

BACKGROUND: This study aimed to investigate the effects of fear of pain (FOP) and threat on attentional biases, using eye-tracking methods. METHOD: One hundred and seven undergraduate students were randomized to receive threatening or reassuring information about the cold pressor task; and divided into high and low FOP groups. Participants completed the dot-probe task, while their eye movements were tracked. RESULTS: Results showed that those who received threatening information were less likely to have their first fixation on pain words, particularly affective pain words. Furthermore, under conditions of high threat, the high FOP group who did fixate on affective pain words, fixated more quickly than for sensory pain words, whereas the opposite was the case under low threat. In regression analyses, initial vigilance towards affective pain words was a significant predictor of reporting pain more quickly on the cold pressor. CONCLUSIONS: Taken together, these results suggest that initial vigilance of affective pain stimuli predicts actual hypervigilance to an acute experimental pain task. However, under conditions of high threat, participants show evidence of avoidance of affective pain words, even though when they do fixate on these stimuli, the high FOP group does so more quickly. These results confirm that attentional processes, characterized by vigilance avoidance, appear important. SIGNIFICANCE: Interventions that change attention towards pain to reduce vigilance and subsequent avoidance may be indicated to improve pain outcomes.

Leptomeningeal carcinomatosis in esophageal cancer: a case series and systematic review of the literature.

The aim of this study was to more clearly define the clinical course of leptomeningeal carcinomatosis due to esophageal cancer. A single institution retrospective case series was conducted. Additionally, a systematic review of the literature was performed. We present a large case series (n = 7) of leptomeningeal carcinomatosis due to esophageal cancer. Our case series and systematic review of the literature report similar findings. In our series, we report a predominance of male patients (86%) with adenocarcinoma histology (77%). Variable onset of leptomeningeal involvement of esophageal cancer in relation to the original diagnosis of the primary disease (5 months to 3 years and 11 weeks) was noted. Disease progresses quickly and overall survival is poor, measured in weeks (2.5-16 weeks) from the diagnosis of leptomeningeal involvement. Four of our patients initiated whole-brain radiation therapy with only two completing the course prior to clinical deterioration. Our patient with the longest survival (16 weeks) received intrathecal topotecan and oral temozolomide. Leptomeningeal carcinomatosis secondary to esophageal cancer has a poor prognosis. A clearly beneficial treatment modality is lacking.

Cognitive exposure versus avoidance in patients with chronic pain: adherence matters.

BACKGROUND: Behavioural exposure methods can reduce pain-avoidance behaviours, but outcomes vary. One possible explanation is that patients employ cognitive (experiential) avoidance during behavioural exposure. If so, reducing cognitive avoidance during behavioural exposure should help. One option is interoceptive exposure (IE), which involves sustained exposure (via attention) to pain sensations. In order to test if IE could improve outcomes from behavioural exposure, this study with mixed chronic pain patients compared outcomes from a cognitive behavioural therapy (CBT) pain management programme incorporating either IE or distraction from pain. METHODS: One hundred forty chronic pain patients were randomly assigned to CBT + IE or CBT + distraction. Outcome measures included pain, disability, depression and medication. Measures reflecting degree of threat of pain were also employed (catastrophizing, fear-avoidance, pain self-efficacy and pain acceptance). An intention-to-treat approach, using mixed-effects model repeated measures, as well as conventional inferential statistical tests, effect sizes and reliable change indices were employed to evaluate the outcomes up to 1-year post-treatment. RESULTS: Significant improvements were achieved by both treatment conditions on all outcome measures and on measures reflecting the threatening nature of pain, with no differences between treatment conditions. CONCLUSIONS: The addition of IE to behavioural exposure did not improve outcomes. However, higher adherence to either attentional strategy was associated with larger effect sizes on all measures, suggesting factors shared by the two treatments could have contributed to the outcomes. Taken as a whole, the results suggest that increasing adherence to treatment strategies, possibly by motivational measures, would improve the overall outcomes of these interventions.

Mesoporous europo-gadolinosilicate nanoparticles as bimodal medical imaging agents and a potential theranostic platform.

