Detox Of The Opiate Dependent Pain Patient And Ongoing Pain Control No Diag 12 13 08

DETOX OF THE OPIATE DEPENDENT PAIN PATIENT AND ONGOING PAIN CONTROL (Pre-Publication Draft Version) R. Chavez, M.D. © copyright, all rights reserved)

There is no way to understand the severity of a person's pain unless you've felt it. . . And there is no way to truly understand the nature of the beast of drug dependance unless you have been trapped in its belly."

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Rick Chavez M.D At THE P.A.I.N. INSTITUTE, we have developed a unique program utilizing the drug buprenorphine to help addicted or opiate-dependent chronic pain patients get off of their doctor prescribed opiate analgesics with minimal discomfort and withdrawal, and markedly improved pain management. Patients, after many months to years of prolonged exposure to opiate analgesic medications, have developed "opioid-induced hyperalgesia" and drug tolerance. Often physicians have continued to prescribe opiate analgesics without a plan to eventually alter the chronic opioid use or get the individual off of these very addictive drugs. When patients are on maximum amount of Doctor prescribed opiate analgesic medications and these medications no longer provide sufficient pain relief, unless the pain sufferer is taken off of these opiate analgesics, the potential for development of addiction or pseudo-addiction is quite high. Add to this the toxicity of acetaminophen to the liver, or other kinds of complications, and the patient may slide down the slippery slope towards much more potent opioid analgesic drugs such as methadone, morphine, fentanyl, or actiq. Patients suffering with a great deal of pain despite being on the current large doses of Doctor prescribed opiates have two choices if there is a need to get help getting off of opiates, if the buprenorphine treatment plan is not instituted, then the only options for this patient are to get off of the opiate without help or "cold turkey" or to increase the opiate analgesic dosing schedule or prescriptions for stronger medication. Going to a "traditional 12 Step drug rehabilitation program" is usually inappropriate because these patients who have become addicted to Doctor prescribed opiate analgesics are not necessarily drug addicts nor are they necessarily responsible for having been started on their opiate analgesics in the first place. Most Chronic PAIN STATISTICS pain patient's set themselves apart from addiction, and do not 50 TO 80 Million Americans Have Chronic Pain agree that they are drug addicts, after all, it is often iatrogenic, Low Back & Spine Pain Alone Affects or Doctor-induced, and thus a complication of treat-ment. Between 15 To 30 Million Americans Per Year The information below provides the basis for this unique Pain Lasts on Average > 6 Months and cost effective approach: THE P.A.I.N. INSTITUTE The GreyingOf America Buprenorphine Treatment Program , the first program of its type U.S. population is 4% of world population consumes 80% of the in the U.S.today, created and developed to treat Doctor opiates in the world. prescribed opiate dependent or addicted chronic pain patients. THE P.A.I.N. INSTITUTE Traditional 12-Step Inpatient rehab or an insistence on "will power" do not work and are inappropriate and inhumane for this chronically suffering patient group. Fig. 1 Chronic pain is one of the most widespread and expensive disorders in the United States today. Pain has reached epidemic proportions with between 50 and 80 million Americans suffering from some sort of chronic pain, costing the U.S. more than $150 billion annually. Depending on the literature source, it is estimated that between 15%- 50% of these individuals may become physiologically dependent, "pseudo-addicted," or addicted to their doctor prescribed opiate analgesic.(Fig. 1) In addition to this problem, prescription drug abuse is also at epidemic proportions and is now the fastest growing drug problem in children, adolescents, and young adults. There is often no rational or coherent approach to the treatment of pain. It is easy for physicians to write a prescription for pain medication but, it is another thing to get the patient off of the doctor

Fig. 2

prescribed opiate analgesic medication. (Fig. 2) No discussion about cutting edge spine surgery and new spinalpain therapies, procedures, and interventions would be complete without including a discussion about cutting edge pain medicine concepts and new and exciting ideas about outpatient opiate addiction and dependency treatment. New theories on "opioid induced hyperalgesia" and how it affects Pre- and Post-Op surgical management must be part of the overall treatment plan. Knowing how to evaluate and deal with this problem helps patients to get off of their doctorprescribed opiate analgesic(s) before or after surgery and can make the difference between a successful outcome or failure. Writing opiate prescriptions can be "like flying a plane. . . Don't take off unless you know how to land." All too often, the patient ends up in the air and no one knows how to get them down safely or off of their doctor prescribed opiate analgesic(s), and the resultant outcome(s) may be a catastrophic "crash landing." Managing opiate dependent patients who suffer with multiple chronic pain issues has been hampered up until now by limited or nonexistent and effective pain treatment. Additionally, the stigma and shame that our society, as well as the medical system, has placed on patients who require opiate analgesics for pain control has made thoughtful and effective use of these often very effective medications difficult. There is no question that the use of opiate analgesics in treating chronic pain is an important therapeutic option for many individuals and, all too often, chronic pain patients are made to feel like criminals when they end up being treated by their physicians with opiate analgesic medications. The types of patients treated are "your average Joe, the clean-cut store manager of Sears, the IT software executive, the burnt out over achiever who runs a multimillion dollar company, a local real estate agent, the Longshoreman, the college jock, the State Senator, the local mechanic, the schoolteacher, the police officer, the emergency room doctor, the soccer mom . . . . these are the invisible walking wounded of America." These hard-working, seemingly functional Americans who, because of stress, chronic pain, or an unfortunate accident, have become "addicted or dependent" on their opiate medication and are secretly hiding the fact that they have become mentally, physically, and emotionally dependent on their doctor prescribed opiate analgesic medication. Addiction crosses every line: it is a scourge that doesn't care what color, race, religion, Politics-conservative, liberal, democrat, and republican; socioeconomic standing, job, gender, education, profession, or age you are. It is very democratic, no one is left out. Understanding the treatment and management of chronic pain is a very complex issue and understanding the treatment and management of drug addiction is also a very complex issue. Addiction Medicine and Pain Medicine are two specialized fields of medical practice that share a strong common interest in the mechanisms, clinical use, risks, and benefits associated with the use of opioid drugs and other therapies involving potentially abusable medications. In addition to these pharmacologic issues, there are profound clinical interactions between the potential to develop addictive disorders in the treatment of unrelieved and unresolved pain that influence both the management of substance use disorders and the care of chronic pain patients. (Fig. 3) Unfortunately, many Addiction Specialists do not understand the use of opiates in pain management, often taking a total abstinence approach to pain treatment. Ironically, many Pain Specialists do not understand the dangers of opiate addiction when treating chronic pain patients, taking a "use at your own peril" and "if you develop tolerance and need more pain medication, you are on your own" attitude. In fact, paradoxically, many pain physicians are not interested in managing opiate therapy at all, because it is highly regulated by the government and usually very time consuming.

