Life Beyond Norco ADVANCES IN PAIN MANAGEMENT EUGENE WANG, D.O. HARBORSIDE SPINE & SPORTS CENTER, PRESIDENT NMSAS RECOVERY CENTER, MEDICAL DIRECTOR
New Arsenal
Objectives Participants will be updated on changes in treatment algorithms for pain management Participants will gain a better understanding of nonpharmacologic treatment options for various MSK disorders Participants will gain knowledge of the advances in MSK Regenerative Medicine
Previous Pain Treatment Algorithm Chronic Pain APAP/NSAIDS Ice/Heat/TENS/Rest PT/OMT Opioids/ Neuromodulators Surgical Consultation and/or Interventional Pain Procedures the creep
Strategies to combat the opioid crisis Altering Guidelines More Pharmacological Solutions Use of Non-Opioid Treatments An entire industry for opioid side effects $2 Billion annual revenue for OIC drugs
CDC Opioid Rx Guidelines 2016 The nation's top federal health agency urged doctors to avoid prescribing powerful opiate painkillers for patients with chronic pain, saying the risks from such drugs far outweigh the benefits for most people. "We know of no other medication routinely used for a nonfatal condition that kills patients so frequently." "For chronic pain, narcotics should be the last resort." Thomas Frieden MD, Former Director CDC
Current Pain Treatment Algorithm NEW ARSENAL Interventional Pain Treatments Chronic Pain APAP/NSAIDS/non opioid medications Ice/Heat/TENS/ Rest PT/OMT Opioids Surgical Consultation
Case 1: Dan 45 y/o male with longstanding history of right L5 radiculopathy despite a L4-5, L5-S1 CAGE fusion 3 years ago. He reports his radicular and back pain worsened after the surgery.
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What is Spinal Cord Stimulation? Spinal Cord Stimulation (SCS) is an established, safe therapy that involves the delivery of energy to the spinal cord through small wires in the back SCS works by delivering small electrical pulses to the pain sensing pathways of the spinal cord, effectively altering the pain signals traveling to the brain. Typically prescribed for the treatment of pain of the back, trunk, or limbs Minimally invasive procedure and reversible therapy Recent advances in SCS include high frequency stimulation at 10,000 Hz and stimulators that can deliver multiple stimulation paradigms simultaneously or sequentially. The primary purpose of SCS is to aid in the management of chronic intractable neuropathic pain The efficacy of SCS has been well documented over the past 40 years Medical Policy Spinal Cord Stimulation for Pain January, 2007:Revised 1/09, 1/11, 01/13 Lee AW, Pilitsis JG. Spinal Cord Stimulation: indications and outcomes. Neurosurg Focus 2006; 21:E3., British Pain Society. Spinal cord stimulation for the management of pain: recommendations for best clinical practice. London: British Pain Society, 2005.
SENZA-RCT Summary (n=198) Long Term, Durable Pain Relief: 24 MONTHS 76% responder rate (>50% Relief) 2.4 cm VAS Reported 12 Month Opioid Reductions 35.5% patients decreased or eliminated opioid use Daily dose 112.9 mg/day reduced to 87.9 mg/day Kapural L, et al. Comparison of 10-kHz High-Frequency and Traditional Low-Frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: 24-month Results from a Multicenter, Randomized, Controlled Pivotal Trial. Neurosurgery. Published 11 2016
Decreased Opioid Use in SENZA-EU Trial with HF10 therapy After Two Years % Of Patients Using Opioids 86% 34% reduction in # of patients using opioids Mean Mg Morphine Equivalent Per Patient 84 68% reduction in dose 54%* 57%* 29* 27* Baseline (n=72) 12 Month (n=67) 24 Month (n=65) Baseline (n=72) 12 Month (n=67) 24 Month (n=65) * p-value < 0.001 compared to Baseline Al-Kaisy A, Van Buyten JP, Smet I, Palmisani S, Pang D, Smith T. Sustained effectiveness of 10 khz high-frequency spinal cord stimulation for patients with chronic, low back pain: 24- month results of a prospective multicenter study. Pain Med. 2014 Mar; 15(3):347-54. Epub 2013 Dec 5. doi: 10.1111/pme.12294.
