Efficacy of Spinal Manipulation Therapy or Mindfulness-based Reduction Therapy on Patients With Chronic Low Back Pain

Efficacy of Spinal Manipulation Therapy or Mindfulness-based Reduction Therapy on Patients With Chronic Low Back Pain

Evaluating Specific and Non-Specific Mechanisms in Two Distinct Complementary/Integrative Interventions for Chronic Pain

Chronic Pain Management (CPM) has increasingly utilized long-term opioid analgesic therapy, a change associated with increased opioid abuse (a greater exposure in vulnerable individuals), non-pain health consequences (hormone changes, falls), and a dramatic rise in opioid-related overdoses and deaths. Treatment strategies that minimize the need for chronic high-dose opioids are sorely needed. This project will aim to test what degree mindfulness therapy (MT) and spinal manipulation therapy (SMT) produce pre- to mid- to post-treatment changes in endogenous opioid (EO) function.

This project will determine whether enhancing endogenous opioids (via SMT or MT) permits achieving desired levels of analgesia with lower dosages of opioid analgesics, and fewer side effects and abuse-relevant drug effects. This X year project will test study hypotheses in a sample of 240 chronic low back pain patients. The study will have 2 key elements: 1) a randomized, controlled SMT or MT in chronic pain (CP) patients completing daily take home exercises and 2) laboratory evoked thermal pain protocols pre- and post- therapy, permitting the quantification of EO function and the examining of treatment-induced changes in EO function (placebo vs. naloxone). The study will employ a mixed between/within-subjects design using double-blinded and placebo-controlled administration of the opioid antagonist (naloxone). The study will use a 8 week supervised MT or SMT manipulation with subjects randomly assigned to one of the groups. All participants will undergo 6 laboratory pain-induction sessions in total. 2 during the pre-treatment phase, 2 during the mid-treatment phase, and 2 post-treatment. The laboratory sessions are identical with the exception of one of the 2 mid-treatment laboratory sessions, where extra questionnaires are administered. Each laboratory session will be roughly 2-3 days apart and the first 2 laboratory sessions will occur prior to the randomization to the treatment condition.

Participants are randomly assigned to an 8 week SMT treatment group conducted by certified physical therapists. Immediately before and after the treatment sessions along with midway through the treatment (after 4 sessions), participants will undergo the placebo/naloxone administration intervention to assess mechanisms of SMT or MT-related changes.

Participants are randomly assigned to an 8 week MT treatment group conducted by certified clinical therapists. Immediately before and after the treatment sessions along with midway through the treatment (after 4 sessions), participants will undergo the placebo/naloxone administration intervention to assess mechanisms of SMT or MT-related changes.

2 SMT techniques are administered each session, both of which are scripted interactions between the physical therapist (PT) providing the SMT and the subjects: 1) Participants will lie on the SMT table for 20 mins, while the PT sits approximately 6 ft away. As part of the script, the PT will review with subjects the inclusion/exclusion criteria ostensibly to ensure that nothing has changed. 2) The PT will perform the 2 SMT techniques during the next 20 mins. 3) Subjects will sit upright in a chair for the remaining 20 mins, while the PT sits approximately 6 feet away. The PT will review home exercises with participant.

In randomized order (crossover) across 2 laboratory sessions each approximately 3 days apart, participants will receive either 1) 2 doses of saline placebo (20ml each) or 2) weight-adjusted doses of Naloxone beginning with a dose of 0.11mg/kg followed by a weight-adjusted dose of 0.055 mg/kg

In randomized order (crossover) across 2 laboratory sessions each approximately 3 days apart, participants will receive either 1) 2 doses of saline placebo (20ml each) or 2) weight-adjusted doses of Naloxone beginning with a dose of 0.11mg/kg followed by a weight-adjusted dose of 0.055 mg/kg

