Investigating the hypoalgesic effects of spinal manipulative therapy using hidden pain conditioning and positive expectation in patients with chronic low back pain: protocol for a randomised controlled trial

Introduction Placebo effects are responses capable of modulating pain and influencing treatment response. Two mechanisms are commonly related to placebo effects: expectations and conditioning. However, the research in this field is focused on laboratory studies with healthy participants. This study aims to identify whether a conditioning procedure with positive induced expectations about spinal manipulative therapy (SMT) will result in greater hypoalgesic effects in adults with chronic low back pain (CLBP) in a clinical trial design. Methods and analysis This trial will enrol 264 patients with non-specific CLBP, aged 18–60 years. Patients will undergo a calibration test to determine the thermal pain threshold for the hidden pain conditioning procedure. Afterward, they will be randomised to one of the three groups: hidden pain conditioning with positive induced expectations—group one (G1); positive expectations—group two (G2) and neutral expectations—group three (G3). Patients will receive instructions to manipulate the expectations. The pretreatment heat pain test will be performed before the SMT and after the intervention patients will undergo again the heat pain intensity test. However, only patients in G1 will receive hidden pain conditioning to reinforce the association between SMT and pain intensity reduction. All patients will undergo five sessions of SMT. The outcomes will be assessed immediately after the last session and at the 6 weeks and 3-month follow-ups. All statistical analyses will be conducted following intention-to-treat principles, and the treatment effects will be determined with linear mixed models. Ethics and dissemination The Federal University of São Carlos approved this research (Process n° 52359521.1.0000.5504). All participants will give written informed consent. Dissemination of the results will include publications in peer-reviewed journals and presentations at conferences. If positive expectations and classical conditioning improve outcomes, it may support the administration of such intervention. Trial registration number NCT05202704.

[1]  C. Killingback,et al.  Impact of contextual factors on patient outcomes following conservative low back pain treatment: systematic review , 2022, Chiropractic & Manual Therapies.

[2]  Grant D. Huang,et al.  Sequential and comparative evaluation of pain treatment effectiveness response (SCEPTER), a pragmatic trial for conservative chronic low back pain treatment. , 2019, Contemporary clinical trials.

[3]  Michael J. Schneider,et al.  Interventions for the Management of Acute and Chronic Low Back Pain: Revision 2021. , 2021, The Journal of orthopaedic and sports physical therapy.

[4]  Kia-Chong Chua,et al.  Psychometric properties of the PHQ-9 measure of depression among Brazilian older adults , 2021, Aging & mental health.

[5]  G. Moseley,et al.  Imprecise visual feedback about hand location increases a classically conditioned pain expectancy effect. , 2021, The journal of pain.

[6]  Z. Zimmer,et al.  Pain Trends Among American Adults, 2002–2018: Patterns, Disparities, and Correlates , 2020, Demography.

[7]  E. Balman,et al.  National Institute for Health and Care Excellence (NICE) , 2017, The Grants Register 2022.

[8]  Eun Sug Park,et al.  Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019 , 2020, Lancet.

[9]  F. Benedetti,et al.  Context matters: the psychoneurobiological determinants of placebo, nocebo and context-related effects in physiotherapy , 2020, Archives of Physiotherapy.

[10]  F. Blyth,et al.  Global low back pain prevalence and years lived with disability from 1990 to 2017: estimates from the Global Burden of Disease Study 2017 , 2020, Annals of translational medicine.

[11]  P. Bąbel.  Classical Conditioning as a Distinct Mechanism of Placebo Effects , 2019, Front. Psychiatry.

[12]  F. Benedetti,et al.  Magnitude, response, and psychological determinants of placebo effects in chronic low-back pain: a randomised, double-blinded, controlled trial , 2019, Pain reports.

[13]  J. Hartvigsen,et al.  Expectations influence treatment outcomes in patients with low back pain. A secondary analysis of data from a randomized clinical trial , 2019, European journal of pain.