Emerging New Evidence with SCS therapy Established Evidence Emerging Evidence Upper Limb Pain Back Pain SENZA-RCT Leg Pain SENZA-RCT *Investigational only not on-label or indicated for use. Neck Pain* SENZA-ULN Upper Limb Pain SENZA-ULN Chronic Abdominal Pain* SENZA-CAP Post-Surgical Pain SENZA-CPSP Painful Diabetic Neuropathy SENZA-PDN Peripheral Polyneuropathy SENZA-PPN Peripheral Polyneuropathy NSRBP (Non-Surgical Refractory Back Pain)
Al-Kaisy NSRBP* Pilot Study: Design Single Arm, Prospective Study 20 successful implants 3 year observation Predominant back pain Baseline 7.9cm VAS Multiple outcomes assessed: Opioid usage Function (ODI) Published results at 12 and 36 months *Nonsurgical Refractory Back Pain
Non-surgical Back Pain Study - 36 months published in Pain Medicine 36 Month Results Average VAS at 36 mo: 1.0 cm
Opioid Reduction in NSRBP Pilot 100% 90% 90% 90% of patients on opioids at baseline 12% of all subjects were using opioids at 36 months 80% 70% 60% 50% 40% 30% 20% 10% 12% 0% Baseline 36 Months
Case 2: Linda 39 y/o female with 10 year history of axial neck pain that worsens with work and home activities and improves with rest and lying supine.
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What is radiofrequency ablation? Goal of treatment: Stop nerve conduction of a painful joint or nerve with a heat lesion Minimally invasive procedure Performed under fluoroscopy Pain relief for 6 months-2 years
Anatomy: relevant nerves Dorsal root ganglion Medial branch
Radiofrequency ablation Radiofrequency needles are placed parallel to the medial branch Typically 1-2 lesions are performed Lateral view, needles are placed in junction of anterior 1/3 and posterior 2/3 of SAP
Clinical use Facet Arthropathy (Cervical/Thoracic/Lumbar) SIJ Dysfunction Knee DJD (Genicular Nerves) Occipital Neuralgia Radiculopathies (DRG) Focal Peripheral Neuropathy(Meralgia Paresthetica, Ilioinguial/Iliohypogastric Neuralgia, Intercostal Neuralgia) CRPS (Stellate Ganglion)
Does it work? RF Studies Region of spine Study No. of patients Greater than 50% pain relief for: 12 3 months 6 months months Lumbar Thoracic Cervical Dreyfus et al. Efficacy and Validity of radiofrequency neurotomy for chronic lumbar zygapophysial joint pain. Spine. 2000; 25:1270-1277. Stolker et al. Percutaneous facet denervation in chronic thoracic pain. Acta Neurochir. 1993; 122:82-90. McDonald et al. Long-term follow-up of patients treated with cervical radiofrequency neurotomy for chronic neck pain. Neurosurgery. 1999; 45:61-68. 15 93% 87% 87% 40 83% 83% 83% 28 71% 71% 71%
Does it work? RF Studies Multicenter, retrospective clinical data analysis of 262 chronic low back pain patients who underwent Radiofrequency Ablation (Neurotomy) Study originally designed to determine if there was a difference in efficacy for those that received >50% relief vs. >80% relief with the diagnostic blocks prior to the RFA There ended up being no difference between groups but the study did show that >50% of the participants experienced >50% relief s/p RFA and 66-67% of participants had a positive Global Perceived Effect (GPE) Cohen SP, Stojanovic MP, Crooks M. Lumbar zygapophysial (facet) joint radiofrequency denervation success as a function of pain relief during diagnostic medial branch blocks; a multicenter analysis. The Spine Journal. 8(2008)498-504.
