Pain, Prejudice and Opioids: Emerging Policy and Integrative Practice

Integrative Healthcare Symposium February 23, 2016

John Weeks

Jane Ballantyne, MD

Heather Tick, MD

Objectives: Participants Will Be Able To

.. • Discuss the level of inclusion of non-

pharmacologic approaches in emerging pain

policy

• Evaluate the role of interprofessionalism

and being at the table on the creation of

policy directions

• Discuss the level of risk with non-

pharmacologic approaches to pain.

• Explore the necessity for policy and

practice changes regarding the role of

opioids in the management of chronic pain

Disclosure: I have no conflicts of interest. I do have multiple alignments of interest, volunteer roles and limited

consulting with not-for-profit organizations on pain related issues.

Opioid/Pain Policy

The Awakening to Non-Pharmacologic

and Integrative Approaches

Early Opioid Guidance -

2011 Center with

significant CAM

research – but

no reference to

CAM

in guideline.

Why? Dan Cherkin, PhD

Is it possible that a

characteristic of a

reductive mind

is that it can’t

access common

sense?

Relieving Pain in America 2011 - IOM

Rick Marinelli, ND, LAc

• IOM Committee on Advancing Pain Research, Education and Care

– ND, LAc pain expert Marinelli

– UCLA Integrative pediatrician Zelzer

• “CAM” included in 15 relevant segments

– Re cost-effective, education, under barriers, self-management, interdisciplinary teams, reimbursement, etc.

http://theintegratorblog.com/index.php?option=com_content&task=view&id=759&Itemid=93

• Antecedent to the National Pain Strategy

Pain focus in NCCAM Strategic Plan Highlighted in Strategic Objective #1

Lonnie Zelzer, MD

Joint Commission - November 2014

CDC’s Opioid

Guidance

DRAFT CDC Guideline: Were Integrative Health

and CAM Professionals on the Team?

• Stakeholder Review Group had no

representatives

• National Center for Injury

Prevention and Control’s Board

of Scientific Counselors had no

apparent representation

DRAFT Guideline: CDC “Non-Pharmacologic”

Methods December 2015

“Nonpharmacologic therapy and

nonopioid pharmacologic therapy are

preferred for chronic pain.

DRAFT: explicitly included as non-

pharma:

“ … complementary and alternative

therapies (e.g., manipulation, massage,

and acupuncture ) … “

What happened with the draft?

CDC Comment Period

Multiple integrative health

organizations respond

Publicized and promoted response

FINAL CDC Description of “Non-Pharmacologic”

Methods

“Nonpharmacologic therapy and nonopioid

pharmacologic therapy are preferred for

chronic pain.”

FINAL: Explicit Options for Non-Pharma:

“Exercise, aquatic, aerobic, psychological,

cognitive behavioral therapy, and

bio-psycho-social interventions”

RECALL DRAFT: Also explicitly included:

“ … complementary and alternative therapies (e.g., manipulation,

massage, and acupuncture ) … “

What happened with the draft?

Integrative Health and Medicine Representatives on Teams?

• Oversight Panel: No experts from

IHM/CAM

• 6 Working Groups (80 total members) • Working Group on Prevention and Care: None

• Working Group on Disparities: None

• Working Group on Service Delivery and Payment:

None Working Group on Professional Education

and Training: one, Brian Berman, MD

• Working Group Public Education &

Communication: None

Brian Berman,

MD

Is it possible that a characteristic of a reductive mind is

that it can’t access common sense?

CAM/IHM Inclusion

as “Collaborators”

Vision Statement: 8th of 14 bullets, under education, at the end of list of prioritized areas:

“the role of complementary and integrative medicine.”

Listed among “Collaborators”

-Service Delivery & Payment Objective #1: “Define and evaluate integrated, multimodal

and interdisciplinary care ...” urged inclusion of “licensed integrative health practitioners.”

-Same section, Objective #3,: “Tailor payment to promote and incentivize high-quality,

coordinated pain care ...” reaches out to “licensed integrative health care providers.”

-Disparities, Objective #1: “Reduce bias (implicit, conscious, and unconscious) and its

impact on pain treatment by improving understanding ...” calls out to include “social

service providers (including licensed practitioners who provide integrative and

complementary health approaches).”

-Prevention and Care, Objective #2: “Develop nationwide pain self-management

programs...” invites collaboration with “licensed complementary and integrative health

fields.”

Brian Berman,

MD

Is it possible that a characteristic of a reductive mind is

that it can’t access common sense?

