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Reconnecting the Brain With the Rest of the Body in Musculoskeletal Pain Research
Helene M.Langevin
doi : 10.1016/j.jpain.2020.02.006
Volume 22, Issue 1, January 2021, Pages 1-8
A challenge in understanding chronic musculoskeletal pain is that research is often siloed between neuroscience, physical therapy/rehabilitation, orthopedics, and rheumatology which focus respectively on 1) neurally mediated effects on pain processes, 2) behavior and muscle activity, 3) tissue structure, and 4) inflammatory processes. Although these disciplines individually study important aspects of pain, there is a need for more cross-disciplinary research that can bridge between them. Identifying the gaps in knowledge is important to understand the whole body, especially at the interfaces between the silos—between brain function and behavior, between behavior and tissue structure, between musculoskeletal and immune systems, and between peripheral tissues and the nervous system. Research on “mind and body” practices can bridge across these silos and encourage a “whole person” approach to better understand musculoskeletal pain by bringing together the brain and the rest of the body.
Inter-Individual Differences in the Responses to Pain Neuroscience Education in Adults With Chronic Musculoskeletal Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
James AWatson*Cormac GRyan*GregAtkinson*PhilipWilliamson‡DominicEllington†RobbieWhittle†JohnDixon*Denis JMartin*
doi : 10.1016/j.jpain.2020.03.006
Volume 22, Issue 1, January 2021, Pages 9-20
Pain neuroscience education (PNE) is an approach used in the management of chronic musculoskeletal pain. Previous reviews on PNE and other pain interventions, have focused on mean treatment effects, but in the context of “precision medicine,” any inter-individual differences in treatment response are also important to quantify. If inter-individual differences are present, and predictors identified, PNE could be tailored to certain people for optimizing effectiveness. Such heterogeneity can be quantified using recently formulated approaches for comparing the response variance between the treatment and control groups. Therefore, we conducted a systematic review and meta-analysis on the extracted standard deviations of baseline-to-follow up change to quantify the inter-individual variation in pain, disability and psychosocial outcomes in response to PNE. Electronic databases were searched between January 1, 2002 and June 14, 2018. The review included 5 randomized controlled trials (n?=?428) in which disability outcomes were reported. Using a random effects meta-analysis, the pooled SD (95% confidence interval) for control group-adjusted response heterogeneity to PNE was 7.36 units /100 (95% confidence interval?=??3.93 to 11.12). The 95% prediction interval for this response heterogeneity SD was wide (?10.20 to 14.57 units /100). The control group-adjusted proportion of “responders” in the population who would be estimated to exceed a clinically important change of 10/100 ranged from 18 to 45%. Therefore, when baseline-to-follow up random variability in disability is taken into account (informed by the control arm), there is currently insufficient evidence for the notion of clinically important inter-individual differences in disability responses to PNE in people with chronic musculoskeletal pain. The protocol was published on PROSPERO (CRD42017068436).
Exercise-Induced Hypoalgesia in Healthy Individuals and People With Chronic Musculoskeletal Pain: A Systematic Review and Meta-Analysis
Michael A.Wewege*†Matthew D.Jones*†
doi : 10.1016/j.jpain.2020.04.003
Volume 22, Issue 1, January 2021, Pages 21-31
Exercise-induced hypoalgesia (EIH) is a reduction in pain that occurs during or following exercise. Randomized controlled studies published from 1980 to January 2020 that examined experimentally induced pain before and during/following a single bout of exercise in healthy individuals or people with chronic musculoskeletal pain were systematically reviewed. Data were analyzed using random-effects meta-analyses and studies were appraised using the Cochrane Risk of Bias tool and GRADE. Five thousand eight hundred twenty-nine records were screened, with 13 studies ultimately included. In healthy individuals, aerobic exercise caused large EIH (7 studies, 236 participants; g?=??.85 [?1.58, ?.13]), dynamic resistance exercise caused small EIH (2 studies, 23 participants; g?=??.45 [?.69, ?.22]), and isometric exercise did not cause EIH (3 studies, 177 participants; g?=??.16 [?.36,.05]). In chronic musculoskeletal pain, isometric exercise did not cause EIH (3 studies, 114 participants; g?=??.41 [?1.08,.25]); aerobic (0 studies) and dynamic resistance (1 study) exercise were not analyzed. We conclude that, based on small studies with unclear risk of bias, aerobic and dynamic resistance exercise reduce experimental pain in healthy individuals. Further research is needed to determine whether EIH exists for experimental and clinical pain in people with chronic musculoskeletal pain.