Each MT session consists of (a) body scan meditation accompanied by awareness of breathing and other bodily sensations while in a lying position, (b) sitting meditation, focusing on awareness of breathing, bodily sensations, thoughts, and emotions (c) gentle movement exercises intended to develop awareness (mindfulness) during movement. In-session activities include suggestions for application of mindfulness as a method for responding positively to stress; dealing with the challenges of pain; and exercises focusing on the challenges and achievements patients experience in integrating mindfulness into their lives and the stressful situations they encounter. Additional discussion will focus on stress reactivity and they will be taught problem-solving skills to develop solutions to meet MT goals. Finally, patients will develop a written maintenance plan that includes a list of short- and long-term goals for applying mindfulness methods and a plan for dealing with possible setbacks.

Interference in daily activities attributed to chronic pain as reported by subjects. The PROMIS Pain Interference scale consists of 8 questions with a 5-point response scale ranging from Not at all - Very much. Participants are asked how much in the past 7 days everyday activities were affected by their pain. Higher scores indicate more pain interference in daily activities.

Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity (Short Form)

Intensity of chronic pain reported by subject. The PROMIS Pain Intensity scale consists of 3 questions with a 5-point response scale ranging from Had no pain - Very severe. Participants are asked how intense their pain has been in the past 7 days. Higher scores indicate more intense pain.

Degree of depressive symptoms reported by subject. The PROMIS Depression scale consists of 8 questions with a 5-point response scale ranging from Never - Always. Participants are asked how often they felt depressive emotions in the past 7 days. Higher scores indicate more depressive emotions.

Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (Short Form)

Amount of physical activity reported by subject. The PROMIS Physical Function scale consists of 27 questions with a 5-point response scale ranging from Without any difficulty - Unable to do. Participants are asked how much their pain affects their physical functioning. Higher scores indicate more inability to perform specific physical activities due to pain.

Degree of sleep disturbance reported by subject. The PROMIS Sleep Disturbance scale consists of 8 questions with a 5-point response scale ranging from Not at all - Very much. Participants are asked how much in the past 7 days their pain interfered with their sleep. Higher scores indicate more sleep disruptions.

Inclusion Criteria: significant daily chronic pain intensity (≥4 on a 10-point scale) and interference in performing daily activities due to pain (≥3 on a 10-point scale) for at least 3 months age 18-75 years (inclusive) not using opioid analgesics on a daily basis or within 3 days of each laboratory session (confirmed via urine drug screen) Intact cognitive status and ability to provide informed consent ability to read and write in English sufficiently to understand and complete study questionnaires Exclusion Criteria: meet criteria for alcohol or substance abuse problems meet criteria for past or present psychotic or bipolar disorders inability to understand English well enough to complete questionnaires or participate in therapy pain due to malignant conditions, rheumatoid arthritis, migraine or tension headache, complex regional pain syndrome, or fibromyalgia syndrome lumbar surgery within past 6 months pregnant signs of nerve root compression (ie, positive straight-leg raise <45○). liver diseases (e.g hepatitis or cirrhosis) suicide ideation with intent osteoporosis or bone demineralization opioid-dependency inability to hold breathe for 15 seconds acute trauma to spine long term use of corticosteroids spinal cord stimulator or IT pump inserted in back they have a BMI equal to or above 40

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Airaksinen O, Brox JI, Cedraschi C, Hildebrandt J, Klaber-Moffett J, Kovacs F, Mannion AF, Reis S, Staal JB, Ursin H, Zanoli G; COST B13 Working Group on Guidelines for Chronic Low Back Pain. Chapter 4. European guidelines for the management of chronic nonspecific low back pain. Eur Spine J. 2006 Mar;15 Suppl 2(Suppl 2):S192-300. doi: 10.1007/s00586-006-1072-1. No abstract available.

American Physical Therapy Association.. Guide to Physical Therapist Practice. Second Edition. American Physical Therapy Association. Phys Ther. 2001 Jan;81(1):9-746. No abstract available.