Obama and Congressional Opioid Plans

(2016)

• Obama strategy: IHM absent

• Congressional plan: IHM absent

The Uneven Entrance of Non-Pharma Approaches

as Tools in the Opioid Crisis http://altarum.org/health-policy-blog/the-uneven-entrance-of-nonpharmacologic-approaches-as-tools-in-the-opioid-

crisis

Leadership: Get into the Opioid Conversation!

• American Public Health Association resolution – Nursing section backed

– Support from Chiropractic Section and Integrative, Complementary and Traditional Health Practices Section

• Foundation for Chiropractic Progress(F4CP) white paper

• AANP reaches out to AMA as resource

• IHPC Task Force – planning 2017 action

Michele Maiers, DC, PhD APHA Chiropractic Section

Beth Sommers, PhD, MPH, LAc APHA Integrative, Complementary and

Traditional Medicine Section

Steve Welsh, DC IHPC Task Force Chair

Leadership: Will States - and Lobbying by

State Professional Associations - Take the

Lead? • Oregon Inclusion in Coordinated Care

Organizations (Medicaid) – “The following integrative treatments are among

the recommended therapies: acupuncture, chiropractic manipulation, cognitive behavioral therapy, osteopathic manipulation.”

– “In addition, yoga, intensive rehabilitation, massage, and/or supervised exercise therapy are recommended to be included in the comprehensive treatment plans.”

– Naturopathic doctors already allowed to run Coordinated Care Organizations

• Vermont – S. 243, Sec. 15A An act relating to combatting opioid abuse

– $463,000 for acupuncture pilot

John Singer, Lac Vermont Acupuncture Association Laura Ocker, LAc

Oregon Acupuncture Assn.

Kimberly Tippens, ND, MSAOM, MPH National Univresity of Natural

Medicine

NCCIH/Mayo Scientific Guidance

for PCPs Team led by Richard Nahin, PhD

-Acupuncture and yoga for back pain

-Acupuncture and tai chi for osteoarthritis of the knee

-Massage therapy for neck pain with adequate doses

and for short term benefit

-Relaxation techniques for severe headaches and

migraine

September 2016

Convergence: Integrative Pain

Care

New Back Pain Guideline

“Noninvasive Treatments for

Acute, Subacute, and

Chronic Low Back Pain: A

Clinical Practice Guideline

From the American College

of Physicians”

February 2017

Proposed Standards Revisions Related to Pain

Assessment and Management.

"The hospital promotes access to non-pharmacologic

pain treatment (this may include alternative modalities,

such as chiropractic, relaxation therapy, music

therapy).”

February 20, 2017 comment period closed

Last Week!

From “Never Only Opioids” to

“Never only (drug name here)”

Thank You!

Managing chronic pain: the age before and after opioids

JANE C BALLANTYNE

UNIVERSITY OF WASHINGTON, SEATTLE

“Make me fully understand that the ills of the body are nothing else than the punishment and the encompassing symbol for the ills of the soul ….. the greatest sickness is insensibility … Let me feel this pain sharply so that I can make whatever is left of my life a continual penance to wash away the offenses I have committed.” Blaise Pascal “Priere pour demander a dieu le bon usage des maladies” prayer circa 1659

Before Descartes

L'homme de Rene Descartes. Paris: 1664

Pain carried in a line labelled system

• Early reductionist view

• First to describe pain as a perception, existing in the brain

• Distinguished from sensory transduction

“Many investigators seem grimly determined to establish ….that for a given stimulus there must be a given response; that is, for so much stimulation of nerve endings, so much pain will be experienced, and so on. This fundamental error had led to enormous waste. It is evident ….. that there is no simple relationship between stimulus and subjective response. It is also made evident that the reason for this is the interposition of conditioning, of the processing component, of the psychic reaction.”

Beecher HK Increased stress and effectiveness of placebos and “activity” drugs Science 132;91-2 July 1960

Developed approaches to dealing with pain that were groundbreaking at the time (1960s) Used behavioral principles to encourage chronic pain patients to become active again and cut back on pain medication Led the way to the integration of psychological principles and psychologists into the care of chronic pain Developed the idea of operant conditioning

Pain doesn’t just produce pain behaviors, attitudes, movements and postures, but is produced by them.

