Optimization of Spinal Manipulative Therapy Protocols: A Factorial Randomized Trial Within a Multiphase Optimization Framework

Published:December 09, 2020DOI:


      • Research has typically studied SMT as a unimodal treatment.
      • Clinicians usually provide SMT as part of a multimodal treatment package.
      • We used a factorial randomized trial to develop a multimodal SMT protocol.
      • Disability was improved by combining SMT and multifidus activating exercises.
      • Future research using optimized SMT protocols may increase treatment effects.


      Spinal manipulative therapy (SMT) is a common nonpharmacological treatment for low back pain (LBP). Although generally supported by systematic reviews and practice guidelines, clinical trials evaluating SMT have been characterized by small effect sizes. This study adopts a Multiphase Optimization Strategy framework to examine individual components of an SMT delivery protocol using a single-blind trial with the goal of identifying and optimizing a multicomponent SMT protocol. We enrolled 241 participants with LBP. All participants received 2 SMT treatment sessions in the first week then were randomly assigned additional treatment based on a fully factorial design. The 3 randomized treatment components provided in twice weekly sessions over 3 weeks were multifidus activating exercise, spinal mobilizing exercise, and additional SMT dose. Primary outcomes included clinical (Oswestry Disability Index, numeric pain intensity rating) and mechanistic (spinal stiffness, multifidus muscle activation) measures assessed at baseline, 1, 4, and 12 weeks. Significant differences were found for the Oswestry index after 12 weeks for participants receiving multifidus activating exercise (mean difference = −3.62, 97.5% CI: −6.89, −0.35; P= .01). There were no additional significant main or interaction effects for other treatment components or different outcome measures. The optimized SMT protocol identified in this study included SMT sessions followed by multifidus activating exercises.


      Optimizing the effects of nonpharmacological treatments such as SMT for LBP is challenging due to uncertainty regarding mechanisms and the complexity of multicomponent protocols. This factorial randomized trial examined SMT protocols provided with differing co-interventions with mechanistic and patient-centered outcomes. Patient-centered outcomes were optimized by inclusion of lumbar multifidus strengthening exercises.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Andronis L
        • Kinghorn P
        • Qiao S
        • Whitehurst DG
        • Durrell S
        • McLeod H
        Cost-effectiveness of non-invasive and non-pharmacological interventions for low back pain: A systematic literature review.
        Appl Health Econ Health Policy. 2017; 15: 173-201
        • Beliveau PJH
        • Wong JJ
        • Sutton DA
        • Simon NB
        • Bussieres AE
        • Mior SA
        • French SD
        The chiropractic profession: A scoping review of utilization rates, reasons for seeking care, patient profiles, and care provided.
        Chiropr Manual Therap. 2017; 25: 35
        • Bialosky JE
        • Beneciuk JM
        • Bishop MD
        • Coronado RA
        • Penza CW
        • Simon CB
        • George SZ
        Unraveling the mechanisms of manual therapy: Modeling an approach.
        J Orthop Sports Phys Ther. 2018; 48: 8-18
        • Bialosky JE
        • Bishop MD
        • Price DD
        • Robinson ME
        • George SZ
        The mechanisms of manual therapy in the treatment of musculoskeletal pain: A comprehensive model.
        Man Ther. 2009; 14: 531-538
        • Bronfort G
        • Haas M
        • Evans R
        • Kawchuk G
        • Dagenais S
        Evidence-informed management of chronic low back pain with spinal manipulation and mobilization.
        Spine J. 2008; 8: 213-225
        • Burns JW
        • Nielson WR
        • Jensen MP
        • Heapy AA
        • Czlapinski RA
        • Kerns RD
        Does change occur for the reasons we think it does? A test of specific therapeutic operations during cognitive-behavioral treatment of chronic pain.
        Clin J Pain. 2015; 31: 603-611
        • Childs JD
        • Fritz JM
        • Flynn TW
        • Irrgang JJ
        • Johnson KK
        • Majkowski GR
        • Delitto A
        Validation of a clinical prediction rule to identify patients with low back pain likely to benefit from spinal manipulation.
        Ann Intern Med. 2004; 141: 920-928
        • Childs JD
        • Piva SR
        • Fritz JM
        Responsiveness of the numeric pain rating scale in patients with low back pain.
