Introduction: Why “Rainbow”?

Many have asked about our name, e.g. are you gay? Or hippie? Woo woo? The answer is none of the above. Rainbows symbolize the relief we feel when we see such a beautiful signal of the end of a storm, when the sun is breaking through. Rainbows also suggest inclusiveness, diversity, the “pot of gold”, and (from the Old Testament) renewal and redemption.

What is Integrative Medicine & Why?

With over two decades of experience working with chronic pain patients, I have learned that patient outcomes may be improved significantly when a multi-disciplinary team including professionals with traditional and non-traditional training provides coordinated treatment. A “whole person wellness” approach can reduce recovery time and dependency on pharmaceutical compounds and increase personal productivity.

We are working to develop and to implement a holistic, or integrative medicine, approach to the treatment of persons with chronic pain and related illnesses.

Despite widespread recognition of a crisis in the American healthcare system, what to do about the problem remains controversial. As costs rise inexorably, quality seems elusive. Our failure to adequately address chronic illness, particularly chronic pain, has been a major contributing factor. Every patient with chronic pain represents a failure of our current medical and healthcare system.

We want to apply what we know about improving the health of people with chronic pain and to research the effectiveness of various approaches to addressing their problems. Our goals include reduced pain & suffering, increased quality of life, and net savings in health care expenditures. My colleagues and I seek to combine allopathic medicine with selected “complementary and alternative” healthcare approaches, such as mindfulness practices, psychotherapy and other forms of counseling, chiropractic, body work, acupuncture, Chinese medicine, movement therapies, physical therapy, nutritional counseling, etc. Using a quality improvement model, we plan to evaluate systematically the effectiveness of our work to determine which approaches are most useful for which types of problems and persons.

We welcome the participation of interested individuals. We need ideas, energy, time, and money from like-minded individuals willing to help make transformation of pain a reality.

From Pain to Health:

We know much of what is needed to achieve and to maintain optimal health. Anyone can become healthier. Unfortunately, modern medicine has increasingly focused on disease and injury. Little in modern medical practice concerns health or what health might be. We conceptualize health as “wholeness”. A person is a “whole person”, even with one or more body parts missing. We propose that helping persons to experience and to manifest their wholeness ought to be a central focus of healthcare providers, particularly regarding people with chronic illnesses.

The requirements for good health include good nutrition, bodily movement, adequate sleep, intimate and other social interactions, “spiritual” practices, “positive” attitudes, community involvement, stress management, avoidance of toxins and addictions, a healthy environment/ecosystem, and love for self and others. Medical care, when necessary for diagnosis and treatment of diseases and injuries and for prevention (e.g. immunizations, blood pressure & lipid monitoring, etc.), can make a significant contribution to health and healing. Health-promoting behaviors and life-styles and public health efforts are equally important for both individuals and our communities.

Pain is part of the human condition. Nociception clearly has survival value; humans have evolved nervous systems with elaborate nociceptive and anti-nociceptive networks. Chronic pain, however, unlike the acute pain of tissue damage or threat of tissue damage, has no survival value.  Chronic pain in fact can be viewed as a disease (or dis-ease) condition in its own right. Chronic pain may be in fact a mis-perception of ongoing tissue damage, when the underlying condition has had more than enough time to heal. But more than time is needed for healing. Certain diseases such as rheumatoid arthritis, for example, involve on-going or recurrent episodes of inflammation and damage to tissues. Nevertheless, any person, no matter how persistent and/or severe his or her pain, can be healthier, that is to say, more aware of healing and wholeness. The capacity to heal is part of our birthright as humans.

How? On one level, as noted previously, we know many of the factors that are needed for optimum health. Consistently performing behaviors that promote health and healing, however, or helping others to perform these behaviors, remains problematic. For example, nearly every American knows that smoking tobacco is harmful to health, but many begin to smoke every year, and many more smoke tobacco habitually, despite multiple techniques and tools for smoking cessation. Similarly, many others struggle with seemingly intractable health problems, such as obesity, heart disease, cancer, substance abuse/addiction, and so-called psychosomatic illnesses (e.g. fibromyalgia, migraines, etc.). Nevertheless, we can identify some approaches that can help change harmful behaviors or habits into healthful behaviors and habits. Even the best practices cannot help if they are not available, however, and many who could benefit from these practices do not, due to ignorance, financial barriers (including the expectation that health insurance should pay), and insufficient motivation.

