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Carbonate clumped isotope thermometry, based on the temperature-dependence of clumping of 13C and 18O in the carbonate molecule (Δ47) is a promising tool for paleoclimate reconstruction. In the last few years many discrepancies among Δ47-temperature calibrations have been resolved across the range of relevant paleoclimate temperatures (Meinicke et al., 2020; Anderson et al., 2021). However, there might be other environmental effects on biogenic carbonates from parameters such as the pCO2 and growth rates of the organisms that are still unresolved. We provide a new assessment of the temperature dependence of clumped isotopes in laboratory grown biogenic carbonate at well-constrained experimental conditions, with results from three species of coccolithophores across a growth temperature range of 6-27°C. The three cultured species cover a range of growth rates, growth conditions and species-specific carbon and oxygen vital effects. Because variations in pCO2 and media carbon chemistry are known to trigger vital effects in carbon and oxygen isotopes in coccoliths, we decoupled the temperature solubility effect on CO2 by manipulating culture CO2 independently. Three pCO2 levels at reduced, present day and elevated levels; 200, 400 and 1000 ppm respectively, were kept constant for at least two different temperatures through a continuous culturing set-up. Our new multi-parameter comparison, using updated standardization approaches, provides a critical test of previous conclusions (Katz et al., 2017) that coccolithophore clumped isotopes show little to no vital effects and are close to abiotic equilibrium. Thus, we have performed the first calibration of coccolith calcite and clumped isotopes combining different temperature and pCO2 conditions.References:Anderson, N. T., J. R. Kelson, S. Kele, M. Daëron, M. Bonifacie, J. Horita, T. J. Mackey, et al. 2021. "A Unified Clumped Isotope Thermometer Calibration (0.5–1,100°C) Using Carbonate‐Based Standardization." Geophysical Research Letters 48 (7).Katz, A., M. Bonifacie, M. Hermoso, P. Cartigny, D. Calmels. 2017. “Laboratory-grown coccoliths exhibit no vital effect in clumped isotope (Δ47) composition on a range of geologically relevant temperatures.” Geochimica et Cosmochimica Acta 208: 335-353.Meinicke, N., S.L. Ho, B. Hannisdal, D. Nürnberg, A. Tripati, R. Schiebel, and A.N. Meckler. 2020. "A robust calibration of the clumped isotopes to temperature relationship for foraminifers." Geochimica et Cosmochimica Acta 270: 160-183.

Objective Robust evidence suggests children's catastrophizing about their own pain is a risk factor for poor child pain-related outcomes. In children of parents with chronic pain, child catastrophizing about their parents' pain might be a unique predictor of child pain-related outcomes given their increased exposure to parental chronic pain and disability. The objective of this study was to examine associations between child and parent catastrophizing about their own and each other's pain and child and parent pain-related outcomes. Methods Seventy-two parents with chronic pain and their children (ages 8-15) completed questionnaires assessing their trait catastrophizing about their own and each other's pain, their own pain, and the child's internalizing symptoms. Children completed the cold pressor task (CPT) in the presence of their parent. Parents and children rated children's worst pain intensity and their own anxiety during the task. Analyses were guided by the Actor-Partner Interdependence Model. Results Greater child catastrophizing about parent pain was associated with children's and parents' increased catastrophizing about their own pain. Child catastrophizing about parent pain was associated with greater child- and parent-reported child internalizing symptoms and greater CPT pain intensity for the child, but not parent/child usual pain or CPT anxiety, over and above the influence of parent and child catastrophizing about their own pain. Conclusions Child catastrophizing about parent pain is a potential vulnerability factor associated with poor pain-related outcomes in children of parents with chronic pain that should be considered in future research and clinical settings. Statement of contribution What is already known on this subject? Higher rates of pain and internalizing symptoms are observed in offspring of parents with vs. without chronic pain. Greater child and parent pain catastrophizing are associated with poorer pain-related outcomes in children. Child catastrophizing about parent chronic pain and its association with child outcomes has not been examined. What does this study add? Greater child catastrophizing about parent chronic pain is associated with greater child internalizing and CPT pain. These effects were seen beyond the association of child and parent catastrophizing about their own pain.

BACKGROUND Retrobulbar hematoma (RH) is a rare but devastating complication of sinus surgery. It is treated initially with a lateral canthotomy and cantholysis at the bedside. Due to the high stakes and urgency of this complication, teaching this in the clinical setting is difficult. The objective of this study was to develop a cadaveric model for addressing this problem. METHODS A fresh-frozen human cadaveric model of RH was created using a Foley catheter to simulate elevated intraocular pressure. Residents who participated in an emergencies in otolaryngology-head & neck surgery "boot camp" were included in the study. A survey measuring confidence levels in performing lateral canthotomy and cantholysis was administered. After completing the skill station, a postintervention survey was administered to assess the confidence of the learner as well as fidelity and usefulness of the task trainer. RESULTS Thirty-three residents participated in the boot camp. Residents rated their confidence preintervention at 1.3/5, which suggests the majority were unable to perform the procedure. After using the model, residents rated their confidence at 3.5/5, which falls between basic knowledge and reasonably confident; this improvement achieved statistical significance (p < 0.0001). The fidelity of the model was rated 3.9/5; a score of 4 is defined as realistic. The residents rated the usefulness of the model as 4.7; a score of 5 is defined as very useful. CONCLUSION A cadaveric model of RH was successfully developed. This novel simulator was perceived to be useful, realistic, and effective by junior residents.

