DETOX OF THE OPIATE DEPENDENT PAIN PATIENT AND ONGOING PAINCONTROL

(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 thereis no way to truly understand the nature of the beast of drug dependance unless you have been

trapped in its belly."

Rick Chavez M.DAt THE P.A.I.N. INSTITUTE, we have developed a unique program utilizing the drug buprenorphine to help addicted oropiate-dependent chronic pain patients get off of their doctor prescribed opiate analgesics with minimal discomfort andwithdrawal, and markedly improved pain management. Patients, after many months to years of prolonged exposure toopiate analgesic medications, have developed "opioid-induced hyperalgesia" and drug tolerance. Often physicians havecontinued to prescribe opiate analgesics without a plan to eventually alter the chronic opioid use or get the individual offof these very addictive drugs. When patients are on maximum amount of Doctor prescribed opiate analgesic medicationsand these medications no longer provide sufficient pain relief, unless the pain sufferer is taken off of these opiateanalgesics, the potential for development of addiction or pseudo-addiction is quite high. Add to this the toxicity ofacetaminophen to the liver, or other kinds of complications, and the patient may slide down the slippery slope towardsmuch more potent opioid analgesic drugs such as methadone, morphine, fentanyl, or actiq. Patients suffering with a greatdeal of pain despite being on the current large doses of Doctor prescribed opiates have two choices if there is a need toget help getting off of opiates, if the buprenorphine treatment plan is not instituted, then the only options for this patientare to get off of the opiate without help or "cold turkey" or to increase the opiate analgesic dosing schedule orprescriptions for stronger medication. Going to a "traditional 12 Step drug rehabilitation program" is usually inappropriatebecause these patients who have become addicted to Doctor prescribed opiate analgesics are not necessarily drugaddicts nor are they necessarily responsible for having beenstarted on their opiate analgesics in the first place. Most Chronicpain patient's set themselves apart from addiction, and do notagree that they are drug addicts, after all, it is often iatrogenic,or Doctor-induced, and thus a complication of treat-ment.The information below provides the basis for this uniqueand cost effective approach: THE P.A.I.N. INSTITUTEBuprenorphine Treatment Program , the first program of its typein the U.S.today, created and developed to treat Doctorprescribed opiate dependent or addicted chronic pain patients.Traditional 12-Step Inpatient rehab or an insistence on "willpower" do not work and are inappropriate and inhumane for thischronically suffering patient group. Fig. 1

Chronic pain is one of the most widespread and expensive dis-orders in the United States today. Pain has reached epidemicproportions with between 50 and 80 million Americanssuffering from some sort of chronic pain, costing the U.S. morethan $150 billion annually. Depending on the literature source,it is estimated that between 15%- 50% of these individualsmay become physiologically dependent, "pseudo-addicted," oraddicted to their doctor prescribed opiate analgesic.(Fig. 1)

In addition to this problem, prescription drug abuse is also atepidemic proportions and is now the fastest growing drugproblem in children, adolescents, and young adults. There isoften no rational or coherent approach to the treatment of pain.It is easy for physicians to write a prescription for pain medicationbut, it is another thing to get the patient off of the doctor Fig. 2

PAIN STATISTICS50 TO 80 Million Americans Have Chronic PainLow Back & Spine Pain Alone AffectsBetween 15 To 30 Million Americans Per YearPain Lasts on Average > 6 MonthsThe GreyingOf AmericaU.S. population is 4% of world population consumes 80% of theopiates in the world.

THE P.A.I.N. INSTITUTE

prescribed opiate analgesic medication. (Fig. 2)

No discussion about cutting edge spine surgery and new spinalpain therapies, procedures, and interventions would becomplete without including a discussion about cutting edge pain medicine concepts and new and exciting ideas aboutoutpatient opiate addiction and dependency treatment.

New theories on "opioid induced hyperalgesia" and how it affects Pre- and Post-Op surgical management must be part ofthe overall treatment plan. Knowing how to evaluate and deal with this problem helps patients to get off of theirdoctorprescribed opiate analgesic(s) before or after surgery and can make the difference between a successful outcomeor failure.

Writing opiate prescriptions can be "like flying a plane. . . Don't take off unless you know how to land." All too often, thepatient ends up in the air and no one knows how to get them down safely or off of their doctor prescribed opiateanalgesic(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 bylimited or nonexistent and effective pain treatment. Additionally, the stigma and shame that our society, as well as themedical system, has placed on patients who require opiate analgesics for pain control has made thoughtful and effectiveuse of these often very effective medications difficult. There is no question that the use of opiate analgesics in treatingchronic pain is an important therapeutic option for many individuals and, all too often, chronic pain patients are made tofeel 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, theburnt out over achiever who runs a multimillion dollar company, a local real estate agent, the Longshoreman, the collegejock, the State Senator, the local mechanic, the schoolteacher, the police officer, the emergency room doctor, the soccermom . . . . 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 becomementally, physically, and emotionally dependent on their doctor prescribed opiate analgesic medication. Addictioncrosses every line: it is a scourge that doesn't care what color, race, religion, Politics-conservative, liberal, democrat, andrepublican; socioeconomic standing, job, gender, education, profession, or age you are. It is very democratic, no one isleft out.

Understanding the treatment and management of chronic pain is a very complex issue and understanding the treatmentand management of drug addiction is also a very complex issue. Addiction Medicine and Pain Medicine are twospecialized fields of medical practice that share a strong common interest in the mechanisms, clinical use, risks, andbenefits associated with the use of opioid drugs and other therapies involving potentially abusable medications.