Fig. 3

The primary reason for this situation is that the majority of "pain specialists" in the US today are really anesthesiologists who are "PAIN Interventionalists" and treat pain by utilizing various invasive treatments like Epidural injections, Facet blocks, Radiofrequency Thermo coagulation, Nucleoplasty, or Implantation of Morphine Pumps, or Spinal Cord Stimulators. While these interventions play an important role in Chronic Pain Management, they are invasive and quite costly and, unfortunately, only serve a small percentage of pain patients. "The REAL" specialty of Pain management does not exist and most patients are treated by an amalgam of Primary Care, Family Medicine, Physical Medicine and Rehabilitation, Rheumatology, Neurology, Orthopedics, Psychiatry, Addiction, and various other specialties. Most Anesthesiologists have very little clinical experience beyond injection therapy, yet we continue to expect them to be able to treat one of the most complicated and broadest medical specialties in the U.S. today. Many chronic pain patients have been labeled as "Addicted" or "Drug Seekers." All too often, the medical system forgets that these patients, who control their chronic pain medication under the guidance of their physician(s) should not be considered "ADDICTED" but rather, "PHYSIOLOGICALLY DEPENDENT" to their opiate analgesic.

The disorder of "ADDICTION" is a disease which basically exhibits a set of aberrant human behaviors, whereas a physiologically dependent, but "COMPLIANT" patient on opiates, while often complaining of the same physical changes that occur in addicts, is not exhibiting "ABERRANT" behavior, and thus should not be called an "ADDICT." Opiate dependent chronic pain patients who are unable to continue treating their pain effectively because of the development of tolerance or progression of their painful disorder are often unable to receive sufficient quantities of opiate medication or receive therapeutic supervision of their opiate analgesics by their treating physician. These patients are described as having a "PSEUDO-ADDICTION" which, in effect, describes an individual who is forced to treat their pain themselves, since their physician and the mainstream medical system has abandoned them. The individual seeks out opiate analgesics illegally or surreptitiously, thus being forced to exhibit aberrant behavior in their search for adequate quantities of opiate analgesic medications to control their chronic pain and prevent a horrible withdrawal situation. In fact, a very common and frustrating situation seen in many communities across the U.S. today is one in which the treating Primary Care Physician or Medicine Specialist, who has referred their patient to the local "pain management doctor" (Anesthesiologist) expecting to get help managing their opiate analgesic therapy end up becoming frustrated when their patients return only to find out that their patient was treated with multiple ineffective or temporaril y helpful invasive procedures. The Interventional pain physician is like a general surgeon, once the intervention(s) are completed these patients are returned to their originating physician's care having not received effective medical management or other recommendations regarding their chronic opiate analgesic therapy. Managing opiate medications is a very complicated and time consuming therapy. It requires a great deal of patient education and behavioral management. State Medical Boards and the Drug Enforcement Agency (DEA) of the Federal Government expect physicians to keep thorough and accurate records about each patient. (Fig. 4) The complexity of issues and factors which must be taken into account when treating patients who suffer with chronic pain and who have been on years of opiate therapy often reaches a plateau and the pain syndrome begins to deteriorate as tolerance and "opiate induced hyperalgesia" develop. The concept of "opioid induced hyperalgesia" may account for the difficulty that many people have in overcoming chronic pain while on opiate drugs. In addition to relieving pain, opiates may, over time, actually make a person hypersensitive to pain. As this sensitivity increases, so does the body's need for the narcotic analgesic.(Fig. 5)

Fig. 4

For instance, if one takes a pair of laboratory animals, like a pair of rabbits, and places one of the pair on a chronic opiate regimen using a morphine-like drug, in 3 to 6 months, if both animals are given the same measured pain stimulus, such as an electrical shock or a cold presser test, we can show that the opiate dependent animal will feel more pain, in other words, over time, chronic exposure to opiates will change the rabbit's threshold sensitivity to painful stimulus as compared to the control rabbit, and this can be measured by objective physiologic vital signs and behavioral changes. In patients, ones own natural pain control – endorphin system is altered and may shut down due to the negative effects of the long-term opiate analgesic exposure. This commonly observed phenomenon is the explanation for what has been termed "Opioid Induced Hyperalgesia" and is why so many distressed patients feel that the chronic pain they now experience is often times much worse than their original pain. (Fig. 6) Fig. 5 Fortunately, we now have a medication, BUPRENORPHINE (Subutex), which has revolutionized the treatment of opiate addiction and dependence in the U.S. today. This new, highly effective drug has provided patients with the ability to eliminate opiates from their system without the devastating side affects of withdrawal. In the Chronic Pain patient, what is most remarkable is that once the patient is free of opiates and the MU receptor system has been stabilized by Buprenorphine, they may discover that their pain levels have either diminished considerably or have been eliminated altogether. This drug, although originally developed in 1979, and used in France since the early 1990's, finally became available in the U.S. in 2002 through the Drug Addiction Treatment Act (DATA) of 2000 which enabled physicians for the very first time to

Fig. 6

provide Office-Based Opioid Treatment (OBOT) for this devastating addiction. This act allows physicians to prescribe schedule III, IV, or V "narcotic" medications that are approved by the U.S. FDA for the treatment of patients with "opioid use disorders." In 2002, the FDA approved Buprenorphine (Subutex) and a combination drug, Buprenorphine/Naloxone (Suboxone) to manage opiate dependence. Both of these drugs are schedule III medications. The pharmacology of BUPRENORPHINE is that it primarily affects the MU opioid receptor, where it acts as a partial agonist/partial antagonist. (Fig. 7) Receptor activation increases as the dose increases until it reaches a plateau. Full opioid agonists such as OxyContin, Heroin, Vicodin, Codeine, and Methadone continue to activate the MU receptor as the dose increases without reaching a safe plateau. With the advent of Buprenorphine, certified physicians who have completed an 8 hour training course are now able to "detox opioid dependent and addicted patients" and effectively withdraw these patients off of their opiate analgesic as outpatients in a comfortable office setting without much discomfort or distress. Unfortunately, there are often-times confusing statements in the literature, which mislead both physicians and the public, describing BUPRENORPHINE as being a much more "potent drug" then other opiates, like Morphine, Dilaudid, and OxyContin, and this description has often been misinterpreted as meaning that the drug itself is a more potent opioid agonist, or "stronger painkiller." I have seen statements in the literature which claim that it is "200 times more potent then morphine" when, In reality, what this statement really means is that Buprenorphine turns on and activates the MU receptor sooner and with much more intensity and vigor, thus adhering to the MU receptor earlier, at smaller comparable concentrations, rapidly, and in a "stickier" way.(Fig. 8)

Fig. 7

In fact, when compared to other opiates, it is the PARTIAL rather than the FULL MU activation which makes BUPRENORPHINE less likely to be a drug of abuse. This high affinity for and slow dissociation from the MU opioid receptor blocks out other opiates, and also allows for an easier withdrawal process. Since it is "stickier" then other opiate drugs to the MU receptor, Buprenorphine should only be started after the patient has begun to manifest withdrawal symptoms. (Fig. 9) In other words, if the patient has not waited a long enough period of time after ingestion of their last opioid drug in order to allow their "on-board" opiate medication to leave their system, then BUPRENORPHINE may cause a syndrome called "precipitated withdrawal," and these patients can become quite ill. Because of the potential for causing the opiate dependent pain patient with severe discomfort due to "precipitated withdrawal," the Federal Government/DEA through the DATA 2000 legislation requires that interested physicians be certified in the use of BUPRENORPHINE for opiate withdrawal and addiction treatment by completing an 8 hour certification process. (Fig. 10) These physicians are given a new special DEA number once they have completed certification. The active ingredient in sublingual Subutex is Buprenorphine, however Naloxone was added to sublingual Suboxone to prevent addicts from attempting to change the drug into an INJECTABLE drug which can be abused. Naloxone is not significantly absorbed sublingually and therefore plays no therapeutic role sublingually. However, Naloxone injected with Buprenorphine by an addict who has altered the medication for illicit IV use will render intravenous injected Suboxone (Buprenorphine/Naloxone) useless.