Giant gastropods are among the largest mollusks in the fossil record, but their potential as paleoseasonality archives has received little attention. Here, we combine stable isotope and trace element analyses with microscopic observations and growth modeling on shells of two species of the gastropod genus Campanile: the extinct Campanile giganteum from Lutetian (~45 Ma) deposits in the Paris Basin (France), the longest gastropod known from the fossil record, and its modern relative Campanile symbolicum from southwestern Australia. The C. giganteum shells contain original aragonite and have pristine nacre in their apertures. We show that these gastropods attained growth rates exceeding 600 mm/year along their helix, depositing over 300 cm3 aragonite per year. High growth rates and excellent preservation make C. giganteum excellent archives for reconstructing environmental change at high (potentially daily) temporal resolution, while providing enough material for methods such as clumped isotope analysis. Growth models show that Campanile gastropods grew nearly year-round, albeit slower in winter. Stable oxygen isotope ratios in modern C. symbolicum faithfully record a seasonal variability of 18–25°C in sea surface temperature, only failing to record the coolest winter temperatures (down to ~16°C). Similarly, C. giganteum specimens likely record a nearly complete seasonal temperature range. Assuming constant sea water isotope composition, their oxygen isotope seasonality of up to 2.5‰ would translate to a Lutetian temperature range of 21–32°C in the Paris Basin. We hypothesize that these high and seasonally variable temperatures formed the breeding ground for the Lutetian shallow marine biodiversity hotspot in the Paris Basin.

During the Eocene greenhouse (56.0–33.9 Ma), northwest Europe was dominated by a semi-arid para-tropical climate but the paleohydrological conditions are poorly known. To gain more insight into seasonal hydrological conditions in the region, we compare Lutetian (middle Eocene, ∼ 44–45 Ma) mollusk δ18O records from two shallow marine basins on either side of the English Channel, i.e., the Paris and Hampshire Basins. The semi-circular Paris Basin was open to the Atlantic Ocean, while the Hampshire Basin was more enclosed and influenced by the draining of several rivers. The proximity of the basins and the similarity of their faunal assemblages suggest that they experienced roughly similar seawater temperatures but the seasonal hydrology is expected to have been different between these basins. Among the numerous mollusks present in both basins are several members of Conidae, a gastropod family that is particularly well-suited for paleoseasonality reconstructions. To assess the paleohydrological differences between these basins we analyzed the stable oxygen isotopic composition of three specimens of Eoconus deperditus from the Banc à Verrains in the middle part of the Calcaire Grossier Formation of the Paris Basin (France), and three specimens of Eoconus edwardsi from the Shepherd’s Gutter Bed in the upper part of the Selsey Formation of the Hampshire Basin (United Kingdom). While the seasonal variability appears to have been similar between these basins, the δ18O values of the Hampshire Basin specimens are consistently lower than those in the Paris Basin, suggesting a regional difference in δ18Osw of 1–2‰ between the basins. This difference in δ18Osw was likely related to the greater influence of fluvial discharge within the Hampshire basin, compared to the Paris Basin.

Backboards have been shown to cause pain in uninjured patients. This may alter physical exam findings, leading emergency department (ED) providers to suspect a spinal injury when none exists resulting in additional imaging of the thoracolumbar spine. New York had previously employed a "Spinal Immobilization" protocol that included compulsory backboard application for all patients with suspected spinal injuries. In 2015, New York instituted a new "Spinal Motion Restriction" protocol that made backboard use optional for these patients. The objective of this study was to determine if this protocol change was associated with decreased backboard utilization and ED thoracolumbar spine imaging.This was a retrospective before-and-after chart review of subjects transported by a single emergency medical services (EMS) agency to one of four EDs for emergency calls dispatched as motor vehicle collisions (MVC). EMS and ED data were included for all calls within a 6-month interval before and after the protocol change. The protocol change was implemented in the second half of 2015. Subject demographics, backboard use, and spine imaging were reviewed for the intervals January-June 2015 and January-June 2016.There were 818 subjects in the before period and 796 subjects in the after period. Subjects were similar in terms of gender, age and type of MVC in both periods. A backboard was utilized for 440 (54%) subjects in the before period and 92 (12%) subjects in the after period (p0.001). ED thoracic spine imaging was performed on 285 (35%) subjects in the before period, and 235 (30%) subjects in the after period (p = 0.02). ED lumbar spine imaging was performed for 335 (41%) subjects in the before period, and 281 (35%) subjects in the after period (p = 0.02).A shift from a spinal immobilization protocol to a spinal motion restriction protocol was associated with a decrease in backboard utilization by EMS providers and a decrease in thoracolumbar spine imaging by ED providers.

Children of parents with chronic pain have higher rates of pain and internalizing (eg, anxiety and depressive) symptoms than children of parents without chronic pain. Parental modeling of pain behaviour and reinforcement of child pain have been hypothesized to underlie these relationships. These mechanisms were tested in a sample of 72 parents with chronic pain and their children (aged 8-15 years). Standardized measures were completed by parents (pain characteristics, pain interference, and child internalizing) and children (pain catastrophizing, pain over previous 3 months, and internalizing). In a laboratory session, children completed the cold pressor task in the presence of their parent, and parent-child verbalizations were coded. Significant indirect effects of parental pain interference on child self-reported (B = 0.12, 95% confidence interval [CI]: 0.01-0.29) and parent-reported (B = 0.16, 95% CI: 0.03-0.40) internalizing symptoms through child pain catastrophizing were found (parental modeling mechanism), and were not moderated by child chronic pain status. Significant indirect effects were found between parent pain-attending verbalizations and child self-reported (B = 2.58, 95% CI: 1.03-5.31) and parent-reported (B = 2.18, 95% CI: 0.93-4.27) cold pressor task pain intensity and tolerance (B = -1.02, 95% CI: -1.92 to -0.42) through child pain-attending verbalizations (parental reinforcement mechanism). Although further understanding of the temporal relationships between these variables is needed, the current study identifies constructs (eg, parent pain interference, child pain catastrophizing, and parent reinforcement of child pain) that should be further examined as potential targets for prevention and intervention of pain and internalizing symptoms in children of parents with chronic pain.