In addition to these pharmacologic issues, there are profoundclinical interactions between the potential to develop addictivedisorders in the treatment of unrelieved and unresolved painthat influence both the management of substance use disordersand the care of chronic pain patients. (Fig. 3) Unfortunately, manyAddiction Specialists do not understand the use of opiates inpain management, often taking a total abstinence approach topain treatment. Ironically, many Pain Specialists do notunderstand the dangers of opiate addiction when treatingchronic pain patients, taking a "use at your own peril" and "ifyou develop tolerance and need more pain medication, you areon your own" attitude. In fact, paradoxically, many painphysicians are not interested in managing opiate therapy at all,because it is highly regulated by the government and usuallyvery time consuming. Fig. 3

The primary reason for this situation is that the majority of "pain specialists" in the US today are really anesthesiologistswho are "PAIN Interventionalists" and treat pain by utilizing various invasive treatments like Epidural injections, Facetblocks, Radiofrequency Thermo coagulation, Nucleoplasty, or Implantation of Morphine Pumps, or Spinal CordStimulators. While these interventions play an important role in Chronic Pain Management, they are invasive and quitecostly 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, andvarious other specialties. Most Anesthesiologists have very little clinical experience beyond injection therapy, yet wecontinue 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 forgetsthat these patients, who control their chronic pain medication under the guidance of their physician(s) should not beconsidered "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 aphysiologically dependent, but "COMPLIANT" patient on opiates, while often complaining of the same physical changesthat occur in addicts, is not exhibiting "ABERRANT" behavior, and thus should not be called an "ADDICT." Opiatedependent chronic pain patients who are unable to continue treating their pain effectively because of the development oftolerance or progression of their painful disorder are often unable to receive sufficient quantities of opiate medication orreceive 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 totreat their pain themselves, since their physician and the mainstream medical system has abandoned them. The individualseeks out opiate analgesics illegally or surreptitiously, thus being forced to exhibit aberrant behavior in their search foradequate quantities of opiate analgesic medications to control their chronic pain and prevent a horrible withdrawalsituation. In fact, a very common and frustrating situation seen in many communities across the U.S. today is one inwhich the treating Primary Care Physician or Medicine Specialist, who has referred their patient to the local "painmanagement doctor" (Anesthesiologist) expecting to get help managing their opiate analgesic therapy end up becomingfrustrated when their patients return only to find out that their patient was treated with multiple ineffective or temporarilyhelpful invasive procedures. The Interventional pain physician is like a general surgeon, once the intervention(s) arecompleted these patients are returned to their originating physician's care having not received effective medicalmanagement or other recommendations regarding their chronic opiate analgesic therapy.

Managing opiate medications is a very complicated and timeconsuming therapy. It requires a great deal of patient educationand behavioral management. State Medical Boards and theDrug Enforcement Agency (DEA) of the Federal Governmentexpect physicians to keep thorough and accurate recordsabout each patient. (Fig. 4)

The complexity of issues and factors which must be taken intoaccount when treating patients who suffer with chronic pain andwho have been on years of opiate therapy often reaches a plateauand the pain syndrome begins to deteriorate as tolerance and"opiate induced hyperalgesia" develop. The concept of "opioidinduced hyperalgesia" may account for the difficulty that manypeople have in overcoming chronic pain while on opiate drugs.In addition to relieving pain, opiates may, over time, actually makea person hypersensitive to pain. As this sensitivity increases, sodoes the body's need for the narcotic analgesic.(Fig. 5) Fig. 4

For instance, if one takes a pair of laboratory animals, like a pairof rabbits, and places one of the pair on a chronic opiate regimenusing a morphine-like drug, in 3 to 6 months, if both animals aregiven the same measured pain stimulus, such as an electricalshock or a cold presser test, we can show that the opiatedependent animal will feel more pain, in other words, over time,chronic exposure to opiates will change the rabbit's thresholdsensitivity to painful stimulus as compared to the control rabbit,and this can be measured by objective physiologic vital signs andbehavioral changes. In patients, ones own natural pain control –endorphin system is altered and may shut down due to thenegative effects of the long-term opiate analgesic exposure.This commonly observed phenomenon is the explanation forwhat has been termed "Opioid Induced Hyperalgesia" and iswhy so many distressed patients feel that the chronic pain theynow experience is often times much worse than their original pain.(Fig. 6)

Fig. 5Fortunately, we now have a medication, BUPRENORPHINE(Subutex), which has revolutionized the treatment of opiateaddiction and dependence in the U.S. today. This new, highlyeffective drug has provided patients with the ability to eliminateopiates from their system without the devastating side affectsof withdrawal. In the Chronic Pain patient, what is mostremarkable is that once the patient is free of opiates and the MUreceptor system has been stabilized by Buprenorphine, they maydiscover that their pain levels have either diminishedconsiderably or have been eliminated altogether.

This drug, although originally developed in 1979, and usedin France since the early 1990's, finally became available in theU.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 prescribeschedule III, IV, or V "narcotic" medications that are approved by the U.S. FDA for the treatment of patients with "opioiduse 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 partialagonist/partial antagonist. (Fig. 7) Receptor activation increases as the dose increases until it reaches a plateau. Fullopioid agonists such as OxyContin, Heroin, Vicodin, Codeine, and Methadone continue to activate the MU receptor as thedose increases without reaching a safe plateau.