The idea of multidisciplinary pain management: • PT to improve conditioning and body awareness • Learn CBT strategies for managing pain and developing

healthy habits • Learn injury avoidance and unlearn fear avoidance • Use drugs and interventions as indicated but do not focus on

them

Wibert Evans “Bill” Fordyce 1923-2009

We were in a very good place …........ And then along came opioids

0

1

2

3

4

5

6

7

8

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Rate

Year

Opioid Sales KG/10,000

Rates of Opioid Sales, OD Deaths, and Treatment, 1999–2010

CDC. MMWR 2011

Primary non-heroin opiates/synthetics admission rates, by State

(per 100,000 population aged 12 and over)

Public health impact of opioid pain reliever use

Based on 15,597 OPR overdose deaths in 2009. Treatment admissions are for primary use of opioids from Treatment Exposure Data set for 2009. Emergency department (ED) visits are from DAWN (Drug Abuse Warning Network) for 2009, https://dawninfo.samhsa.gov/default.asp Abuse/dependence and nonmedical use in the past year are from the 2009 National Survey on Drug Use and Health

Past Year Nonmedicalusers

People withabuse/dependence

ED visits for misuse orabuse

Abuse treatmentadmissions

For every opioid overdose death in 2009 there were:

30

118

795

9

32

Mortality by cause, white non-Hispanics ages 45–54

Case A, Deaton A. Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century. Proceedings of the National Academy of Sciences. November 2, 2015

1. Palliative care physicians promoted opioids for chronic pain

2. Pharmaceutical industry promoted opioids for chronic pain

3. US healthcare system factors

4. US cultural factors Ventafridda et al Int J Tiss React 1985 Scholten & Henningfield J Pain Palliat Care Pharmacother 2016 WHO Persisting Pain in Children 2012 Ballantyne et al BMJ 2016

Why did it happen?

34

Industry-funded “educational” messages

•Physicians are allowing patients to suffer needlessly because of “opiophobia.”

•Opioid addiction is rare in pain patients.

•Opioids can be easily discontinued.

•Opioids are safe and effective for chronic pain.

•Palliative care principles such as titration-to-effect apply equally to chronic pain.

Porter & Jick NEJM 1080 Portenoy & Foley PAIN 1986 Sullivan & Ballantyne Arch Int Med 2012 Ballantyne & Sullivan NEJM 2015

Source: United States General Accounting Office: Dec. 2003, “OxyContin Abuse and Diversion and

Efforts to Address the Problem.”

Dollars Spent Marketing OxyContin (1996-2001)

JCAHO Pain Management Standards 2001 Zgierska et al JAMA 2012

What’s wrong with using opioids long-term and continuously?

1. Misunderstands chronic pain: suffering is related less to intensity than to meaning, disability, role function, attitude and expectation, all of which can be changed

2. Commandeers the endogenous opioid system: a system that is important for defining who we are and how we react to the world – destroys natural defenses

3. Causes neuroadaptations: tolerance and dependence are linked adaptations that account for opioid failure

4. Susceptible individuals will become addicted at a fairly constant rate (between 12 and 20%): the more that is prescribed, the more addiction will occur

5. Activity and exercise are therapeutic for many pain conditions, especially musculoskeletal pain: opioids are deactivating

• The pain and opioid systems evolved through

evolutionary processes over millions of years

• Giving exogenous opioids overwhelms these natural systems and prevents the protective, defensive mechanisms from taking place

• Central control (top down) contributes as much as nociception to the experience of pain and is a powerful means of controlling pain

• Opioid systems are intimately involved in the group processes, the top down effects

• Isolation, withdrawal, distress, family, job, culture all influence the development of chronic pain and are indicators of derangement in natural (opioid) systems

Current theories about the purposes of the endogenous opioid system suggest two important categories: • to provide stress-related pain relief and pain

enhancement (injury-related “physical pain”)

• to facilitate maternal-infant and other attachments

The overuse of opioids for chronic pain is a distinctly US problem ….... What is the US going to do about it?

Systems map for obesity

• Employing self management programs to improve patient quality of life as an important component of acute and chronic pain prevention and management

• Use of integrated, multimodal and interdisciplinary treatment approaches

• Reducing incentives for treatments with little absolute benefit or a limited benefits relative to risks

• Increasing incentives and reimbursement strategies to promote high-quality coordinated pain care through an integrated biopsychosocial approach

• “Safe use campaign” for opioids

Draft National Pain Strategy A comprehensive population health-level strategy for pain 2015; http://iprcc.nih.gov/docs/DraftHHSNationalPainStrategy.pdf

• Suffering may be expressed as physical pain, but its roots often lie much deeper

• These roots are created by past experiences and present fears, not found in the body or explained by pathology

• Modern imaging enables us to see most pathological causes of pain

• Thus, we understand that two individuals with the same pathology on an image may experience this condition very differently

• For one person the physical pain becomes the focus for a life of suffering, while for another, the physical pain is sublimated, or even disappears.