The mesoporous structure of sol-gel prepared gadolinium and europium doped silicate nanoparticles has been found to be highly dependent on the formulated composition, with synthesised samples displaying both disordered and hexagonally ordered mesoporous packing symmetry. The degree of pore ordering within the nanoparticles has a strong correlation with the total lanthanide (Gd(3+) and Eu(3+) ) concentration. The gadolinosilicates are excellent magnetic resonance imaging (MRI) longitudinal (T1 ) agents. The longitudinal relaxivity (r1 ) and transverse (r2 ) relaxivity, a measure of MRI contrast agent efficiency, were up to four times higher than the clinically employed Omniscan (gadodiamide); with r1 up to 20.6 s(-1) mM(-1) and r2 of 66.2 s(-1) mM(-1) compared to 5.53 and 4.64 s(-1) mM(-1) , respectively, for Omniscan. In addition, the europium content of all the samples studied is below the self-quenching limit, which results in a strong luminescence response from the nanoparticles on excitation at 250 nm. The Eu-Gd silicate nanoparticles act as bimodal imaging agents for MRI and luminescence. These mesoporous nanoparticles also have the potential to serve as encapsulation and controlled release matrices for pharmaceuticals. They are therefore a promising multimodal theranostic platform.

Mesoporous gadolino-aluminosilicate nanoparticles as magnetic resonance imaging contrast agents.

Enhanced T1 MRI contrast was observed in mesoporous gadolinosilicates co-doped with aluminium. The effect of gadolinium and aluminium dopant concentration was explored using a high-throughput workflow. The T1 relaxivity increases with lower gadolinium and higher aluminium loadings.

A comparison of the effect of mindfulness and relaxation on responses to acute experimental pain.

BACKGROUND: This study aimed to investigate the efficacy of mindfulness training in comparison with relaxation training on pain, threshold and tolerance during the cold pressor task. METHODS: Undergraduate psychology students (n = 140) were randomly assigned to receive reassuring or threatening information about the cold pressor. Participants were then re-randomized to receive mindfulness or a control intervention: relaxation training. RESULTS: Analyses confirmed that the threat manipulation was effective in increasing worry, fear of harm and expectations of pain, and reducing coping efficacy. Interaction effects revealed that mindfulness was effective in increasing curiosity and reducing decentring under conditions of high threat but not low threat. Other interactions on cognitive variables (attentional bias to pain and self-focus) confirmed that mindfulness and relaxation appeared to exert influences under different conditions (i.e. mindfulness: high threat; and relaxation: low threat). Despite these cognitive effects being discerned under different conditions, there were no differences between mindfulness and relaxation on pain, tolerance or threshold in either threat group. CONCLUSIONS: These results show that a single, brief session of mindfulness based on body scanning is not sufficient to change the way in which individuals approach an experimental pain task in comparison with relaxation, which has previously been shown to be ineffective.

High-throughput preparation of hexagonally ordered mesoporous silica and gadolinosilicate nanoparticles for use as MRI contrast agents.

The development of biomedical nanoparticulate materials for use in diagnostics is a delicate balance between performance, particle size, shape, and stability. To identify materials that satisfy all of the criteria it is useful to employ automated high-throughput (HT) techniques for the study of these materials. The structure and performance of surfactant templated mesoporous silica is very sensitive to a wide number of variables. Variables, such as the concentration of the structure-directing agent, the cosolvent and dopant ions and also the temperature and concentration of quenching all have an influence on the structure, surface chemistry, and therefore, the performance of the mesoporous silica nanoparticles generated. Using an automated robotic synthetic platform, a technique has been developed for the high-throughput preparation of mesoporous silica and gadolinium-doped silicate (gadoliniosilicate) nanoparticulate MRI contrast agents. Twelve identical repeats of both the mesoporous silica and gadolinosilicate were synthesized to investigate the reproducibility of the HT technique. Very good reproducibility in the production of the mesoporous silica and the gadolinosilcate materials was obtained using the developed method. The performance of the gadolinosilicate materials was comparable as a T(1) agent to the commercial MRI contrast agents. This HT methodology is highly reproducible and an effective tool that can be translated to the discovery of any sol-gel derived nanomaterial.

Is adherence to pain self-management strategies associated with improved pain, depression and disability in those with disabling chronic pain?

There is generally good evidence that pain management interventions that include self-management strategies can substantially reduce disability and improve psychological well-being in patients with chronic pain. Reductions in unhelpful responses, especially catastrophising and fear-avoidance beliefs, have been established as key contributors to these gains. In contrast, there is surprisingly little evidence that adherence to self-management strategies contributes to achieving these outcomes. Difficulties in defining and measuring the use of pain self-management strategies have been obstacles for this research. Using a pragmatic way of assessing the practice of specific strategies this study investigated their ability to account for changes in pain, disability and depressive symptoms after a 3-week cognitive-behavioural pain management program. The post-treatment outcomes on these dimensions were found to be statistically and, for many, clinically significant. Consistent with previous research, reductions in catastrophising and fear-avoidance beliefs, and increased pain self-efficacy beliefs, were also associated with these gains. But the key new finding was that there was a clear gradient between adherence to specific self-management strategies and reductions in pain, disability and depressive symptoms. Furthermore, adherence to the self-management strategies was predictive of better outcomes even after controlling for the moderating effects of initial catastrophising, fear-avoidance and pain self-efficacy beliefs.