Background Pain expectancy may be an important variable that has been found to influence the effectiveness of treatments for pain. Much of the literature supports a self-fulfilment perspective where expectations for pain relief predict the actual pain experienced. However, in conditions such as neuropathic pain (NeP) where pain relief is difficult to attain, expectations for pain relief could be unrealistic. The objective of this study was to investigate the relationship between realistic/unrealistic expectations and 6-month, post-treatment outcomes. Methods We performed a retrospective analysis of a large cohort of patients with NeP (n = 789) attending tertiary care centres to determine the association between unrealistic (both positive and negative) and realistic expectations with outcomes after multidisciplinary treatment. An expectation variable with three categories was calculated: realistic expectations were those whose expected reduction in pain was similar to the observed mean group reduction in pain, while optimistic and pessimistic expectations were those who over- or under-estimated the expected response to treatment, respectively. The association between baseline realistic/unrealistic expectations and 6-month pain-related disability, catastrophizing and psychological distress was assessed. Results Univariable analyses suggested that realistic expectations were associated with lower levels of disability, catastrophizing and psychological distress, compared to unrealistic expectations. However, after adjustment for baseline symptom severity, multivariable analysis revealed that patients with optimistic expectations had lower levels of disability, than those with realistic expectations. Those with pessimistic expectations had higher levels of catastrophizing and psychological distress at follow-up. Conclusions These findings are largely congruent with the self-fulfilment perspective to expectations. Significance This study defined realistic pain expectations with patient data. Examining the relationship between expectations between pain and disability in a large cohort of patients with neuropathic pain.

New regulations are in place at the federal and provincial levels in Canada regarding the way medical cannabis is to be controlled. We present them together with guidance for the safe use of medical cannabis and recent clinical trials on cannabis and pain. The new Canadian regulations on the use of medical cannabis, the provincial regulations, and the various cannabis products available from the Canadian Licensed Producers were reviewed from Health Canada, provincial licensing authorities, and the licensed producers website, respectively. Recent clinical trials on cannabis and pain were reviewed from the existing literature. Health Canada has approved a new regulation on medical marijuana/cannabis, the Marihuana for Medical Purposes Regulations: The production of medical cannabis by individuals is illegal. Health Canada, however, has licensed authorized producers across the country, limiting the production to specific licenses of certain cannabis products. There are currently 26 authorized licensed producers from seven Canadian provinces offering more than 200 strains of marijuana. We provide guidance for the safe use of medical cannabis. The recent literature indicates that currently available cannabinoids are modestly effective analgesics that provide a safe, reasonable therapeutic option for managing chronic non-cancer-related pain. The science of medical cannabis and the need for education of healthcare professionals and patients require continued effort. Although cannabinoids work to decrease pain, there is still a need to confirm these beneficial effects clinically and to exploit them with acceptable benefit-to-risk ratios.

Background:Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers.Methods:Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction.Results:At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012).Conclusion:Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.

Offspring of parents with chronic pain may be at risk for poorer outcomes than offspring of healthy parents. The objective of this research was to provide a comprehensive mixed-methods, systematic synthesis of all available research on outcomes in offspring of parents with chronic pain. A systematic search was conducted for published articles in English examining pain, health, psychological, or family outcomes in offspring of parents with chronic pain. Fifty-nine eligible articles were identified (31 population-based, 25 clinical, 3 qualitative), including offspring from birth to adulthood and parents with varying chronic pain diagnoses (e.g., mixed pain samples, arthritis). Meta-analysis was used to synthesize the results from population-based and clinical studies, while meta-ethnography was used to synthesize the results of qualitative studies. Increased pain complaints were found in offspring of mothers and of fathers with chronic pain, and when both parents had chronic pain. Newborns of mothers with chronic pain were more likely to have adverse birth outcomes, including low birthweight, preterm delivery, caesarean section, intensive care admission, and mortality. Offspring of parents with chronic pain had greater externalizing and internalizing problems and poorer social competence and family outcomes. No significant differences were found on teacher-reported externalizing problems. The meta-ethnography identified six key concepts (developing independence, developing compassion, learning about health and coping, missing out, emotional health, and struggles communicating with parents). Across study designs, offspring of parents with chronic pain had poorer outcomes than other offspring, although the meta-ethnography noted some constructive impact of having a parent with chronic pain.

Objective To evaluate the association between opioid dosage and ongoing therapy with physical function and disability in patients with neuropathic pain (NeP). Design Secondary analysis of a prospective cohort. Setting Multicenter clinical NeP registry. Subjects Seven hundred eighty-nine patients treated for various NeP diagnoses. Methods The following measures were included: dependent variables. 12-month self-reported physical function (pain disability index [PDI] and medical outcomes study short form-12 physical function [PCSS-12]); independent variables: baseline opioid dose (none, ≤200 mg and >200 mg of morphine equivalent), ongoing opioid use; potential confounding variables: age, sex, baseline pain intensity, and psychological distress (profile of mood states). Analysis of covariance models was created to examine the relationship between opioid therapy and both physical functioning outcomes with adjustment for confounding. Results Complete data was available for 535 patients (68%). Compared with the lower and high dose opioid groups, NeP patients not taking opioids had statistically lower disability and higher physical functioning scores, after adjusting for disease severity. Compared with patients prescribed opioid therapy on an ongoing basis, NeP patients who were not prescribed had statistically lower disability and higher physical functioning scores, after adjusting for disease severity. Improvements in disability and physical functioning scores from baseline and 12-months in all groups were modest and may not be clinically significant. Conclusions Physical functioning and disability did not improve in patients with NeP who were prescribed opioids compared with those who are not prescribed, even after adjusting for disease severity.