Fig. 8

When treating patients who suffer from prescription drug dependancy and chronic pain issues, the likelihood that these patients will alter the drug illicitly is unlikely and they are considered to be at low risk for changing Subutex into an injectable drug. In France, where there is a system of socialized medicine and the medication is available for minimal cost, one can see why addicts might go to the trouble of changing the drug into an illicit injectable drug. But Fig. 9 here in the U.S., Buprenorphine is relatively expensive when compared to cheaper street heroin, so addicts are not likely to go to this extreme for minimal euphoria or “high,” if any. It is more likely that if Subutex is abused, it would be used as a “bridge” to help prevent withdrawal symptoms in the opiate addict until the drug abuser can get their next “fix” of heroin. Interestingly, at THE P.A.I.N. BUPRENORPHINE INSTITUTE, clinically, in about 10% of patients, it has been noticed when using Suboxone (Buprenorphine/Naloxone) that the Naloxone may be

absorbed sublingually and may cause noticeable side effects in some patients, including less pain relief. It is for this reason that I will primarily use Subutex over Suboxone when treating an opioid dependent chronic pain patient. BUPRENORPHINE bioavailability with the sublingual form is roughly 30% to 50% of the intravenous dose and the maximal plasma concentration is reached within one hour. The mean half-life is 37 hours so, as a treatment for addiction, there is no question that it is effective and can often be given as a once a day or, in some cases, every other day dose. However, in the treatment of opioid dependence or addiction in the chronic pain patient, it is best given multiple times during the day in split doses two to four times daily. This phenomenon has to do with the peak plasma concentration occurring within one hour of each dose and because “pain patients” are behaviorally programmed for multiple daily doses. BUPRENORPHINE is considered one of the safest drugs available and the only overdose death ever reported was related to its concomitant use with injectable benzodiazepine. Common side effects include constipation, urinary retention, sedation, migraine headaches, nausea, and vomiting. (Fig. 11) Because of its slow dissociation from the Mu receptor and its long half-life, it is much easier to taper off of and discontinue BUPRENORPHINE than other Mu receptor drugs. While the maximum dosage recommended by the manufacturer is 32 mg per day, treating patients clinically is an individualized situation. There are some individuals who will require higher doses, and a number of physicians have treated patients who have required up to seven or eight X 8 mg tablets or up to 64 mg per day. There are other individuals who are highly sensitive to this drug and only require 0.5-1 mg or less per day. Basically, every patient is different, and the number of Mu receptors that are being filled will vary based on a person's genetics. Clinically, our goal is to fill 80-90% of the individual's Mu receptors. The amount of medication needed will depend on many factors--the patient's ability to absorb the drug, the patient's metabolism of the drug which occurs at the liver, the number of Mu receptors that the patient has, and the type of Mu receptors that are being affected-to name a few. Most of the data that we have to date is based on the treatment of heroin addicts in France, methadone patients, or animal studies. The use of this drug in opiate dependent pain patients is a new approach and there clearly is not sufficient data available to answer the question of what maximum dose can be used? Buprenorphine is an opiate agonist/antagonist but, like opiate agonists in general, it's dosing should be individualized to the patient. In fact, the agonist ceiling effect or plateau makes Subutex/Suboxone one of the safest drugs available. Chronic pain patients do not take Vicodin or Percocet in order to get high. Initially, they take their doctor prescribed opiate analgesic to find relief from unrelenting pain. But after weeks, months, and often time's years, the patient wakes up to find that their minds and bodies are now being held prisoner. The grip is real, it is terrifying, and millions of chronic pain patients have and will become addicted or chemically dependent to their doctor prescribed opiate analgesic. The irony or "catch 22" in these patients is that, despite treatment with opiate pain medications, patients continue to find themselves in chronic pain, only now the pain has become exacerbated by a heavy and prolonged regime of opioid analgesics.

Fig. 10

Fig. 11

Physicians become concerned about continuing the patient on larger and larger doses of opioid analgesics, and, either begin to titrate the analgesics to lower doses, which predictably causes more pain and suffering, or convince the patient that they can no longer prescribe large doses of opiate analgesics because of fear of "creating an addict" or fear of "government regulation." The patient is often dismissed without a viable withdrawal regime or is labeled a "drug seeker." This action may push the confused patient into the realm of "pseudo-addiction" and they are often forced to seek opiate analgesics by "doctor shopping," or buying drugs illegally on the streets or over the Internet, in other words they begin exhibiting "aberrant behavior" in their search for adequate pain relief. This phenomenon is called "Pseudo-Addiction." Unfortunately, for these patients, added to their original painful condition is the pain of intermittent withdrawal and worsening tolerance. Often, the chronic pain patient desperately wants to stop taking their doctor prescribed opiate analgesic, but is terrified about having to go through the pain and distress of withdrawal. Every time the patient tries to stop their doctor prescribed pain medicine, they will feel the pernicious tentacles of worsening pain due to drug withdrawal, opioid induced hyperalgesia, and of course their pain syndrome itself. This torturing syndrome wreaks havoc on their bodies and is destructive emotionally, psychologically, and spiritually. The chronic pain patient doesn't realize that physiologically, if their body is not properly fed a steady stream of opiate analgesics every four to six hours, they will go through horrendous withdrawal every 4 to 6 hours, and as anyone who has ever been addicted knows, there is probably nothing worse, short of being boiled in a vat of oil, then to go through that kind of agony.