With the advent of Buprenorphine, certified physicians who havecompleted an 8 hour training course are now able to "detox opioid

dependent and addicted patients" and effectively withdraw thesepatients off of their opiate analgesic as outpatients in a comfortableoffice setting without much discomfort or distress. Unfortunately,there are often-times confusing statements in the literature, whichmislead both physicians and the public, describingBUPRENORPHINE as being a much more "potent drug" then otheropiates, like Morphine, Dilaudid, and OxyContin, and thisdescription has often been misinterpreted as meaning that the drugitself is a more potent opioid agonist, or "stronger painkiller." I haveseen statements in the literature which claim that it is "200 timesmore potent then morphine" when, In reality, what this statementreally means is that Buprenorphine turns on and activates the MUreceptor sooner and with much more intensity and vigor, thusadhering to the MU receptor earlier, at smaller comparableconcentrations, rapidly, and in a "stickier" way.(Fig. 8) Fig. 7

In fact, when compared to other opiates, it is the PARTIAL ratherthan the FULL MU activation which makes BUPRENORPHINE lesslikely to be a drug of abuse. This high affinity for and slowdissociation 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 begunto manifest withdrawal symptoms. (Fig. 9)

In other words, if the patient has not waited a long enough periodof time after ingestion of their last opioid drug in order to allow their"on-board" opiate medication to leave their system, thenBUPRENORPHINE may cause a syndrome called "precipitated with-drawal," and these patients can become quite ill. Because of thepotential for causing the opiate dependent pain patient with severediscomfort due to "precipitated withdrawal," the FederalGovernment/DEA through the DATA 2000 legislation requires thatinterested physicians be certified in the use of BUPRENORPHINE Fig. 8for opiate withdrawal and addiction treatment by completing an 8hour certification process. (Fig. 10) These physicians are given a newspecial DEA number once they have completed certification. Theactive ingredient in sublingual Subutex is Buprenorphine, howeverNaloxone was added to sublingual Suboxone to prevent addicts fromattempting to change the drug into an INJECTABLE drug which canbe abused. Naloxone is not significantly absorbed sublingually andtherefore plays no therapeutic role sublingually. However, Naloxoneinjected with Buprenorphine by an addict who has altered themedication for illicit IV use will render intravenous injectedSuboxone (Buprenorphine/Naloxone) useless.

When treating patients who suffer from prescription drug depen-dancy and chronic pain issues, the likelihood that these patients willalter the drug illicitly is unlikely and they are considered to be at lowrisk for changing Subutex into an injectable drug. In France, wherethere is a system of socialized medicine and the medication is avail-able for minimal cost, one can see why addicts might go to thetrouble of changing the drug into an illicit injectable drug. But Fig. 9here in the U.S., Buprenorphine is relatively expensive when compared to cheaper street heroin, so addicts arenot likely to go to this extreme for minimal euphoria or “high,” if any. It is more likely that if Subutex is abused, itwould be used as a “bridge” to help prevent withdrawal symptoms in the opiate addict until the drug abuser canget their next “fix” of heroin. Interestingly, at THE P.A.I.N. BUPRENORPHINE INSTITUTE, clinically, in about 10% ofpatients, 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 forthis reason that I will primarily use Subutex over Suboxone when treating an opioid dependent chronic painpatient. BUPRENORPHINE bioavailability with the sublingual form is roughly 30% to 50% of the intravenous doseand the maximal plasma concentration is reached within one hour. The mean half-life is 37 hours so, as atreatment for addiction, there is no question that it is effective and can often be given as a once a day or, insome cases, every other day dose. However, in the treatment of opioid dependence or addiction in the chronicpain patient, it is best given multiple times during the day in split doses two to four times daily. Thisphenomenon 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 relatedto 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 andits long half-life, it is much easier to taper off of and discontinue BUPRENORPHINE than other Mu receptordrugs.

While the maximum dosage recommended by the manufacturer is32 mg per day, treating patients clinically is an individualizedsituation. There are some individuals who will require higher doses,and a number of physicians have treated patients who have requiredup to seven or eight X 8 mg tablets or up to 64 mg per day. There areother individuals who are highly sensitive to this drug and onlyrequire 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 basedon a person's genetics. Clinically, our goal is to fill 80-90% of theindividual's Mu receptors. The amount of medication needed willdepend on many factors--the patient's ability to absorb the drug, thepatient's metabolism of the drug which occurs at the liver, thenumber of Mu receptors that the patient has, and the type of Mureceptors that are being affected-to name a few. Most of the datathat we have to date is based on the treatment of heroin addicts inFrance, methadone patients, or animal studies. The use of this drug Fig. 10in opiate dependent pain patients is a new approach and there clearlyis not sufficient data available to answer the question of whatmaximum dose can be used? Buprenorphine is an opiateagonist/antagonist but, like opiate agonists in general, it's dosingshould be individualized to the patient. In fact, the agonist ceilingeffect or plateau makes Subutex/Suboxone one of the safest drugsavailable.