One key to success is the approach called mindfulness. Experience and data suggest that people with chronic pain (and other chronic illnesses) who learn and practice mindfulness (e.g. Mindfulness-Based Stress Reduction, aka MBSR) can achieve an “orthogonal rotation” in their perceptions and come to “own” and to manage their health problems, a process that includes reduction of suffering and improvement in overall self-care and quality of life (see Jon Kabat-Zinn’s book, Coming to Our Senses). The capacity for mindfulness, described by Dr. Kabat-Zinn as “an openhearted, moment-to-moment, non-judgmental awareness” is part of being human and is “optimally cultivated through meditation” and related practices.

We can provide healthcare system that actually promotes health and wellness. Typically, chronic pain cannot be completely eliminated. As a subjective phenomenon, pain cannot be measured with much validity. Many experts have proposed that the aim of treatment of chronic pain ought to be increased functionality. This view has merit, as function can be to some degree measured objectively, but patients are interested in more than improved function; they want relief from pain and suffering. Moreover, everyone wants the maximum possible quality of life (QOL), another difficult-to-measure concept. We will seek out the best available measures of QOL and use them as a major part of our assessment.

Summary:

From our perspective, the most successful treatments for persons with chronic pain involve the “multidisciplinary” approach. Chronic pain is a multifactorial problem, and the most successful approaches therefore address the problem from multiple perspectives, e.g. analgesia (via medications, acupuncture, heat and/or cold, nerve blocks, hypnosis, etc.), cognitive behavioral psychotherapy (to address the emotional, attitudinal, motivational, etc. aspects), physical therapy (&/or other forms of rehabilitation), stress management, chiropractics, exercise, etc. The model commonly used in multidisciplinary pain clinics includes comprehensive assessment by a team of providers with different kinds of expertise and subsequent development by that team of a treatment plan to be carried out by some or all of that team, as well as by others to be determined by the needs of the patient. In our holistic or wellness model, the team will include “complementary and alternative” practitioners, therapists, counselors, nutritionists, etc., as well as allopathic physicians, and the treatment plans will include preventive efforts, patient education, “energy” practices, mindfulness, movement training, counseling/psychotherapy, and others as deemed necessary.

A Smooth Landing vs. “Crash and Burn”: The Exit Strategy for Chronic Pain Patients

An ASAM presentation by Herbert Malinoff, MD

Pain & Addiction: Common Threads XI             April 16, 2010

Reviewed by Franklin Perry, M.D., Ph.D.

· Dr. Malinoff, the Medical Director of Pain Recovery Solutions and Clinical Faculty at the U of Michigan Medical Center presented this masterful and thought-provoking talk at the recent ASAM meetings in San Francisco about the exceptionally challenging topic of how to manage the situation in which a person is taking high doses of opioids and still experiencing significant pain.

· Objectives included learning diagnostic approaches to chronic pain, chemical dependency, opioid hyperalgesia, and other co-morbidities; identifying failure of opioid therapy in chronic pain patients; and investigating clinical strategies.

· Typical physician’s strategy for treating non-malignant pain progresses from ibuprofen to hydrocodone (“Vicodin”) to something stronger to more to even more to discharging the patient.

· What is pain? A simple clinical definition (attributed to Scott Fishman, MD): “Whatever the patient states it is unless proven otherwise by poor adherence to the agreed upon medical regimen.”

· Chronic pain syndrome = “central” pain syndrome. Neuroplasticity (rewiring or reconnecting of neurons in the brain and spinal cord) is influenced by excitotoxicity, central sensitization, genetic predisposition, possible trauma/abuse, addiction/psychiatric co-morbidities, and neurohormonal derangements.

· Pain is the most highly modulated sensory experience. Pain (noxious) signals coming toward the brain are subject to inhibitory and/or facillatory processes in the spinal cord and brain. Opioid analgesics enhance inhibition initially, but may facilitate later in the course (hyperalgesia). Addictive illness facilitates.

· Many with chronic pain have co-morbidities including 4 overlapping domains: chronic pain, psychiatric illness, medical co-morbidities, and addiction.

· Dependence ≠ addiction: tolerance and withdrawal are universal with prolonged opioid treatment; aberrant behavior is required to diagnose addiction.

· Diagnosing addiction? The first and easiest question is: “Do you smoke?” The second is: Have you ever smoked? An affirmative answer to the first question indicates ongoing addiction. An affirmative answer to the second question indicates addiction that may be in remission.

· Medical co-morbidities that are common and significant include sleep apnea, deficiency states (Vitamin D, testosterone), acute pain, chronic painful conditions (rheumatologic, neurologic, statins), and brain injury.