The pain, ironically, causes the patient to believe that they need more opioid to combat the worsening pain, not less. The hypothesis to explain this conundrum is what is described as "opiate induced hyperalgesia," a novel concept proposed in pain patho-physiology to explain a resetting of the threshold for pain sensation. Instead of curing what ails us, pain medications, over time, actually "increase" the body's propensity to instigate more pain, thereby creating a vicious cycle of biologic, physiologic, psychological, and emotional chaos within our bodies. The concept of "opioid induced hyperalgesia" stipulates that when our bodies become chemically dependent to opiates, our brain stops manufacturing, blocks, or removes the body's own "Pain Killers" or "Endorphins" which are "naturally" present to help our systems combat or ameliorate pain and discomfort. It is as if our own defense team has shut down to allow the enemy to take over. We are seduced into believing that the pain we feel is due to our original pain syndrome and not due to the fact that our body is withdrawing every four to six hours from the arsenal of opiates ingested day after day. Along with opioid induced hyperalgesia, there are multiple other complicating factors involved in the development of this phenomenon. (Fig. 12) Once caught in this vicious cycle it is impossible to escape. When the patient requests help, they are often appalled when their Doctor can only offer them two options: Taper themselves off of the opiate analgesic and/or withdraw cold turkey, or enter a chemical dependency rehabilitation facility for detoxification. Use of BUPRENORPHINE is a far more attractive, effective, cost efficient, and simple solution. Managing chronic pain in patients who have become addicted or dependent to their doctor prescribed opiate analgesics is a complex dilemma. Associated with this problem, the patient often experiences depression, anxiety, and hopelessness. Not surprisingly, many patients undergo unneeded procedures and surgeries because they falsely believe that their pain experience "must be due to a surgically or procedurally correctable problem" rather than the vicious cycle of opiate withdrawal. The irony is that these patients who have now become dependent and/or addicted to their doctor prescribed opiate analgesic medication find that their chronic pain has forced them to see more and more doctors and specialists, who, unable to provide an alternative to the severe pain, end up offering a cycle of more surgery or invasive procedures. After multiple surgeries and injections, the patient often wonders why they are not getting better. The patient's physicians are also in a quandary as to what to do next? More medication? More surgery? More Consultants? More Diagnostic tests? More of the same? After observing this cycle occur time and time again, it was hypothesized that if the chronic pain of patients who became caught up in this vicious cycle and offering them detoxification off of their doctor prescribed opiate analgesics prior to proceeding with surgery was studied in a recent abstract by Chavez, Dillin, and Amass presented at the College of Problems in Drug Dependency (CPDD) in Scottsdale, Arizona on June 17, 2006. (Fig. 13)

Fig. 12

The Abstract, "Buprenorphine Treatment as an Alternative to Orthopedic Surgery in Patients Dependent on Prescription Opiates," acknowledged that the analgesic properties of Buprenorphine are well known, but theorized that the development of Opioid tolerance and Opioid induced hyperalgesia altered the patient's pain experience to such a degree that they were willing to accept the risks and dangers of spinal surgical intervention in the hopes of relieving their chronic pain syndrome. By utilizing the Buprenorphine sublingual tablet (Subutex/Suboxone) pre-operatively in the opiate dependent chronic pain patient who was awaiting spine surgery, considered a unique and novel approach, the treatment appeared to stabilize the pain experience significantly, resulting in 16 of the 18 patients postponing or canceling their scheduled surgery. These results seemed to Fig. 13 indicate that worsening pain may be due to both opioid tolerance and opioid induced hyperalgesia, and result in both patient and surgeon mistaking it as a signal to proceed with surgery. Buprenorphine's anti-hyperalgesic effects may benefit these patients by reducing pain and enabling surgery to be postponed or cancelled. The study evaluated 18 opioid tolerant patients who were taking prescription opiates for severe pain. 16 patients had severe spinal pain due to lumbar-sacral disk disease and 2 patients suffered with cervical spine degenerative disc disease. All patients were preoperative and had been referred to The P.A.I.N. Institute prior to being scheduled for spine surgery. 11 Patients were male and 7 females. Their average age was 48 years old with the range being between 33 -66 years. 89% were white, 100 % were insured, 95% were employed, and 95% had 1-4 years of college Prior to Buprenorphine treatment, patients had been maintained on prescription opiates for a mean of 4.9 years with a range of 1 -15 years, 12 had no previous surgery and 6 had had between 1 and 5 prior surgeries. (Fig. 14) After treatment, 13 with Subutex and 5 with Suboxone, a remarkable 89% or 16 of the 18 preoperative patients no longer wanted surgery.

At this time Surgery is still being considered for patient #17 after 22 months on Subutex and patient #18 had surgery and ironically has since returned to Subutex. To date, 89% or 16 of 18 have continued on Buprenorphine maintenance therapy at a mean daily dose of 19.1 mg with the range being between 1mg-32mg for a mean of 20.7 months and range of 7mo-36 months. No patient has become tolerant to Buprenorphine, nor has there been any medication misuse, diversion or safety issues. Urine drug screens have been negative for opiate use, Pain ratings on a 10-point scale averaged 6.9 before treatment and decreased to 2.7 during treatment and continue in this range today. In prior abstracts presented in 2004 at three different venues, at The World Institute of Pain (WIP) 3rd "Congress On Issues In Pain" at Barcelona, Spain, Aug. 2004, The 6th Annual Pain & Chemical Dependency Conference in New York City Feb. 2004, and at the 65th Annual College on Problems on Drug Dependency (CPDD) in Puerto Rico June 2004. (Fig. 15)

Fig. 14

The abstract chronicled what transpired after 65 opiate dependent chronic pain patients who had presented to the P.A.I.N. Institute were taken off of their doctor prescribed opiate analgesic successfully with Buprenorphine and were observed to have a change in the average chronic pain ratings from an average of 6.8 to an average of 2.9., which mirrored the orthopedic abstracts findings. The main difference in this study was that these patients were not pre-operative but rather, they suffered with common chronic pain problems such as Spinal pain, Fibromyalgia, RSD, Neuropathic Pain, Headaches, Trigeminal Neuralgia, Interstitial Cystitis, Chronic Pelvic Pain, recurrent abdominal pain, Rheumatoid arthritis, and Chronic Pancreatitis. The clinical findings and outcome of both of these studies support the use of Subutex or Suboxone for stabilization and reduction of chronic pain in both Chronic pain patients and pre-operative and pre-procedure patients who are opiate dependent or addicted. The potential medical and economic benefits of this approach for both the individual pain patient and for society in general in avoiding surgical complications, time and work lost, and monetary costs are tremendous. Imagine if prior to surgical intervention or implantation of a morphine pump or a spinal cord stimulator the patient is required to undergo a safe and inexpensive opioid detoxification first as a requirement, and that 25%-75% of these procedures are deemed unnecessary if "Opioid Induced Hyperalgesia" is shown to be the primary reason for the chronic pain problem. Even if only 10% were found to be due to this phenomenon, it would not be insignificant. Not only would we save the patient from potential future pain Fig. 15 and suffering due to complications or failed interventions, but billions of dollars could be saved in our already fiscally strained medical and insurance system. In Europe, the rate of surgical intervention or implantation procedures is 10%15% the rate in the U.S., yet their outcomes are just as good, and in some cases better. Americans suffering with pain, to our detriment, tend to reach for the surgical knife much sooner then the rest of the world. The clinical findings and observations of this abstract create more questions than answers. There clearly are other unknown biochemical and physiologic changes that are occurring in the opiate dependent chronic pain patient. We know that BUPRENORPHINE itself does provide some intrinsic pain relief, however, never directly to the degree observed in this abstract. The current available research and information on what is happening at the biochemical level in the opiate dependent pain patient is quite limited. It appears that stabilization of the pain associated with withdrawal and reducing the symptoms of addiction play an important role in reducing the overall pain experience. The actual pain relief seen seems to be due to other as of yet unknown factors. The unique qualities of Buprenorphine coverage is that at an average dose of 16 mg (Figure 16), more than 80%-90% of the opiate or endorphin receptors in the human body and brain are filled, and this may be at the heart of the answer. As a partial Mu receptor agonist, it does not completely block the function of the receptor, thus