Chronic pain, including neuropathic pain, has a high prevalence and, therefore, its management is an important public health issue. Aggressive management guided by pain specialists can provide adequate pain relief; however, delays in access to these specialists can negatively impact patient’s well-being. The economic value of managing chronic neuropathic pain in academic centres is discussed, in addition to determining the long term outcomes of this type of pain management., BACKGROUND: The management of chronic pain, including neuropathic pain (NeP), is a major public health issue. However, there is a paucity of data evaluating pain management strategies in real-life settings. OBJECTIVE: To inform policy makers about the economic value of managing chronic NeP in academic centres by conducting a subeconomic assessment of a Canadian multicentre cohort study aimed at determining the long-term outcomes of the management of chronic NeP in academic pain centres. Specific questions regarding the economic value of this type of program were answered by a subset of patients to provide further information to policy makers. METHODS: Baseline demographic information and several pain-related measurements were collected at baseline, three, six and 12 months in the main study. A resource use questionnaire aimed at determining NeP-related costs and the EuroQoL-5 Dimension were collected in the subset study from consenting patients. Statistical analyses were conducted to compare outcomes over time and according to responder status. RESULTS: A total of 298 patients were evaluated in the present economic evaluation. The mean (± SD) age of the participants was 53.7±14.0 years, and 56% were female. At intake, the mean duration of NeP was >5 years. Statistically significant improvements in all pain and health-related quality of life outcomes were observed between the baseline and one-year visits. Use decreased over time for many health care resources (eg, visits to the emergency room decreased by one-half), which resulted in overall cost savings. CONCLUSION: The results suggest that increased access to academic pain centres should be facilitated in Canada.

Primary care physicians have reported a lack of confidence in managing pain, yet it is the topic of one-third of primary care visits. Telephone consultations between pain specialists and primary care physicians may have a significant impact on the care of patients experiencing chronic pain. The authors of this study evaluated this impact using a pragmatic, experimental design to evaluate whether this technique led to benefits for patients compared with wait-list controls., BACKGROUND: The impact of telephone consultations between pain specialists and primary care physicians regarding the care of patients with chronic pain is unknown. OBJECTIVES: To evaluate the impact of telephone consultations between pain specialists and primary care physicians regarding the care of patients with chronic pain. METHODS: Patients referred to an interdisciplinary chronic pain service were randomly assigned to either receive usual care by the primary care physician, or to have their case discussed in a telephone consultation between a pain specialist and the referring primary care physician. Patients completed a numerical rating scale for pain, the Pain Disability Index and the Short Form-36 on referral, as well as three and six months later. Primary care physicians completed a brief survey to assess their impressions of the telephone consultation. RESULTS: Eighty patients were randomly assigned to either the usual care group or the standard telephone consultation group, and 67 completed the study protocol. Patients were comparable on baseline pain and demographic characteristics. No differences were found between the groups at six months after referral in regard to pain, disability or quality of life measures. Eighty percent of primary care physicians indicated that they learned new patient care strategies from the telephone consultation, and 97% reported that the consultation answered their questions and helped in the care of their patient. DISCUSSION: Most primary care physicians reported that a telephone consultation with a pain specialist answered their questions, improved their patients’ care and resulted in new learning. Differences in patient status compared with a usual care control group were not detectable at six-month follow-up. CONCLUSIONS: While telephone consultations are clearly an acceptable strategy for knowledge translation, additional strategies may be required to actually impact patient outcomes.

Objectives: Several tools have been developed to screen for neuropathic pain. This study examined the sensitivity of the Douleur Neuropathique en 4 Questions (DN4) in screening for various neuropathic pain syndromes. Materials and methods: This prospective observational study was conducted in 7 Canadian academic pain centers between April 2008 and December 2011. All newly admitted patients (n=2199) were approached and 789 eligible participants form the sample for this analysis. Baseline data included demographics, disability, health-related quality of life, and pain characteristics. Diagnosis of probable or definite neuropathic pain was on the basis of history, neurological examination, and ancillary diagnostic tests. Results: The mean age of study participants was 53.5 years and 54.7% were female; 83% (n=652/789) screened positive on the DN4 (≥4/10). The sensitivity was highest for central neuropathic pain (92.5%, n=74/80) and generalized polyneuropathies (92.1%, n=139/151), and lowest for trigeminal neuralgia (69.2%, n=36/52). After controlling for confounders, the sensitivity of the DN4 remained significantly higher for individuals with generalized polyneuropathies (odds ratio [OR]=4.35; 95% confidence interval [CI]: 2.15, 8.81), central neuropathic pain (OR=3.76; 95% CI: 1.56, 9.07), and multifocal polyneuropathies (OR=1.72; 95% CI: 1.03, 2.85) compared with focal neuropathies. Discussion: The DN4 performed well; however, sensitivity varied by syndrome and the lowest sensitivity was found for trigeminal neuralgia. A positive DN4 was associated with greater pain catastrophizing, disability and anxiety/depression, which may be because of disease severity, and/or these scales may reflect magnification of sensory symptoms and findings. Future research should examine how the DN4 could be refined to improve its sensitivity for specific neuropathic pain conditions.

Catastrophizing is recognized as a key psychosocial factor associated with pain-related negative outcomes in individuals with chronic pain. Longitudinal studies are needed to better understand the temporal relationship between these constructs. The aim of this study was to determine if changes in catastrophizing early in treatment predicted subsequent changes in pain intensity and interference later in treatment, or alternately, if early changes in pain intensity and interference predicted subsequent changes in catastrophizing. A total of 538 patients with neuropathic pain were recruited from 6 multidisciplinary pain clinics across Canada. Study participants were asked to complete measures of catastrophizing, pain intensity, and interference when first seen in the clinic and then again at 3- and 6-month follow-ups. Cross-lagged panel analyses were used to determine the temporal associations among the study variables. The results showed that decreases in catastrophizing early in treatment prospectively predicted improvement in both pain intensity and interference later in treatment. Converse temporal relationships were also found, where a reduction in pain intensity and interference early in treatment predicted a subsequent diminishing of catastrophizing. All 4 unique cross-lagged correlations significantly accounted for an additional 4% to 7% of the total variance. The findings are consistent with theoretical models hypothesizing a causal impact of catastrophizing on pain, suggesting a mutual causation between these factors. The results support that treatments targeting catastrophizing may influence other pain-related outcomes, and conversely that treatments aiming to reduce pain could potentially influence catastrophizing. There may therefore be multiple paths to positive outcomes.