· Psychiatric co-morbidities include mood disorders, PTSD, anxiety disorders, thought disorders, personality disorders, OCD

· Consider these needs!! Need to address all 4 areas of co-morbidity for success AND the need to avoid “crosstalk” (when one doctor’s treatment undoes another’s)

· Why use opioids? TO IMPROVE FUNCTION!! (and relieve pain). This is the position now taken by the American Pain Society among others.

· The trouble with opioids: tolerance and withdrawal, addiction potential, hyperalgesia (central sensitization), adverse effects, regulatory fears

· Opioid hyperalgesia: “If any man wants to learn sympathetic charity, let him keep pain subdued for six months by morphia, and then make the experiment of giving up the drug. By this time he will have become irritable, nervous and cowardly. The nerves, muffled, so to speak, by narcotics, will have grown to be not less sensitive, but acutely, abnormally capable of feeling pain and of feeling as pain a multitude of things not usually competent to cause it.” S. W. Mitchell, MD (Civil War surgeon in U.S. Army).

· Patients maintained on long-term opioids develop diminished pain tolerance as demonstrated in many studies.

· Opioids should be stopped if and when: they are not clearly beneficial, like any other medication.

· Medical withdrawal from high doses of opioids: can be done safely with inpatient management, even with patients with significant co-morbidity. Needed: hospital, nurses, patient-controlled analgesia (PCA) with hydromorphone (Dilaudid), and buprenorphine (Suboxone).

· Buprenorphine (Suboxone or Subutex): a synthetic opioid that functions as a partial agonist at the µ opioid receptor (only partially activates, thus safer regarding respiratory depression), high affinity for the µ receptor (binds more tightly than other opioids), dissociates slowly from the receptor (therefore milder withdrawal), and functions as an antagonist at the κ receptor (may be responsible for effects on chronic pain).

· Admitting diagnoses: intractable pain (338.2) and medication toxicity (995.2); must document need for inpatient care (e.g. nursing observation of unstable patient & need for parenteral meds).

· Buprenorphine induction recipe: Stop all opioids on admission; start PCA and allow 3-5 half-lives of the patient’s opioids; address sedatives; get appropriate consultations; stop PCA; wait for opioid withdrawal (6-8 hours); give buprenorphine SL or IM q6h x 4; discharge patient home on SL meds; office follow up in 7-10 days.

· Methadone detox (for pain): follow methadone blood levels; use PCA until methadone level falls below 30 mg/ml (may be 5-7 days); proceed with buprenorphine induction.

· Sedatives (benzodiazepines, muscle relaxers, Soma, Ambien, etc.) in chronic pain patients: do not use, because they cause cognitive dysfunction.

· Medical withdrawal from sedatives: consult with prescribing MD, stop sedatives and start oral phenobarbital at 30 – 60 mg TID/QID; titrate to symptoms; aim for sub-therapeutic blood levels (< 15 ng/ml); taper slowly over 6-12 months; consider gabapentin, oxcarbazine, pregabalin as adjuncts/alternatives.

· Outcomes: (see Malinoff, H., Weiner, M., Michaels, E., et al. 2010). 57% of patients reported significant improvement in pain control; 64% reported significant improvement in functional capacity 9 months later.

· Adverse effects: GI/GU symptoms, headache, sweating, NO DEATHS.

· “They don’t make pills for your problem!”

· Recovery from chronic pain:

o Physical health and function: manage underlying medical issues; improve physical strength and endurance; decrease pain and suffering.

o Neuropsychiatric healing: stabilize brain chemistry and functioning; improve cognitive ability, memory, and physical coordination; decrease perceived pain.

o Emotional well-being: decrease anxiety, depression, sleep disturbances; restore self-esteem; reduce pain-related suffering.

o Spiritual growth: Reconnect with family, friends, and peers; re-establish life direction and purpose; gain peace of mind and serenity. Volunteer work!

· Summary: Chronic pain, addiction, and psychopathology are common, related, and interdependent brain illnesses. Attempting to manage one without the others leads to failure and futility in all. Hyperalgesia and sedation complicate the management of chronic pain patients and lead to adverse outcomes. Medical withdrawal from high doses of opioids and sedatives can be accomplished safely and comfortably in the inpatient setting.

· There are many cannabis species and >460 known chemical constituents. ∆9 THC is the principal psychoactive component.

· Therapeutic properties of cannabis were described as early as 200 A.D. in Chinese medicine writings.

· Cannabinol was discovered and synthesized in 1940.

· THC was discovered in 1960 by Dr. Mechoulam of Hebrew University.

· THC binding sites in the nervous system were discovered in 1988.

· The first cannabinoid (CB) receptor (CB1) was cloned in 1990.