Fig. 16

preventing withdrawal symptoms by allowing some function at the receptor site. But the agonist function plateaus and does not provide the pain relief and euphoria seen with full agonists once higher doses are reached. By stabilizing the chronic pain situation and removing the issue of tolerance, pain is diminished markedly. The pain relief provided is not anything like one would see with a full agonist such as Methadone or Morphine, and the antagonist effect is nothing like the blockade and loss of agonist function that is seen with a full antagonist like Naloxone or Naltrexone. So what is really happening? By allowing partial blockade of agonist function, and also allowing partial agonist function at more than 90% of the human body's endorphin receptors, it is possible that the 10% of receptors that are left available or open, are able to interact with, and be utilized by the body's natural endorphins, thus providing a "reset" of the pain threshold level and a stabilization of the chronic pain syndrome . (Fig. 17) In the literature, BUPRENORPHINE has been described as being much more potent than morphine, but clinically, this is not observed because it is only a partial agonist and the agonist effect plateaus. The potency really refers to the ability of Buprenorphine to latch on to the endorphin or Mu receptor with much more strength and intensity at low doses early on. As the dose of Buprenorphine increases the potency or agonist effect decreases and eventually plateaus. Thus, BUPRENORPHINE is not actually more potent in pain control but rather it is "stickier" or more adherent to the Mu receptor early on, which is why "precipitated withdrawal" occurs if a patient has not been properly prepared by their physician to allow for sufficient time to pass after the last dose of their opiate agonist analgesic. This phenomena also relies on whether the opiate analgesic is short, intermediate, or long acting. If the patient is not in early clinical opiate withdrawal at the time Fig. 17 Buprenorphine is instituted, based on signs and symptoms such as described utilizing the COWS (Clinical Opioid Withdrawal Scale), then the treating clinician would be wise to withhold subutex until the patient begins to exhibit these physical signs. For this reason Buprenorphine should NEVER be prescribed to allow the patient to begin his or her treatment unsupervised outside of the physician's office or clinic. Treatment Protocol should always have the patient starting in the physician's office or in a hospital setting. What does all this mean for the practicing medical clinician and how can this new technique be used by physicians clinically? Most of us came out of medical school and residency with very little information in the areas of Addiction Medicine and Chronic Pain Management. Yet, these two areas of medicine make up at least 50% of the medical problems that we deal with directly and indirectly in all fields of medicine. Like the effect of food addiction and the health benefits one derives in treating obesity, treating chronic pain and addiction with new medications like Buprenorphine will have extraordinary effects on patients emotional, physical, psychological, and spiritual well being. Painful disorders occur in all specialties of medicine from GYN to Pediatrics, Psychiatry to Orthopedics, Neurology to Emergency room, Dermatology to Ophthalmology and, in fact, every single specialty of medicine. If we use opiates to treat pain, then, as physicians, we need to know how to get people off of opiates easily and safely. Becoming certified in the use of Buprenorphine for office based opiate detoxification is as basic as learning Basic Cardiac Life Support (BCLS). Not only will office based Buprenorphine treatment help to reduce opiate abuse and use but, the possible reduction in unnecessary surgeries and procedures would be a beneficial outcome of this therapy to the patient and society in general. By creatively using Buprenorphine as a pre-operative/pre-procedure diagnostic and therapeutic evaluation tool when dealing with opiate tolerance and "opioid induced hyperalgesia" we will advance our ability to understand the physiologic changes that occur in our patients whose acute pain has now become chronic pain, and whose "doctor prescribed opiate medication" tolerance has escalated out of control. The potential to decrease medical costs and medical complications by halting unnecessary procedures due to the phenomenon of "opioid induced hyperalgesia" should have insurance companies and the federal government pushing for more research in this area. The amount of money that can be saved is substantial, but more important than this is the potential improvement in healthcare outcomes when unnecessary procedures and surgeries are avoided and the prevalence of complications and iatrogenic caused disease related to these unnecessary therapies are reduced as a result of this highly beneficial approach. In most chronic pain patients, the dose of opiate analgesic increases rapidly to cover the persistent chronic pain. However, due to this described phenomenon known as "opiate induced hyperalgesia," the patient can no longer effectively tolerate their pain, even when given heavier doses of opiate analgesics. The patient now is faced with a difficult problem. Should he or she increase the opiate analgesic by switching to a more powerful agent? Or, should the patient be detoxified off of the opiate medication utilizing Buprenorphine, which has been designed specifically for this problem in the treatment of addiction? Based on the protocols developed here at THE P.A.I.N. INSTITUTE, it has become clinically apparent (see abstracts) that staying on Subutex or Suboxone in maintenance treatment after detoxification off of the doctor prescribed opiate analgesics seems to stabilize the patient's chronic pain situation.