OBJECTIVES The Canadian STOP-PAIN Project assessed the human and economic burden of chronic pain (CP) in individuals on waitlists of Canadian multidisciplinary pain treatment facilities. This article focuses on sex differences. Objectives were to (1) determine the pain characteristics and related biopsychosocial factors that best differentiated women and men with CP; and (2) examine whether public and private costs associated with CP differed according to sex. MATERIALS AND METHODS Sample consisted of 441 women and 287 men who were evaluated using self-administered questionnaires and a structured interview protocol. A subsample (233 women and 137 men) recorded all pain-related expenditures in a comprehensive diary over 3 months. RESULTS Results revealed that the burden of illness associated with CP was comparable in both sexes for average and worst pain intensity, pain impact on daily living, quality of life, and psychological well-being. The same was true for pain-related costs. The results of a hierarchical logistic regression analysis, in which sex was treated as the dependent variable, showed that factors that differentiated men and women were: work status, certain circumstances surrounding pain onset, present pain intensity, intake of particular types of pain medication, use of certain pain management strategies, pain beliefs, and utilization of particular health care resources. DISCUSSION This study suggests that women and men who are referred to multidisciplinary pain treatment facilities do not differ significantly in terms of their pain-related experience. However, the aspects that differ may warrant further clinical attention when assessing and managing pain.

Background The treatment of chronic pain is still unsatisfactory. Despite the availability of different drugs, most patients with chronic pain do not receive satisfactory pain relief or report side effects. Converging evidence implicates involvement of the immune system in the pathogenesis of different types of nociceptive and neuropathic chronic pain. Design At a workshop in Liverpool, UK (October 2012), experts presented evidence suggesting immunological involvement in chronic pain and recent data supporting the concept that the established immune-modulating drug, polyvalent immunoglobulin G (IgG), either given intravenously (IVIg) or subcutaneously (SCIg), may reduce pain in some peripheral neuropathies and a range of other pain disorders. Workshop's attendees discussed the practicalities of using IVIg and SCIg in these disorders, including indications, cost-effectiveness, and side effects. Results IgG may reduce pain in a range of nociceptive and neuropathic chronic pain conditions, including diabetes mellitus, Sjogren's syndrome, fibromyalgia, complex regional pain syndrome, post-polio syndrome, and pain secondary to pathological autoantibodies. Conclusions IgG is a promising treatment in several chronic pain conditions. IgG is a relatively safe therapeutic strategy, with uncommon and mild side effects but high costs. Randomized, controlled trials and predictive tests are needed to better support the use of IgG for refractory chronic pain.

Neuropathic pain is defined as a lesion or disease of the somatosensory system, and may involve the central or peripheral nervous systems. Treatment of neuropathic pain is a challenge for clinicians involved in affected patients' care. In 2007, the first guidelines for the treatment of neuropathic pain in the Canadian context were produced by the Canadian Pain Society. This update to these guidelines incorporates new evidence published since the first guidelines were released., BACKGROUND: Neuropathic pain (NeP), redefined as pain caused by a lesion or a disease of the somatosensory system, is a disabling condition that affects approximately two million Canadians. OBJECTIVE: To review the randomized controlled trials (RCTs) and systematic reviews related to the pharmacological management of NeP to develop a revised evidence-based consensus statement on its management. METHODS: RCTs, systematic reviews and existing guidelines on the pharmacological management of NeP were evaluated at a consensus meeting in May 2012 and updated until September 2013. Medications were recommended in the consensus statement if their analgesic efficacy was supported by at least one methodologically sound RCT (class I or class II) showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment were based on the degree of evidence of analgesic efficacy, safety and ease of use. RESULTS: Analgesic agents recommended for first-line treatments are gabapentinoids (gabapentin and pregabalin), tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors. Tramadol and controlled-release opioid analgesics are recommended as second-line treatments for moderate to severe pain. Cannabinoids are now recommended as third-line treatments. Recommended fourth-line treatments include methadone, anticonvulsants with lesser evidence of efficacy (eg, lamotrigine, lacos-amide), tapentadol and botulinum toxin. There is support for some analgesic combinations in selected NeP conditions. CONCLUSIONS: These guidelines provide an updated, stepwise approach to the pharmacological management of NeP. Treatment should be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Additional studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes and treatment of pediatric, geriatric and central NeP.

Developing educational interventions about pain may lead to improved pain management for older people. A public group educational session, entitled “Pain in the Older Person,” was presented in 7 cities across Canada (Vancouver, Calgary, London, Toronto, Ottawa, Montreal, and Halifax). The presentation lasted approximately 90 minutes and was followed by a question and answer period of at least 20 minutes. Prior to the educational session, participants provided demographic data and completed measures of pain intensity, frequency, interference, and treatment; of subjective health; and of knowledge about pain. Following the session, participants completed the same knowledge items again as well as items assessing satisfaction. Data were provided by 54 health care workers (HCW) and 54 older community members (66.3 ± 10.2 years old). Prior to the educational session, knowledge gaps were evident among the older community members, especially about analgesic use. Among the HCW, knowledge gaps were found about addiction and the relationship between pain and aging. Comparison of knowledge scores before and after the educational session revealed that both groups demonstrated significant knowledge gains. Satisfaction scores were very high, with no significant difference between HCW and older community members. This is the first study to show that a brief educational intervention is associated with gains in knowledge about pain and aging among both older community members and HCW. These results suggest that a brief public educational session is a promising method of pain education that may reduce barriers to pain management in older people. Perspective This article describes the results of a brief public educational session about pain and aging attended by older members of the community and health care workers. This intervention could potentially improve pain management for older people.

