A Comprehensive, Integrative Approach to Chronic Pain

AARM

September 29, 2018

Todd A. Born, ND, CNS

Born Naturopathic Associates, Inc.

Disclosures

• Co-owner and medical director

• www.bornnaturopathic.com

Born Naturopathic Associates,

Inc.

• Head of new product development, Scientific Advisor, Editor-in-chief of Focus Newsletter

• Clinical Education

• Thought Leader

Allergy Research Group LLC

• President, Advisor and Lead Educator

• http://isnm-us.org/

International Society for

Naturopathic Medicine

Objectives1. Understand the different types of pain, along with common causes.

2. Treatment options for chronic pain generally fall into six major categories.

a. pharmacologic, physical medicine, behavioral medicine, neuromodulation, interventional, and surgical approaches

3. Optimal patient outcomes often result from multiple approaches utilized in concert and coordinated via a multidisciplinary team.• Kamper SJ, Apeldoorn AT, Chiarotto A, et al. Multidisciplinary biopsychosocial rehabilitation for chronic low back

pain: Cochrane systematic review and meta-analysis. BMJ. 2015;350:h444. Epub 2015 Feb 18.

4. Discuss most common evidence-based pharmacological and non-pharmacological options to improve patient outcomes and quality of life.

Quick (Depressing) Factoids• Affects more than 100 million people in the United States accounts for 20% of outpatient

visits, 12% of all prescriptions, and over $100 billion dollars in direct and indirect expenses.

• Alford DP, et al. Update in pain medicine. J Gen Intern Med. 2010;25(11):1222. Epub 2010 Jul 15.

• Pain-related expenditures (direct costs and lost wages) in the US exceed those for cancer, heart disease, and diabetes combined.

• Pizzo PA and Clark NM. Alleviating suffering 101--pain relief in the United States. N Engl J Med. 2012 Jan;366(3):197-9.

• “The use and misuse of opioids for management of chronic pain is a major concern, with problems arising from their multiple adverse side effects including drug dependency, from drug diversion, and from under-treatment of chronic pain symptoms for fear of opioid abuse. Chronic pain is thus a major medical and social issue, affecting the quality of life of individual patients, their friends and families, the work force, and society in general.”

• Rosenquist EWK. Evaluation of chronic pain in adult. Uptodate. Accessed 7/13/2018.

Categories

• Neuropathic

• Musculoskeletal

• Inflammatory• (infections, arthropathies)

• Mechanical/compressive

****Note, those with chronic pain typically fall into multiple categories.

Hardt J, et al. Prevalence of chronic pain in a representative sample in the United States. Pain Med. 2008;9(7):803.

Approach to the Patient

• Thorough eval with comprehensive HPI and PE

• Standardized pain scales

• Assess psychosocial factors

• What have they tried?

• What’s worked, what’s not worked?

• Why?

Approach to the Patient

Diagnostic imaging

Blood tests

• Standard testing (CBC, CMP, etc.), Inflammatory (CRP, hs-CPR, ESR, Hcy, IL-16, TNF-α), Hormones (DHEA-S, Pregnenolone, Testosterone, Progesterone, Estrogen), Autoimmune (ANA, CCP, RF), Infections, Thyroid panel (TSH, FT3, FT4, TPO), Vitamin D, Celiac Panel, HLA DQ2/D8, MMA, B12, B6, RBC Folate, Ionized calcium

Other testing

• NCV, EMG, Interventional testing

• Consider pain sensitization syndrome (aka central sensitization)• Nociceptor inputs can trigger a prolonged but reversible

increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways• Woolf CJ. Central sensitization: Implications for the

diagnosis and treatment of pain. Pain. 2011 Mar; 152(3 Suppl): S2–15.

Comorbidities

• Depression & Anxiety • Up to 75%!

• Insomnia

• Fatigue

Dahan A., et al. Comorbidities and the Complexities of Chronic Pain. Anesthesiology 10 2014, Vol.121, 675-677.

Cosio D. Sleep-Wake Disorders and Chronic Pain: Reciprocal and Interactive Effects. Practical Pain Management. Volume 17, Issue #6.

The Integrative Team

Naturopathic

Chiropractic

Acupuncture

Massage therapy

“Energetic” practitioners

Physiatry

PT/OT

Orthopedics

Neurology

Mind/body

Interventions

Conventional approach

• Treatment options for chronic pain generally fall into six major categories.

1. Pharmacologic

2. Physical

3. Behavioral

4. Neuromodulation

5. Interventional

6. Surgical

Unfortunately, these only provide a 30% reduction in pain

• Turk DC, et al. Treatment of chronic non-cancer pain. Lancet. 2011;377(9784):2226.