It is important to emphasize at this juncture, that this approach utilizes the medications Subutex and Suboxone exactly in the way that they were released for by the FDA. They are not being used "off label" because many times we are withdrawing the patient off of opiates that they have become dependent on because of their chronic pain situation having gotten out of control. Buprenorphine is used in the way it was designed to be used, that is, to detoxify patients off of opiates which they have become dependent on or addicted to due to their chronic pain. The only difference between dependence and addiction being a dependent patient who has developed aberrant behaviors due to their inability to obtain adequate doses of opiate analgesics from the medical system to relieve their pain. While most chronic pain patients on opiate therapy have not developed the diagnosis of "ADDICTION" based on DSM IV criteria, they, like the patient who has become physiologically dependent on, and exceedingly tolerant to, their doctor prescribed opiate analgesic medications is not physiologically unlike what happens to the opiate addict. It is difficult, and in fact impossible, to withdraw chronic pain patients who are opiate dependent differently than opiate addicts when detoxifying either group off of opiate drugs and medications. Whether considered physiologically opiate dependent or opiate addicted, both patient groups will react the same therapeutically to Subutex/Suboxone treatment. The main differentiation is that most chronic pain patients who are not opiate addicted do not benefit from entering a chemical dependency unit or treatment through a 12-step AA/NA program, because they are NOT ADDICTS. They are CHRONIC PAIN PATIENTS who, just like the opiate addict, must be taken off of their doctor prescribed opiate medications because they have now developed a progressively negative situation in which opiate tolerance combined with changes in brain neurotransmitter chemistry will cause feedback controlled suppression of the individual's natural endorphin production and alter other neuro-endocrine-biochemical transmitter changes. These neuro-biologic changes occur in the human brain, regardless of whether the patient is an opiate addict or an opiate dependent chronic pain patient. These changes may bring on depression, emotional instability, feelings of isolation, worsening sexual libido, diminished testosterone production, worsening mental function and memory changes, chronic fatigue, insomnia, and unfortunately, worsening of the patient's chronic pain situation. There is no question, that by reversing the "opiate induced hyperalgesia," chronic pain patients can re-establish a normal pain threshold which in turn will enhance the patient's ability to tolerate pain, reverse progression of depression, enhance endorphin production, improve fatigue and insomnia, and definitely improve the patient's cerebral function and emotional state overall. THEORETICAL DISCUSSION The following theoretical discussion is simply my way of explaining to the reader why Buprenorphine is different then other opioid chemicals, and thus, why it works in the way it does in slowing the development of tolerance. The best way to explain this phenomenon is through a theory that I have developed that explains why this approach is medically beneficial. To simplify the discussion, let's say that every human has 1000 endorphin or MU receptors. Also, let's assume that normal pain tolerance requires that the "NORMAL" individual produces 300 endorphin units per day to fill 300 of 1000 endorphin receptors. Someone with chronic pain like a "chronic pain patient," on the other hand, may need another 100 receptors filled, or 400 receptors total filled, in order to live with their chronic pain syndrome comfortably. As an example, let's assume that clinically the patient needs two Vicodin tablets 3 times daily to fill the additional 100 endorphin or MU receptors. After using two Vicodin tablets 3 times daily for one year, tolerance may have developed. It appears, from much of the research available today, that one factor that Eexplains tolerance may actually include the creation of more new MU or endorphin receptors within the organism. So, in this example, after one year let's assume due to tolerance, there are now 1100 MU receptors within the organism, and let us imagine that two Vicodin 3 times daily only fills 100 MU receptors, the example patient is now filling 400 of 1100 receptors instead of the original 400 of 1000 receptors. The altered situation for this patient is now essentially back to the original baseline number of 700 open receptors (1000- 300 = 700; 1100-400 = 700) at onset of opiate treatment. In other words, it takes 2 vicodin three times daily, just to stay even or "normal." Now the patient's pain threshold will be in a negative state if Vicodin is stopped abruptly. Originally, the patient started with their own natural endorphins filling 300 of 1000 receptors and 2 Vicodin three times daily increased the number to 400 of 1000, but with tolerance development over 1 year in this hypothetical example, the patient now has 400 of 1100 filled, which is a net gain of zero filled MU receptors. This means that due to tolerance the patient will not have any continuing pain relief despite being on the original 2 Vicodin three times daily because now, the patient must stay on this dose just to maintain the normal physiologic state that was present prior to starting opiate treatment. At this point, the hypothetical patient must increase, or double, his or her dose to 2 Vicodin tablets 6 times daily in order to recover the 100 receptors required for adequate pain control, which increases the total Vicodin filled MU or endorphin receptors to 200 of 1100 (up from 100 of 1000 MU receptors), plus the baseline patient's endorphins filling 300 MU receptors which results in a net increase of 100 receptors or now 500 (200 vicodin artificial endorphins + 300 endogenous) of 1100 MU receptors filled, thus giving the patient the needed 100 receptors filled to maintain pain relief. However, as more time passes, more receptors are created which then causes either an increase in the amount of opiates taken by the organism, or an increase in the strength or agonist activity of the opiate medication by switching to stronger drugs like Morphine, OxyContin, Fentanyl, or Methadone. Of course this scenario also ignores the liklihood that, through negative feedback mechanisms, reduced production of endorphins endogenously. So what we will see is both a need for more endorphins to fill MU receptors created by the opiate dependent organism or human, and an overall reduction in the

original endogenous opioid baseline level. In addition, this system is genetically influenced so that environmental exposure helps to determine the possibility of addictive behavior. This is why long-term opiate use in some patients may lead to excessive amounts of doctor prescribed opiate analgesics being prescribed over time in order to maintain clinically significant pain relief. Eventually, the individual cannot functionally tolerate the large doses of opiates, without overdosing or developing other complications, and cannot keep up with the constantly increasing tolerance due to increasing receptors. This may be one of the contributing reasons for the phenomena of "opioid induced hyperalgesia" and at that point in pain treatment, the patient is desperate and unable to maintain control over their pain. (Fig. 6) If the patient stops the opiates, they will have an excess of MU receptors which now means a baseline of 300 natural endorphins to fill 1100 MU receptors. The new problem is that the 6 Vicodin daily also have caused a negative feedback situation which might diminish the circulating endorphins, thus the negative opioid state is exacerbated because the organism no longer makes the baseline number of endorphins and this negative state causes the organism to start craving opiates, which may result in pseudo-addiction or addiction. Buprenorphine, on the other hand, is a very different type of opiate. It is an opiate agonist/antagonist which has the unique quality of being able to attach to the opiate or endorphin receptor "like superglue." During detoxification of the opiate addict or opiate dependent chronic pain patient, as the opiate medication or drug is leaving the receptor early on in detoxification treatment, Buprenorphine is able to rapidly attach to the endorphin receptors and keep all agonist opiates from attaching to these receptors. Within 24 hours of beginning treatment with Buprenorphine, at an average dose of 16 mg per day, virtually 90% of the opiate or endorphin receptors are under the influence of Buprenorphine . Now, let's imagine that this same individual, at year one, after tolerance has developed, is treated with Subutex. The patient is able to rapidly and successfully get off of their Vicodin therapy. At this point, there are now 1100 instead of 1000 receptors available. Let's simplify the situation for the sake of discussion. Assume that a "normal individual" creates 300 endorphin units per day. The opiate dependent patient not only has 100 more receptors after 1 year of daily Vicodin use for pain control, but now has suppressed endorphin production due to feedback suppression and may now only produce 200 MU endorphin units per day for example, which might now mean that their new baseline sensitivity to pain may actually be worse because of a net loss in circulating natural Endorphins. Subutex/Suboxone (Buprenorphine or Buprenorphine/naloxone) is an exciting and unique drug. It is the only opiate agonist/antagonist which, at an average dose of 16 mg/day, virtually controls 90% of all of the Endorphin, Opiate, or MU receptors (see Figure 13). So, within 24 hours of the time of transfer from Vicodin to Subutex, 90% of the 1100 (example patient) MU or Endorphin receptors are filled. Thus, in this example, 990 receptors (90% of 1100) are now filled by Subutex. However, this blockade is much different than that produced by the pure opiate antagonist Naltrexone. Naltrexone effectively blocks the receptor without any agonist effect, whereas, Subutex allows some agonist activity, and by doing so, is able to partially "TURN ON" the "pain control or MU ENDORPHIN system" sufficiently to make a difference in the individual's overall chronic pain experience. Virtually no tolerance is seen with this drug. Therefore, the dosing regimen is constant or, in some cases, decreases over time. Since Buprenorphine fills 90% of all MU/Endorphin receptors, regardless of the number of receptors present, any increase in receptors over time due to tolerance, will continue to have 90% of those new receptors being filled with Buprenorphine and therefore the net increase in unfilled receptors is negligible and clinically not noticed. Let's now look at this same patient at Year 2, after another year has passed, if tolerance is still developing at the same rate, the example patient may now have 1200 MU/Endorphin receptors available. But, this time the patient is on Buprenorphine, thus if 90% of ALL MU receptors are filled, 1080 Endorphin receptors (90% of 1200) will now be filled, which, in effect, does not change the pain tolerance of the individual since the net change in number of MU or endorphin receptors is negligible (-20). Imagine the following situation where a full opiate agonist like methadone, OxyContin, Vicodin, Hydromorphone, or Morphine attaches to the Endorphin, MU, or Opiate receptor in the human body. Think of each receptor as being like starting an automobile engine, and since these drugs are FULL OPIATE AGONISTS, it is like stepping on the gas pedal and pushing it to the floor, maximally revving the "MU receptor engine." Doing this for a long and constant period of time would make any automobile engine "Over Heat," and so, as one might suspect, hypothetically this might happen to the physiologic "MU engines." In this case, the Endorphin or MU receptors may similarly "burnout" or temporarily become functionally unresponsive and ultimately begin to malfunction. Buprenorphine or Subutex, on the other hand, as an Opiate Agonist/Antagonist which fills 90% of all of the individual's MU receptors may, in effect, turn on 1080 of the 1200 receptor engines. However, as a partial agonist/antagonist, the "Endorphin Engines" are only partially turned on, and rather than "pressing the pedal to the Metal," so to speak, the MU or Endorphin "receptor engines" are only on "Idle" which means that the engines are "minimally revved." In theory, these "MU engines" will never "Over Heat or Burnout" because they are working in a controlled and lowered or mild agonist physiological state. Obviously, my theory simplifies a very complex and not well understood situation, never-the-less, it might explain why converting opiate dependent Chronic Pain Patients or Opiate Addicts to Subutex or Suboxone not only safely and effectively withdraws the patient off of opiates, but with maintenance treatment, stabilizes the new "Hyper-Algesic State" into a new "Hyper-Tolerant State," the Hyper-Algesic State having developed due to chronic opiate use. For the ADDICT this means no withdrawal and no craving and for the CHRONIC PAIN PATIENT it means pain control at least as good as

