Counting your chickens before they hatch: improvements in an untreated chronic pain population, beyond regression to the mean and the placebo effect.

Introduction: Isolating the effect of an intervention from the natural course and fluctuations of a condition is a challenge in any clinical trial, particularly in the field of pain. Regression to the mean (RTM) may explain some of these observed fluctuations. Objectives: In this paper, we describe and quantify the natural trajectory of questionnaire scores over time, based on initial scores. Methods: Twenty-seven untreated chronic low back pain patients and 25 healthy controls took part in this observational study, wherein they were asked to complete an array of questionnaires commonly used in pain studies during each of 3 visits (V1, V2, V3) at the 2-month interval. Scores at V1 were classified into 3 subgroups (extremely high, normal, and extremely low), based on z-scores. The average delta (∆ = V2 - V1) was calculated for each subgroup, for each questionnaire, to describe the evolution of scores over time based on initial scores. This analysis was repeated with the data for V2 and V3. Results: Our results show that high initial scores were widely followed by more average scores, while low initial scores tended to be followed by similar (low) scores. Conclusion: These trajectories cannot be attributable to RTM alone because of their asymmetry, nor to the placebo effect as they occurred in the absence of any intervention. However, they could be the result of an Effect of Care, wherein participants had meaningful improvements simply from taking part in a study. The improvement observed in patients with high initial scores should be carefully taken into account when interpreting results from clinical trials.

Paraspinal Muscle Changes in Individuals with and without Chronic Low Back Pain over a 4-Month Period: A Longitudinal MRI Study.

Background and Objectives: Previous research has shown associations between atrophy and fatty infiltration of the lumbar paraspinal musculature and low back pain (LBP). However, few studies have examined longitudinal changes in healthy controls and individuals with LBP without intervention. We aimed to investigate the natural variations in lumbar paraspinal musculature morphology and composition in this population over a 4-month period. Materials and Methods: Healthy controls and individuals with LBP were age- and sex-matched and completed several self-administered questionnaires. MRIs of L1-L5 were taken at baseline, 2 months, and 4 months to investigate cross-sectional area (CSA), along with DIXON fat and water images. A total of 29 participants had clear images for at least one level for all three time points. Means and standard deviations were calculated for the participant demographics. A two-way repeated measures ANOVA was performed to investigate CSA, fat signal fraction, and CSA asymmetry. Results: A total of 27 images at L3/L4, 28 images at L4/L5, and 15 images at L5/S1 were included in the final analysis. There were significant main effects of group for psoas CSA at the L3/L4 level (p = 0.02) and erector spinae (ES) CSA % asymmetry at the L3/L4 level (p < 0.001). There was a significant main effect of time for lumbar multifidus (LM) CSA % asymmetry at L4/L5 level (p = 0.03). Conclusions: This study provides insights into LM, ES, and psoas morphology in both healthy controls and affected individuals over a 4-month period without any intervention. Our findings suggest that psoas CSA at higher lumbar levels and CSA % asymmetry in general may be a better indicator of pathology and the development of pathology over time. Evaluating natural variations in paraspinal musculature over longer time frames may provide information on subtle changes in healthy controls and affected individuals and their potential role in chronic LBP.

The assessment of paraspinal muscle epimuscular fat in participants with and without low back pain: A case-control study.

It remains unclear whether paraspinal muscle fatty infiltration in low back pain (LBP) is i) solely intramuscular, ii) is lying outside the epimysium between the muscle and fascial plane (epimuscular) or iii) or combination of both, as imaging studies often use different segmentation protocols that are not thoroughly described. Epimuscular fat possibly disturbs force generation of paraspinal muscles, but is seldomly explored. This project aimed to 1) compare epimuscular fat in participants with and without chronic LBP, and 2) determine whether epimuscular fat is different across lumbar spinal levels and associated with BMI, age, sex and LBP status, duration or intensity. Fat and water lumbosacral MRIs of 50 chronic LBP participants and 41 healthy controls were used. The presence and extent of epimuscular fat for the paraspinal muscle group (erector spinae and multifidus) was assessed using a qualitative score (0-5 scale; 0 = no epimuscular fat and 5 = epimuscular fat present along the entire muscle) and quantitative manual segmentation method. Chi-squared tests evaluated associations between qualitative epimuscular fat ratings and LBP status at each lumbar level. Bivariate and partial spearman's rho correlation assessed relationships between quantitative and qualitative epimuscular fat with participants' characteristics. Epimuscular fat was more frequent at the L4-L5 (X2 = 13.781, p = 0.017) and L5-S1 level (X2 = 27.825, p < 0.001) in participants with LBP compared to controls, which was not found for the higher lumbar levels. The total qualitative score (combined from all levels) showed a significant positive correlation with BMI, age, sex (female) and LBP status (r = 0.23-0.55; p < 0.05). Similarly, the total area of epimuscular fat (quantitative measure) was significantly correlated with BMI, age and LBP status (r = 0.26-0.57; p < 0.05). No correlations were found between epimuscular fat and LBP duration or intensity. Paraspinal muscle epimuscular fat is more common in chronic LBP patients. The functional implications of epimuscular fat should be further explored.