Chronic pain patients do not take Vicodin or Percocet in order to gethigh. Initially, they take their doctor prescribed opiate analgesicto find relief from unrelenting pain. But after weeks, months, andoften time's years, the patient wakes up to find that their minds andbodies are now being held prisoner. The grip is real, it is terrifying,and millions of chronic pain patients have and will become addictedor chemically dependent to their doctor prescribed opiate analgesic.The irony or "catch 22" in these patients is that, despite treatmentwith opiate pain medications, patients continue to find themselvesin chronic pain, only now the pain has become exacerbated by aheavy and prolonged regime of opioid analgesics. Fig. 11

Physicians become concerned about continuing the patient on larger and larger doses of opioid analgesics, and, eitherbegin to titrate the analgesics to lower doses, which predictably causes more pain and suffering, or convince the patientthat 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 opiateanalgesics by "doctor shopping," or buying drugs illegally on the streets or over the Internet, in other words they beginexhibiting "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 andworsening tolerance. Often, the chronic pain patient desperately wants to stop taking their doctor prescribed opiateanalgesic, but is terrified about having to go through the pain and distress of withdrawal. Every time the patient tries tostop their doctor prescribed pain medicine, they will feel the pernicious tentacles of worsening pain due to drugwithdrawal, opioid induced hyperalgesia, and of course their pain syndrome itself. This torturing syndrome wreaks havocon their bodies and is destructive emotionally, psychologically, and spiritually. The chronic pain patient doesn't realizethat physiologically, if their body is not properly fed a steady stream of opiate analgesics every four to six hours, they willgo through horrendous withdrawal every 4 to 6 hours, and as anyone who has ever been addicted knows, there isprobably 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. Thehypothesis to explain this conundrum is what is described as "opiate induced hyperalgesia," a novel concept proposed inpain patho-physiology to explain a resetting of the threshold for pain sensation. Instead of curing what ails us, painmedications, over time, actually "increase" the body's propensity to instigate more pain, thereby creating a vicious cycleof 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 toallow the enemy to take over. We are seduced into believing that the pain we feel is due to our original pain syndrome andnot 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 thisphenomenon. (Fig. 12)

Once caught in this vicious cycle it is impossible to escape. When the patient requests help, they are often appalled whentheir Doctor can only offer them two options: Taper themselves off of the opiate analgesic and/or withdraw cold turkey, orenter a chemical dependency rehabilitation facility for detoxification.

Use of BUPRENORPHINE is a far more attractive, effective, cost efficient, and simple solution. Managing chronic pain inpatients 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 "mustbe due to a surgically or procedurally correctable problem" rather than the vicious cycle of opiate withdrawal. The irony isthat these patients who have now become dependent and/oraddicted to their doctor prescribed opiate analgesic medicationfind that their chronic pain has forced them to seemore and more doctors and specialists, who, unable to providean alternative to the severe pain, end up offering a cycle of moresurgery or invasive procedures. After multiple surgeries andinjections, the patient often wonders why they are not getting better.The patient's physicians are also in a quandary as to what to donext? More medication? More surgery? More Consultants? MoreDiagnostic tests? More of the same?

After observing this cycle occur time and time again, it washypothesized that if the chronic pain of patients who becamecaught up in this vicious cycle and offering them detoxification offof their doctor prescribed opiate analgesics prior to proceedingwith surgery was studied in a recent abstract by Chavez, Dillin, andAmass presented at the College of Problems in Drug Dependency Fig. 12(CPDD) in Scottsdale, Arizona on June 17, 2006. (Fig. 13)

The Abstract, "Buprenorphine Treatment as an Alternative to Ortho-pedic Surgery in Patients Dependent on Prescription Opiates,"acknowledged that the analgesic properties of Buprenorphine arewell known, but theorized that the development of Opioid toleranceand Opioid induced hyperalgesia altered the patient's painexperience to such a degree that they were willing to accept therisks and dangers of spinal surgical intervention in the hopes ofrelieving their chronic pain syndrome.

By utilizing the Buprenorphine sublingual tablet (Subutex/Suboxone)pre-operatively in the opiate dependent chronic pain patient whowas awaiting spine surgery, considered a unique and novelapproach, the treatment appeared to stabilize the pain experiencesignificantly, resulting in 16 of the 18 patients postponing orcanceling their scheduled surgery. These results seemed to Fig. 13indicate that worsening pain may be due to both opioid tolerance and opioid induced hyperalgesia, and result in bothpatient 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 bepostponed or cancelled. The study evaluated 18 opioid tolerant patients who were taking prescription opiates for severepain. 16 patients had severe spinal pain due to lumbar-sacral disk disease and 2 patients suffered with cervical spinedegenerative disc disease. All patients were preoperative and had been referred to The P.A.I.N. Institute prior to beingscheduled for spine surgery. 11 Patients were male and 7 females. Their average age was 48 years old with the rangebeing between 33 -66 years. 89% were white, 100 % were insured, 95% were employed, and 95% had 1-4 years of collegePrior to Buprenorphine treatment, patients had been maintained on prescription opiates for a mean of 4.9 years with arange 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 longerwanted surgery.

At this time Surgery is still being considered for patient #17 after22 months on Subutex and patient #18 had surgery and ironicallyhas since returned to Subutex. To date, 89% or 16 of 18 havecontinued on Buprenorphine maintenance therapy at a mean dailydose of 19.1 mg with the range being between 1mg-32mg for a meanof 20.7 months and range of 7mo-36 months.

No patient has become tolerant to Buprenorphine, nor has therebeen any medication misuse, diversion or safety issues. Urinedrug screens have been negative for opiate use, Pain ratings on a10-point scale averaged 6.9 before treatment and decreased to2.7 during treatment and continue in this range today.

