The Opioid Epidemic in America and Pain

The Opioid Epidemic

In December, 2016, Thomas Frieden, MD, Chief of the CDC (Centers for Disease Control and Prevention), reported that in year 2015 the drug overdose death toll in America was the highest on record (1). More than 52,000 people died from a drug overdose; 33,000 of these deaths involved a prescription or illicit opioid.  Dr. Frieden said that this situation was made worse by the wide availability of easily available illegal opioids, such as heroin, fentanyl, and other illicit synthetic opioids.  He indicated that control of this problem would be difficult.

Frieden went on to say that this crisis was caused, in large part, by decades of prescribing too many opioids for too many conditions and made worse by the wide availability of cheap, potent, and easily available illegal opioids such as heroin, illicitly made fentanyl, and other, newer illicit synthetic opioids (1).

A study of opioid use by a major newspaper in Sonoma County, California, found that in the year 2014, one in four residents in the county had an opioid prescription.  The most widely prescribed opioid in Sonoma County was hydrocodone.  It comprised 57 percent of the 459,000 opioid prescriptions filled at local pharmacies. The Sonoma County Health Officer indicated that this large usage of opioids was not unique to Sonoma County, but was happening nationwide (2).

The Prescription of Opioids for Pain Relief

The CDC is seriously concerned about why large numbers of deaths are being caused by opioids, whether illicit or obtained by prescription (1).  The most frequent indication for prescribing opioid medications is chronic pain.  According to the Pain Center, a multi-office medical group that specializes in pain control, 116 million Americans suffer with chronic pain (3).  This statistic is substantiated by a scientific review in the Journal of Pain (4).  Thus, it appears likely that a very large number of people in the US are using opioids because their doctors are lawfully prescribing them. Opioids such as hydrocodone are probably the only prescription drugs that are effective against chronic pain.

Based on statistics published by the journal Pain (4) and the National Institutes of Health (NIH) (5), persistent pain impacts about 100 million adults and costs from $560 to $635 billion annually. Additionally, a review in the New England Journal of Medicine begins with the following introduction (6): “The magnitude of pain in the United States is astounding. More than 116 million Americans have pain that persists for weeks to years.”

Medical Co-morbidities of Pain

An excellent study done in Kuwait appears to have discovered the major underlying causes of chronic pain by identifying diseases associated with chronic pain (7). Utilizing a rehabilitation Institute that serves different types of patients, the study examined intake data from 2013 consecutive entering patients with acute and chronic pain; 55% were females, with average age of 43.3 years.

The study discovered that females had a higher incidence of pain and a higher number of medical co-morbidities than males. These co-morbidities were increased incidences of hypertension, osteoarthritis, diabetes, asthma, osteoporosis, and cardiac and respiratory problems.

Note that these co-morbidities of hypertension, osteoarthritis, diabetes, asthma, osteoporosis, cardiac, and respiratory problems are all noninfectious diseases that are now accepted scientifically as being of chronic inflammatory origin.

Inflammation is now widely appreciated in the pathogenesis of many human diseases.  These extend from the well-known inflammatory dis­eases such as arthritis and periodontal disease to those not previously linked to aberrant inflammation that today include diseases affecting many individuals such as cancer, cardiovascular diseases, asthma, and Alzheimer’s disease (7).

The reality that inflammation is a major factor in the development of essentially all of the chronic diseases that the general public has long come to know and accept as accom­pani­ments of old age may be difficult to believe or accept.   Yet the scientific advances made during the last decade in understanding the nature of inflammation and its role in the etiology of chronic diseases presents no other choice (8, p. 20).

Chronic Inflammation and Diet

(From MND Ch. 8, p 209)

Since the early 1900s, it has been known that nutrient deficiencies could cause disease. The classic nutritional diseases of beriberi and pellagra are testimony to that fact.  Today, evidence is mounting that deficiencies of some of the more recently discovered essential nutrients are also causing diseases or disorders, as illustrated by reports of the influence of maternal deficiencies of omega-3 essential fatty acids on maternal and fetal health.  Today, it is clear that what hitherto has been accepted as good nutrition is causing chronic inflammation, and chronic inflammation, in turn, underlies many of the chronic diseases that are part of modern life.

What is Inflammation?