[14]  D. Altman,et al.  Reporting of Multi-Arm Parallel-Group Randomized Trials: Extension of the CONSORT 2010 Statement , 2019, JAMA.

[15]  Michiel R de Boer,et al.  Benefits and harms of spinal manipulative therapy for the treatment of chronic low back pain: systematic review and meta-analysis of randomised controlled trials , 2019, BMJ.

[16]  L. Wiles,et al.  What does best practice care for musculoskeletal pain look like? Eleven consistent recommendations from high-quality clinical practice guidelines: systematic review , 2019, British Journal of Sports Medicine.

[17]  P. Tugwell,et al.  Measurement Properties of Visual Analogue Scale, Numeric Rating Scale, and Pain Severity Subscale of the Brief Pain Inventory in Patients With Low Back Pain: A Systematic Review. , 2019, The journal of pain : official journal of the American Pain Society.

[18]  A. Malfliet,et al.  The Influence of Treatment Expectations on Clinical Outcomes and Cortisol Levels in Patients With Chronic Neck Pain: An Experimental Study , 2019, Pain practice : the official journal of World Institute of Pain.

[19]  Kevin E. Wilk Pt Dpt.  Clinical Orthopaedic Rehabilitation: A Team Approach, 4th Edition , 2019, Medicine & Science in Sports & Exercise.

[20]  Martin Underwood,et al.  What low back pain is and why we need to pay attention , 2018, The Lancet.

[21]  Jessica Gerber,et al.  Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study , 2018, NeuroImage: Clinical.

[22]  G. Rossettini,et al.  Clinical relevance of contextual factors as triggers of placebo and nocebo effects in musculoskeletal pain , 2018, BMC Musculoskeletal Disorders.

[23]  S. George,et al.  Unraveling the Mechanisms of Manual Therapy: Modeling an Approach , 2018, The Journal of orthopaedic and sports physical therapy.

[24]  J. Chenot,et al.  Non-Specific Low Back Pain. , 2017, Deutsches Arzteblatt international.

[25]  L. Florêncio,et al.  Concomitant Migraine and Temporomandibular Disorders are Associated With Higher Heat Pain Hyperalgesia and Cephalic Cutaneous Allodynia , 2016, The Clinical journal of pain.

[26]  G. Rossettini,et al.  Enhance placebo, avoid nocebo: How contextual factors affect physiotherapy outcomes. , 2016, Manual therapy.

[27]  M. Rovers,et al.  Relieving patients' pain with expectation interventions: a meta-analysis , 2016, Pain.

[28]  G. Salum,et al.  Factor structure, reliability, and item parameters of the brazilian-portuguese version of the GAD-7 questionnaire , 2016 .

[29]  R. Gollub,et al.  Not seeing or feeling is still believing: conscious and non-conscious pain modulation after direct and observational learning , 2015, Scientific Reports.

[30]  David R. Nerenz,et al.  Trajectories of Symptoms and Function in Older Adults With Low Back Disorders , 2015, Spine.

[31]  J. Smoller,et al.  Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue Conditioning and Their Association , 2013, PloS one.

[32]  A. Filgueiras,et al.  Positive and Negative Affect Schedule: Psychometric Properties for the Brazilian Portuguese Version , 2013, The Spanish Journal of Psychology.

[33]  D. Rennie,et al.  SPIRIT 2013 statement: defining standard protocol items for clinical trials. , 2013, Annals of internal medicine.

[34]  G. Moseley,et al.  A Randomized-controlled Trial of Using a Book of Metaphors to Reconceptualize Pain and Decrease Catastrophizing in People With Chronic Pain , 2013, The Clinical journal of pain.

[35]  J. S. Skouen,et al.  Efficacy of classification-based cognitive functional therapy in patients with non-specific chronic low back pain: A randomized controlled trial , 2012, European journal of pain.

[36]  Sean Mackey,et al.  Development of the Stanford Expectations of Treatment Scale (SETS): A tool for measuring patient outcome expectancy in clinical trials , 2012, Clinical trials.