In prior abstracts presented in 2004 at three different venues, at TheWorld Institute of Pain (WIP) 3rd "Congress On Issues In Pain" atBarcelona, Spain, Aug. 2004, The 6th Annual Pain & ChemicalDependency Conference in New York City Feb. 2004, and at the65th Annual College on Problems on Drug Dependency (CPDD) inPuerto 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 tohave a change in the average chronic pain ratings from an average of 6.8 to an average of 2.9., which mirrored theorthopedic 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 ChronicPancreatitis.

The clinical findings and outcome of both of these studiessupport the use of Subutex or Suboxone for stabilization andreduction of chronic pain in both Chronic pain patients andpre-operative and pre-procedure patients who are opiatedependent or addicted. The potential medical and economicbenefits of this approach for both the individual pain patientand 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 amorphine pump or a spinal cord stimulator the patient isrequired to undergo a safe and inexpensive opioid detoxifi-cation first as a requirement, and that 25%-75% of theseprocedures are deemed unnecessary if "Opioid InducedHyperalgesia" is shown to be the primary reason for thechronic pain problem. Even if only 10% were found to bedue to this phenomenon, it would not be insignificant.

Not only would we save the patient from potential future pain Fig. 15and suffering due to complications or failed interventions, but billions of dollars could be saved in our already fiscallystrained 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, toour detriment, tend to reach for the surgical knife much sooner then the rest of the world. The clinical findings andobservations of this abstract create more questions thananswers. There clearly are other unknown biochemical andphysiologic changes that are occurring in the opiate depen-dent chronic pain patient. We know that BUPRENORPHINEitself does provide some intrinsic pain relief, however, neverdirectly to the degree observed in this abstract. The currentavailable research and information on what is happening atthe biochemical level in the opiate dependent pain patient isquite limited.

It appears that stabilization of the pain associated with with-drawal and reducing the symptoms of addiction play animportant role in reducing the overall pain experience. Theactual pain relief seen seems to be due to other as of yet un-known factors. The unique qualities of Buprenorphinecoverage is that at an average dose of 16 mg (Figure 16), morethan 80%-90% of the opiate or endorphin receptors in thehuman body and brain are filled, and this may be at the heartof the answer. As a partial Mu receptor agonist, it does not Fig. 16completely block the function of the receptor, thus

preventing withdrawal symptoms by allowing some function at the receptor site. But the agonist function plateaus anddoes not provide the pain relief and euphoria seen with full agonists once higher doses are reached. By stabilizing thechronic pain situation and removing the issue of tolerance, pain is diminished markedly. The pain relief provided is notanything like one would see with a full agonist such as Methadone or Morphine, and the antagonist effect is nothing likethe 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 functionat more than 90% of the human body's endorphin receptors, it is possible that the 10% of receptors that are left availableor open, are able to interact with, and be utilized by the body's natural endorphins, thus providing a "reset" of the painthreshold level and a stabilization of the chronic pain syndrome . (Fig. 17)

In the literature, BUPRENORPHINE has been described asbeing much more potent than morphine, but clinically, thisis not observed because it is only a partial agonist and theagonist effect plateaus. The potency really refers to theability of Buprenorphine to latch on to the endorphin or Mureceptor with much more strength and intensity at low dosesearly on. As the dose of Buprenorphine increases thepotency or agonist effect decreases and eventually plateaus.

Thus, BUPRENORPHINE is not actually more potent in paincontrol but rather it is "stickier" or more adherent to the Mureceptor early on, which is why "precipitated withdrawal" occursif a patient has not been properly prepared by their physician toallow for sufficient time to pass after the last dose of their opiateagonist analgesic. This phenomena also relies on whether theopiate analgesic is short, intermediate, or long acting. If thepatient is not in early clinical opiate withdrawal at the time Fig. 17Buprenorphine is instituted, based on signs and symptoms such as described utilizing the COWS (Clinical OpioidWithdrawal Scale), then the treating clinician would be wise to withhold subutex until the patient begins to exhibit thesephysical signs. For this reason Buprenorphine should NEVER be prescribed to allow the patient to begin his or hertreatment unsupervised outside of the physician's office or clinic. Treatment Protocol should always have the patientstarting 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 physiciansclinically? Most of us came out of medical school and residency with very little information in the areas of AddictionMedicine and Chronic Pain Management. Yet, these two areas of medicine make up at least 50% of the medical problemsthat 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 addictionwith 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 toEmergency room, Dermatology to Ophthalmology and, in fact, every single specialty of medicine. If we use opiates to treatpain, 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 CardiacLife Support (BCLS). Not only will office based Buprenorphine treatment help to reduce opiate abuse and use but, thepossible reduction in unnecessary surgeries and procedures would be a beneficial outcome of this therapy to the patientand society in general. By creatively using Buprenorphine as a pre-operative/pre-procedure diagnostic and therapeuticevaluation tool when dealing with opiate tolerance and "opioid induced hyperalgesia" we will advance our ability tounderstand the physiologic changes that occur in our patients whose acute pain has now become chronic pain, andwhose "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 thephenomenon of "opioid induced hyperalgesia" should have insurance companies and the federal government pushing formore research in this area. The amount of money that can be saved is substantial, but more important than this is thepotential improvement in healthcare outcomes when unnecessary procedures and surgeries are avoided and theprevalence of complications and iatrogenic caused disease related to these unnecessary therapies are reduced as a resultof 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 effectivelytolerate 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 bedetoxified off of the opiate medication utilizing Buprenorphine, which has been designed specifically for this problem inthe treatment of addiction? Based on the protocols developed here at THE P.A.I.N. INSTITUTE, it has become clinicallyapparent (see abstracts) that staying on Subutex or Suboxone in maintenance treatment after detoxification off of thedoctor 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 inthe way that they were released for by the FDA. They are not being used "off label" because many times we arewithdrawing the patient off of opiates that they have become dependent on because of their chronic pain situation havinggotten out of control. Buprenorphine is used in the way it was designed to be used, that is, to detoxify patients off ofopiates which they have become dependent on or addicted to due to their chronic pain. The only difference betweendependence and addiction being a dependent patient who has developed aberrant behaviors due to their inability to obtainadequate 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 IVcriteria, they, like the patient who has become physiologically dependent on, and exceedingly tolerant to, their doctorprescribed opiate analgesic medications is not physiologically unlike what happens to the opiate addict. It is difficult, andin fact impossible, to withdraw chronic pain patients who are opiate dependent differently than opiate addicts whendetoxifying either group off of opiate drugs and medications. Whether considered physiologically opiate dependent oropiate addicted, both patient groups will react the same therapeutically to Subutex/Suboxone treatment. The maindifferentiation is that most chronic pain patients who are not opiate addicted do not benefit from entering a chemicaldependency unit or treatment through a 12-step AA/NA program, because they are NOT ADDICTS. They are CHRONICPAIN PATIENTS who, just like the opiate addict, must be taken off of their doctor prescribed opiate medications becausethey have now developed a progressively negative situation in which opiate tolerance combined with changes in brainneurotransmitter chemistry will cause feedback controlled suppression of the individual's natural endorphin productionand 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 opiatedependent 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, chronicfatigue, 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 normalpain threshold which in turn will enhance the patient's ability to tolerate pain, reverse progression of depression, enhanceendorphin production, improve fatigue and insomnia, and definitely improve the patient's cerebral function and emotionalstate overall.