(From MND Ch. 8, p. 210)

Inflammation is the body’s response to cellular damage, usually by infection or injury.  The classic symptoms of redness, heat, swelling, and pain are the signs of an acute inflammatory process.  Acute inflamma­tion is a protective mechanism by which the body attempts to rid a threat and recover from the offending event, but when inflammation becomes chronic, inflammation becomes detrimental.  How can that be?  How is it possible for a mechanism that is essential to protect against life-threatening traumas to turn on its host and set the stage for develop­ment of chronic disease?  Or are acute inflammation and chronic inflammation discrete entities?

Acute Inflammation versus Chronic Inflammation

(From MND Ch. 8, p. 210)

The answer to the paradox appears to be that acute and chronic inflammation are, indeed, of two different kinds.  Acute inflammation is triggered by infection or injury. It is intense and lasts only long enough to set the stage for the next step, a healthy healing process.  In contrast, chronic inflammation is low level, insidious, and does not have noticeable symptoms, at least not initially, and absent dietary change is unrelenting.

The onset of acute inflammation is rapid, but the onset of chronic inflammation appar­ently is seldom or never recognized; it does not display features of acute inflammation.  Unless remedial action intervenes, chronic inflammation progresses slowly and relen­tlessly until it finally results in chronic disease.  Acute inflammation is a necessary de­fense mechanism, but chronic inflammation does not seem to have any redeeming value.

Because chronic inflammation is biochemically maintained in the body for prolonged periods at a level below which it is perceived, chronic inflammation was appropriately labeled silent inflammation (9).  Its silence is what makes it so dangerous; it gives no signal that something is amiss and must be dealt with.  Thus, no effort is made to rein it in.  Eventually there may be some prodromal symptom that gives an inkling of trouble, such as a strange ache or discomfort, but usually there is no clue until the silent inflammation becomes severe enough to manifest itself as pain or perhaps even as a sudden, unanticipated heart attack.

The Nature of Pain

Pain may be defined as a physical sensation of severe discomfort that signals the brain that there is actual or potential injury to the body (10).  Pain may be either the advanced notice that a chronic disease is in development or, in the case of a heart attack, the announcement of its arrival.

The sensation of pain that accompanies inflammatory disease is resolved by the same biochemistry that governs the resolution of the inflammatory disease itself.  Thus, a discussion of the biochemistry of pain requires a brief explanation of where the biochemicals involved in the process of inflammation came from.  In any event, the only remedy for the pain or the disease is control or elimination of the inflammation.  Elimination of dietary factors that lead to chronic inflammation and their substitution with a healthful diet plan is fundamental to pain control of chronic diseases. This leads us to the biochemistry of the essential fatty acids (EFAs).

The Early Biochemistry

The two families of the essential fatty acids, identified as omega-6 and omega-3 EFAs, are well known and described in nutrition literature, but their end products, named eicosanoids, are little recognized or studied outside the discipline of lipidomics.

Eicosanoids (20-carbons) are short lived, biologically active messenger chemicals that are biosynthesized in all mam­ma­lian cells except red blood cells. They are very potent and cause physi­ological effects at minimal levels.  Their biochemistry, along with their more recently discovered docosanoid (22-carbons) forms, is wide-ranging and complex, but for discussion of inflammation and resolution, the term eicosanoids will apply to both eicosanoids and docosanoids.  Eicosanoids that heal are primarily those derived from the dietary omega-3 fatty acids, EPA and DHA.

A few short years ago, Serhan, et al. reported that healing was not a passive process, but rather required active biochemical programs to enable in­flamed tissues to return to homeostasis (11).  In brief, resolution is a biosynthetically active process, regulated by biochemical mediators and receptor-signaling pathways, and driven by specialized proresolving mediators (12).  This finding was based on discovery of a new group of anti-inflammatory, pain-moderating, and pro-healing eicosanoids.  As a group, they are referred to as lipid mediators.

Members of this new group of lipid mediators that participate in resolution of inflammation are termed resolvins. Resolvins are highly beneficial, anti-inflammatory lipid mediators derived from EPA and DHA.  Those derived from EPA are termed E-series resolvins (RvE).  Those derived from DHA are referred to as D-series resolvins (RvD). The roles of RvE1 and RvD1 are mentioned below.  RvEs and RvDs are biosynthesized in situ from dietary EPA and DHA, respectively (12).