[37]  F. Fregni,et al.  Cross-cultural adaptation and validation of the Brazilian Portuguese version of the pain catastrophizing scale. , 2012, Pain medicine.

[38]  Tor D. Wager,et al.  How expectations shape pain , 2012, Neuroscience Letters.

[39]  K. Wiech,et al.  The Effect of Treatment Expectation on Drug Efficacy: Imaging the Analgesic Benefit of the Opioid Remifentanil , 2011, Science Translational Medicine.

[40]  V F Sadil,et al.  Maitland's Vertebral Manipulation , 2010 .

[41]  D. Price,et al.  The mechanisms of manual therapy in the treatment of musculoskeletal pain: a comprehensive model. , 2009, Manual therapy.

[42]  J. Crippa,et al.  Study of the discriminative validity of the PHQ-9 and PHQ-2 in a sample of Brazilian women in the context of primary health care. , 2009, Perspectives in psychiatric care.

[43]  C. Maher,et al.  Global Rating of Change Scales: A Review of Strengths and Weaknesses and Considerations for Design , 2009, The Journal of manual & manipulative therapy.

[44]  M. Ferreira,et al.  Clinimetric Testing of Three Self-report Outcome Measures for Low Back Pain Patients in Brazil: Which One Is the Best? , 2008, Spine.

[45]  Domenica Le Pera,et al.  Learning potentiates neurophysiological and behavioral placebo analgesic responses , 2008, PAIN.

[46]  S. George,et al.  The influence of expectation on spinal manipulation induced hypoalgesia: An experimental study in normal subjects , 2008, BMC musculoskeletal disorders.

[47]  F. Benedetti.  Mechanisms of placebo and placebo-related effects across diseases and treatments. , 2008 .

[48]  Peter Croft,et al.  Interpreting Change Scores for Pain and Functional Status in Low Back Pain: Towards International Consensus Regarding Minimal Important Change , 2008, Spine.

[49]  M. Nicholas,et al.  Pain‐related self‐efficacy beliefs in a Brazilian chronic pain patient sample: a psychometric analysis , 2007 .

[50]  N. M. Alexandre,et al.  Development of a Brazilian Portuguese Version of the Oswestry Disability Index: Cross-Cultural Adaptation, Reliability, and Validity , 2007, Spine.

[51]  Luci Fuscaldi Teixeira-Salmela,et al.  Análise das propriedades psicométricas da versão brasileira da escala tampa de cinesiofobia , 2007 .

[52]  S. George,et al.  Immediate effects of spinal manipulation on thermal pain sensitivity: an experimental study , 2006, BMC musculoskeletal disorders.

[53]  R. Fillingim,et al.  What is controlled for in placebo-controlled trials? , 2005, Mayo Clinic proceedings.

[54]  J. Haafkens,et al.  Patient Expectations of Treatment for Back Pain: A Systematic Review of Qualitative and Quantitative Studies , 2004, Spine.

[55]  Walter Grassi,et al.  Minimal clinically important changes in chronic musculoskeletal pain intensity measured on a numerical rating scale , 2004, European journal of pain.

[56]  J. Fritz,et al.  Comparison of Classification-Based Physical Therapy With Therapy Based on Clinical Practice Guidelines for Patients with Acute Low Back Pain: A Randomized Clinical Trial , 2003, Spine.

[57]  J. Fritz,et al.  A Clinical Prediction Rule for Classifying Patients with Low Back Pain Who Demonstrate Short-Term Improvement With Spinal Manipulation , 2002, Spine.

[58]  J. Whitman.  Pregnancy, low back pain, and manual physical therapy interventions. , 2002, The Journal of orthopaedic and sports physical therapy.

[59]  D. Watson,et al.  Development and validation of brief measures of positive and negative affect: the PANAS scales. , 1988, Journal of personality and social psychology.

[60]  S. McCleave.  Spinal manipulation. , 1981, Canadian family physician Medecin de famille canadien.

[61]  Ronald Dubner,et al.  Ratio scales of sensory and affective verbal pain descriptors , 1978, Pain.