The prevalence of neuropathic pain approaches 10% in Canada and the United States. Given the aging population and the increasing survival rates following interventions for neuropathic pain, the prevalence of neuropathic pain conditions is expected to rise significantly over the next 20 years. Although pharmacological interventions represent the dominant treatment approach for neuropathic pain, as many as 50% of patients are partially or completely refractory to the available treatments. Pain catastrophizing has been associated with heightened pain experiences in patients with neuropathic pain conditions; however, the clinical relevance of the relationship between catastrophizing and poor treatment outcomes is, to date, unclear. Accordingly, using a numerical rating scale, this study aimed to examine this relationship in patients with varied neuropathic pain conditions who completed a measure of catastrophizing before initiating a course of topical analgesic.BACKGROUND: Previous research suggests that high levels of pain catastrophizing might predict poorer response to pharmacological interventions for neuropathic pain.OBJECTIVE: The present study sought to examine the clinical relevance of the relation between catastrophizing and analgesic response in individuals with neuropathic pain. Clinically meaningful reductions were defined in terms of the magnitude of reductions in pain through the course of treatment, and in terms of the number of patients whose end-of-treatment pain ratings were below 4/10.METHODS: Patients (n=82) with neuropathic pain conditions completed a measure of pain catastrophizing at the beginning of a three-week trial examining the efficacy of topical analgesics for neuropathic pain.RESULTS: Consistent with previous research, high scores on the measure of pain catastrophizing prospectively predicted poorer response to treatment. Fewer catastrophizers than noncatastrophizers showed moderate (≥2 points) or substantial reductions in pain ratings through the course of treatment. Fewer catastrophizers than noncatastrophizers achieved end-of-treatment pain ratings below 4/10.CONCLUSIONS: The results of the present study suggest that the development of brief interventions specifically targeting catastrophic thinking might be useful for enhancing the effects of pharmacological interventions for neuropathic pain. Furthermore, failure to account for the level of catastrophizing might contribute to null findings in clinical trials of analgesic medication.

Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, spinal cord injury, or multiple sclerosis. These syndromes are much less common than peripheral etiologies, with less known regarding optimal treatment. The objective of this study was to determine the long-term clinical effectiveness of the management of central relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified from a prospective observational cohort from seven Canadian tertiary centers. Data regarding patient -characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome was the composite of reduced average pain intensity and pain interference. Secondary outcomes included assessments of function, mood, and quality-of-life. Results: At 12-month follow-up, 13.5% (95%CI,5.6-25.8) of patients achieved ≥30% reduction in pain, whereas 38.5% (95%CI,25.3-53.0) achieved a ≥1 point reduction in pain interference; 9.6% (95%CI,3.2-21.0) of patients achieving both these measures. Patients with peripheral neuropathic pain were more likely to achieve this primary outcome at 12-months (25.3% of patients; 95%CI,21.4-29.5) (p=.012). Conclusions: Patients with central neuropathic pain were less likely to achieve a meaningful improvement in pain and function compared to patients with peripheral neuropathic pain at 12-month follow-up.

The Canadian STOP-PAIN Project was designed to document the human and economic burden of chronic pain in individuals on waitlists of Multidisciplinary Pain Treatment Facilities (MPTF). This paper describes the societal costs of their pain. A subgroup of 370 patients was selected randomly from The Canadian STOP-PAIN Project. Participants completed a self-administered costing tool (the Ambulatory and Home Care Record) on a daily basis for three months. They provided information about publicly financed resources, such as health care professional consultations and diagnostic tests as well as privately financed costs, including out-of-pocket expenditures and time devoted to seeking, receiving, and providing care. To determine the cost of care, resources were valued using various costing methods, and multivariate linear regression was used to predict total cost. Overall, the median monthly cost of care was $1,462 (CDN) per study participant. Ninety-five percent of the total expenditures were privately financed. The final regression model consisted of the following determinants: educational level, employment status, province, pain duration, depression, and health-related quality of life. This model accounted for 35% of the variance in total expenditure (P

The Canadian STOP-PAIN Project assessed the human and economic burden of chronic pain in individuals on waitlists of Multidisciplinary Pain Treatment Facilities (MPTF). This article presents the patients’ bio-psycho-social profile. A sample of 728 patients was recruited from waitlists of eight university-affiliated MPTFs across Canada. Subjects completed validated questionnaires to: 1) assess the characteristics and impact of their pain; and 2) evaluate their emotional functioning and quality of life (QoL). Follow-up questionnaires were completed by a subgroup of 271 patients three months later. Close to 2/3 of the participants reported severe pain (≥ 7/10) that interfered substantially with various aspects of their daily living and QoL. Severe or extremely severe levels of depression were common (50.0%) along with suicidal ideation (34.6%). Patients aged > 60 yr were twice as likely to experience severe pain (≥ 7/10) as their younger counterparts (P = 0.002). Patients with frequent sleep problems were more at risk of reporting severe pain (P ≤ 0.003). Intense pain was also associated with a greater tendency to catastrophize (P

OBJECTIVE: The present exploratory, descriptive study aimed to determine the designated time for mandatory pain content in curricula of major Canadian universities for students in health science and veterinary programs before being licensed.METHOD: Major Canadian university sites (n=10) were chosen where health science faculties included at least medicine (n=10) and nursing (n=10); many also included dentistry (n=8), pharmacy (n=7), physical therapy (n=8) and/or occupational therapy (n=6). These disciplines provide the largest number of students entering the workforce but are not the only ones contributing to the health professional team. Veterinary programs (n=4) were also surveyed as a comparison. The Pain Education Survey, developed from previous research and piloted, was used to determine total mandatory pain hours.RESULTS: The majority of health science programs (67.5%) were unable to specify designated hours for pain. Only 32.5% respondents could identify specific hours allotted for pain course content and/or additional clinical conferences. The average total time per discipline across all years varied from 13 h to 41 h (range 0 h to 109 h). All veterinary respondents identified mandatory designated pain content time (mean 87 h, range 27 h to 200 h). The proportion allotted to the eight content categories varied, but time was least for pain misbeliefs, assessment and monitoring/follow-up planning.CONCLUSIONS: Only one-third of the present sample could identify time designated for teaching mandatory pain content. Two-thirds reported ‘integrated’ content that was not quantifiable or able to be determined, which may suggest it is not a priority at that site. Many expressed a need for pain-related curriculum resources.