when the patient was on a "Full Agonist" and for the majority of patients observed clinically, remarkably better pain control. Subutex/Suboxone therapy is the most appropriate and clinically sound approach to the treatment of opiate dependence or addiction. I have been working with this drug for more than 4 years and I have treated more opiate dependent chronic pain patients than many of the physicians using this medication in the U.S. today. The 4 abstracts that we have produced are fairly straightforward and seem to support the above theory. Especially important, are the results of the most recent abstract, presented at The Annual CPDD conference this last summer in July 2006. Written with renowned Buprenorphine researcher Dr. Leslie Amass and Orthopedic surgeon Dr. William Dillin of Kerlan-Jobe Medical Group in Los Angeles, the results were beyond our expectations, and to date, all of the studied patients continue to do well. Today, some of these patients (16 of 18) continue on maintenance Buprenorphine treatment, 50 months later. For the majority of these patients, it does appear that if Subutex is stopped, the pain may return, albeit to a lower level than when on full opiate agonist treatment, which might result in the patient going back to the surgeon or returning to full opiate agonist therapy . The interesting and fascinating observation is that no tolerance development has been observed, and that all of the patients remain on the same or less original maintenance dose (Average 16 mg/day) The explanation for why average pain levels dropped from 6.9/10 (on full opiate agonist therapy) to 2.7/10 (on Subutex) is NOT because Buprenorphine works directly as a full opiate agonist like Vicodin or morphine. What seems to be occurring is that Buprenorphine stabilizes the patient's chronic pain syndrome by affecting the biochemical-physiologicneurotransmitter "Chronic Pain Control System" in the human physiology. As an analgesic, Subutex is not a very effective painkiller against acute pain or, it appears, in "non-opiate primed" or "opiate naïve" chronic pain patients. In other words, if one fractures their arm or strains their back acutely, Vicodin will be chosen over Buprenorphine by the patient for acute pain control every time. However, as a medication to help opiate dependent chronic pain patients and opiate addicts get off of their opiate drug or medication, and rebalance their complex internal chronic pain-neuro-transmitter system, it seem to be the ideal effective detoxification and therapeutic approach. In reality, the number, type, and function of every individual human being's endorphin or MU receptor system is genetically predetermined and unique. Many humans can be exposed to opiates without any sensitization whatsoever and are able to discontinue opiate drugs rapidly and readily. From our experience with many American soldiers who came back from the Vietnam War addicted to heroin, it was observed that many of these soldiers were able to discontinue opiate dependence and abuse easily and without having had to go through a traditional chemical dependency or 12-step program. Unfortunately, for a large number of people, perhaps 10% to 20% of the population, a genetically pre-determined "internal switch" is turned on when the individual is exposed to opiates, whether they be doctor prescribed opiates or illicit drugs like heroin, which causes an intense "craving" for continued opiate use. This group of individuals may develop either an opiate addiction, that is, a physiologic and emotional dependence coupled with aberrant behavior or a straight forward physiologic dependence with the inability to turn off the brain's "Opiate craving switch." The only difference between these two sets of patients is the presence or not of Aberrant Behavior and the presence or not of Chronic Pain. The compliant chronic pain patient theoretically does not have any history of aberrant behavior; therefore, these patients cannot be treated under the DSM IV diagnosis category of "Opiate Drug Addiction and Abuse." But, compliant patients can be treated for "Opiate Physiologic Dependence" or "Pseudo-Addiction" due to subjective chronic pain because of their inability to taper off of or get off of their doctor prescribed opiate analgesic medications. Therefore, whether the patient is an "opiate addict or a physiologically dependent pain patient," there is no question that Subutex or Suboxone is the only way for either of these two types of patients to successfully control their opiate craving or subjective chronic pain symptoms and detoxify off of the opiates successfully. The physiology is exactly the same, only the emotional, spiritual, and psychological state is different. DSM IV definition of Opiate Addiction or Opiate dependence may be a description of either type of patient. Drug Addiction, Pseudo-addiction, and Physiologic drug dependence are genuine disorders, and as such must be treated rationally and scientifically when medical therapy is instituted. Of Course, it goes without saying that treatment of each of these disease states requires the inclusion of psychological therapy and behavior modification. A major problem is that when the patient's insurance company says that a patient is being treated for "pain" and not "addiction" they are revealing their total ignorance and lack of understanding of the "Syndromes of Opiate Physiologic Dependence." The physiology of opiate use is exactly the same whether the patient is compliant or not. The definition of Addiction from Webster's Unabridged Dictionary of the English Language is "the state of being given up or having yielded to a habit or practice or to something that is habit forming, such as narcotics, to such an extent that its cessation causes severe trauma." An addict is "a person who is addicted to a practice or habit and is someone who has given oneself over as to a habit or pursuit; and is applying or devoting habitually." All chronic pain patients who have been on opiate analgesics (either sub-acutely: 1-6 months; or chronically: > 6 months) and their physicians realize that they are on habit forming medications and that cessation of these drugs would be highly detrimental, potentially damaging, and "TRAUMATIC" to the patient. Cessation of doctor prescribed opiate analgesics in the Chronic pain patient would fulfill this definition. Thus, the "trauma" that can occur in the chronic pain patient is not any different than what is seen in the opiate addicted individual. Like the laboratory opiate dependent rabbit described earlier, on chronic morphine for many months, when compared to a control rabbit, appears that we have created a "Hyperalgesic" rabbit. The morphine dependent hyper-algesic rabbit will show increased physiologic vital signs attributable to acute pain when it is shocked with the same amount of electrical impulse or cold pressor test that is also given to the "control non-opiate dependent" rabbit. As a living organism, the rabbit doesn't know whether it is addicted or physiologically dependent, but it will never-the-less have changes in behavior