The Canadian version of the National Institutes of Health minimum dataset for chronic low back pain research: reference values from the Quebec Low Back Pain Study.

ABSTRACT: The National Institutes of Health (NIH) minimum dataset for chronic low back pain (CLBP) was developed in response to the challenge of standardizing measurements across studies. Although reference values are critical in research on CLBP to identify individuals and communities at risk of poor outcomes such as disability, no reference values have been published for the Quebec (Canada) context. This study was aimed to (1) provide reference values for the Canadian version of the NIH minimum dataset among individuals with CLBP in Quebec, both overall and stratified by gender, age, and pain impact stratification (PIS) subgroups, and (2) assess the internal consistency of the minimum data set domains (pain interference, physical function, emotional distress or depression, sleep disturbance, and PIS score). We included 2847 individuals living with CLBP who completed the baseline web survey of the Quebec Low Back Pain Study (age: 44.0 ± 11.2 years, 48.1% women) and were recruited through social media and healthcare settings. The mean score was 6.1 ± 1.8 for pain intensity. Pain interference, physical function, emotional distress or depression, sleep disturbance, and PIS scores were 12.9 ± 4.1, 14.4 ± 3.9, 9.8 ± 4.4, 13.0 ± 3.6, and 26.4 ± 6.6, respectively. Emotional distress or depression showed floor effects. Good-to-excellent internal consistency was found overall and by language, gender, and age subgroups for all domains (alpha: 0.81-0.93) and poor-to-excellent internal consistency for PIS subgroups (alpha: 0.59-0.91). This study presents reference values and recommendations for using the Canadian version of the NIH minimum dataset for CLBP that can be useful for researchers and clinicians.

Transcutaneous electrical nerve stimulation (TENS): towards the development of a clinic-friendly method for the evaluation of excitatory and inhibitory pain mechanisms.

Background: Temporal summation and conditioned pain modulation (CPM) can be measured using a thermode and cold pressor test (CPTest). Unfortunately, these complex and expensive tools are ill-suited for routine clinical assessments. Aims: We aimed to compare the temporal summation and CPM obtained with the thermode + CPTest paradigm to those obtained with a novel paradigm using transcutaneous electrical nerve stimulation (TENS). Methods: We assessed temporal summation and CPM in 29 healthy participants, using two paradigms (random order): TENS, and thermode + CPTest. In the TENS paradigm, both the conditioning stimulus (CS) and the test stimulus (TS) were delivered using TENS; in the thermode + CPTest paradigm, the CS consisted of a CPTest and the TS was delivered using a thermode. We compared the average temporal summation and CPM evoked by the two paradigms. Results: Average temporal summation was similar for both modalities (P = 0.90), and the number of participants showing temporal summation was similar in both paradigms (19 with thermode vs. 18 with TENS; P = 1.00). Average CPM response was larger following the thermode + CPTest than following the TENS (P = 0.005), and more participants showed CPM with the thermode + CPTest paradigm compared to the TENS paradigm (24 vs. 14; P = 0.01). Conclusions: Both paradigms were roughly equivalent in the ability to evoke temporal summation (although response to one modality did not predict response to the other), but the TENS paradigm appeared to be less apt to induce a CPM response than the thermode + CPTest paradigm.

