Publications

2023

Karayannis, Nicholas Vasilis, John A Sturgeon, Mike K Kemani, Sean C Mackey, Carol M Greco, Rikard K Wicksell, and Lance M McCracken. (2023) 2023. “Pain Acceptance and Psychological Inflexibility Predict Pain Interference Outcomes for Persons With Chronic Pain Receiving Pain Psychology”. Scandinavian Journal of Pain 23 (3): 464-75. https://doi.org/10.1515/sjpain-2022-0107.

OBJECTIVES: Awareness (being present), acceptance, and engagement (committed action) are three dimensions of psychological flexibility. Understanding these in the context of chronic pain may identify treatment targets to help refine individual treatment. Our objective was to test the predictive capacity of three dimensions within the psychological flexibility model on the longitudinal trajectory of pain interference.

METHODS: Patients receiving pain psychology treatment at a pain management center participated in this pragmatic clinical longitudinal study (n=86 with at least three assessments; Mean age=51 years; Gender=60 females, 26 males). Measures included the Five Facet Mindfulness Questionnaire (FFMQ-SF); Chronic Pain Acceptance Questionnaire (CPAQ-8); Psychological Inflexibility in Pain Scale (PIPS-12); and Committed Action Questionnaire (CAQ-8). The dependent variable was the Patient Reported Outcomes Information System (PROMIS) Pain Interference (PI). We used latent growth modelling to analyze scores assessed within 180 days of patient care.

RESULTS: Psychological inflexibility (PIPS-12) and pain acceptance (CPAQ-8) measured at baseline predicted PI outcomes (n=86). PIPS-12 showed a direct relationship with pain interference (PI), where higher PIPS-12 scores predicted significantly higher PI mean scores on average across the study period ( ρ =0.422, r2=0.382) but also predicted significantly greater decreases in PI across time ( ρ =-0.489, r2=0.123). Higher CPAQ-8 scores predicted significantly lower PI mean scores on average across the study period ( ρ =-0.478, r2=0.453) but also significantly smaller decreases in PI across time ( ρ =0.495, r2=0.076). Awareness (FFMQ-SF) and engagement (CAQ-8) were not predictive of PI outcomes.

CONCLUSIONS: Patients who entered pain psychology treatment with lower pain acceptance and higher psychological inflexibility showed the largest reductions in pain interference across time. These results contribute towards a novel prognostic understanding of the predictive roles of an enhancing dimension and limiting dimension of psychological flexibility.

2022

Mackey, Sean, Gadi Gilam, Beth Darnall, Philippe Goldin, Jiang-Ti Kong, Christine Law, Marissa Heirich, et al. (2022) 2022. “ Mindfulness-Based Stress Reduction, Cognitive Behavioral Therapy, and Acupuncture in Chronic Low Back Pain: Protocol for Two Linked Randomized Controlled Trials ”. JMIR Research Protocols 11 (9): e37823. https://doi.org/10.2196/37823.

BACKGROUND: Nonpharmacologic mind-body therapies have demonstrated efficacy in low back pain. However, the mechanisms underlying these therapies remain to be fully elucidated.

OBJECTIVE: In response to these knowledge gaps, the Stanford Center for Low Back Pain-a collaborative, National Institutes of Health P01-funded, multidisciplinary research center-was established to investigate the common and distinct biobehavioral mechanisms of three mind-body therapies for chronic low back pain: cognitive behavioral therapy (CBT) that is used to treat pain, mindfulness-based stress reduction (MBSR), and electroacupuncture. Here, we describe the design and implementation of the center structure and the associated randomized controlled trials for characterizing the mechanisms of chronic low back pain treatments.

METHODS: The multidisciplinary center is running two randomized controlled trials that share common resources for recruitment, enrollment, study execution, and data acquisition. We expect to recruit over 300 chronic low back pain participants across two projects and across different treatment arms within each project. The first project will examine pain-CBT compared with MBSR and a wait-list control group. The second project will examine real versus sham electroacupuncture. We will use behavioral, psychophysical, physical measure, and neuroimaging techniques to characterize the central pain modulatory and emotion regulatory systems in chronic low back pain at baseline and longitudinally. We will characterize how these interventions impact these systems, characterize the longitudinal treatment effects, and identify predictors of treatment efficacy.

RESULTS: Participant recruitment began on March 17, 2015, and will end in March 2023. Recruitment was halted in March 2020 due to COVID-19 and resumed in December 2021.

CONCLUSIONS: This center uses a comprehensive approach to study chronic low back pain. Findings are expected to significantly advance our understanding in (1) the baseline and longitudinal mechanisms of chronic low back pain, (2) the common and distinctive mechanisms of three mind-body therapies, and (3) predictors of treatment response, thereby informing future delivery of nonpharmacologic chronic low back pain treatments.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02503475; https://clinicaltrials.gov/ct2/show/NCT02503475.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37823.

2019

Karayannis, Nicholas, V, Isabel Baumann, John A Sturgeon, Markus Melloh, and Sean C Mackey. (2019) 2019. “ The Impact of Social Isolation on Pain Interference: A Longitudinal Study ”. Annals of Behavioral Medicine : A Publication of the Society of Behavioral Medicine 53 (1): 65-74. https://doi.org/10.1093/abm/kay017.