Cleland JA, Fritz JM, Whitman JM, Childs JD, Palmer JA. The use of a lumbar spine manipulation technique by physical therapists in patients who satisfy a clinical prediction rule: a case series. J Orthop Sports Phys Ther. 2006 Apr;36(4):209-14. doi: 10.2519/jospt.2006.36.4.209.

Kazdin AE. Mediators and mechanisms of change in psychotherapy research. Annu Rev Clin Psychol. 2007;3:1-27. doi: 10.1146/annurev.clinpsy.3.022806.091432.

Burns JW, Day MA, Thorn BE. Is reduction in pain catastrophizing a therapeutic mechanism specific to cognitive-behavioral therapy for chronic pain? Transl Behav Med. 2012 Mar;2(1):22-9. doi: 10.1007/s13142-011-0086-3.

Williams AC, Eccleston C, Morley S. Psychological therapies for the management of chronic pain (excluding headache) in adults. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD007407. doi: 10.1002/14651858.CD007407.pub3.

Veehof MM, Oskam MJ, Schreurs KMG, Bohlmeijer ET. Acceptance-based interventions for the treatment of chronic pain: a systematic review and meta-analysis. Pain. 2011 Mar;152(3):533-542. doi: 10.1016/j.pain.2010.11.002. Epub 2011 Jan 19.

Leemann S, Peterson CK, Schmid C, Anklin B, Humphreys BK. Outcomes of acute and chronic patients with magnetic resonance imaging-confirmed symptomatic lumbar disc herniations receiving high-velocity, low-amplitude, spinal manipulative therapy: a prospective observational cohort study with one-year follow-up. J Manipulative Physiol Ther. 2014 Mar-Apr;37(3):155-63. doi: 10.1016/j.jmpt.2013.12.011. Epub 2014 Mar 11.

Klyne DM, Schmid AB, Moseley GL, Sterling M, Hodges PW. Effect of types and anatomic arrangement of painful stimuli on conditioned pain modulation. J Pain. 2015 Feb;16(2):176-85. doi: 10.1016/j.jpain.2014.11.005. Epub 2014 Nov 15.

Wong AY, Kawchuk G, Parent E, Prasad N. Within- and between-day reliability of spinal stiffness measurements obtained using a computer controlled mechanical indenter in individuals with and without low back pain. Man Ther. 2013 Oct;18(5):395-402. doi: 10.1016/j.math.2013.02.003. Epub 2013 Mar 1.

Zeidan F, Adler-Neal AL, Wells RE, Stagnaro E, May LM, Eisenach JC, McHaffie JG, Coghill RC. Mindfulness-Meditation-Based Pain Relief Is Not Mediated by Endogenous Opioids. J Neurosci. 2016 Mar 16;36(11):3391-7. doi: 10.1523/JNEUROSCI.4328-15.2016.

Sharon H, Maron-Katz A, Ben Simon E, Flusser Y, Hendler T, Tarrasch R, Brill S. Mindfulness Meditation Modulates Pain Through Endogenous Opioids. Am J Med. 2016 Jul;129(7):755-8. doi: 10.1016/j.amjmed.2016.03.002. Epub 2016 Apr 1.

Zeidan F, Martucci KT, Kraft RA, Gordon NS, McHaffie JG, Coghill RC. Brain mechanisms supporting the modulation of pain by mindfulness meditation. J Neurosci. 2011 Apr 6;31(14):5540-8. doi: 10.1523/JNEUROSCI.5791-10.2011.

Youssef AM, Macefield VG, Henderson LA. Pain inhibits pain; human brainstem mechanisms. Neuroimage. 2016 Jan 1;124(Pt A):54-62. doi: 10.1016/j.neuroimage.2015.08.060. Epub 2015 Sep 4.

Valet M, Sprenger T, Boecker H, Willoch F, Rummeny E, Conrad B, Erhard P, Tolle TR. Distraction modulates connectivity of the cingulo-frontal cortex and the midbrain during pain--an fMRI analysis. Pain. 2004 Jun;109(3):399-408. doi: 10.1016/j.pain.2004.02.033.