Case 3: Joann 41 y/o female with 10 year history of migraine headaches. She experiences them more than half the month with each episode lasting 6 hours to 2 days.
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According to the WHO, Migraine Is One of the Most Disabling Conditions Globally Migraine is the 6 th most disabling condition in the world 1 A severe migraine attack is as disabling as a day lived with active psychosis or quadriplegia 2 World Health Organization. 2016; 2. World Health Organization. 2004
Injection Targets
Injection Targets
Does it work? COMPEL study Trial design: Open-label study (n = 716) in which enrolled patients received 155 Units of BOTOX Administration: 31 sites in a fixed-site, fixed-dose paradigm across 7 head/neck muscles every 12 weeks for 9 treatment cycles (108 weeks) Primary end point: Reduction in headache days at week 108 56% of patients enrolled received all 9 treatments and 52% received all study treatments and attended the final follow-up visit. Missing data were imputed with the last observation carried forward method.
Data from the subgroup of patients who did not use an oral preventive medication anytime during the study are presented (n = 340) 8.0, 10.0, 10.5, and 11.6 fewer headaches days per month from baseline at weeks 24, 60, 84, and 108, respectively Blumenfeld AM, Stark RJ, Freeman MC, Orejudos A, Manack Adams A. Long-term study of the efficacy and safety of OnabotulinumtoxinA for the prevention of chronic migraine: COMPEL study. J Headache Pain. 2018;19(1):1-12.
Case 4: George 42 y/o runner with longstanding history of bilateral knee OA. He is generally an active guy and runs on a regular basis, but is getting more and more difficult due to his knee pain. I just want it fixed
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Current MSK Treatment Paradigm Band-Aids Medications Corticosteroid Injections HA Injections Acupuncture? Neuromodulation Radiofrequency Ablation Botox Injections Surgery Healing Physical Therapy (Directly and Indirectly) Manual Medicine???
Regenerative Medicine Options PRP The Workhorse Regenerative Power ++ Mild to Moderate Joint Arthritis Tendon / Ligament Injury or Partial Tear Degenerative Disk Use Autologous Blood Treatment Cost $ Orthobiologics A2M The Inflammatory Shield Regenerative Power ++ Ideal for inflammatory arthritis conditions. It forms a protective shield for cartilage in joints. Faster Recovery Time than PRP (Super PRP) Use Autologous Blood Treatment Cost $$ Stem Cell The Cadillac Regenerative Power ++++ Moderate to Severe Joint Arthritis Tendon / Ligament Injury or Partial Tear Degenerative Disk Use Bone Marrow From Pelvis (or adipose) Treatment Cost $$$
What is PRP? Whole blood consists of: Plasma, Red Cells, White Cells, Platelets Platelet Rich Plasma is procured through concentrating the platelet concentration 1 million platelets/ul or 4 to 7 times the baseline count of 200,000 is required to provide clinical benefits (Marx) PRP consists of: Platelets, plasma, +/- Leukocytes Platelets initiate the healing cascade by releasing growth factors to act as mobile paramedics to attract Mesenchymal Stem Cells and Endothelial Cells, promote angiogenesis, promote cell differentiation and proliferation, and tissue remodeling
What is Stem Cell? Medicinal (previously Mesenchymal) Stem Cells are pluripotent cells in the body that can differentiate into multiple types of tissue (ie. Tendon, bone, muscle) Currently they are harvested from bone marrow and adipose tissue (FDA has limitations on adipose use) Preparation of Stem Cells for injection also includes PRP as it does require the Growth Factors to help with healing Recent studies indicate that a great number of MSCs do not survive in vivo, and the true mechanism of action of MSCs are to act as a powerful signaling cell to attract other native MSCs to the area of injury.