In many countries timely access to care is a growing problem. As medical costs escalate health care resources must be prioritized. In this context there is an increasing need for benchmarks and best practices in wait-time management. The Canadian Pain Society struck a Task Force in December 2005 to identify benchmarks for acceptable wait-times for treatment of chronic pain. As part of the mandate a systematic review of the literature regarding the relationship between waiting times, health status and health outcomes for patients awaiting treatment for chronic pain was undertaken. Twenty-four studies met the inclusion criteria for the review. The current review supports that patients experience a significant deterioration in health related quality of life and psychological well being while waiting for treatment for chronic pain during the 6 months from the time of referral to treatment. It is unknown at what point this deterioration begins as results from the 14 trials involving wait-times of 10 weeks or less yielded mixed results with wait-times amounting to as little as 5 weeks, associated with deterioration. It was concluded that wait-times for chronic pain treatment of 6 months or longer are medically unacceptable. Further study is necessary to determine at what stage the deterioration begins from the onset of pain to treatment and the impact of waiting on treatment outcomes. Most important is the need to improve access to appropriate care for patients with chronic pain, an escalating public health care problem with significant human and economic costs.

BACKGROUND: Chronic noncancer pain (CNCP) is a global issue, not only affecting individual suffering, but also impacting the delivery of health care and the strength of local economies.OBJECTIVES: The current study (the Canadian Chronic Pain Study II [CCPSII]) was designed to assess any changes in the prevalence and treatment of CNCP, as well as in attitudes toward the use of strong analgesics, compared with a 2001 study (the CCPSI), and to provide a snapshot of the current standards of care for pain management in Canada.METHODS: Standard, computer-assisted telephone interview survey methodology was applied in two segments, ie, a general population survey and a survey targeting randomly selected primary care physicians (PCPs) who treat moderate to severe CNCP.RESULTS AND DISCUSSION: The patient-reported prevalence of CNCP within Canada has not markedly changed since 2001 but the duration of suffering has decreased. There have been minor changes in regional distribution and generally more patients receive medical treatment, which includes prescription analgesics. Physicians continue to demonstrate opiophobia in their prescribing practices; however, although this is lessened relating to addiction, abuse remains an important concern to PCPs. Canadian PCPs, in general, are implementing standard assessments, treatment approaches, evaluation of treatment success and tools to prevent abuse and diversion, in accordance with guidelines from the Canadian Pain Society and other pain societies globally, although there remains room for improvement and standardization.

controlled, parallel-group trial studying the analgesic effects of two different doses of nabilone, a synthetic analogue of THC, in managing acute postoperative pain following major surgery. 5 Unfortunately, the study was prematurely terminated after 18 months. The results of this study demonstrated that nabilone administration was not associated with a decrease in morphine consumption in patients following major surgery. In addition, nabilone at high doses significantly increased pain scores at rest and upon movement. The investigator concluded that, although cannabinoids may be effective in relieving chronic pain in humans, their role in the treatment of acute postoperative pain is uncertain, and requires further clinical evaluation. Small sample size, early termination of the study, and the lack of standardization of surgical procedures with possible variation in intensity of postoperative pain (e.g., total hip replacement vs total knee replacement) may limit the conclusions that can be drawn from this study. Previous studies examining cannabinoids in treating postoperative pain have also demonstrated only a modest analgesic effect. 6 A systematic review concluded that cannabinoids are no more effective than codeine in controlling acute pain, although this was a conclusion based upon only one Phase II study. 7 While the current study suggests a very limited role for cannabinoids in postoperative pain, it is important to recognize that this may change as novel, more potent and more specific synthetic cannabinoid analogs, with limited central nervous system effects, are developed. The role of cannabinoids in managing chronic pain is more promising. A systematic review of studies available prior to 2002 identified seven randomized controlled trials examining cannabinoids in chronic pain. These studies demonstrated that oral THC preparations exhibit a moderate analgesic effect, equivalent

Abstract: Previous research has found that pain can exert a disruptive effect on cognitive processing. This experiment was conducted to extend previous research with participants with chronic pain. This report examines pain's effects on early processing of auditory stimulus differences using the Mismatch Negativity (MMN) in healthy participants while they experienced experimentally induced pain. Event-related potentials (ERPs) were recorded using target and standard tones whose pitch differences were easy- or difficult-to-detect in conditions where participants attended to (active attention) or ignored (passive attention) the stimuli. Both attention manipulations were conducted in no pain and pain conditions. Experimentally induced ischemic pain did not disrupt the MMN. However, MMN amplitudes were larger to difficult-to-detect deviant tones during painful stimulation when they were attended than when they were ignored. Also, MMN amplitudes were larger to the difficult- than to the easy-to-detect tones in the active attention condition regardless of pain condition. It appears that rather than exerting a disruptive effect, the presence of experimentally induced pain enhanced early processing of small stimulus differences in these healthy participants.