        Spine. 2005; 30: 1331-1335
        • Chou R
        • Deyo R
        • Friedly J
        • Skelly A
        • Hashimoto R
        • Weimer M
        • Fu R
        • Dana T
        • Kraegel P
        • Griffin J
        • Grusing S
        • Brodt E
        Noninvasive treatments for low back pain. Comparative effectiveness review no. 169. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2012-00014-I.).
        in: AHRQ Publication No. 16-EHC004-EF. Agency for Healthcare Research and Quality, Rockville, MD2016
        • Chou R
        • Deyo R
        • Friedly J
        • Skelly A
        • Hashimoto R
        • Weimer M
        • Fu R
        • Dana T
        • Kraegel P
        • Griffin J
        • Grusing S
        • Brodt ED
        Nonpharmacologic therapies for low back pain: Systematic review for an American College of Physicians Clinical Practice Guideline.
        Ann Intern Med. 2017; 166: 493-505
        • Cleland JA
        • Fritz JM
        • Kulig K
        • Davenport TE
        • Eberhart S
        • Magel JS
        • Childs JD
        Comparison of the effectiveness of three manual physical therapy techniques in a subgroup of patients with low back pain who satisfy a clinical prediction rule: A randomized clinical trial.
        Spine. 2009; 34: 2720-2729
        • Coffman CJ
        • Edelman D
        • Woolson RF
        To condition or not condition? Analysing ‘change’ in longitudinal randomised controlled trials.
        BMJ Open. 2016; 6e013096
        • Collins LM
        • Murphy SA
        • Nair VN
        A strategy for optimizing and evaluating behavioral interventions.
        Ann Behav Med. 2005; 30: 65-73
        • Collins LM
        • Murphy SA
        • Strecher V
        The Multiphase Optimization Strategy (MOST) and the sequential multiple assignment randomized trial (SMART): New methods for more potent eHealth interventions.
        Am J Prev Med. 2007; 32: S112-S118
        • Colloca CJ
        • Keller TS
        Stiffness and neuromuscular reflex response of the human spine to posteroanterior manipulative thrusts in patients with low back pain.
        J Manip Physiol Ther. 2001; 24: 489-500
        • Damschroder LJ
        • Aron DC
        • Keith RE
        • Kirsh SR
        • Alexander JA
        • Lowery JC
        Fostering implementation of health services research findings into practice: A consolidated framework for advancing implementation science.
        Implement Sci. 2009; 4: 50
        • Department of Veterans Affairs
        VA/DoD clinical practice guideline for diagnosis and treatment of low back pain. Veterans Affairs Dept; Office of Quality, Safety and Value, Washington, D.C.2018
        • Deyo RA
        • Dworkin SF
        • Amtmann D
        • Andersson G
        • Borenstein D
        • Carragee E
        • Carrino J
        • Chou R
        • Cook K
        • DeLitto A
        • Goertz C
        • Khalsa P
        • Loeser J
        • Mackey S
        • Panagis J
        • Rainville J
        • Tosteson T
        • Turk D
        • Von Korff M
        • Weiner DK
        Focus article report of the NIH task force on research standards for chronic low back pain.
        Clin J Pain. 2014; 30: 701-712
        • Di Blasi Z
        • Harkness E
        • Ernst E
        • Georgiou A
        • Kleijnen J
        Influence of context effects on health outcomes: A systematic review.
        Lancet. 2001; 357: 757-762
        • Dickx N
        • Cagnie B
        • Parlevliet T
        • Lavens A
        • Danneels L
        The effect of unilateral muscle pain on recruitment of the lumbar multifidus during automatic contraction. An experimental pain study.
        Man Ther. 2010; 15: 364-369
        • Dieleman JL
        • Cao J
        • Chapin A
        • Chen C
        • Li Z
        • Liu A
        • Horst C
        • Kaldjian A
        • Matyasz T
        • Scott KW
        • Bui AL
        • Campbell M
        • Duber HC
        • Dunn AC
        • Flaxman AD
        • Fitzmaurice C
        • Naghavi M
        • Sadat N
        • Shieh P
        • Squires E
        • Yeung K
        • Murray CJL
        US health care spending by payer and health condition, 1996-2016.