Let us go back to what Beecher and Fordyce recognized a long time ago

Cultural transformation needed is demedicalization of the most common pain conditions

OLD PATHWAY NEW PATHWAY

2016 The CDC Guideline

What’s new?

• Offers different patient selection criteria (1.) • Discourages use of long-acting opioids (4.) • Suggests dose limitations (5.) • Recognizes ‘legacy patients’ as a different category (5.) • Considers acute use as a pathway to chronic use (6.)

Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016 wwwcdcgov/mmwr/volumes/65/rr/rr6501e1htm 2016.

New teaching based on new evidence

• People who have failed all other treatments tend to have a high-risk profile thus opioids are often a bad choice if used for the reason that all other treatments have failed

• Opioids cause problematic use in up to 30%, and addiction in up to 20% • Risk mitigation strategies have not been shown to reduce adverse

outcome, 80% do not get good long-term efficacy • Copious evidence now links adverse outcomes to high dose • Long acting opioids are more likely to produce tolerance leading to loss of

efficacy and dose escalation without protecting from addiction

Compare with old teaching

• Opioids are a reasonable option if all other treatments have failed

• Opioids rarely cause addiction if used to treat pain (5% incidence)

• Provided cautions are used, most COT

is safe and effective

• There is no ceiling dose

• Long acting opioids provide consistent analgesia with less risk of addiction

Sullivan et al Arch Intern Med 2006;166:2087 Vowles et al Pain 2015;156:569 Chou et al Ann Intern Med 2015;162:276 Le Marec et al Psychopharmacology 2011;216:297 Yu et al J Pscyhiatr Res 2014;59:161

BENEFIT RISK

Intractable pain-producing disease

Goal is comfort

Substance abuse Hx, including smoking

Family Hx sub abuse

Childhood sexual abuse

PTSD

Anxiety

Depression

Other MHD

Young age

Is the patient a suitable candidate for opioids?

1.Sullivan MD, Ballantyne JC. Arch Int Med. 2012;172(5):433-434. 2.Martin BC, Fan MY, Edlund MJ et al J Gen Intern Med. Dec 2011;26(12):1450-1457. 3.Schwartz AC, Bradley R, Penza KM, et al. Psychosomatics. Mar-Apr 2006;47(2):136-142.

4.Seal KH, Shi Y, Cohen G et al JAMA. 2012;307(9):940-947.

The 90% of chronic pain for which opioids have not proven helpful

Axial low back pain without a pathoanatomic diagnosis

Fibromyalgia

Headache

Franklin GM. Neurology 2014;83:1277-84.

CONCLUSIONS

• The over-prescribing of opioids in the 1990s and 2000s produced the worst iatrogenic catastrophe ever

• Opioids have a very limited role in the treatment of chronic pain because they carry enormous risk and have not been shown to be beneficial if used continuously long-term

• Use of opioids for chronic pain misunderstands chronic pain

• If we can teach people to live well with chronic pain and provide them with the right tools, that is the best we can do

INTEGRATIVE PAIN MEDICINE

Transformational Care

Heather Tick MA, MD

Clinical Associate Professor

of Family Medicine

and Anesthesia & Pain Medicine

UW Medicine DIVISION OF PAIN MEDICINE

DISCLOSURE

• Author of Holistic Pain Relief

• Heathertickmd.com

Seven Habits of Successful Conventional Physicians

• We are well intentioned

• Rushed

• We are buried in electronic “paperwork”

• We rely on tests

• We focus on getting a diagnosis

• 54% in primary care suffer “burn out”

• We are part of the system that is the third leading cause of death (Makary MD,BMJ 2016;353:i2139)

A lot of trust in…

• Validity of tests

• Their applicability to the unique patient we are treating

• The latest trend: how did we label/treat patients before this trend, how certain were we that it was the right approach.

• Drug solutions-and more drug solutions to the side effects

Less trust in…

• The laying on of hands (Skinner, kangaroo care, nursing literature,

increased vagal activity-Early Hum Dev. 2014 Mar;90(3):137-40. doi: 10.1016/j.earlhumdev.2014.01.009. Epub 2014 Jan 27; )

• Micronutrient deficiencies (Ames B, PNAS 2006 103 (47)

17589-17594;Agarwal S, J Am Coll Nutr. 2015;34(2):126-34. doi: 10.1080/07315724.2014.901196. Epub 2015 Jan 7.)

• The ability of the body to heal

• The interconnectedness of all systems (Langevain H,

http://uctv.tv/shows/Stretching-Connective-Tissue-Chronic-Pain-and-Cancer-30714. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis PNAS 2016 113 (29) 8284-8289. Tracey K, TNFa reduction with vagal stim )

Less experience with…

• The offer an intervention whose side effects include better health instead of renal failure

• How good it feels to refocus the conversation on the pursuit of health

• How a focus on health as a positive attribute helps our patients and ourselves.