Nanostructured protic ionic liquids retain nanoscale features in aqueous solution while precursor Brønsted acids and bases exhibit different behavior.

Small- and wide-angle X-ray scattering (SWAXS) has been used to investigate the effect that water has on the nanoscale structure of protic ionic liquids (PILs) along with their precursor Brønsted acids and bases. The series of PILs consisted of primary, secondary, and tertiary alkylammonium cations in conjunction with formate, nitrate, or glycolate anions. Significant differences were observed for these systems. The nanoscale aggregates present in neat protic ionic liquids were shown to be stable in size on dilution to high concentrations of water, indicating that the water is localized in the ionic region and has little effect on the nonpolar domains. The Brønsted acid-water solutions did not display nanostructure at any water concentration. Primary amine Brønsted bases formed aggregates in water, which generally displayed characteristics of poorly structured microemulsions or a form of bicontinuous phase. Exceptions were butyl- and pentylamine with high water concentrations, for which the SWAXS patterns fitted well to the Teubner-Strey model for microemulsions. Brønsted base amines containing multiple alkyl chains or hydroxyl groups did not display nanostructure at any water concentration. IR spectroscopy was used to investigate the nature of water in the various solutions. For low PIL concentrations, the water was predominately present as bulk water for PIL molar fractions less than 0.4-0.5. At high PIL concentrations, in addition to the bulk water, there was a significant proportion of perturbed water, which is water influenced in some way by the cations and anions. The molecular state of the water in the studied amines was predominately present as bulk water, with smaller contributions from perturbed water than was seen in the PILs.

Intrusive pain and worry about health in older men: the CHAMP study.

The role of anxiety in pain is less well understood than the role of depression. Based on recent conceptual thinking about worry and pain, we explored the relationship between pain status and worry about health and anxiety in 1217 community-dwelling men aged 70 years or older who participated in the baseline phase of the Concord Health and Ageing in Men Project study, a large population-based epidemiological study of healthy ageing based in Sydney, Australia. We hypothesised that worry about health would be associated with having persistent pain, and that the association would be stronger in the presence of co-existing pain-related interference with activities (intrusive pain). Of men in the study, 12.5% had persistent and intrusive pain, 22.4% were worried about their health, and 6.3% had anxiety. We found a strong association between worry about health and pain that was both persistent and intrusive, and that remained after accounting for age, number of comorbidities, depression, self-rated health status, arthritis, and gait speed (adjusted odds ratio 2.9; 95% confidence interval 1.8-4.7), P<0.0001). The corresponding adjusted odds ratio for the association between anxiety and pain was 2.3 (95% confidence interval 1.0-4.8; P=0.0363). These findings suggest that at a population level, subthreshold anxiety and pain are strongly related, and worry about health occurs much more commonly than anxiety itself. To our knowledge, this is the first study to explore, specifically, the relationship between pain status and worry about health in older men. In older community-dwelling men, pain was robustly associated with worry about health, highlighting the potential importance of subthreshold anxiety-related psychological factors.

A comparison of the effect of attention training and relaxation on responses to pain.

This study aimed to investigate the efficacy of an attention training technique (ATT) on pain ratings, threshold and tolerance during the cold pressor task. One hundred and three undergraduate students were randomly assigned to receive either threat-alleviating or threat-inducing information about the task. Participants were then re-randomized to receive either ATT or progressive muscle relaxation (PMR). Hence, the present study had a 2 (threat expectancy: high vs. low)x2 (training: ATT vs. PMR) design. Analyses confirmed that the threat manipulation was effective in increasing the harm associated with the task. ATT resulted in a relative reduction in hypervigilance to sensory pain words compared to PMR. ATT was also associated with a lower degree of focus on internal sensations, but not mindfulness or difficulty disengaging from pain words. Results showed that, relative to relaxation training, those receiving ATT reported pain less quickly than those receiving relaxation, although there were no differences between the training groups for tolerance or pain ratings. These results show that ATT changes the cognitive processes of internal/external focus and hypervigilance towards sensory pain words, but not difficulty disengaging or mindfulness. Although ATT changed threshold, the fact that neither pain ratings nor tolerance was affected suggests that a single, brief session of ATT may not be sufficient to affect broader change. Nonetheless, this study shows that ATT can change cognitive processes thought to be associated with heightened perception of pain and that this changes how quickly pain is registered and is therefore worthy of further investigation.