        JAMA. 2020; 323: 863-884
        • Dowell D
        • Haegerich TM
        • Chou R
        CDC guidelines for prescribing opioids for chronic pain—United States, 2016.
        JAMA. 2016; 315: 1624-1645
        • Ekstrom RA
        • Osborn RW
        • Hauer PL
        Surface electromyographic analysis of the low back muscles during rehabilitation exercises.
        J Orthop Sports Phys Ther. 2008; 38: 736-745
        • Ellingsen DM
        • Napadow V
        • Protsenko E
        • Mawla I
        • Kowalski MH
        • Swensen D
        • O'Dwyer-Swensen D
        • Edwards RR
        • Kettner N
        • Loggia ML
        Brain mechanisms of anticipated painful movements and their modulation by manual therapy in chronic low back pain.
        J Pain. 2019; 19: 1352-1365
        • Elnaggar IM
        • Nordin M
        • Sheikhzadeh A
        • Parnianpour M
        • Kahanovitz N
        Effects of spinal flexion and extension exercises on low-back pain and spinal mobility in chronic mechanical low-back pain patients.
        Spine. 1991; 16: 967-972
        • Filiz MB
        • Firat SC
        Effects of physical therapy on pain, functional status, sagittal spinal alignment, and spinal mobility in chronic non-specific low back pain.
        Eurasian J Med. 2019; 51: 22-26
        • Flynn T
        • Fritz J
        • Whitman J
        • Wainner R
        • Magel J
        • Rendeiro D
        • Butler B
        • Garber M
        • Allison S
        A clinical prediction rule for classifying patients with low back pain who demonstrate short term improvement with spinal manipulation.
        Spine. 2002; 27: 2835-2843
        • Fritz JM
        • Irrgang JJ
        A comparison of a modified Oswestry disability questionnaire and the Quebec back pain disability scale.
        Phys Ther. 2001; 81: 776-788
        • Fritz JM
        • Koppenhaver SL
        • Kawchuk GN
        • Teyhen DS
        • Hebert JJ
        • Childs JD
        Preliminary investigation of the mechanisms underlying the effects of manipulation: Exploration of a multivariate model including spinal stiffness, multifidus recruitment, and clinical findings.
        Spine. 2011; 36: 1772-1781
        • Fritz JM
        • Sharpe JA
        • Lane E
        • Santillo D
        • Greene T
        • Kawchuk GN
        Optimizing treatment protocols for spinal manipulative therapy: Study protocol for a randomized trial.
        Trials. 2018; 19: 306
        • Global Burden of Disease Collaborators
        Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015.
        Lancet. 2016; 388: 1545-1602
        • Goubert D
        • Oosterwijck JV
        • Meeus M
        • Danneels L
        Structural changes of lumbar muscles in non-specific low back pain: A systematic review.
        Pain Physician. 2016; 19: E985-E1000
        • Guastaferro K
        • Collins LM
        Achieving the goals of translational science in public health intervention research: The Multiphase Optimization Strategy (MOST).
        Am J Public Health. 2019; 109: S128-s129
        • Gwadz MV
        • Collins LM
        • Cleland CM
        • Leonard NR
        • Wilton L
        • Gandhi M
        • Scott Braithwaite R
        • Perlman DC
        • Kutnick A
        • Ritchie AS
        Using the Multiphase Optimization Strategy (MOST) to optimize an HIV care continuum intervention for vulnerable populations: A study protocol.
        BMC Public Health. 2017; 17: 383
        • Haas M
        • Vavrek D
        • Peterson D
        • Polissar N
        • Neradilek MB
        Dose-response and efficacy of spinal manipulation for care of chronic low back pain: A randomized controlled trial.
        Spine J. 2014; 14: 1106-1116
        • Hadizadeh M
        • Kawchuk GN
        • Parent E
        Reliability of a new loaded rolling wheel system for measuring spinal stiffness in asymptomatic participants.
        BMC Musculoskelet Disord. 2019; 20: 176
        • Harris PA
        • Taylor R
        • Thielke R
        • Payne J
        • Gonzalez N
        • Conde JG
        Research Electronic Data Capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support.
        J Biomed Inf. 2009; 42: 377-381
        • Hartvigsen J
        • Hancock MJ
        • Kongsted A
        • Louw Q
        • Ferreira ML
        • Genevay S
        • Hoy D
        • Karppinen J
        • Pransky G
        • Sieper J
        • Smeets RJ
        • Underwood M
        What low back pain is and why we need to pay attention.