• With respect to neuroplasticity: Which circuits do we want to reinforce.

Less trust in…

• Marcia Angel, NEJM, The Truth About Drug Companies

• Richard Horton The Lancet, “much of the scientific literature, perhaps half, may simply be untrue”, blaming, among other things, studies with small sample sizes, researchers’ conflicts of interest and “an obsession” among scientists for pursuing fashionable trends of dubious importance”.

• Harvey Markovitch, (2010) “Editors, Publishers, Impact Factors, and Reprint Income”. PLoS Med 7(10): e1000355. doi:10.1371/journal.pmed.1000355

Trust?

Risk of Standard of Care

• Prescription opioid inadvertent ODs kill more people than heroin and cocaine combined (46/d)

• Escalating drug use and procedures and no improvement in outcomes Overtreating chronic back

pain: Time to back off? Deyo RA, Mirza SK, Turner JA, Martin BI. J am board Fam Med 2009;22(1):62–8. The Spine Journal. 2010;10(6):568. doi:10.1016/j.spinee.2010.04.022.

Manchikanti L, Pampati V, Falco FJE, Hirsch JA. Growth of spinal Interventional pain management techniques. Spine. 2013;38(2):157– 168. doi:10.1097/brs.0b013e318267f463. Manchikanti L, Pampati V, Falco FJE, Hirsch JA. Growth of spinal Interventional pain management techniques. Spine. 2013;38(2):157– 168. doi:10.1097/brs.0b013e318267f463.

HOW DID WE GET THIS SO WRONG?

• The pressures of modern practice have pushed us to accept simple solutions to complex problems.

• We also have a story telling problem: We are a bit too quick to come up with explanations for things we really don’t have an explanation for.

(Malcolm Gladwell)

“Medical care is a public health hazard.”

(Don Berwick IHI)

THE MORAL ERA

• YouTube: Address to the 27th annual meeting of Institute for Healthcare Improvement

• https://www.youtube.com/watch?v=DKK-yFn7e_0

• Difference between QI, and transformation

HEALTH CREATION

OR HEALTHCARE

• Our health care model is a disease management model

• Personalized, individualized care

• Time, attention

• Silver Bullet model- does not work for chronic conditions

• “healing is always possible”

• Our health care model produces life long customers for many different types of services

• Was this our intention?

HEALTH CREATION

OR HEALTHCARE

WHAT DISTINGUISHES

IM/IPM?

• Diagnosis:

• Benefits?

• Disadvantages?

an agreed upon label for a set of symptoms

It helps in urgent, acute situations Billing, coding Entitlements

What distinguishes IM/IPM?

Medicine is like a game of connect the dots

What about the connectors?

PREVENTABLE WITH LIFESTYLE CHANGES

EPIC: European Prospective Investigation into Cancer and Nutrition

23,000 people for 7.8 years

– Not smoking

– Exercise 3.5 hr/week

– Healthy diet: veg, fruit, beans, whole grains, nuts, seeds, low meat consumption

– BMI <30

E. S. Ford et al., “Healthy Living Is the Best Revenge: Findings from the European Prospective Investigation into Cancer and Nutrition — Potsdam Study,” Archives of Internal Medicine 169, no. 15 (2009): 1355–62.

THE KEY TO HEALTH

• Average US person consumes 150 pounds of sugar per year

• ½ pound each day

SUGAR

Metchnikoff

• Nobel Prize in 1908 for work in immunity

• He discovered macrophages, phagocytosis and cell mediated immunity (co-recipient Paul Erlich established the principles of humeral immunity)

• He also developed the concept of good and bad bacteria in the gut and their association with health and prolonged life.

THE GUT

• 80% of serotonin is in the gut

• Enough neurons in the gut for a small mammals brain

• 70-80% of the immune system lines the gut

• Has a profound effect on inflammation, the immune system and our mood

THE MICROBIOME

• 200x more DNA

• Affects digestion and nutrient absorption

• 10x as many cells as human cells

• Affects weight, inflammatory biomarkers, abdominal pain, intestinal permeability, autoimmunity, mood, temperament, epigenetics, circadian rhythm…….

MICROBIOME

MICROBIOME

MICROBIOME EFFECTS

Abdominal pain

O’ Mahony SM, Dinan TG, Cryan JF. The gut Microbiota as a key regulator of visceral pain. PAIN. November 2016:1. doi:10.1097/j.pain.0000000000000779.