THEORETICAL DISCUSSIONThe following theoretical discussion is simply my way of explaining to the reader why Buprenorphine is different then other opioidchemicals, 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 ismedically 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 fill300 of 1000 endorphin receptors. Someone with chronic pain like a "chronic pain patient," on the other hand, may needanother 100 receptors filled, or 400 receptors total filled, in order to live with their chronic pain syndrome comfortably. Asan example, let's assume that clinically the patient needs two Vicodin tablets 3 times daily to fill the additional 100endorphin or MU receptors.

After using two Vicodin tablets 3 times daily for one year, tolerance may have developed. It appears, from much of theresearch available today, that one factor that Eexplains tolerance may actually include the creation of more new MU orendorphin receptors within the organism. So, in this example, after one year let's assume due to tolerance, there are now1100 MU receptors within the organism, and let us imagine that two Vicodin 3 times daily only fills 100 MU receptors, theexample patient is now filling 400 of 1100 receptors instead of the original 400 of 1000 receptors. The altered situation forthis 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 thepatient'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 timesdaily increased the number to 400 of 1000, but with tolerance development over 1 year in this hypothetical example, thepatient now has 400 of 1100 filled, which is a net gain of zero filled MU receptors. This means that due to tolerance thepatient will not have any continuing pain relief despite being on the original 2 Vicodin three times daily because now, thepatient must stay on this dose just to maintain the normal physiologic state that was present prior to starting opiatetreatment. At this point, the hypothetical patient must increase, or double, his or her dose to 2 Vicodin tablets 6 timesdaily in order to recover the 100 receptors required for adequate pain control, which increases the total Vicodin filled MUor endorphin receptors to 200 of 1100 (up from 100 of 1000 MU receptors), plus the baseline patient's endorphins filling300 MU receptors which results in a net increase of 100 receptors or now 500 (200 vicodin artificial endorphins + 300endogenous) 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 opiatestaken by the organism, or an increase in the strength or agonist activity of the opiate medication by switching to strongerdrugs like Morphine, OxyContin, Fentanyl, or Methadone. Of course this scenario also ignores the liklihood that, throughnegative feedback mechanisms, reduced production of endorphins endogenously. So what we will see is both a need formore 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 environmentalexposure 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 analgesicsbeing prescribed over time in order to maintain clinically significant pain relief. Eventually, the individual cannotfunctionally tolerate the large doses of opiates, without overdosing or developing other complications, and cannot keep upwith the constantly increasing tolerance due to increasing receptors. This may be one of the contributing reasons for thephenomena of "opioid induced hyperalgesia" and at that point in pain treatment, the patient is desperate and unable tomaintain control over their pain. (Fig. 6) If the patient stops the opiates, they will have an excess of MU receptors whichnow means a baseline of 300 natural endorphins to fill 1100 MU receptors. The new problem is that the 6 Vicodin dailyalso have caused a negative feedback situation which might diminish the circulating endorphins, thus the negative opioidstate is exacerbated because the organism no longer makes the baseline number of endorphins and this negative statecauses 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 theunique quality of being able to attach to the opiate or endorphin receptor "like superglue." During detoxification of theopiate addict or opiate dependent chronic pain patient, as the opiate medication or drug is leaving the receptor early on indetoxification treatment, Buprenorphine is able to rapidly attach to the endorphin receptors and keep all agonist opiatesfrom attaching to these receptors. Within 24 hours of beginning treatment with Buprenorphine, at an average dose of 16mg 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. Thepatient is able to rapidly and successfully get off of their Vicodin therapy. At this point, there are now 1100 instead of 1000receptors available. Let's simplify the situation for the sake of discussion. Assume that a "normal individual" creates 300endorphin units per day. The opiate dependent patient not only has 100 more receptors after 1 year of daily Vicodin usefor pain control, but now has suppressed endorphin production due to feedback suppression and may now only produce200 MU endorphin units per day for example, which might now mean that their new baseline sensitivity to pain mayactually 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 opiateagonist/antagonist which, at an average dose of 16 mg/day, virtually controls 90% of all of the Endorphin, Opiate, or MUreceptors (see Figure 13). So, within 24 hours of the time of transfer from Vicodin to Subutex, 90% of the 1100 (examplepatient) MU or Endorphin receptors are filled. Thus, in this example, 990 receptors (90% of 1100) are now filled bySubutex. 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, andby doing so, is able to partially "TURN ON" the "pain control or MU ENDORPHIN system" sufficiently to make a differencein 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 overtime. Since Buprenorphine fills 90% of all MU/Endorphin receptors, regardless of the number of receptors present, anyincrease in receptors over time due to tolerance, will continue to have 90% of those new receptors being filled withBuprenorphine 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, doesnot 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, orMorphine attaches to the Endorphin, MU, or Opiate receptor in the human body. Think of each receptor as being likestarting an automobile engine, and since these drugs are FULL OPIATE AGONISTS, it is like stepping on the gas pedal andpushing it to the floor, maximally revving the "MU receptor engine." Doing this for a long and constant period of timewould make any automobile engine "Over Heat," and so, as one might suspect, hypothetically this might happen to thephysiologic "MU engines." In this case, the Endorphin or MU receptors may similarly "burnout" or temporarily becomefunctionally 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 MUreceptors 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 orEndorphin "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 agonistphysiological state.

