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.

The effects of an 8-week knitting program on osteoarthritis symptoms in elderly women: A pilot randomized controlled trial.

BACKGROUND: Exercise therapy is effective in reducing symptoms and disability associated with hand osteoarthritis (HOA) but often has low adherence. An intervention consisting in a meaningful occupation, such as knitting, may improve adherence to treatment. This pilot randomized controlled trial (RCT) studied the adherence and clinical effectiveness of a knitting program in older females suffering from HOA to evaluate the acceptability of this intervention and assess the feasibility of a larger-scale RCT. METHODS: Single-blind, two-arm pilot RCT with a parallel group design with 37 participants (18 control, 19 intervention). Control participants were given an educational pamphlet and assigned to a waiting list. The knitting program (8-week duration) had two components: bi-weekly 20-min group knitting sessions and daily 20-min home knitting session on the 5 remaining weekdays. Measures included knitting adherence (implementation outcomes) as well as stiffness, pain, functional status, hand physical activity level, patient's global impression of change, health-related quality of life, self-efficacy, and grip strength (clinical outcomes measured throughout the 8-week program and 4 weeks after the intervention). RESULTS: Our protocol is feasible and the intervention was acceptable and enjoyable for participants, who showed high adherence. No difference was observed between the two groups for any of the clinical outcome measures (all p > .05). CONCLUSION: Knitting is a safe and accessible activity for older women with HOA. However, our 8-week knitting program did not result in improvements in any of our outcome measures. Knitting for a longer period and/or with higher frequency may yield better outcomes.

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.

The effect of conditioning stimulus intensity on conditioned pain modulation (CPM) hypoalgesia.

Background: The magnitude and duration of conditioned pain modulation (CPM) likely depends on the nature and intensity of the conditioning stimulus (CS). Aims: The aim of this study was to measure the effect of CS intensity on the duration of CPM hypoalgesia. Methods: In this single-blind, nonrandomized, repeated measures study, we assessed CPM hypoalgesia in 20 healthy participants following cold pressor tests (CPT) at 7°C and 12°C. The test stimulus, a 60-s heat stimulation, was administered before the CPT and immediately after, and again at 5-min intervals until participants' pain scores returned to pre-CS levels. Two hypoalgesia thresholds were used to establish return to pre-CS level: within -10/100 of baseline and within -20/100 of baseline. Results: CPM hypoalgesia, when defined as a reduction in pain levels >10/100, did not last longer following the more intense 7°C CPT compared to the 12°C CPT (32 min vs. 20 min, respectively; P = 0.06); similar results were obtained when CPM hypoalgesia was defined as a reduction in pain levels of >20/100 (16 min following the 7°C CPT vs. 9 min following the 12°C CPT; P = 0.33). The duration of CPM hypoalgesia was significantly longer when the 10/100 threshold was used compared to the 20/100 threshold, regardless of CPT temperature (P = 0.008 for the 12°C CPT; P < 0.001 for the 7°C CPT). Conclusions: The more intense CS did not induce CPM hypoalgesia of longer duration compared to the less intense CS. The choice of threshold for what constitutes CPM hypoalgesia did have a significant effect on the results.

Contexte: L'ampleur et la durée de la modulation de la douleur conditionnée (MDC) dépendent probablement de la nature et de l'intensité du stimulus de conditionnement.Objectifs: Le but de cette étude était de mesurer l'effet de l'intensité du stimulus de conditionnement sur la durée de l'hypoalgésie par MDC.Méthodes: Dans cette étude en simple aveugle, non randomisée, à mesures répétées, nous avons évalué l'hypoalgésie par MDC chez 20 participants en bonne santé à la suite de tests au froid à 7 ° C et 12 ° C. Le stimulus du test, une stimulation thermique de 60 secondes, a été administré avant le test au froid et immédiatement après, puis à nouveau à des intervalles de cinq minutes jusqu'à ce que les scores de douleur des participants reviennent aux niveaux antérieurs au stimulus de conditionnement.Deux seuils d'hypoalgésie ont été utilisés pour établir le retour au niveau antérieur au stimulus de conditionnement : à l'intérieur de - 10 / 100 de la situation de départ et à l'intérieur de - 20 / 100 de la situation de départ.Résultats: L'hypoalgésie par MDC, définie comme une réduction des niveaux de douleur > 10 / 100, n'a pas duré plus longtemps après le test au froid plus intense de 7 ° C que le test au froid de 12 ° C (32 minutes comparativement à 20 minutes, respectivement ; P = 0,06) ; des résultats similaires ont été obtenus lorsque l'hypoalgésie par MDC était définie comme une réduction des niveaux de douleur > 20 / 100 (16 minutes après le test au froid à 7 ° C comparativement à 9 minutes après le test au froid à 12 ° C ; P = 0,33).La durée de l'hypoalgésie par MDC était significativement plus longue lorsque le seuil 10 / 100 était utilisé comparativement au seuil 20 / 100, quelle que soit la température du test au froid (P = 0,008 pour le test au froid à 12 ° C ; P < 0,001 pour le test au froid à 7 ° C).Conclusions: Le stimulus de conditionnement plus intense n'a pas induit d'hypoalgésie par MDC de plus longue durée comparativement au stimulus de conditionnement moins intense. Le choix du seuil pour ce qui constitue une hypoalgésie par MDC a eu un effet significatif sur les résultats.

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.