NMDA Receptor Modulates Spinal Iron Accumulation Via Activating DMT1(-)IRE in Remifentanil-Induced Hyperalgesia
RuichenShu*†LinlinZhang‡HaoZhang§YuanLi*†ChunyanWang‡LinSu‡HongweiZhao*†GuolinWang‡
doi : 10.1016/j.jpain.2020.03.007
Volume 22, Issue 1, January 2021, Pages 32-47
N-methyl-D-aspartate (NMDA) receptor activation is known to be critical in remifentanil-induced hyperalgesia. Evidence indicates that iron accumulation participates in NMDA neurotoxicity. This study aims to investigate the role of iron accumulation in remifentanil-induced hyperalgesia. Remifentanil was delivered intravenously in rats to induce hyperalgesia. The NMDA receptor antagonist MK-801 was intrathecally administrated. The levels of divalent metal transporter 1 without iron-responsive element [DMT1(-)IRE] and iron were detected. Behavior testing was performed in DMT1(-)IRE knockdown rats and rats treated with iron chelator DFO. Meanwhile, the spinal dorsal horn neurons were cultured and transfected with DMT1(-)IRE siRNA, and then respectively incubated with remifentanil and MK-801. The levels of intracellular Ca2+ and iron were assessed by fluorescence imaging. Our data revealed that spinal DMT1(-)IRE and iron content significantly increased in remifentanil-treated rats, and MK-801 inhibited the enhancements. DMT1(-)IRE knockdown and DFO prevented against remifentanil-induced hyperalgesia. Notably, the levels of Ca2+ and iron increased in remifentanil-incubated neurons, and these growths can be blocked by MK-801. DMT1(-)IRE knockdown attenuated iron accumulation but did not influence Ca2+ influx. This study suggests that DMT1(-)IRE-mediated iron accumulation is likely to be the downstream event following NMDA receptor activation and Ca2+ influx, contributing to remifentanil-induced hyperalgesia.
Development and Psychometric Evaluation of the PROMIS Pediatric Pain Intensity Measure in Children and Adolescents with Chronic Pain
Constance A.Mara*†SusmitaKashikar-Zuck*†‡NatoshiaCunningham*†Kenneth R.Goldschneider*‡BinHuang*§CarltonDampier¶David D.Sherry?LoriCrosby*†JenniferFarrell Miller??KimberlyBarnett††Esi M.Morgan*‡‡
doi : 10.1016/j.jpain.2020.04.001
Volume 22, Issue 1, January 2021, Pages 48-56
The goal of the current study was to enhance the measurement of the pediatric chronic pain experience through a methodologically rigorous approach. This paper outlines the development and initial validation of a pain intensity measure for pediatric patients with chronic pain using Patient-Reported Outcomes Measurement Information System methodology. Measure development incorporated feedback from children with painful conditions. Based on input from pediatric participants and content experts, 4 candidate items assessing pain intensity were included for large scale testing. Children completed self-report items pertaining to their pain experience that were developed as part of a larger pool of new candidate Patient-Reported Outcomes Measurement Information System pediatric pain domain items as well as measures of pain interference, depressive symptoms, fatigue, pain behavior, pain intensity, and pain catastrophizing. The final sample for the large scale testing included N?=?442 pediatric patients between the ages 8 to 18 years (Mean age?=?13.54, Standard Deviation?=?2.78; 71.27% female) experiencing chronic pain. Psychometric analysis resulted in a final measure that included 3 items with evidence of reliability (Cronbach alpha?=?.82) and convergent validity. The Likert format of the response options may be preferable to the traditional numeric rating scale for use in pediatric populations who experience chronic pain based on patients’ feedback, which was directly utilized in designing the scale. Further, the inclusion of fewer and clinically meaningful response options should reduce ambiguity for young respondents.
An Initial Psychometric Evaluation of the Pain Concepts Questionnaire in a Low-SES Setting
Andrea K.Newman*Calia A.Morais†Benjamin P.Van Dyke‡Beverly E.Thorn*
doi : 10.1016/j.jpain.2020.05.002
Volume 22, Issue 1, January 2021, Pages 57-67
The examination of pain beliefs for chronic pain assessment and treatment has been a growing area of interest. A variety of questionnaires have been developed to assess pain beliefs, however, these questionnaires often require high levels of literacy and education. The pain concepts questionnaire (PCQ) was developed with literacy-adaptations to better evaluate pain beliefs in a low socioeconomic (SES) population. This study is an initial exploratory evaluation of the PCQ in a sample of patients with chronic pain and multiple disparities as part of the learning about my pain (LAMP) trial, a randomized controlled trial comparing literacy-adapted psychosocial treatments for chronic pain. All data were collected at pretreatment. Exploratory factor analysis was performed to examine the underlying factor structure of the PCQ and cross-sectional correlational analyses examined relationships between pain beliefs with sociodemographic factors and chronic pain-related variables. Results suggested a 2-factor solution with a Biopsychosocial factor and Biomedical factor. Consistent with the literature, correlational analyses highlighted racial and SES disparities in pain beliefs and the importance of beliefs in pain- and cognitive/affective-related functioning. The study emphasizes the importance of pain beliefs in chronic pain management and recommends future research to further examine additional psychometric properties of the PCQ.