EPA, a major component of fish oil, had long been considered to have multiple beneficial effects, but the first biochemical-level evidence for health-promoting contributions of EPA was provided by the discovery that EPA generates E-series resolvins that have stereochemically defined structures and show potent anti-inflammatory and pro-resolving actions (12).

The discoveries of these new lipid mediators are tremendously important because they elucidate the biochemical processes that end inflammation, initiate healing, protect involved tissues, control pain, and return damaged tissues to homeostasis (8, p.193).

The Biochemistry of Pain

Peripheral and central mechanisms of inflammatory pain are not fully understood; however, it is known that proinflammatory cytokines such as TNF-α and IL-1β are indispensable for the pathogenesis of inflammatory pain (13).

A recent research project by Ramsden and colleagues (14) found that unbalanced lipid mediators also cause chronic headache pains. Sixty-seven subjects with chronic headaches were randomized into two groups. Of those, 56 completed a food-based 12-week dietary intervention. One half of the group received a diet rich in omega-3 fatty acids plus a low amount of omega-6 fatty acids. The other half received a diet with only the low amount of omega-6 fatty acids.  The outcome was the diet rich in omega-3 fatty acids plus a low amount of omega-6 fatty acids produced significantly reduced headache pains. The group receiving the diet with only the low amount of omega-6 fatty acids continued to have headaches.  It is noteworthy that omega-6 fatty acids are found primarily in vegetable oils.

Resolvins, at very low doses effectively reduced inflammatory pain symptoms via both peripheral and central actions. Further, resolvins have been shown to reduce inflammatory pain rapidly, within minutes (13).  Considerable experimental data have indicated that resolvins have remarkable potency to abolish cytokine-induced pain of inflammation.

Research in biochemistry of resolvins and the many other lipid modulators that thus far have been identified is ongoing; new discoveries are being reported regularly.  However this post would not be complete without a mention of a special influence of aspirin on eicosanoid biochemistry that was discovered a few years ago.  When present at the site of biosynthesis of a lipid mediator, aspirin triggers the biosynthesis of epimers (biochemically similar) of the lipid mediator that are slightly more potent and much more stable and longer lasting than the naturally-formed lipid mediator itself.

The research literature indicates that lipid mediators are produced by both natural and aspirin-triggered (AT) biochemical pathways when the host uses aspirin.  The advantage of AT epimers is that they increase the efficiency of resolution.  In brief, aspirin “jump-starts” the endogenous pathways of resolution and healing by biosynthesis of aspirin-triggered pro-resolving lipid mediators (15).

A final thought about opioids, inflammation, and pain is that given the remarkable potency of resolvins along with the well known adverse side effects of opioids, resolvins probably represent a more effective method, albeit natural as opposed to synthetic, for treating inflammatory pain.

An Anti-inflammatory Diet Plan

The great numbers of people with chronic pain are evidence of the ineffectiveness of the American diet and health care system.  The situation may be described as chaos moving to catastrophe.  There is no general agreement regarding the components of a healthful (anti-inflammatory) diet and even less concerning which nutritional philosophy holds the secret of optimum health that should prevail.

It is said that every one of us alive today is descended from a single prehistoric ancestor.  Independent of the origin of the single ancestor, we are all genetically classed as humans.  Yet as far as is known, there are no two of humans that are exactly alike in any aspect that can be measured – anatomically, physiologically, biochemically, or nutritionally.  How can that be (16)?

Genetic science has shown that minor genetic changes are constantly occurring within individuals and across generations of individuals of a given species.  The accumulation of these small mutations within a species through the millennia is not sufficiently powerful to form a new species, but they can produce individual variations within the species.  That is the reason why humans differ in their dietary needs; they are biochemically unique (16).

When discussing the subject of human dietary programs, the fact that humans are individuals biochemically must be taken into consideration.  Humans all are governed by the broad nutritional rules that apply to the human race, but they also vary in response to individual foods in the great variety of possible choices within each rule.

The Broad Rules

The broad rules, aka natural laws, of optimum human nutrition evolved together with prehistoric Man and, in general, have been recognized as basic requirements for optimum human health.  It must be stressed here that optimum nutrition is anti-inflammatory nutrition by necessity and coincidence of evolution.  These natural laws, or truths, are broad based and general in nature; their directives are absolute for all members of the human race, yet they apply to no individual member (16).