Obviously, my theory simplifies a very complex and not well understood situation, never-the-less, it might explain whyconverting opiate dependent Chronic Pain Patients or Opiate Addicts to Subutex or Suboxone not only safely andeffectively 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 ADDICTthis 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 paincontrol.

Subutex/Suboxone therapy is the most appropriate and clinically sound approach to the treatment of opiate dependenceor addiction. I have been working with this drug for more than 4 years and I have treated more opiate dependent chronicpain patients than many of the physicians using this medication in the U.S. today. The 4 abstracts that we have producedare fairly straightforward and seem to support the above theory. Especially important, are the results of the most recentabstract, presented at The Annual CPDD conference this last summer in July 2006. Written with renowned Buprenorphineresearcher Dr. Leslie Amass and Orthopedic surgeon Dr. William Dillin of Kerlan-Jobe Medical Group in Los Angeles, theresults 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 themajority of these patients, it does appear that if Subutex is stopped, the pain may return, albeit to a lower level than whenon full opiate agonist treatment, which might result in the patient going back to the surgeon or returning to full opiateagonist therapy . The interesting and fascinating observation is that no tolerance development has been observed, andthat 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) isNOT because Buprenorphine works directly as a full opiate agonist like Vicodin or morphine. What seems to be occurringis that Buprenorphine stabilizes the patient's chronic pain syndrome by affecting the biochemical-physiologic-neurotransmitter "Chronic Pain Control System" in the human physiology. As an analgesic, Subutex is not a very effectivepainkiller 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 acutepain control every time. However, as a medication to help opiate dependent chronic pain patients and opiate addicts getoff of their opiate drug or medication, and rebalance their complex internal chronic pain-neuro-transmitter system, it seemto 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 geneticallypredetermined and unique. Many humans can be exposed to opiates without any sensitization whatsoever and are able todiscontinue opiate drugs rapidly and readily. From our experience with many American soldiers who came back from theVietnam War addicted to heroin, it was observed that many of these soldiers were able to discontinue opiate dependenceand 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 "internalswitch" is turned on when the individual is exposed to opiates, whether they be doctor prescribed opiates or illicit drugslike heroin, which causes an intense "craving" for continued opiate use. This group of individuals may develop either anopiate addiction, that is, a physiologic and emotional dependence coupled with aberrant behavior or a straight forwardphysiologic dependence with the inability to turn off the brain's "Opiate craving switch." The only difference betweenthese two sets of patients is the presence or not of Aberrant Behavior and the presence or not of Chronic Pain. Thecompliant chronic pain patient theoretically does not have any history of aberrant behavior; therefore, these patientscannot be treated under the DSM IV diagnosis category of "Opiate Drug Addiction and Abuse." But, compliant patientscan be treated for "Opiate Physiologic Dependence" or "Pseudo-Addiction" due to subjective chronic pain because oftheir inability to taper off of or get off of their doctor prescribed opiate analgesic medications. Therefore, whether thepatient is an "opiate addict or a physiologically dependent pain patient," there is no question that Subutex or Suboxone isthe only way for either of these two types of patients to successfully control their opiate craving or subjective chronic painsymptoms 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 ofeither type of patient.

Drug Addiction, Pseudo-addiction, and Physiologic drug dependence are genuine disorders, and as such must be treatedrationally and scientifically when medical therapy is instituted. Of Course, it goes without saying that treatment of each ofthese disease states requires the inclusion of psychological therapy and behavior modification. A major problem is thatwhen the patient's insurance company says that a patient is being treated for "pain" and not "addiction" they are revealingtheir total ignorance and lack of understanding of the "Syndromes of Opiate Physiologic Dependence." The physiology ofopiate 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 upor having yielded to a habit or practice or to something that is habit forming, such as narcotics, to such an extent that itscessation causes severe trauma." An addict is "a person who is addicted to a practice or habit and is someone who hasgiven oneself over as to a habit or pursuit; and is applying or devoting habitually." All chronic pain patients who havebeen on opiate analgesics (either sub-acutely: 1-6 months; or chronically: > 6 months) and their physicians realize thatthey are on habit forming medications and that cessation of these drugs would be highly detrimental, potentiallydamaging, and "TRAUMATIC" to the patient. Cessation of doctor prescribed opiate analgesics in the Chronic pain patientwould fulfill this definition. Thus, the "trauma" that can occur in the chronic pain patient is not any different than what isseen in the opiate addicted individual.