Combining transcutaneous electrical nerve stimulation with therapeutic exercise to reduce pain in an elderly population: a pilot study.

PURPOSE: Chronic pain is a highly prevalent and debilitating condition, and there is a pressing need to find safe, effective and affordable treatments to tackle this public health issue. This pilot study aimed to assess whether therapeutic exercises supplemented by transcutaneous electrical nerve stimulation induces a greater hypoalgesic effect than therapeutic exercises supplemented by sham transcutaneous electrical nerve stimulation, in an elderly population suffering from chronic pain. MATERIALS AND METHODS: Eighteen elderly participants suffering from chronic pain completed a therapeutic exercise program consisting of 45-min group sessions administered twice a week for 4 weeks. Half of the participants received real transcutaneous electrical nerve stimulation during the exercise sessions, while the others received sham transcutaneous electrical nerve stimulation. Participants completed pain questionnaires (McGill Pain Questionnaire, Brief Pain Inventory, Beck Depression Index) before and after the intervention, and recorded their pain levels on an 11-point numerical rating scale before and after each session (Clinical Trial.Gov ID: NCT02445677). RESULTS AND CONCLUSION: Our results suggest that supplementing exercise sessions with transcutaneous electrical nerve stimulation does not improve the long-term outcomes of elderly patients suffering from chronic pain, but does induce short-term hypoalgesia during exercise sessions. Our study also offers valuable guidelines for the implementation of a future and adequately powered study looking at this research question.Implications for rehabilitationThe application of transcutaneous electrical nerve stimulation during exercises is well tolerated by elderly individuals suffering from chronic pain.Supplementing exercises with transcutaneous electrical nerve stimulation does not seem to improve general outcome in elderly suffering from chronic pain.Notwithstanding, the addition of transcutaneous electrical nerve stimulation tends to produce a marked hypoalgesic effect during the exercise sessions, an effect that could prompt indirect benefits for pain patients.

Decreased Initial Peak Pain Sensation with Aging: A Psychophysical Study.

BACKGROUND AND PURPOSE: Aging is associated with an impairment of diverse physiological functions, including nociception. For example, older adults in comparison to young adults, show an overall increase in pain thresholds, reflecting a decline in pain sensitivity and changes in the nociceptive pathways. These results are, however, debated as they were not always replicated depending on the stimulus modality, duration, and location. The aim of the current study was to determine how the temporal evolution of pain intensity during a continuous tonic heat pain test is influenced by aging. More specifically, we wanted to 1) assess the effect of age on initial peak and late-phase pain and 2) determine whether potential age effects depend on the stimulation site. PARTICIPANTS AND METHODS: 13 young adults (average of 27.9 years old) and 13 older adults (average of 67.5 years old) participated in this study. Experimental heat pain was evoked on an appendicular (forearm) and axial (lower-back) body region, using a thermode (2-minute stimulation at a constant, individually-adjusted temperature). During the nociceptive stimulation, participants used a computerized visual analogue scale to continuously rate their pain. RESULTS: We show that initial peak (0-30 seconds) pain sensation was significantly lower in older adults compared to young adults, while late-phase (30-120 seconds) pain sensation was similar across the two age groups. These results hold true for both stimulation sites, suggesting the existence of an age effect on both appendicular and axial body regions. CONCLUSION: The lower magnitude of initial peak pain observed in older adults, which affects both appendicular and axial body regions, could reflect generalized peripheral or central alterations of the nociceptive system in older adults. These alterations in older adults could have significant clinical impacts, such as an increased vulnerability to injury or an underestimation of the severity of their pain condition.

Perturbing the activity of the superior temporal gyrus during pain encoding prevents the exaggeration of pain memories: A virtual lesion study using single-pulse transcranial magnetic stimulation.

BACKGROUND: Past studies have shown that pain memories are often inaccurate, a phenomenon known as mnemonic pain bias. Pain memories are thought to play an important role on how future pain is felt. Recent evidence from our laboratory suggests that individuals who exaggerate past pain display increased superior temporal gyrus (STG) activity during the encoding of experimental painful stimulations, suggesting that this brain structure plays an important role in pain memories. OBJECTIVE: /hypothesis. To determine whether a virtual lesion paradigm, targeting the STG during pain encoding, can affect long-lasting pain memories. We hypothesized that interfering with the activity of the STG would attenuate mnemonic bias. METHODS: Randomized double-blind study with two parallel groups. Participants received either sham (n = 21) or real (n = 21) transcranial magnetic stimulation (TMS - virtual lesion paradigm) over the STG during pain encoding (milliseconds after the administration of a painful stimuli). Pain intensity and unpleasantness were evaluated using a visual analog scale (VAS; 0 to 10) immediately after the painful event, and at recall, 2 months later. The mnemonic pain bias (calculated by subtracting the pain scores obtained at recall from the pain score obtained during encoding) was compared between the two groups for both pain intensity and unpleasantness. RESULTS: Participants in both groups did not differ in terms of age and gender (real TMS = 27 years ±â€¯9, 43% female; sham TMS = 25 years ±â€¯4, 49% female; p > 0.64). The mnemonic bias related to pain intensity was similar in both groups (p = 0.83). However, the mnemonic bias related to pain unpleasantness was lower in the real TMS group (p = 0.04). CONCLUSIONS: Our results provide the first evidence that the STG, is causally involved in the formation of biased memories of pain unpleasantness.