Background: A double-blind, randomized, placebo-controlled 3-week study evaluated the efficacy of topical 2% amitriptyline, 1% ketamine, and a combination of both in treating patients with neuropathic pain. Methods: Ninety-two patients with diabetic neuropathy, postherpetic neuralgia, or postsurgical/posttraumatic neuropathic pain with allodynia, hyperalgesia, or pinprick hypesthesia were randomly assigned to receive one of four creams (placebo, 2% amitriptyline, 1% ketamine, or 2% amitriptyline‐1% ketamine combined). The primary outcome measure was change in average daily pain intensity (baseline week vs. final week) using an 11-point numerical pain rating scale. Secondary outcomes included the McGill Pain Questionnaire, measures of allodynia and hyperalgesia, and patient satisfaction. Results: A reduction in pain scores of 1.1‐1.5 units was observed in all groups, and there was no difference between groups. Blood concentrations revealed no significant systemic absorption. Minimal side effects were encountered. Conclusion: This randomized, placebo-controlled trial examining topical 2% amitriptyline, 1% ketamine, and a combination in the treatment of neuropathic pain revealed no difference between groups. Optimization of doses may be required, because another study has revealed that higher concentrations of these agents combined do produce significant analgesia. NEUROPATHIC pain is now understood to involve neural responses in which both peripheral and central mechanisms contribute to the generation of spontaneous pain and evoked aspects of pain, including allodynia and hyperalgesia. 1– 4 The involvement of peripheral mechanisms suggests the use of topical approaches in the treatment of neuropathic pain. Both capsaicin 5,6 and local anesthetics 7–9 can be useful in the relief of neuropathic pain when administered locally to peripheral sites as a cream or a patch, respectively. Additional novel drug classes may also be effective in alleviating neuropathic pain after topical administration. 10 Therefore, tricyclic antidepressants have been shown to produce a peripherally mediated antinociception in preclinical models of ongoing and neuropathic

Objective: The involvement of ongoing peripheral activity in the generation of nociceptive input in neuropathic pain suggests that topical drug delivery may be useful as a treatment strategy. This is a pilot study providing initial information regarding the use of novel topical preparations containing amitriptyline (AMI), ketamine (KET), and a combination of both in the treatment of neuropathic pain. Methods: The study design included a 2 day randomized, double blind, placebo controlled, 4 way cross-over trial of all treatments, followed by an open label treatment phase using the combination cream for 7 days. Twenty volunteers with chronic neuropathic pain were randomly assigned to treatment order and applied 5 mls of each topical treatment (1% AMI, 0.5% KET, combination AMI 1%/KET 0.5%, and placebo) for 2 days. Measures of pain at the end of each block included the short form McGill Pain Questionnaire (MPQ) and visual analog scales (VAS) for present pain intensity and pain relief. Eleven subjects who judged subjective improvement from any treatment in the initial trial entered the open-label trial and used the combination cream for 7 days. Pain levels were recorded daily using the same measures. Blood levels for amitriptyline and ketamine were performed at 7 days to determine whether systemic absorption had occurred. Results: There was no statistically significant difference from placebo after 2 days for any treatment during the double blind component of the trial. In the 11 subjects who used the combination cream, there was a statistically significant effect, with subjects reporting significantly greater analgesia by days 3 to 7 according to measures of pain and pain relief. Blood levels revealed that there was no significant systemic absorption of amitriptyline or ketamine. Only 2 subjects experienced side effects; these were minor and did not lead to discontinuation of the cream. Conclusion: This pilot study demonstrated a lack of effect for all treatments in the 2 day double blind placebo controlled trial, followed by analgesia in an open label trial in a subgroup of subjects who chose to use the combination cream for 7 days. Blood analysis revealed no significant systemic absorption of either agent after 7 days of treatment, and creams were well tolerated. A larger scale randomized trial over a longer interval is warranted to examine further effects observed in the open label trial.

Adenosine analogs produce analgesic actions in nociceptive paradigms and alleviate manifestations of neuropathic pain in nerve injury models in rodents. In humans, previous work indicates an analgesic effect for adenosine administered intravenously in postoperative and neuropathic pain. In this double blind placebo controlled crossover trial, we used an enriched enrolment design to determine the effects of intravenous adenosine (50 microg/kg/min over 60min) on neuropathic pain. In Phase 1 of the trial, adenosine was administered in an open label manner, while in Phase 2 adenosine was administered in a double blind placebo controlled manner to 23 adenosine responders who had experienced a 30% or greater response in the open trial. Outcome measures included the McGill pain questionnaire (MPQ), which generates a pain rating index (PRI), and contains a visual analog scale (VAS) of pain intensity, the neuropathy pain scale (NPS), and a VAS for pain relief. Subjects also graded the degree of allodynia and hyperalgesia using a VAS. Adenosine led to a significant reduction in spontaneous pain according to the MPQ-PRI, the MPQ-VAS and the VAS for pain relief. The NPS showed a pattern similar to the MPQ-PRI, with statistically significant reductions in scales 1 (intensity), 3 (hot), 6 (sensitive), 7 (itchy) and 9 (unpleasant). Adenosine also led to a significant reduction in pinprick hyperalgesia, but not in allodynia. Three patients from Phase 1 of the trial experienced long term resolution of their pain following intravenous adenosine (5,16,25 months). The results of this study support previous reports that indicate intravenous adenosine alleviates neuropathic pain and hyperalgesia.

BACKGROUND: Varicella zoster virus (VZV) is the etiological agent for both varicella (chickenpox) and herpes zoster (HZ) (shingles). HZ results from the reactivation of VZV acquired during childhood. Postherpetic neuralgia (PHN) is the most common complication of HZ infection in immunocompetent patients. There is no universally accepted definition of PHN. While the mechanisms producing pain associated with PHN are not fully understood, peripheral and central processes are thought to be important.METHODS: The literature on the pathophysiology and the treatment of postherpetic neuralgia was reviewed for the past 30 years by using Index Medicus.CONCLUSIONS: Many modalities to treat PHN are available; none of them are very effective. The most commonly used modalities are tricyclic antidepressants, anticonvulsants, opioid analgesics, topical medications, physical modalities such as acupuncture and transcutaneous nerve stimulation, and nerve blocks. The tricyclic antidepressants have the most evidence supporting their role in treating PHN, although only half of the patients with PHN benefit. Recent studies support the use of opioid analgesics in PHN. There is a growing body of evidence in support of the use of gabapentin for PHN. Physical modalities and topical medications are probably most useful as adjuncts to centrally acting agents, not as a primary treatment modality. Injections (nerve blocks) are effective in relieving PHN anecdotally, although there are no controlled clinical trials showing efficacy.