and physiology as a result of the opiate dependence. Once off of the opiate, withdrawal symptoms will occur, again, regardless of the reason why the organism is on the opiate. Therefore, pain and discomfort will be present in both the addict and chronic pain patient and use of Buprenorphine will help stabilize pain in both types of patients. Thus, one cannot really say that the patient cannot be treated with Buprenorphine for their "painful" situation. Are the addict and chronic pain patient in "PAIN or the discomfort of WITHDRAWAL?" Subutex does treat pain, but it is not a very good pain killer, as anyone who has had a tooth pulled or broken a thumb can testify, however it is an excellent stabilizer 0f the consequences of opiate dependence, which include pain and craving of the physiologic opiate dependence. The definition of Addiction from Webster's dictionary and DSM IV (Figure 18) crosses over with the diagnosis of opiate dependent chronic pain patients. Insurance companies do not understand that the situation is a very complicated situation. If the chronic pain patient takes extra pain medication without telling their doctor, or take 2 extra pills above the prescribed amount, are they now an Addict? If the patient gets pain medication from the ER and fails to tell their physician, or if they borrow their grandmother's pain medication because they've lost their insurance and fail to tell their doctor, or the Dentist gives them extra Tylenol with Codeine, are they an Addict? Why would this patient who now fits the definition now qualify to get Subutex/Suboxone and the compliant patient not? Morally and ethically, insurance companies are wrong to refuse Subutex/Suboxone treatment in the opiate dependent chronic pain patient because the amount of suffering and pain that may occur by refusing this medication is significant. Chronic pain patients often develop "opioid induced hyperalgesia" as well as opioid tolerance and, over time, the doses of opiates therapeutically are insufficient to control their chronic pain. Should the chronic pain patient continue increasing opiate medications to control chronic pain? Or should they be "detoxed" off of their opiate analgesic(s) and stabilize and improve their chronic pain by resetting their "chronic pain threshold" using Buprenorphine maintenance treatment? There are many chronic pain patients who are ideal candidates to try the Subutex Detoxification Protocol. Opiate dependent chronic pain patients who proceed with Buprenorphine treatment here at THE P.A.I.N. INSTITUTE appear to have an 80% chance of having much of their pain, depression, fatigue, and other chronic symptoms improved, and at a minimum, the patient often feels better than they did when they were on their "doctor prescribed opiate analgesic." Interestingly, this does not happen in "Opiate Naïve" Chronic pain patient(s). This phenomenon seems to be observed only in patients who have been "primed" with long-term opiate therapy. This observation seems to substantiate the argument that Buprenorphine should not be given to opioid naïve patients to treat their chronic pain directly. Fig. 18 Chronic use of opiates will suppress natural endorphin production. Many of the symptoms of Pain, depression, emotional instability, fatigue, and anxiety are reversed when the patient is detoxified off of their doctor prescribed opiate and placed on maintenance Buprenorphine. Buprenorphine seems to extinguish all craving for opiates in the opiate addict and therefore, in addiction treatment, it is recommended that the patient stay on Buprenorphine for an extended period of maintenance treatment (3-18 months and sometimes longer) until the addict has successfully altered their behavior and extinguished the cues and triggers in their environment which can often cause relapse in opiate dependent or addicted individuals. The opiate dependent chronic pain patient is treated in the same way. The cravings for opiates are the same in either individual because of the long-term neurotransmitter changes that occur in the brain while on long-term opiate use or abuse. Both opiate addicts and opiate dependent chronic pain patients may develop behavioral cues and triggers which cause an intense desire for opiates and these behaviors often require sufficient time to extinguish. There is no specific recognized standard protocol in existence today which justifies early discontinuation of Buprenorphine or limitations as to length of treatment or limits on the quantities of medication. The official recommendations are that one may use up to a maximum of four 8 mg sublingual tablets per day. Therefore, the treatment protocol for "opiate addiction" and "opiate dependence due to chronic pain" are the same when Buprenorphine is used to detoxify either group of patients off of their opiates. The main difference is that opiate addicts should receive psychological and emotional treatment which addresses their aberrant drug abuse, drug seeking behaviors, and opiate craving, while " opiate dependent chronic pain patients" need to receive appropriate psychological, emotional, and medical treatment to control their chronic pain, pain behaviors, cues, opiate cravings, and address any emotional dependence that may have developed or occurred. In addition, it appears that Buprenorphine has qualities which seem to stabilize the patient's chronic pain neuro-endocrinephysiologic system, and by doing so, it not only successfully may allow the opiate dependent chronic pain patient to get off of their opiate medication but it may help the patient to better Fig. 19

withstand their chronic pain situation. It appears that Buprenorphine use in this group of patients may be the most beneficial mode of therapy for the chronic pain patient who is on long-term opiate therapy. By periodically reassessing the patient and detoxifying them off of opiates with Subutex, it helps the physician and patient to re-evaluate the development of "opiate induced hyperalgesia," prevent potential development of opiate addiction, prevent pseudo-addiction, and most importantly, prevent potentially dangerous and expensive surgical interventions or anesthesia based implantation of pain devices such as morphine pumps and spinal cord stimulators, as well as inappropriate injection therapy like Epidurals and Facet blocks. Finally, the most rational reason for Subutex/Suboxone therapy is that the patient has nothing to lose, and everything to gain by detoxifying off of opiates prior to surgery or implantation of "Anti-pain" devices or undergoing injection therapies, because the ease with which this therapeutic approach can be applied and the potential patient and societal benefits are quite remarkable and undeniable. (Fig. 19) Rick Chavez, M.D. Medical Director, Board Certified, American Board of Pain Medicine Certified, American Society of Addiction Medicine (ASAM) Diplomate, American Academy of Pain Management Certified, Utilization Review Expert Board Certified, American Board of Family Medicine Assistant Clinical Professor of Family Medicine, UCLA David Geffen School of Medicine

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