MICROBIOME EFFECTS

• van den Eisen LW, Poyntz HC et al "Embracing the Gut Microbiota: The New Frontier for Inflammatory and Infectious Diseases." 6, no. 1, 2017, Vol.6(1). “As such, beneficial modulation of the gut microbiota is a promising clinical target for many prevalent diseases including inflammatory bowel disease, metabolic abnormalities such as obesity, reduced insulin sensitivity and low-grade inflammation, allergy and protective immunity against infections.

MICROBIOME EFFECTS

• Christian LM, Galley JD, Hade EM, Schoppe-Sullivan S, Kamp Dush C, Bailey MT. Gut microbiome composition is associated with temperament during early childhood. Brain, Behavior, and Immunity. 2015;45:118–127. doi:10.1016/j.bbi.2014.10.018.

MICROBIOME EFFECTS

• Voigt R, Forsyth c, Green S, Engen P, Keshavarzian A. Circadian Rhythm and the Gut Microbiome. International Review of Neurobiology. 2016;(131):193–205.

EPIGENETICS

Epigenetic gene regulation comprises the heritable changes in gene expression that occur in the absence of changes to the DNA sequence itself…. acetylation, methylation, phosphorylation….. potential for nutritional and environmental factors to influence fetal, adult, and transgenerational epigenetic gene regulation, resulting in numerous phenotypic consequences

Dolinoy DC, The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenom, Nutr Rev. 2008 Aug; 66(Suppl 1): S7–11.

The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal

epigenome

Dolinoy DC, Nutr Rev. 2008 Aug; 66(Suppl 1): S7–11. doi10.1111/j.1753-4887.2008.00056.x

Stress, VAGUS NERVE AND GUT

Prenatal stress causing epigenetic changes in the fetus

Bonaz B, Anti-inflammatory properties of the vagus nerve:potential therapeutic implications of vagus nerve stimulation. Physiol. 2016 Apr 5. doi: 10.1113/JP271539

HEARTBURN AND GI HEALTH

• Acid stimulates

– Unfolding of proteins

– Gastric emptying

– Pancreatic enzymes

– Sterilizes food

– Optimizes microbiome

– nutrient absorption

inflammation

• Omega 3’s anti-inflammatory prostaglandin pathways

• >3 gm DHA + EPA/day reduced pain

Maroon et al, Surg Neurol.2006;65:326-331

Omega 3: DHA and EPA

Omega 3: side effects

Effective for: Lowering TG

Likely: Reduced risk of dying of heart disease

Possibly: Reduced risk for HT, RA, Dysmenorrhea, ADHD, Raynauds, Stroke, Osteoporosis

IgA nephropathy etc

http://www.nlm.nih.gov/medlineplus/druginfo/natural/993.html

Essential Fatty Acids: Inflammation

• R. J. Goldberg and J. Katz, “A Meta-analysis of the

Analgesic Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation for Inflammatory Joint Pain,” Pain 129 (2007): 210–23.

• A. P. Simopoulos, A. Leaf, and N. Salem Jr. “Workshop Statement on the Essentiality of and Recommended Dietary Intakes for Omega-6 and Omega-3 FattyAcids,” Prostaglandins, Leukotrienes and Essential Fatty Acids 63, no. 3 (2000):119–21

Vitamin D for pain

• Low vit D levels correlated to higher opioid use (2x) and longer duration of use (2x)

• “vitamin D inadequacy may represent an under-recognized source of nociception and impaired neuromuscular functioning among patients with chronic pain”

Turner et al, Mayo Clinic Pain Med. 2008 Nov;9(8):979-84

• Decreased inflammation

• Increased bone density

• Less susceptibility to infections such as flu

• Less diabetes

• Less auto-immune disorders

• Possible role in cardiac and brain health

• Overdose extremely rare (over 150ng/ml)

Holick MF , MD PhD, Vitamin D Deficiency, N Engl J Med 2007; 357:266-281July 19, 2007DOI: 10.1056/NEJMra070553

VITAMIN D

MAGNESIUM

•

•

•

•

•

•

• Mg inhibits release of Ach from motor end plates -muscle relaxation (FM, MFPS, cramps)

• Magnesium depletion

facilitates neuromuscular excitability, producing tremor, cramps, and tetany. Cohen S et al,

Anesthesiology2004;101:495-526

MAGNESIUM

•

•

•

•

•

•

• Recent rat studies on mechanisms NMDA receptors and nerve pain

• Improves constipation and irritable bowel,

• Sleep disorders

• Bone health, Collagen formation

MAGNESIUM

•

•

•

•

•

•

Hypomagnesemia is probably the most underdiagnosed electrolyte deficiency in current medical practice. hypomagnesemia is not necessarily present in a magnesium-deficient state Am J Med 1987Mar 20;82(3A)24-9. Magnesium deficiency: pathogenesis, prevalence, and clinical implications. Whang R.