Pharmacologic approaches are the most widely used

therapeutic options to ameliorate persistent pain.

• Nonopioid analgesic agents

• Opioids

• Alpha 2 adrenergic agonists

• Antidepressants

• Antiepileptic drugs

• (gabapentin, pregabalin, and other anticonvulsants)

• Muscle relaxants

• N-methyl-d-aspartate (NMDA) receptor antagonists

• Topical analgesic agents

• DMARDs

• Steroids

Medication Ladder

“Despite significant progress, chronic pain remains refractory to treatment, with only one-third to two-thirds of patients reporting adequate (>50%) pain relief. Moreover, first-line drugs, non-steroidal anti-inflammatory agents (NSAIDS; e.g., aspirin) and opioids (e.g., morphine), are associated with adverse dose-limiting side-effects, dependence, and tolerance.” Tsantoulas C & McMahon SB. Opening paths to novel analgesics: the role of potassium channels in chronic pain. Trends Neurosci. 2014 Mar;37(3):146-58

Integrative Approach to Interventions

Evidence points to combo therapies more effective•Scascighini L, et al. Multidisciplinary treatment for chronic pain: a systematic review of interventions and outcomes. Rheumatology (Oxford). 2008;47(5):670.

Evaluation of the cause

Nociceptive vs neuropathic

Integrative Approach to Interventions

• Karagülle M & Karagülle MZ. Effectiveness of balneotherapy and spa therapy for the treatment of chronic low back pain: a review on latest evidence. Clin Rheumatol. 2015 Feb;34(2):207-14.

Hydrotherapy & Balneotherapy

• Any manual therapy

• Gordon R & Bloxham S. A Systematic Review of the Effects of Exercise and Physical Activity on Non-Specific Chronic Low Back Pain. Healthcare (Basel). 2016 Jun; 4(2): 22.

Physiotherapy

• Qaseem A, et al. 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(7):514-530.

“American College of Physicians low back pain guideline recommends

spinal manipulation along with heat,

massage and acupuncture.”

Integrative Approach to Interventions

• Small electrical impulses to repair tissue, stimulate muscles and increase sensations and muscle strength.

• E-stim, U/S, LLT• Rajifur J, et al. Efficacy of Selected Electrical Therapies

on Chronic Low Back Pain: A Comparative Clinical Pilot Study. Med Sci Monit. 2017; 23: 85–100.

Electrotherapy

• Anti-inflammatory•Seaman DR. The diet-induced proinflammatory state: a cause of

chronic pain and other degenerative diseases? J Manipulative Physiol Ther. 2002 Mar-Apr;25(3):168-79.

• Allergy/elimination

• 30-40% reduction in pain•Shen H. Should You Switch to an Elimination Diet to Fight

Chronic Pain? Cleveland Clinic. April 2016.

Diet

Integrative Approach to Interventions

➢Homeopathy➢“Homeopathy for Musculoskeletal Healing,” by Asa Hershoff

➢Singh MM. Homeopathy and pain relief. Response to Management of chronic pain using complementary and integrative medicine. BMJ 2017;357:j1284.

➢Linde K, et al. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet. 1997 Sep 20;350(9081):834-43.➢ “The results of our meta-analysis are not compatible with the hypothesis that the clinical

effects of homeopathy are completely due to placebo.”

Integrative Approach to Interventions

Botanicals➢Analgesics/Anodynes

➢Salix alba➢ Providing 120-240 mg salicin

Schmid B, et al. Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial. Phytother Res. 2001 Jun;15(4):344-50.

➢Anti-arthritic/anti-inflammatory

➢Curcuma longa (500-4000 mg)

➢Standardized to % curcuminoidsJäger R, et al. Comparative absorption of curcumin formulations. Nutr J. 2014 Jan 24;13:11.

Daily JW, et al. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2016 Aug 1; 19(8): 717–729.

➢Boswellia serrata (300-1500 mg)

➢Standardized to % boswellic acidsMaroon JC, et al. Natural anti-inflammatory agents for pain relief. Surg Neurol Int. 2010; 1: 80.

Integrative Approach to Interventions

➢Anti-arthritic/anti-inflammatory➢Harpagophytum procumbens

➢Providing 30-100 mg harpagosidesGagnier JJ, et al. Harpgophytum procumbens for osteoarthritis and low back pain: a systematic review. BMC Complement AlternMed. 2004 Sep 15;4:13.