Contexte: La sommation temporelle et la modulation de la douleur conditionnée (MDC) peuvent être mesurées à l'aide d'une thermode et d'un test au froid. Malheureusement, ces tests complexes et coûteux sont mal adaptés aux évaluations cliniques de routine.Objectifs: Nous avons cherché à comparer la sommation temporelle et la modulation de la douleur conditionnée obtenues avec le paradigme thermode + test au froid à ceux obtenus avec un nouveau paradigme utilisant la neurostimulation électrique transcutanée (TENS).Méthodes: Nous avons évalué la sommation temporelle et la modulation de la douleur conditionnée chez 29 participants en bonne santé, en utilisant les deux paradigmes (ordre aléatoire) : TENS, et thermode + test au froid. Dans le paradigme TENS, Le stimulus de conditionnement et le stimulus d'essai ont été transmis à l'aide de la neurostimulation électrique transcutanée ; dans le paradigme thermode + test au froid, le stimulus de conditionnement consistait en un test au froid et le stimulus d'essai était transmis à l'aide d'une thermode. Nous avons comparé la sommation temporelle et la modulation de la douleur conditionnée moyennes évoqués par les deux paradigmes.Résultats: La sommation temporelle moyenne était similaire pour les deux modalités (P = 0,90), et le nombre de participants ayant montré une sommation temporelle étaient similaires dans les deux paradigmes (19 avec la thermode contre 18 avec la TENS; P = 1,00). La réponse moyenne de modulation de la douleur conditionnée était plus importante après la thermode + test au froid qu'après la neurostimulation électrique transcutanée (P = 0,005), et un plus grand nombre de participants ont montré une modulation de la douleur conditionnée avec la thermode + test au froid par rapport au paradigme TENS (24 contre 14 ; P = 0,01).Conclusions: Les deux paradigmes sont à peu près équivalents en ce qui concerne la capacité d'évoquer la sommation temporelle (bien que la réaction à une modalité ne prévoie pas la réaction à l'autre), mais le paradigme TENS semble moins apte à induire une réponse de modulation de la douleur conditionnée que le paradigme thermode + test au froid.

Comparison of Thermal and Electrical Modalities in the Assessment of Temporal Summation of Pain and Conditioned Pain Modulation.

Temporal summation of pain (TSP) and conditioned pain modulation (CPM) can be measured using a thermode and a cold pressor test (CPT). Unfortunately, these tools are complex, expensive, and are ill-suited for routine clinical assessments. Building on the results from an exploratory study that attempted to use transcutaneous electrical nerve stimulation (TENS) to measure CPM and TSP, the present study assesses whether a "new" TENS protocol can be used instead of the thermode and CPT to measure CPM and TSP. The objective of this study was to compare the thermode/CPT protocol with the new TENS protocol, by (1) measuring the association between the TSP evoked by the two protocols; (2) measuring the association between the CPM evoked by the two protocols; and by (3) assessing whether the two protocols successfully trigger TSP and CPM in a similar number of participants. We assessed TSP and CPM in 50 healthy participants, using our new TENS protocol and a thermode/CPT protocol (repeated measures and randomized order). In the TENS protocol, both the test stimulus (TS) and the conditioning stimulus (CS) were delivered using TENS; in the thermode/CPT protocol, the TS was delivered using a thermode and the CS consisted of a CPT. There was no association between the response evoked by the two protocols, neither for TSP nor for CPM. The number of participants showing TSP [49 with TENS and 29 with thermode (p < 0.001)] and CPM [16 with TENS and 30 with thermode (p = 0.01)] was different in both protocols. Our results suggest that response to one modality does not predict response to the other; as such, TENS cannot be used instead of a thermode/CPT protocol to assess TSP and CPM without significantly affecting the results. Moreover, while at first glance it appears that TENS is more effective than the thermode/CPT protocol to induce TSP, but less so to induce CPM, these results should be interpreted carefully. Indeed, TSP and CPM response appear to be modality-dependent as opposed to an absolute phenomenon, and the two protocols may tap into entirely different mechanisms, especially in the case of TSP.

Development and Validation of a Predictive Model of Pain Modulation Profile to Guide Chronic Pain Treatment: A Study Protocol.

Introduction: Quantitative sensory testing is frequently used in research to assess endogenous pain modulation mechanisms, such as Temporal Summation (TS) and Conditioned Pain Modulation (CPM), reflecting excitatory and inhibitory mechanisms, respectively. Numerous studies found that a dysregulation of these mechanisms is associated with chronic pain conditions. In turn, such a patient's "profile" (increased TS and/or weakened CPM) could be used to recommend different pharmacological treatments. However, the procedure to evaluate these mechanisms is time-consuming and requires expensive equipment that is not available in the clinical setting. In this study, we aim to identify psychological, physiological and socio-demographic markers that could serve as proxies to allow healthcare professionals to identify these pain phenotypes in clinic, and consequently optimize pharmacological treatments. Method: We aim to recruit a healthy participant cohort (n = 360) and a chronic pain patient cohort (n = 108). Independent variables will include psychological questionnaires, pain measurements, physiological measures and sociodemographic characteristics. Dependent variables will include TS and CPM, which will be measured using quantitative sensory testing in a single session. We will evaluate one prediction model and two validation models (for healthy and chronic pain participants) using multiple regression analysis between TS/CPM and our independent variables. The significance thresholds will be set at p = 0.05, respectively. Perspectives: This study will allow us to develop a predictive model to compute the pain modulation profile of individual patients based on their biopsychosocial characteristics. The development of the predictive model is the first step toward the overarching goal of providing clinicians with a set of quick and cheap tests, easily applicable in clinical practice to orient pharmacological treatments.