What is A2M? Alpha 2 Macroglobulin is a protein isolated in plasma that acts as an inflammatory shield from cartilage destroying proteases when injected into joints Multi-purpose protease inhibitor High concentration blood (0.1 6mg/ml) Inhibits MMPs & ADAMTS Proteases Binds to and regulates cytokines and growth factors Super PRP RCTs are limited currently but research shows great promise
Does it work? PRP and Tendonosis Paradigm shift in treatment to embrace inflammation. PRP vs steroid injections in treatment of Lateral Epicondylitis. Gosens& Peerbooms et al. AJSM. 2010. 38 (2) & June 2011 Vol 39#6, 1200-1208 Randomized controlled trial 100 patients : 51 PRP, 49 steroid. Peppering technique plus site of maximal tenderness, clock like manner VAS scores: 49% improved in steroid vs 73% in PRP group, DASH: 51% in steroid vs 73% in PRP group. PRP group continued improvement versus cortisone returned to baseline PRP: 64% improvement in pain, 84% disability vs. Corticosteroid: 24% improvement in pain, 17% disability *2 yr f/u showed continued improvements in pain & function with PRP*
PRP and Muscular Injury Challenging to study resulting in Limited data available Cugat: unpublished case series 2005 International society of arthroscopy 14 professional athletes (soccer and basketball) -16 muscular injuries PRP injected under ultrasound after hematoma aspiration 50% reduction in time to return to play in less severe injuries Appears safe & effective with little downside Platelet Poor Plasma(PPP) appears to result in better myoblast differentiation than PRP=better muscle healing (need RCTs) Post injection rehabilitation program unknown
PRP and Joint Arthritis Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis Jonathan C. Riboh,* y MD, Bryan M. Saltzman,y MD, Adam B. Yanke,y MD, Lisa Fortier,z DVM, PhD, and Brian J. Cole,y MD, MBA Investigation performed at the Division of Sports Medicine, Rush University Medical Center, Chicago, Illinois, USA Meta-analysis of 6 randomized controlled trials (evidence level 1) and 3 prospective comparative studies (evidence level 2) with a total of 1055 patients. Injection of LP-PRP resulted in significantly better WOMAC scores than did injection of hyaluronic acid (mean difference, 21.14; 95% CI, 39.63 to 2.65) or placebo (mean difference, 17.84; 95% CI, 34.95 to 0.73). No such difference was observed with LR-PRP (mean difference, 14.28; 95% CI, 44.80 to 16.25)
Stem Cell and Joint Arthritis Int Orthop. 2018 Mar 27. doi: 10.1007/s00264-018-3916-9. [Epub ahead of print] Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee. Hernigou P 1, Auregan JC 2, Dubory A 2, Flouzat-Lachaniette CH 2, Chevallier N 2, Rouard H 2. 12 year study Looked at osteonecrosis and OA Treated bilateral OA 1 side gets a TKA vs the other gets subchondral stem cells. 60 knees: 30 Patients Quantified Cell content of the injectate (avg. 6500 MSC/ml) 21 patients preferred the knee with cell therapy and 9 preferred the knee with TKA Stem Cells more popular than TKA in patients that had both Lower rate of complications and subsequent surgery associated with Stem Cell injection Outcomes about the same between both knees
Stem Cells and Discs Stem Cells do reverse the disc degenerative process radiographically Spine (Phila Pa 1976). 2010 May 15;35(11):E47580. doi: 10.1097/BRS.0b013e3181cd2cf4. Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Yoshikawa T, Ueda Y, Miyazaki K, Koizumi M, Takakura Y. Stem Cells clinically improves discogenic pain long-term International Orthopaedics (SICOT) (2017) 41:2097 2103 DOI 10.1007/s00264-017-3560-9 Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up Kenneth A. Pettine 1 & Richard K. Suzuki 2 & Theodore T. Sand2 & Matthew B. Murphy2,3
hope
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