The first rule of optimum human nutrition says that the carbohydrate component of the diet must be restricted.  Note that this rule requires “restriction” but does not specify “how much!”

The second rule of optimum human nutrition says that the omega-6 and omega-3 essential fatty acids (EFAs) of the diet must be balanced.  Note that this rule requires “balance” but does not specify quantities of either EFA or acceptable degree of divergence from (1:1).

The third rule says that micronutrients (vitamins and minerals) must be included in amounts adequate to prevent overt nutritional disease.  Note that this rule does not define “adequate amounts.  The fact that micronutrients generally have been accepted as essential for many generations and by most dietary philosophies suggest that this rule should be recognized as the first, not the third, law of optimal human nutrition.

Biochemical Individuality

The reality that no two humans are exactly the same in their requirements for optimum nutrition precludes the crafting of single diet plan that could serve any single individual.  The unfortunate result is that every individual must learn for him- or herself where he or she fits within the parameters of each rule; there is no other option.  Keep in mind the three rules as you experiment with your own diet: restricted carbohydrates; balanced eicosanoids; and adequate micronutrients.

A Saving Grace

A saving grace for a person who has a desire to make healthful dietary changes but is uncertain how to proceed, the ketogenic (keto-) diet is the ideal starting place.  The keto-diet, which reduces consumption of carbohydrates to an absolute minimum, is not an easy diet for people addicted to sugar or sweets.  There is a wealth of information in the scientific literature suggesting that the ketogenic diet in not only an anti-inflammatory diet but is also the diet most in accordance with the body’s ability to self-heal.

You will never regret the time and effort you spend in learning of and adjusting to your body’s nutritional individuality.

References

1. http://www.foxnews.com/opinion/2016/12/17/exclusive-cdc-chief-frieden-how-to-end-americas-growing-opioid-epidemic.html. Accessed 03/18/17.
2. http://www.pressdemocrat.com/home/5080748-181/1-in-4-sonoma-county. Accessed 03/18/17.
3. http://www.thepaincenter.com/about/the-problem/. Accessed 03/18/17.
4. Gaskin DJ, Richardy P. The Economic Costs of Pain in the United States. The Journal of Pain. 2012; 13(8): 715-724.
5. National Heart, Lung, and Blood Institute: Fact Book Fiscal Year 2010. Bethesda, MD: U.S. Dept. of Health and Human Services, National Heart, Lung, and Blood Institute, 2011.
6. Pizzo, PA, Clark, NM. Alleviating Suffering: Pain Relief in the United States. The NEW ENGLAND JOURNAL  of MEDICINE, Perspective, January 19, 2012.
7. Maureen C, et al. Chronic Pain, Comorbid Medical Conditions, and Associated Risk Factors in Kuwait: Gender and Nationality Differences. Pain Medicine 2015; 16: 2204–2211 Wiley Periodicals, Inc.
8. Ottoboni A, Ottoboni Fred. The Modern Nutritional Diseases, 2^nd Edition., Fernley, NV: Vincente Books, 2015.
9. Sears B. The Anti-inflammation Zone. New York, NY: Regan Books/Harper Collins, 2005.
10. http://medical-dictionary.thefreedictionary.com/pain. Accessed 03/18/17
11. Serhan CN, et al. Resolving inflammation: dual anti-inflammatory and pro resolution lipid mediators. National Review of Immunology. 2008; 8(5): 348-361.
12. Serhan CN, Petasis NA. Resolvins and Protectins in Inflammation-Resolution. NIH Public Access. Published in final edited form as: Chem Rev. 2011; 111(10): 5922–5943. doi:10.1021/cr100396c.
13. Xu ZZ, et al. Resolvins RvE1 and RvD1Attenuate Inflammatory Pain via Central and Peripheral Actions. NIH Public Access. Published in final edited form as:  Nat Med. 2010; 16(5): 592–597. doi:10.1038/nm.2123.
14. Ramsden CE, et al. Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: A randomized trial. Pain. 2013; 154(11). doi:10.1016/j.pain.2013.07.028.
15. Serhan CN. Novel Lipid Mediators and Resolution Mechanisms in Acute Inflammation. American Journal of Pathology, 2010; 177(4) : 1576-1591.
16. A Tale of Two Truths: http://ketopia.com/a-tale-of-two-truths/. Accessed 03/18/17.