Exposure to Contact Sports Results in Maintained Performance During Experimental Pain
ClaireThornton*DavidSheffield†AndrewBaird†
doi : 10.1016/j.jpain.2020.03.008
Volume 22, Issue 1, January 2021, Pages 68-75
During pain, motor performance tends to decline. However, athletes who engage in contact sports are able to maintain performance despite the inherent pain that accompanies participation. This may be the result of being challenged rather than threatened by pain; adaptive coping strategies; habituation to pain; or finding pain less bothersome. This study aimed to measure performance of a novel motor task both in pain and not in pain within experienced contact athletes (n?=?40), novice contact athletes (n?=?40), and noncontact athletes (n?=?40). Challenge and threat perceptions were manipulated during the pain condition and measures of pain tolerance, perception, coping styles, and bothersomeness were taken. Results indicated that contact athletes, regardless of experience, were able to maintain their performance during painful stimulation. Noncontact athletes, conversely, performed significantly worse during pain stimulation. In addition, contact athletes tended to be more challenged and the noncontact athletes more threatened within the pain condition. Experienced contact athletes demonstrated higher levels of pain tolerance and direct coping, and reported lower levels of pain bothersomeness and intensity than the other groups. The results suggest that even relatively brief exposure to contact sports may be enough to help maintain performance in pain. Being in a challenged state appears to be an important factor during performance in pain. Moreover, pain tolerance, intensity, and bothersomeness may differentiate novice and experienced athletes.
Chronic Musculoskeletal Pain and Foot Reaction Time in Older Adults
YurunCai*†Suzanne G.Leveille†‡§Jeffrey M.Hausdorff¶**Jonathan F.Bean††‡‡§§BradManor§‡¶¶Robert R.McLean§‡¶¶TongjianYou***
doi : 10.1016/j.jpain.2020.05.003
Volume 22, Issue 1, January 2021, Pages 76-85
This cross-sectional study examines the association between chronic musculoskeletal pain and foot reaction time (RT) among older community-living adults. Participants were 307 adults aged 71 years and older in the MOBILIZE Boston Study II. Pain severity, interference, and location were measured by the Brief Pain Inventory and a joint pain questionnaire. With participants seated, simple foot reaction time was measured as self-selected foot response time to an intermittent light, and choice foot reaction time was measured as response time to the light on the corresponding side of the sensored gait mat. We performed multivariable linear regression to determine associations of pain and foot RT, adjusted for sociodemographic and health characteristics, and serially adjusted for cognitive function (MMSE or Trail Making A). Pain severity and interference were associated with slower simple foot reaction time (P < .05). Pain severity and knee pain were associated with slower choice foot reaction time (P < .05). Adjustment for cognitive measures had little impact on the pain-RT relationship. This significant relationship was only observed among participants with less education. These results support the idea that chronic pain may lead to slower foot RT, thus could represent a fall hazard in older adults. Neuromotor mechanisms underlying the pain-fall relationship warrant further investigation.
Transcranial Direct Current Stimulation and Visual Illusion Effect According to Sensory Phenotypes in Patients With Spinal Cord Injury and Neuropathic Pain
DolorsSoler*†DavidMori?a‡HaticeKumru*†JoanVidal*†XavierNavarro*§
doi : 10.1016/j.jpain.2020.06.004
Volume 22, Issue 1, January 2021, Pages 86-96
Treatment of neuropathic pain (NP) in patients with spinal cord injury (SCI) remains a major challenge. The aim of the present study is to investigate if the effect of transcranial direct current stimulation combined with visual illusion, following a previously published protocol, has differential effects on pain-related sensory symptoms according to sensory phenotypes profiles. One hundred and thirty SCI patients with NP participated in this open-label trial. Sixty-five patients were given a daily 20-minutes combined treatment of transcranial direct current stimulation and visual illusion for 2 weeks. Sixty-five patients served as a control group. Clinical assessment was performed before and 2 weeks later, by using Neuropathic Pain Symptom Inventory (NPSI), Brief Pain Inventory, and Patient Health Questionnaire-9. There was significant improvement in the combined treatment group according to NPSI, Brief Pain Inventory, and Patient Health Questionnaire-9, but no changes in the control group. Following a cluster analysis of NPSI items at baseline assessment, 5 subgroups of patients with different pain-related characteristics were identified among the treated group, although differences between clusters were not significant. There was also improvement in mood, sleep quality, and enjoyment of life in the treated group. Despite a reduction of NP with the combined treatment, the analysis of sensory phenotype pain profiles does not provide a predictive value regarding the analgesic results of this combined neuromodulatory treatment.
En Pointe: Dancers Report Their Pain Less Variably Than Do Controls
RitaCanaipa*1DiogoMendonça†1MarianaAgostinho†VandaNascimento‡LiatHonigman§RoiTreister§
doi : 10.1016/j.jpain.2020.06.005
Volume 22, Issue 1, January 2021, Pages 97-105
The subjective nature of pain and the lack of a gold standard for objective measurement hinders effective assessment, diagnosis, and treatment. Some individuals, such as professional dancers, are better in assessing and reporting bodily sensations. This observational study aimed to assess whether dancers report their pain less variably, than other people do.