➢Uncaria tomentosa (100-3600 mg)Mur E., et al. Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of uncariatomentosa for the treatment of rheumatoid arthritis. The Journal of Rheumatology April 2002, 29 (4) 678-681.

Rodriguez JP, et al. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflammation Research. September 2001, Volume 50, Issue 9, pp 442–448.

➢Zingiber officinale (500-1000 mg)➢Standardized to gingerols

➢ Haghighi M, et al. Comparing the effects of ginger (Zingiber officinale) extract and ibuprofen on patients with osteoarthritis. Arch Iran Med 2005;8:267-71.

Integrative Approach to Interventions

• Cimicifuga (Actea) racemosa

• Dioscorea villosa

• Matricaria spp

• Piscidia piscipula

• Viburnum sp

Anti-spasmotics

• Ginsengs

• Withania somnifera

• Rhodiola rosea

• Ocimum sanctum/tenuiflorum

• Glycyrrhiza glabra

Adaptogens

Integrative Approach to Interventions

➢Immunomodulators➢Cordyceps sinesis

➢All mushrooms

➢Phospholipid colostrum

➢Fucoidan

➢Nervines➢Eschscholzia californica

➢Matricaria recutita

➢Melissa officinalis

➢Avena sativa

Vitamins

• B-vits• Ex: B1, B6 & B12

• Jurna I. [Analgesic and analgesia-potentiating action of B vitamins]. Schmerz. 1998 Apr 20;12(2):136-41.

• Medina-Santillán R, et al. Treatment of diabetic neuropathic pain with gabapentin alone or combined with vitamin B complex. preliminary results. Proc West Pharmacol Soc. 2004;47:109-12.

• Vitamin D 1000-5000 IU• “Optimal” blood levels 50 ng/mL• Suppresses PG action, inhibition of p38 stress kinase signaling, tumor angiogenesis, invasion, and metastasis

and inhibition of NF-κB signaling• Krishnan AV & Feldman D. Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D. Annu Rev Pharmacol

Toxicol. 2011;51:311-36.

• Moyad MA. Vitamin D: a rapid review. Urol Nurs. 2008 Oct;28(5):343-9, 384; quiz 350.

• Vitamin E family 100-800 IU/mg daily• Inhibits macrophage migration inhibitory factor (MIF), reducing neuropathic pain

• Hedge B, et al. Vitamin E is a MIF Inhibitor. Biochem Biophys Res Commun. 2012 Feb 10;418(2):384-9.

Minerals

• Nielsen FH. Update on human health effects of boron. J Trace Elem Med Biol. 2014 Oct;28(4):383-7.Boron 6 mg

• Are your medications causing nutrient deficiency? Harvard Health Letter. August 2016.

Calcium 500-1000

mg

• Bagis S, et al. Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia? Rheumatol Int. 2013 Jan;33(1):167-72.

• Rosanoff A, et al. Suboptimal magnesium status in the United States: are the health consequences underestimated? Nutr Rev. 2012 Mar;70(3):153-64.

Magnesium 300-1400

mg

Amino Acids

• Acetyl-l-carnitine 500-3000 mg• Stimulates phospholipid synthesis

• Neuromodulatory

• Protein and gene expression

• NGFSima AA, et al. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care. 2005 Jan;28(1):89-94.

• DL-Phenylalanine 500-2000 mg• Walsh NE, et al. Analgesic effectiveness of D-phenylalanine in chronic pain patients. Arch Phys Med Rehabil.

1986 Jul;67(7):436-9.

• Budd K. Use of D-phenylalanine, an enkephalinase inhibitor, in the treatment of intractable pain. Adv Pain Res Ther. 1983. 5: 305-308.

Essential Fatty Acids

• Omega-3 1000 mg-10 grams• Suppression of NFkappaB, COX-2, tumor necrosis factor (TNF)-alpha, and interleukin

(IL)-1beta.• Lipid mediators: resolvins, protectins

Maroon JC & Bost JW. Omega-3 fatty acids (fish oil) as an anti-inflammatory: an alternative to nonsteroidal anti-inflammatory drugs for discogenic pain. Surg Neurol. 2006 Apr;65(4):326-31.

Kang JX & Weylandt KH. Modulation of inflammatory cytokines by omega-3 fatty acids. Subcell Biochem. 2008;49:133-43.

• Omega-6 (Gamma Linolenic Acid) 300-600 mg• Inhibits IL-1-beta & NF-kB

Chang CS, et al. Gamma-linolenic acid inhibits inflammatory responses by regulating NF-kappaB and AP-1 activation in lipopolysaccharide-induced RAW 264.7 macrophages.Inflammation. 2010 Feb;33(1):46-57.