NIH FUNDED

CARDIA

STUDY

•

•

•

•

•

•

• Prospective study of 4,497 Americans no DM

• Mg favorably affects inflammation, insulin resistance and reduces onset of DM

• Mg intake inversely associated with inflammatory markers (hsCRP, IL6,fibrinogen) and fasting insulin

Kim DJ et al. Diabetes Care 2010;33(12): 2604-10

REFERENCES-MAGNESIUM • Jane Higdon, “Magnesium,” Linus Pauling Institute, Oregon State

University website, last updated August 2007, http://lpi.oregonstate.edu/infocenter/minerals/magnesium/

• D. J. Kim et al., “Magnesium Intake in Relation to Systemic Inflammation, Insulin Resistance, and the Incidence of Diabetes,” Diabetes Care 33, no. 12 (December 2010): 2604–10.

• Alexander Mauskop and Jasmine Varughese, “Why All Migraine Patients Should Be Treated with Magnesium,” Journal of Neural Transmission 119, no. 5 (2012): 575–79.

• F. H. Nielsen, L. K. Johnson, and H. Zeng, “Magnesium Supplementation Improves Indicators of Low Magnesium Status and Inflammatory Stress in Adults Older Than 51 Years with Poor Quality Sleep,” Magnesium Research 23, no. 4 (2010): 158–68;

• S. Brill et al., “Efficacy of Intravenous Magnesium in Neuropathic Pain,” British Journal of Anaesthesia 89, no. 5 (2002): 711–14.

VITAMIN B12

• Vitamin B12 in low back pain: a randomised, double-blind, placebo-controlled crossover study daily injections of 1000mcg

• Reduction of pain in both active arms of the crossover

Mauro GL, Eur Rev Med Pharmacol Sci - 01-MAY-2000; 4(3): 53-8

VITAMIN B12

• Powerful methylator (mitochondria and detox)

• Co factor for methionine synthase: lowers homocysteine

• Possibly helpful: Diabetic neuropathy

Fatigue

Fractures(Mayo Clinic)

TURMERIC

(Curcuma Longa) •

•

107 knee OA patients: 800 mg/d ibuprofen=2g/d curcumin for pain Kuptniratsaikul V et al, J Altern Complement Med 2009; 15(8):891-7

•

•

Laparascopic cholecystectomy: Less pain and fatigue and analgesic use in curcumin group vs placebo (500mg q6h) DBPC RCT Agarwal KA et al.,Surg Endosc (2011) 25:3805–3810 DOI 10.1007/s00464-011-1793-z

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• Neuroprotective- animal models

• New neurons in the hippocampus

• Studied in Alzheimers prevention and improved function in Alzheimers patients

TURMERIC SIDE EFFECTS

• Langvain H, http://uctv.tv/shows/Stretching-Connective-Tissue-Chronic-Pain-and-Cancer-30714.

• Myers, T. Fascia is more of a connector than a tissue demarcation

FASCIA

• Ultrasonographic elastography allowing us to image fascial thickening and decreased movement of the fascial planes in LBP patients vs controls which correlated with pain and functional limitations

• Langevin et al. BMC Musculoskeletal Disorders 2011, 12:203 http://www.biomedcentral.com/1471-2474/12/203

MYOFASCIAL PAIN

• Travell and Simons, Myofascial Pain and Dysfunction: The Trigger Point Manual, vol 1, 2

• C Chan Gunn “The Gunn Approach to the

Treatment of Chronic Pain: Intramuscular Stimulation for Myofascial Pain of Radiculopathic Origin”

• Cannon and Rosenbluth, The Supersensitivity of

Denervated Structures: A Law of Denervation, 1949

MYOFASCIAL PAIN most common cause of pain

• Ten percent of all patients and 30% of pain patients in a general medical clinic met criteria for MFPS.

Skootsky SA, Jaeger B, Oye RK, Prevalence of Myofascial Pain in General Internal Medicine Practice, Western Journal of Medicine 151, no. 2 (1989): 157–60.

• David Simons cites a series of studies where between 50-85% of pain patients had evidence of myofasical pain syndromes.

Institute of Medicine (US) Committee on Pain, Disability, and Chronic Illness Behavior; Osterweis M, Kleinman A, Mechanic D, editors. Pain and Disability: Clinical, Behavior- al, and Public Policy Perspectives. Washington (DC): National Academies Press (US); 1987. APPENDIX MYOFASCIAL PAIN SYNDROMES DUE TO TRIGGER POINTS.