BACKGROUND: Evidence suggests social interactions play an important role in pain perception.

PURPOSE: The aim of this study was to determine whether social isolation (SI) in people with persistent pain determines pain interference (PI) and physical function over time.

METHODS: Patients seeking care at a tertiary pain management referral center were administered the Patient Reported Outcome Measurement Information System (PROMIS®) SI, PI, physical function, depression, and average pain intensity item banks at their initial consultation and subsequent visits as part of their routine clinical care. We used a post hoc simulation of an experiment using propensity score matching (n = 4,950) and carried out a cross-lagged longitudinal analysis (n = 312) of retrospective observational data.

RESULTS: Cross-lagged longitudinal analysis showed that SI predicted PI at the next time point, above and beyond the effects of pain intensity and covariates, but not vice versa.

CONCLUSIONS: These data support the importance of SI as a factor in pain-related appraisal and coping and demonstrate that a comprehensive assessment of the individuals' social context can provide a better understanding of the differential trajectories for a person living with pain. Our study provides evidence that the impact of pain is reduced in individuals who perceive a greater sense of inclusion from and engagement with others. This study enhances the understanding of how social factors affect pain and have implications for how the effectiveness of therapeutic interventions may be improved. Therapeutic interventions aimed at increasing social connection hold merit in reducing the impact of pain on engagement with activities.

2018

Known, Not. (2018) 2018. “ Orthopaedic Section Platform Presentations (Abstracts OPL1-OPL64) ”. The Journal of Orthopaedic and Sports Physical Therapy 48 (1): A1-A29. https://doi.org/10.2519/jospt.2018.48.1.A1.

These abstracts are presented here as prepared by the authors. The accuracy and content of each abstract remain the responsibility of the authors. In the identification number above each abstract, OPL designates an Orthopaedic Section platform presentation. J Orthop Sports Phys Ther 2018;48(1):A1-A29. doi:10.2519/jospt.2018.48.1.A1.

Karayannis, Nicholas, V, Gwendolen A Jull, Michael K Nicholas, and Paul W Hodges. (2018) 2018. “ Psychological Features and Their Relationship to Movement-Based Subgroups in People Living With Low Back Pain ”. Archives of Physical Medicine and Rehabilitation 99 (1): 121-28. https://doi.org/10.1016/j.apmr.2017.08.493.

OBJECTIVE: To determine the distribution of higher psychological risk features within movement-based subgroups for people with low back pain (LBP).

DESIGN: Cross-sectional observational study.

SETTING: Participants were recruited from physiotherapy clinics and community advertisements. Measures were collected at a university outpatient-based physiotherapy clinic.

PARTICIPANTS: People (N=102) seeking treatment for LBP.

INTERVENTIONS: Participants were subgrouped according to 3 classification schemes: Mechanical Diagnosis and Treatment (MDT), Treatment-Based Classification (TBC), and O'Sullivan Classification (OSC).

MAIN OUTCOME MEASURES: Questionnaires were used to categorize low-, medium-, and high-risk features based on depression, anxiety, and stress (Depression, Anxiety, and Stress Scale-21 Items); fear avoidance (Fear-Avoidance Beliefs Questionnaire); catastrophizing and coping (Pain-Related Self-Symptoms Scale); and self-efficacy (Pain Self-Efficacy Questionnaire). Psychological risk profiles were compared between movement-based subgroups within each scheme.

RESULTS: Scores across all questionnaires revealed that most patients had low psychological risk profiles, but there were instances of higher (range, 1%-25%) risk profiles within questionnaire components. The small proportion of individuals with higher psychological risk scores were distributed between subgroups across TBC, MDT, and OSC schemes.

CONCLUSIONS: Movement-based subgrouping alone cannot inform on individuals with higher psychological risk features.

Kong, Jiang-Ti, Brandon MacIsaac, Ruti Cogan, Amanda Ng, Christine Sze Wan Law, Joseph Helms, Rosa Schnyer, et al. (2018) 2018. “Central Mechanisms of Real and Sham Electroacupuncture in the Treatment of Chronic Low Back Pain: Study Protocol for a Randomized, Placebo-Controlled Clinical Trial”. Trials 19 (1): 685. https://doi.org/10.1186/s13063-018-3044-2.

BACKGROUND: Chronic low back pain (CLBP) is the most common chronic pain condition and is often resistant to conventional treatments. Acupuncture is a popular alternative for treating CLBP but its mechanisms of action remain poorly understood. Evidence suggests that pain regulatory mechanisms (particularly the ascending and secondarily the descending pain modulatory pathways) and psychological mechanisms (e.g., expectations, pain catastrophizing and self-efficacy) may be involved in the pathogenesis of CLBP and its response to treatments. We will examine these mechanisms in the treatment of CLBP by electroacupuncture (EA).