Like the laboratory opiate dependent rabbit described earlier, on chronic morphine for many months, when compared to acontrol rabbit, appears that we have created a "Hyperalgesic" rabbit. The morphine dependent hyper-algesic rabbit willshow increased physiologic vital signs attributable to acute pain when it is shocked with the same amount of electricalimpulse or cold pressor test that is also given to the "control non-opiate dependent" rabbit. As a living organism, therabbit 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 willhelp stabilize pain in both types of patients. Thus, one cannot really say that the patient cannot be treated withBuprenorphine for their "painful" situation. Are the addict and chronic pain patient in "PAIN or the discomfort ofWITHDRAWAL?" Subutex does treat pain, but it is not a very good pain killer, as anyone who has had a tooth pulled orbroken a thumb can testify, however it is an excellent stabilizer 0f the consequences of opiate dependence, which includepain 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 opiatedependent chronic pain patients. Insurance companies do not understand that the situation is a very complicatedsituation. If the chronic pain patient takes extra pain medication without telling their doctor, or take 2 extra pills above theprescribed amount, are they now an Addict? If the patient gets pain medication from the ER and fails to tell theirphysician, or if they borrow their grandmother's pain medication because they've lost their insurance and fail to tell theirdoctor, or the Dentist gives them extra Tylenol with Codeine, are they an Addict? Why would this patient who now fits thedefinition 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 dependentchronic 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 ofopiates therapeutically are insufficient to control their chronic pain. Should the chronic pain patient continue increasingopiate medications to control chronic pain? Or should they be "detoxed" off of their opiate analgesic(s) and stabilize andimprove their chronic pain by resetting their "chronic pain threshold" using Buprenorphine maintenance treatment?

There are many chronic pain patients who are ideal candidatesto try the Subutex Detoxification Protocol. Opiate dependentchronic pain patients who proceed with Buprenorphinetreatment here at THE P.A.I.N. INSTITUTE appear to have an 80%chance of having much of their pain, depression, fatigue, andother chronic symptoms improved, and at a minimum, thepatient often feels better than they did when they were on their"doctor prescribed opiate analgesic." Interestingly, this doesnot happen in "Opiate Naïve" Chronic pain patient(s). Thisphenomenon seems to be observed only in patients who havebeen "primed" with long-term opiate therapy. This observationseems to substantiate the argument that Buprenorphine shouldnot be given to opioid naïve patients to treat their chronic paindirectly.

Fig. 18Chronic use of opiates will suppress natural endorphin production. Many of the symptoms of Pain, depression, emotionalinstability, fatigue, and anxiety are reversed when the patient is detoxified off of their doctor prescribed opiate and placedon maintenance Buprenorphine. Buprenorphine seems to extinguish all craving for opiates in the opiate addict andtherefore, in addiction treatment, it is recommended that the patient stay on Buprenorphine for an extended period ofmaintenance treatment (3-18 months and sometimes longer) until the addict has successfully altered their behavior andextinguished the cues and triggers in their environment which can often cause relapse in opiate dependent or addictedindividuals. The opiate dependent chronic pain patient is treated in the same way. The cravings for opiates are the samein either individual because of the long-term neurotransmitter changes that occur in the brain while on long-term opiateuse or abuse. Both opiate addicts and opiate dependent chronic pain patients may develop behavioral cues and triggerswhich 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 ofBuprenorphine or limitations as to length of treatment or limits on the quantities of medication. The officialrecommendations are that one may use up to a maximum offour 8 mg sublingual tablets per day. Therefore, the treatmentprotocol for "opiate addiction" and "opiate dependence due tochronic pain" are the same when Buprenorphine is used todetoxify either group of patients off of their opiates. The maindifference is that opiate addicts should receive psychologicaland emotional treatment which addresses their aberrant drugabuse, drug seeking behaviors, and opiate craving, while "opiate dependent chronic pain patients" need to receiveappropriate psychological, emotional, and medical treat-ment to control their chronic pain, pain behaviors, cues, opiatecravings, and address any emotional dependence that mayhave developed or occurred. In addition, it appears thatBuprenorphine has qualities which seem to stabilize the patient's chronic pain neuro-endocrine-physiologic system, and by doing so, it not only successfullymay allow the opiate dependent chronic pain patient to get offof 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 mostbeneficial 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 patientto 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 oranesthesia based implantation of pain devices such as morphine pumps and spinal cord stimulators, as well asinappropriate 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 togain 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 arequite remarkable and undeniable. (Fig. 19)

Rick Chavez, M.D.Medical Director,Board Certified, American Board of Pain MedicineCertified, American Society of Addiction Medicine (ASAM)Diplomate, American Academy of Pain ManagementCertified, Utilization Review ExpertBoard Certified, American Board of Family MedicineAssistant Clinical Professor of Family Medicine,UCLA David Geffen School of Medicine

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