6/22/2017 Inflammation is Not the Enemy Sean Mulvaney, MD 1
6/22/2017 2
6/22/2017 Lascaux 7.4 Billion 3
This image cannot currently be displayed. 6/22/2017 Goals 4
ANTI INFLAMMATORY THERAPIES NSAIDS 5
Cochrane Database 2002 Evidence about the benefits of oral NSAIDs has been conflicting Oral NSAID use can result in gastrointestinal adverse effects Based on 5 placebo controlled studies Some pain benefit out to 4 weeks, no data suggests improved tissue healing 6
Rat Study (Trappe et al) Do NSAIDs and Acetaminophen interfere with muscle recovery and growth? 3 groups of rats: ibuprofen, acetaminophen, and no medication Same food, same resistance training (running on a weighted rat wheel for time) 7
Similar study, this time on humans Effect of ibuprofen and acetaminophen on post-exercise muscle protein synthesis. Trappe TA. J. Am J Physiol Endocrinol Metab. 2002 Heavy eccentric exercise. Trappe et al. These results suggest that over-thecounter doses of both ibuprofen and acetaminophen suppress the protein synthesis response in skeletal muscle after eccentric resistance exercise. 8
What about Corticosteroids? Do they work to speed recovery and healing? TENDINOPATHY 9
Efficacy and safety of corticosteroid injections for tendonopathy: a systematic review of randomized controlled trials Brooke K et al. Lancet 2010 Level 1 evidence 3824 trials, 41 trials met inclusion (2672 patients) Corticosteroids did provide short-term relief BUT Brooke et al. After the first 4 weeks, the NO INTERVENTION groups had better pain relief and function that the corticosteroid injection group 10
OSTEOARTHRITIS Increased Chondrocyte Death after Steroid and Local Anesthetic Combination Borglaka et al. Clin Orthop Relat Res (2010) Using human chondrocytes en vitro and ex vivo, using flow cytometry and TUNNEL analysis, demonstrated chondrocyte apoptosis after exposure to corticosteriod and local anesthetic. 11
Borglaka et al. The combination of glucocorticoids and local anesthetics has an adverse effect on articular chondrocytes, and it raises a question regarding whether concomitant administration should be used in treating osteoarthritis. Effect of Intra articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial McAlindon et al JAMA 2017 2year follow up, 140 patients, q 3 month injection Serial MRI and functional testing 12
JAMA 2017 2 years of intra articular triamcinolone, compared with intra articular saline, resulted in significantly greater cartilage volume loss and no significant difference in knee pain. LUMBAR SPINE PAIN 13
Epidural Steroids A recent Cochrane review of 21 randomized trials of all types of spinal injection therapy for low back pain concluded that there is currently insufficient evidence to support the use of injection therapy in subacute and chronic LBP. Staal JB et al. Injection therapy for subacute and chronic LBP: an updated Cochraine Review. Spine 2009. Epidural Steroids Recent blinded multicenter trials for chronic lumbar radiculaopathy showed no difference between saline or steroids. Iversen T el al. Epidural steroid injections in the treetment of lumbar spinal stenosis efficacy and predictability of successful response. AM J Phys Med Rehabil 2011. 14
This image cannot currently be displayed. 6/22/2017 The Healing Cascade 15
INFLAMMATORY PHASE Obtain hemostasis The Inflammatory Phase Release chemical messengers (Call out the bodies Home Depot Repair Crew ) Contain infection Activate Macrophages (Clean up Crew) Initiate the Proliferative phase (start the initial repair) 16
The Inflammatory Phase Blood contacts collagen (activates platelets) The alpha granules within the Platelets secrete: Coagulation factors Platelet activating factors Cytokines Chemokines 17
The Inflammatory Phase Anti-microbial Debridement Leads to proliferation phase and tissue healing If interrupted with anti-inflammatory drugs the ability to optimally heal is inhibited PROLIFERATIVE PHASE 18
The Proliferative Phase Fibroblasts migrate to the wound Low oxygen / lactic acid stimulates neovascularization Clot is dissolved to make room for the new blood vessels The Proliferative Phase Fibroblasts peak by day 7 Deposit new collagen Fibroblasts differentiate to whatever cell type is required for the repair Actin fibers form and contract to make the wound smaller Lasts 2-4 weeks 19
REMODELING PHASE Starts when production and break down of collagen equalize Lasts over a year Type III (fast) collagen is replaced by Type I (stronger) collagen 80% normal strength Neovessels resorb 20
INFLAMMATION IS THE VITAL FIRST STEP IN THE HEALING CASCADE Change the Paradigm: Away From Anti Inflammatory approach Facilitated tissue repair 21
Normal Tissue Metabolism Highly regulated balance: synthesis vs degradation 22
Tissue Repair Requires a catabolic phase which: Progresses to a precisely controlled anabolic phase With a return to normal tissue homeostasis after the repair is complete Chronic Injury The bodies inherent repair mechanisms are: Disrupted Insufficiently focused Overwhelmed 23
Proposed Mechanism Damaged cells: put off chemical signals in the space around them Regenerative therapies re initiate, augment and focus these signals Repair System: Attracted to the signals MSCs dock near the damage cell through a ligand receptor system Trophic Factors: secretion of cytokines and growth factors direct cellular metabolism towards tissue regeneration Pro Inflammatory Techniques Stimulate an Anabolic Response Needle tenotomy Prolotherapy (15% dextrose) Platelet Rich Plasma (PRP) Placental Tissue Allografts Alpha 2 Macroglobin Bone Marrow or Adipose Derived Stem Cells 24
Regenerative Medicine Continuum Bone Marrow Concentrate / Adipose Derived Stem Cells/ UC derived stem cells Prolotherapy Autologous Blood Platelet Rich Plasma Placental Tissue Matrix α 2 Macroglobin Needle Tenotomy Epidemic in our ranks 25
REGENERATIVE MEDICINE LECTURE 0840 ON WEDNESDAY IN ROOM 207 Evaluating Musculoskeletal Therapies Is it Safe? Has there been a reasonable trial of physical therapy? Does it interfere with the bodies ability to heal itself? Does it lead to tissue healing and return to best possible function? Is it tolerated by the patient? Is the cost benefit ratio reasonable? 26
Strong new evidence does not support Antiinflammatory treatments for chronic injuries We must eradicate this thinking from our community We need to embrace a productive model of tissue repair 27