· The first endocannabinoid (eCB) was identified in Mechoulam & Partwee (Scotland) in 1992 and named anandamide from the Sanskrit word “anand” (bliss).

· The CB2 receptor was cloned in 1993.

· A 2nd eCB was discovered in 1995 and called 2-AG (2-Arachidonoylglycerol).

· Dr. Gardner and other scientists fully expect the discovery of new eCB receptors, eCBs, eCB enzymes, and therapies.

· A cannabinoid may be defined as a compound that produces cannabinoid psychoactivity, natural or synthetic.

· Note the similar progression here to that seen with the scientific study of the opioid system approximately 10 years earlier: discovery of specific binding sites (receptors) in the central nervous system (CNS, that is, brain and spinal cord), identification and synthesis of specific molecules that bind to these receptors (“agonists” and “antagonists”), cloning of receptors, identification & study of endogenous molecules.

· CB1 & CB2 receptors, like others in the CNS, consist of specific proteins that span nerve cell membranes. The part of the receptor that projects from the cell interacts in a lock and key fashion with molecules that either torn on the receptor (agonists) or turn off the receptor (antagonists). Due to that interaction, the shape and electrical charge of the protein changes in such a way as to affect a specific change in the behavior of the cell.

Characteristics of CB1 & CB2 receptors include:

- Dense distribution throughout the body

- CB1 especially dense in CNS

- CB2 especially dense in periphery, especially in the immune system (!), but also in the CNS with approximate density of μ-opioid receptors

- Located on axon terminals & mediate retrograde signaling (dendrite to axon)

· CB1 localization especially in cortex, hippocampus, basal ganglia, SN, and cerebellum.

· CB1 is “the most widely distributed neurotransmitter system in the nervous system” (!)

· CB1 is also densely present in the VTA (Ventral Tegmental Area, aka the reward & pleasure center, responsible for craving & relapse as well).

· CB1 system activation decreases neurotransmission.

· Endogenous cannabinoids (eCBs): 2 families now known: (1) Amides (e.g. anandamide) and (2) Esters (2-AG). Formed from arachadonic acid (found in cell membranes – Note: also is the source of prostaglandins, which function as local hormones and whose production is blocked by NSAIDs such as ibuprofen. eCBs are “made on demand”.

“Take-Home Messages”

- eCBs are neurotransmitters

- CBs modulate neural activity

- eCBs are involved in synaptic remodeling

Cannabinoids & Pain

· There are peripheral antinociceptive effects (shown in animal studies) that are synergistic with ibuprofen.

· These effects are reversed by application of CB antagonists (AM251 = CB1 antagonist; AM630 = CB2 antagonist).

· CBs are effective in modulating pain in various animal models including: tail flick, hot plate, paw pressure, formalin injection (paw), capsaicin, etc.

Cannabinoids & Addiction

· “There is now an extensive published literature showing anti-addiction efficacy for cannabinoid ligands.”

· AM251 inhibits the cocaine “high” and inhibits cocaine-seeking relapse in animal models.

· “Knock out” animals without the CB1 receptor do not show cocaine psychostimulant effects.

· “Caveats regarding development of cannabinoid agonists as potential pharmacotherapeutic agents”

- CB1 & CB2 receptors are ubiquitous throughout the body leading to the potential for numerous side effects.

- Some CB ligands have poor bioavailability.

- CB1 receptor agonists have addictive potential.

· There is “hard preclinical evidence” for potential treatments for diseases of energy metabolism (e.g. obesity, dyslipidemia, anorexia, diabetes type 2), pain, inflammation, CNS disorders (e.g. traumatic brain injury, neurotoxicity, stroke, spinal cord injury, MS, Alzheimer’s, anxiety, depression, insomnia, PTSD, schizophrenia, addiction), Cardiovascular disease (e.g. hypertension, atherosclerosis), eye disorders (e.g. glaucoma, retinopathy), cancer, GI diseases (e.g. inflammatory bowel disease, hepatitis, cirrhosis), musculoskeletal disorders (e.g. arthritis, osteoporosis, post-fracture bone healing).

· Note: again a similarity to opioids, in that at the proper dose and appropriate time, opioids can produce analgesia; at higher dosage, opioids can produce adverse effects such as sedation, GI problems, decreased cognitive function, decreased respiratory function, death, etc.)

· Note: “Medical marijuana” is not a pharmaceutical agent. Therefore, the dosage of the ingredients is unknown and therefore unpredictable, perhaps dangerous, especially when smoked or used in the presence of other drugs, including prescription drugs!

[1] Eliot L. Gardner, Ph.D., Chief, Neuropsychopharmacology Section, National Institute on Drug Abuse, NIH