Hadjipavlou G, Dunckley P, Behrens TE, Tracey I. Determining anatomical connectivities between cortical and brainstem pain processing regions in humans: a diffusion tensor imaging study in healthy controls. Pain. 2006 Jul;123(1-2):169-78. doi: 10.1016/j.pain.2006.02.027. Epub 2006 Apr 17.

Wager TD, Scott DJ, Zubieta JK. Placebo effects on human mu-opioid activity during pain. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11056-61. doi: 10.1073/pnas.0702413104. Epub 2007 Jun 19.

Wagner KJ, Sprenger T, Kochs EF, Tolle TR, Valet M, Willoch F. Imaging human cerebral pain modulation by dose-dependent opioid analgesia: a positron emission tomography activation study using remifentanil. Anesthesiology. 2007 Mar;106(3):548-56. doi: 10.1097/00000542-200703000-00020.

Burns JW, Quartana PJ, Bruehl S. Anger management style moderates effects of attention strategy during acute pain induction on physiological responses to subsequent mental stress and recovery: a comparison of chronic pain patients and healthy nonpatients. Psychosom Med. 2009 May;71(4):454-62. doi: 10.1097/PSY.0b013e318199d97f. Epub 2009 Feb 27.

Burns JW, Bruehl S, Caceres C. Anger management style, blood pressure reactivity, and acute pain sensitivity: evidence for "Trait x Situation" models. Ann Behav Med. 2004 Jun;27(3):195-204. doi: 10.1207/s15324796abm2703_7.

Laska KM, Gurman AS, Wampold BE. Expanding the lens of evidence-based practice in psychotherapy: a common factors perspective. Psychotherapy (Chic). 2014 Dec;51(4):467-81. doi: 10.1037/a0034332. Epub 2013 Dec 30.

Burns JW, Bruehl S, France CR, Schuster E, Orlowska D, Buvanendran A, Chont M, Gupta RK. Psychosocial factors predict opioid analgesia through endogenous opioid function. Pain. 2017 Mar;158(3):391-399. doi: 10.1097/j.pain.0000000000000768.

Xia T, Long CR, Vining RD, Gudavalli MR, DeVocht JW, Kawchuk GN, Wilder DG, Goertz CM. Association of lumbar spine stiffness and flexion-relaxation phenomenon with patient-reported outcomes in adults with chronic low back pain - a single-arm clinical trial investigating the effects of thrust spinal manipulation. BMC Complement Altern Med. 2017 Jun 9;17(1):303. doi: 10.1186/s12906-017-1821-1.

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Lewis J, Mansour A, Khachaturian H, Watson SJ, Akil H. Opioids and pain regulation. Pain Headache. 1987;9:129-59. No abstract available.

Sullivan, M.J.L., Bishop, S.R., & Pivik, J. (1995). The Pain Catastrophizing Scale: Development and validation. Psychological Assessment, 7, 524-532

Tracey, T.J., & Kokotovic, A.M. (1989). Factor structure of the Working Alliance Inventory. Psychological Assessment: A Journal of Consulting and Clinical Psychology, 1, 207-210

Holt, C., & Heimberg, R. (1990). The Reaction to Treatment Questionnaire: Measuring treatment credibility and outcome expectancies. The Behavior Therapist, 13, 213-214

Burns JW, Johnson BJ, Mahoney N, Devine J, Pawl R. Cognitive and physical capacity process variables predict long-term outcome after treatment of chronic pain. J Consult Clin Psychol. 1998 Apr;66(2):434-9. doi: 10.1037//0022-006x.66.2.434.

Lofland, K.R., Burns, J.W., Tsoutsouris, J., Laird, M.M., Blonsky, E.R., & Hejna, W.F. (1997). Predictors of outcome following multidisciplinary treatment of chronic pain: Effects of changes in perceived disability and depression. International Journal of Rehabilitation and Health, 3, 221-232

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