Myofascial pain

• Engell S, Triano JJ, Fox JR, Langevin HM, Konofagou EE. Differential displacement of soft tissue layers from manual therapy loading. Clin Biomech (Bristol, Avon). 2016 Mar; 33:66-72. PMID: 26954891.

• Tesarz J, Hoheisel U, Wiedenhöfer B, Mense S. Sensory innervation of the thoracolumbar fascia in rats and humans. Neuroscience. 2011 Oct 27;194:302-8. doi: 10.1016/.

MYOFASCIAL PAIN

Myofascial pain

• Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis (Tracey K, PNAS 2016 113 (29) 8284-8289., TNFa reduction with vagal stim )

MYOFASCIAL PAIN

Hypoechoeic trigger point

Focal decrease of color variance indicates a localized stiffer region

upper trapezius

Vibration Sonoelastography of Muscle with MTrP

Uniform echogenecity in uninvolved muscle

Uniform color variance indicates homogeneous stiffness

upper trapezius

Vibration Sonoelastography of Uninvolved Muscle

MOVEMENT AS PAIN RELIEF

Movement Disorders in Chronic pain

• Mary Barbe Temple University. (Peripheral and

central changes combine to induce motor behavioral deficits in a moderate repetition task. Experimental Neurology. 2009;220(2):234–245. doi:10.1016/j.expneurol.2009.08.008.)

• Vitaly Napadow, Harvard (Somatosensory cortical

plasticity in carpal tunnel syndrome treated by acupuncture. Human Brain Mapping. 2006;28(3):159–171. doi:10.1002/hbm.20261.)

• Sahrmann, Washington University St Louis, The

Human Movement System: Our Professional Identity, PHYS THER. March 13, 2014doi: 10.2522/ptj.20130319

TOXICS

• Lerner A, Matthias T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmunity Reviews. 2015;14(6):479–489. doi:10.1016/j.autrev.2015.01.009.

MITOCHONDRIA

• Energy production

• Detoxification

• Susceptible to free radical damage Kim HK, Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain 2004;111:116–24.

• Dependent on robust system of antioxidants Myhill, Int J Clin Exp Med 2013;6(1):1-15

Mitochondria

• OXPHOS defects reduce mitochondrial ATP production, and “can theoretically give rise to any symptom, in any organ or tissue, at any age, with any mode of inheritance.”

Sui B-dong, et al. Understanding the role of mitochondria in the

pathogenesis of chronic pain, Postgrad Med J 2013;89:709–714

MITOCHONDRIA

Mitochondrial Damage

Drugs affecting mitochondrial function: • NSAIDS, Aspirin, acetaminophen,

antidepressants, local anesthetics, anxiolytics, antipsychotics, statins, oral hypoglycemic agents and anticonvulsants

• environmental toxics -80,000 new chemicals Neustadt & Pieczenik Mol. Nutr. Food Res. 2008, 52, 780-8; Amacher, Current Medicinal Chemistry, 2005, 12, 1829-1839, Sui B-dong, et al. Postgrad Med J 2013;89:709–714. Joseph & Levine Mitochondrial electron transport in models of neuropathic and inflammatory pain, Pain 121 (2006) 105–114

MITOCHONDRIA

WHAT IS FIBROMYALGIA?

• microglial activation= central sensitization

• peripheral pain or stress role in central sensitization (S Mense)

• stress induced peripheral sensitization (Khasar, J

Neurosci. 2008 May 28; 28(22): 5721–5730.0

• magnesium deficiency

• disturbed microbiome

What is Fibromyalgia?

• small fiber neuropathy more common than we suspected=inefficient circulation A-V shunting in microvasculature

• mitochondrial dysfunctions =a cause of peripheral neuropathy? (Morris G, Berk M, et al BMC

Medicine. 2015;13:28)

• Inflammatory cytokines=brain fog, mast cells causing bladder irritation (Fabien Marchand et al,

NatureReviews: 2005;7)

WHAT IS FIBROMYALGIA?

What is Fibromyalgia?

• Is pursuit of health an option?

• Is polypharmacy part of the solution or part of the problem?

• Is there an endgame for each new drug you start?

• Movement-another side to neuroplasticity?

• When patients don’t get better what to do?

WHAT IS FIBROMYALGIA?

We have not been looking in the right places!

Integrative Pain Medicine

What? Why?

If not now, when? If not you, who? (Schoomaker and Buckenmaier, Pain Medicine 2/2016)