METHODS: We present the aims and methods of a placebo-controlled, participant-blinded and assessor-blinded mechanistic study. Adult patients with CLBP will be randomized to receiving 16 sessions of real (active) or sham (placebo) EA over the course of 8 weeks. The primary pain regulatory measure for which the study was powered is temporal summation (TS), which approximates ascending pain facilitation. Conditioned pain modulation (CPM), representing a descending pain modulatory pathway, will be our secondary pain regulatory measure. The primary psychological measure is expectations of benefit, and the secondary psychological measures are pain catastrophizing and self-efficacy in managing pain. Main clinical outcomes are back pain bothersomeness on a 0-100 visual analog scale (primary), Roland Morris Disability Questionnaire (secondary), and relevant items from the National Institutes of Health (NIH) Patient-Reported Outcome Measures Information System (secondary). We hypothesize that compared to sham, real EA will lead to greater reduction in TS after 8 treatment sessions (4 weeks); and that reduction in TS (and secondarily, increase in CPM) after 8 treatment sessions will mediate reduction in back pain bothersomeness from baseline to week 10 (clinical response) to EA. We also hypothesize that the three psychological factors are moderators of clinical response. With 100 treatment completers, the study is designed to have 80% power to detect a medium-sized between-group effect (d = 0.5) on temporal summation.

DISCUSSION: To the best of our knowledge, this is the first appropriately powered, placebo-controlled clinical trial evaluating mechanisms of EA in the treatment of CLBP.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02503475 . Registered on 15 July 15 2015. Retrospectively registered.

2017

Zheng, Patricia, Ming-Chih Kao, Nicholas Karayannis V, and Matthew Smuck. (2017) 2017. “ Stagnant Physical Therapy Referral Rates Alongside Rising Opioid Prescription Rates in Patients With Low Back Pain in the United States 1997-2010 ”. Spine 42 (9): 670-74. https://doi.org/10.1097/BRS.0000000000001875.

STUDY DESIGN: A cross-sectional observational study utilizing the National Ambulatory and National Hospital Ambulatory Medical Care Surveys between 1997 and 2010.

OBJECTIVE: The aim of this study was to characterize national physical therapy (PT) referral trends during primary care provider (PCP) visits in the United States.

SUMMARY OF BACKGROUND DATA: Despite guidelines recommending PT for the initial management of low back pain (LBP), national PT referral rates remain low.

METHODS: Race, ethnicity, age, payer type, and PT referral rates were collected for patients aged 16 to 90 years who were visiting their PCPs. Associations among demographic variables and PT referral were determined using logistic regression.

RESULTS: Between 1997 and 2010, we estimated 170 million visits for LBP leading to 17.1 million PT referrals. Average proportion of PCP visits associated with PT referrals remained stable at about 10.1% [odds ratio (OR) 1.00, 95% confidence interval (95% CI) 0.96-1.04)], despite our prior finding of increasing number of visits associated with opioid prescriptions in the same timeframe.Lower PT referral rates were observed among visits by patients who were insured by Medicaid (OR 0.48, 95% CI 0.33-0.69) and Medicare (OR 0.50, 95% CI 0.35-0.72). Furthermore, visits not associated with PT referrals were more likely to be associated with opioid prescriptions (OR 1.69, 95% CI 1.22-2.35).

CONCLUSION: Although therapies delivered by PTs are promoted as a first-line treatment for LBP, PT referral rates remain low. There also exist disparately lower referral rates in populations with more restrictive health plans and simultaneous opioid prescription. Our findings provide a broad overview to PT prescription trend and isolate concerning associations requiring further explorations.

LEVEL OF EVIDENCE: 3.

Karayannis, Nicholas, V, John A Sturgeon, Ming Chih-Kao, Corinne Cooley, and Sean C Mackey. (2017) 2017. “Pain Interference and Physical Function Demonstrate Poor Longitudinal Association in People Living With Pain: A PROMIS Investigation”. Pain 158 (6): 1063-68. https://doi.org/10.1097/j.pain.0000000000000881.

A primary goal in managing pain is to reduce pain and increase physical function (PF). This goal is also tied to continuing payment for treatment services in many practice guidelines. Pain interference (PI) is often used as a proxy for measurement and reporting of PF in these guidelines. A common assumption is that reductions in PI will translate into improvement in PF over time. This assumption needs to be tested in a clinical environment. Consequently, we used the patient-reported outcomes measurement information system (PROMIS) to describe the topology of the longitudinal relationship between PI in relation to PF. Longitudinal data of 389 people with chronic pain seeking health care demonstrated that PI partially explained the variance in PF at baseline (r = -0.50) and over 90 days of care (r = -0.65). The relationship between pain intensity and PF was not significant when PI was included as a mediator. A parallel process latent growth curve model analysis showed a weak, unidirectional relationship (β = 0.18) between average PF scores and changes in PI over the course of 90 days of care, and no relationship between average PI scores and changes in PF across time. Although PI and PF seem moderately related when measured concurrently, they do not cluster closely together across time. The differential pathways between these 2 domains suggest that therapies that target both the consequences of pain on relevant aspects of persons' lives, and capability to perform physical activities are likely required for restoration of a vital life.