Zurier RB, Furse RK, Rosetti RG. Gamma-linolenic acid (GLA) prevents amplification of interleukin-1-beta (IL-1-beta). Altern Ther 2001;7:112.

• Omega-9 (Oleic acid) 50-500 mgCarrillo C, et al. Role of oleic acid in immune system; mechanism of action; a review. Nutr Hosp. 2012 Jul-Aug;27(4):978-90

Other

• Methylsulfonylmethane 1-6 grams• Debbi EM, et al. Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study.

BMC Complement Altern Med. 2011;11:50.• Methylsulfonylmethane (MSM). Monograph. Altern Med Rev. 2003;8(4):438-41.

• Glutathione 300-3000 mg hs• Steele ML, et al. Chronic Inflammation Alters Production and Release of Glutathione and Related Thiols in Human U373 Astroglial

Cells. Cell Mol Neurobiol. 2013 Jan;33(1):19-30.• Labianca R, et al. Adverse effects associated with non-opioid and opioid treatment in patients with chronic pain. Clin Drug Investig.

2012 Feb;32 Suppl 1:53-63.• Cascinu S, et al. Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a

randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2002 Aug 15;20(16):3478-83.

• Alpha Lipoic Acid 300-600 mgReduces TNFα and IL-6• Memeo A & Loiero M. Thioctic acid and acetyl-L-carnitine in the treatment of sciatic pain caused by a herniated disc: a randomized, double-blind,

comparative study. Clin Drug Investig. 2008;28(8):495-500.

• Ziegler D, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care. 1999 Aug;22(8):1296-301.

• Zhang Y, et al. Amelioration of lipid abnormalities by a-lipoic acid through antioxidative and anti-inflammatory effects. Obesity (Silver Spring) 2011;19(8):1647-1653.

Other

• Agmatine Sulfate 890-2670 mg• Keynan O, et al. Safety and Efficacy of Dietary Agmatine Sulfate in Lumbar Disc-associated Radiculopathy. An Open-label,

Dose-escalating Study Followed by a Randomized, Double-blind, Placebo-controlled Trial. Pain Med. 2010 Mar;11(3):356-68.

• Tohidi V, et al. Palliative effects of agmatine sulfate on neuropathic pain in small fiber neuropathy. Poster presentation: P7.094. American Academy of Neurology 66th Annual Meeting 2014

• Lipid replacement Therapy 600-6000 mg• Nicolsen GL & Ash M. Lipid Replacement Therapy: A natural medicine approach to replacing damaged lipids in cellular membranes

and organelles and restoring function. Biochim Biophys Acta. 2014 Jun;1838(6):1657-79.

• Nicolsen GL. Diagnosis and Therapy of Chronic Systemic Co-infections in Lyme Disease and Other Tick-Borne Infectious Diseases. Townsend Letter for Doctors and Patients 2007.

• Ellithorpe R. Lipid Replacement and Antioxidant Nutritional Therapy for Restoring Mitochondrial Function and Reducing Fatigue in Chronic Fatigue Syndrome and Other Fatiguing Illnesses. Journal of Chronic Fatigue Syndrome, Volume 13, 2006 - Issue 1.

Hormones

Hormones

• Dose based upon test results

• DHEA & 7-Keto DHEA, Pregnenolone, Estrogen, Progesterone, Testosterone

• Kalimi M, et al. Anti-glucocorticoid effects of dehydroepiandrosterone (DHEA). Mol Cell Biochem. 1994 Feb 23;131(2):99-104.

• Robinzon B & Cutolo M. Should dehydroepiandrosterone replacement therapy be provided with glucocorticoids? Rheumatology (Oxford). 1999 Jun;38(6):488-95.

• Lapchak PA, Araujo DM. Preclinical development of neurosteroids as neuroprotective agents for the treatment of neurodegenerative diseases. Int Rev Neurobiol. 2001;46:379-97.

• Baulieu EE. Neurosteroids: of the nervous system, by the nervous system, for the nervous system. Recent Prog Horm Res. 1997;5:21-32.

• Gold SM, Voskuhl RR. Testosterone replacement therapy for the treatment of neurological and neuropsychiatric disorders. Curr OpinInvestig Drugs. 2006 Jul;7(7):625-30.

• Gandy S. Estrogen and neurodegeneration. Neurochem Res. 2003 Jul;28(7):1003-8.