        Lancet. 2018; 391: 2356-2367
        • Harvey MP
        • Descarreaux M
        Short term modulation of trunk neuromuscular responses following spinal manipulation: A control group study.
        BMC Musculoskelet Disord. 2013; 14: 92
        • Hebert JJ
        • Koppenhaver SL
        • Parent EC
        • Fritz JM
        A systematic review of the reliability of rehabilitative ultrasound imaging for the quantitative assessment of the abdominal and lumbar trunk muscles.
        Spine. 2009; 34: E848-E856
        • Herbert WJ
        • Heiss DG
        • Basso M
        Influence of feedback schedule in motor performance and learning of a lumbar multifidus muscle task using rehabilitative ultrasound imaging: A randomized clinical trial.
        Phys Ther. 2008; 88: 261-269
        • Hides JA
        • Richardson CA
        • Jull GA
        Multifidus muscle recovery is not automatic after resolution of acute, first-episode low back pain.
        Spine. 1996; 21: 2763-2769
        • Keller TS
        • Colloca CJ
        Mechanical force spinal manipulation increases trunk muscle strength assessed by electromyography: A comparative clinical trial.
        J Manipulative Physiol Ther. 2000; 23: 585-595
        • Kiesel KB
        • Uhl TL
        • Underwood FB
        • Rodd DW
        • Nitz AJ
        Measurement of lumbar multifidus muscle contraction with rehabilitative ultrasound imaging.
        Man Ther. 2007; 12: 161-166
        • Koppenhaver SL
        • Fritz JM
        • Hebert JJ
        • Kawchuk GN
        • Childs JD
        • Parent EC
        • Gill NW
        • Teyhen DS
        Association between changes in abdominal and lumbar multifidus muscle thickness and clinical improvement after spinal manipulation.
        J Orthop Sports Phys Ther. 2011; 41: 389-399
        • Koppenhaver SL
        • Fritz JM
        • Hebert JJ
        • Kawchuk GN
        • Parent EC
        • Gill NW
        • Childs JD
        • Teyhen DS
        Association between history and physical examination factors and change in lumbar multifidus muscle thickness after spinal manipulation in patients with low back pain.
        J Electromyogr Kinesiol. 2012; 22: 724-731
        • Ladeira CE
        • Cheng M
        • Hill CJ
        Physical therapists' treatment choices for non-specific low back pain in Florida: An electronic survey.
        J Man Manipulative Ther. 2015; 23: 109-118
        • MacDonald DA
        • Moseley GL
        • Hodges PL
        Why do some patients keep hurting their back? Evidence of ongoing back muscle dysfunction during remission from recurrent back pain.
        Pain. 2009; 142: 183-188
        • Macedo LG
        • Saragiotto BT
        • Yamato TP
        • Costa LO
        • Menezes Costa LC
        • Ostelo RW
        • Maher CG
        Motor control exercise for acute non-specific low back pain.
        Cochrane Database Syst Rev. 2016; 2Cd012085
        • Marshall PWM
        • Schabrun S
        • Knox MF
        Physical activity and the mediating effect of fear, depression, anxiety, and catastrophizing on pain related disability in people with chronic low back pain.
        PLoS One. 2017; 12e0180788
        • McKenzie RA
        • May S
        The Lumbar Spine: Mechanical Diagnosis and Therapy.
        2nd ed. Orthopedic Physical Therapy Products, Minneapolis, MN2003
        • Okubo Y
        • Kaneoka K
        • Imai A
        • Shiina I
        • Tatsumura M
        • Izumi S
        • Miyakawa S
        Electromyographic analysis of transversus abdominis and lumbar multifidus using wire electrodes during lumbar stabilization exercises.
        J Orthop Sports Phys Ther. 2010; 40: 743-750
        • Ostelo RWJ
        • Deyo RA
        • Stratford P
        • Waddell G
        • Croft P
        • Von Korff M
        • Bouter LM
        • De Vet H
        Interpreting change scores for pain and functional status in low back pain: Towards international consensus regarding minimal important change.
        Spine. 2008; 33: 90-94
        • Owen PJ
        • Miller CT
        • Mundell NL
        • Verswijveren SJ
        • Tagliaferri SD
        • Brisby H
        • Bowe SJ
        • Belavy DL
        Which specific modes of exercise training are most effective for treating low back pain? Network meta-analysis.
        Br J Sports Med. 2020, 1279-1287; 54: 90-94
        • Paige NM
        • Miake-Lye IM
        • Booth MS
        • Beroes JM
        • Mardian AS
        • Dougherty P
        • Branson R
        • Tang B
        • Morton SC
        • Shekelle PG
        Association of spinal manipulative therapy with clinical benefit and harm for acute low back pain: Systematic review and meta-analysis.
        JAMA. 2017; 317: 1451-1460
        • Pasquier M
        • Daneau C
        • Marchand AA
        • Lardon A
        • Descarreaux M
        Spinal manipulation frequency and dosage effects on clinical and physiological outcomes: A scoping review.
        Chiropr Man Ther. 2019; 27: 23
        • Qaseem A
        • Wilt TJ
        • McLean RM
        • Forciea MA
        Noninvasive treatments for acute, subacute, and chronic low back pain: A clinical practice guideline from the American College of Physicians.
        Ann Intern Med. 2017; 166: 514-530
        • Rossettini G
        • Carlino E
        • Testa M
        Clinical relevance of contextual factors as triggers of placebo and nocebo effects in musculoskeletal pain.
        BMC Musculoskel Dis. 2018; 19
        • Rubinstein SM
        • Terwee CB
        • Assendelft WJ
        • de Boer MR
        • van Tulder MW
        Spinal manipulative therapy for acute low back pain: An update of the Cochrane review.
        Spine. 2013; 38: E158-E177
        • Saragiotto BT
        • Maher CG
        • Yamato TP
        • Costa LO
        • Menezes Costa LC
        • Ostelo RW
        • Macedo LG
        Motor control exercise for chronic non-specific low-back pain.
        Cochrane Database Syst Rev. 2016; CD012004
        • Schafer JL
        Multiple imputation: A primer.
        Stat Methods Med Res. 1999; 8: 3-15
        • Skelly AC
        • Chou R
        • Dettori JR
        • Turner JA
        • Friedly JL
        • Rundell SD
        • Fu R
        • Brodt ED
        • Wasson N
        • Winter C
        Noninvasive nonpharmacological treatment for chronic pain: A systematic review. Comparative Effectiveness Review No. 209.
        in: (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2015-00009-I.) AHRQ Publication No 18-EHC013-EF. Agency for Healthcare Research and Quality, Rockville, MD2018
        • Thorn BE
        • Burns JW
        Common and specific treatment mechanisms in psychosocial pain interventions: The need for a new research agenda.
        Pain. 2011; 152: 705-706
        • Triano JJ
        Biomechanics of spinal manipulative therapy.
        Spine J. 2001; 1: 121-130
        • Verbeke G
        • Molenberghs G
        Linear Mixed Models for Longitudinal Data.
        Springer Verlag, Heidelberg, Germany2000
        • Waddell G
        • Newton M
        • Henderson I
        • Somerville D
        • Main CJ
        A Fear-Avoidance Beliefs Questionnaire (FABQ) and the role of fear-avoidance beliefs in chronic low back pain and disability.
        Pain. 1993; 52: 157-168
        • Walker BF
        • French SD
        • Grant W
        • Green S
        Combined chiropractic interventions for low-back pain.
        Cochrane Database Syst Rev. 2010; CD005427
        • Ward SR
        • Kim CW
        • Eng CM
        • Gottschalk LJ
        • Tomiya A
        • Garfin SR
        • Lieber RL
        Architectural analysis and intraoperative measurements demonstrate the unique design of the multifidus muscle for lumbar spine stability.
        J Bone Joint Surg Am. 2009; 91: 176-185
        • Wong AY
        • Parent EC
        • Dhillon SS
        • Prasad N
        • Kawchuk GN
        Do participants with low back pain who respond to spinal manipulative therapy differ biomechanically from nonresponders, untreated controls or asymptomatic controls?.
        Spine. 2015; 40: 1329-1337
        • Young JC
        • Jonsson Funk M
        • Dasgupta N
        Medical use of long-term extended-release opioid analgesics in commercially insured adults in the United States.
        Pain Med. 2020; 21: 724-735