Pharmaceuticals• Prednisone

• Carisoprodol

• Metaxalone

• Cyclobenzaprine

• Diclofenac patch

• Anti-nauseas• Prochlorperazine• Promethazine• Ondansetron

• NSAIDs

• Low-Dose Naltrexone (0.5-4.5 mg hs)• Inhibit microglial activation, suppresses activation of NMDA receptors by decreasing the release of glutamate.• Increases endorphins❖ Caveat: not to be used with opiates or synthetic narcotics. Naltrexone blocks opioid receptors.

• https://ldnresearchtrust.org/content/low-dose-naltrexone-and-chronic-pain-pradeep-chopra-md• https://ldnresearchtrust.org/ldn-clinical-trials• https://ldnresearchtrust.org/sites/default/files/LDN-2018-Fact-Sheet-USA.pdf

Cannabidiol

• Phytocannabinoids (5-150 mg)• MOA: depends on receptor target

• “The endocannabinoid system parallels and interacts at many points with the other major endogenous pain control systems: endorphin/enkephalin, vanilloid/transient receptor potential (TRPV), and inflammatory.”

• Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008 Feb;4(1):245-59.

• Fernández-Ruiz J, et al. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? Br J Clin Pharmacol. 2013 Feb;75(2):323-33.

Tough Cases-What to do?

• Liver/Kidney support• Acetaminophen is found in more than 600 medications

• 50 million Americans take it each week• #1 cause for acute hepatic failure in US

• Pain meds clearance is decreased in those with hepatic insufficiency.Acute Liver Failure: Mayo Clinic. 2017.

Soleimanpour H, et al. Opioid Drugs in Patients With Liver Disease: A Systematic Review. Hepat Mon. 2016 Apr; 16(4): e32636.

• Dysbiosis/SIBO/Rebuild• O'Mahony SM, et al. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res. 2015

Jan 15;277:32-48.• Galland L. The Gut Microbiome and the Brain. J Med Food. 2014 Dec 1; 17(12): 1261–1272. • Mathis D. A gut feeling about arthritis. Elife. 2013 Nov 5;2:e01608.• Vaghef-Mehrabany E, et al. Probiotic supplementation improves inflammatory status in patients with rheumatoid

arthritis. Nutrition. 2014 Apr;30(4):430-5.• Andrew C. Dukowicz, et al. Small Intestinal Bacterial Overgrowth A Comprehensive Review. Gastroenterol Hepatol (N

Y). 2007 Feb; 3(2): 112–122.

Tough Cases-What to do?

• Creams, lotions, potions, gels, patches, castor oil

Topicals

• Kali phos 6x + Calc phos 6x

• Mag phos 6x

Cell/Tissue salts

• Wolfgang BW, et al. The Safety and Efficacy of an Enzyme Combination in Managing Knee Osteoarthritis Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis. 2015; 2015: 251521.

• Paradis ME, et al. Impact of systemic enzyme supplementation on low-grade inflammation in humans. PharmaNutrition. Volume 3, Issue 3, July 2015, Pages 83-88.

Proteolytic enzymes

• Psychotherapy, CBT, hypnotherapy, EFT, etc.• Griffith LJ. Why Psychotherapy Helps the Patient in Chronic Pain. Psychiatry

(Edgmont). 2008 Dec; 5(12): 20–27.

Psychological

Tough Cases-What to do?

Mitochondrial dysfunction

• Sui BD, et al. Understanding the role of mitochondria in the pathogenesis of chronic pain. Postgrad Med J. 2013 Dec;89(1058):709-14.

• Scatena R, et al. The role of mitochondria in pharmacotoxicology: a reevaluation of an old, newly emerging topic. Am J Physiol Cell Physiol. 2007 Jul;293(1):C12-21. Epub 2007 May 2.

• Meeus M, et al. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets? Expert Opin Ther Targets. 2013 Sep;17(9):1081-9.

Regenerative therapies

• PRP, prolotherapy, ozone, prolozone

• Andia L, et al. Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat Rev Rheumatol. 2013 Dec;9(12):721-30.

• Reeves KD & Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med. 2000 Mar;6(2):68-74, 77-80.

• A. M. Elvis and J. S. Ekta. Ozone therapy: A clinical review. J Nat Sci Biol Med. 2011 Jan-Jun; 2(1): 66–70.

• Shallenberger F. ProlozoneTM-Regenerating Joints and Eliminating Pain. Journal of Prolotherapy. 2011;3(2):630-638.

Take Home Messages

Tolle causam

Find the triggers

Multi-faceted, multi-targeted,

multi-team, multi-mechanism

approach works best for even the

most complex cases.

Be systematic and triage.

Sometimes just need to stop the gorilla.

Don’t be afraid to bring in

collateral help

Dosage guidelines

Thank You