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7 Articles in Volume 4, Issue #5
A Case For Intractable Pain Centers: Part 1
Co-Existing Psychological Factors
Cold Lasers in Pain Management
Diagnosing Diffuse Aches and Pains
Occipital Nerve Block for Cervicogenic Headaches
Opioid Therapy in Chronic Non-cancer Pain Management
Reflex Sympathetic Dystrophy (RSD)

Opioid Therapy in Chronic Non-cancer Pain Management

Despite fears fueled by negative press, opioid therapy—with proper evaluation and safeguards—is a legitimate, viable, and essential tool in managing severe, intractable, non-cancer pain.

Opioid therapy for non-cancer pain patients is, at best, controversial for pain management specialists and other medical professionals at this time. Regardless of the studies that show that opioid therapy is beneficial for patients with chronic pain, medical providers are becoming afraid of prescribing these drugs for fear of litigation and potential state and federal investigation and prosecution. Yet a dilemma exists in that the Federation of State Medical Boards and JCAHO are promoting the use of adequate levels of opioids for severe, intractable pain and patients — informed of their rights to have adequate pain management — are demanding that their pain be controlled to a tolerable level. Many pain specialists, however, are concerned about maintaining their practice to help these patients because of governmental scrutiny to prevent prescription drug-abuse. Indeed, there is even a consideration in California to change hydrocodone compounds to become a Schedule II narcotic, making access to one of the most widely prescribed opioid analgesics restricted.

Due to the uncertainty, fear of addiction, and perceived risk surrounding opioid use, legitimate need often goes unheeded to the detriment of the patient. A case in point is a patient, an ophthalmic specialist known to one author, who was being treated with oxycodone sustained release for six months prior to lumbar surgery and who found that lack of communication (or, perhaps disagreement) between surgeon, anesthesiologist, and pain doctor (coupled with holiday absences) resulted in a couple of days of virtually no post-operative pain medications. The excruciating agony of pain was compounded by withdrawal symptoms from the abrupt cessation of his prescribed opioids due to the floor nurses’ hesitation to administer them for fear of respiratory depression. Ensuing confusion surrounding physical dependence and withdrawal versus true ‘addiction’ further resulted in needless embarrassment, humiliation, and emotional distress to the point of severe depression.

The following article will provide some background on basic opioid pharmacology, patient and physician concerns of tolerance and addiction, and some guidelines for opioid utilization. In summation, some recommendations are offered not only to optimize clinical outcomes but also to minimize legal complications.


Clearly, when patients present for evaluation and request pain medications, they are not usually thinking about gabapentin. Morphine and its analogues are the ‘Gold Standard’ for analgesics for both physicians and patients. Opioids are effective at treating both nociceptive and neuropathic pain. Effector sites include the spinal cord, brain, and periphery such as joints and skin. Multiple delivery systems are available, including oral, dermal, mucosal, parenteral, rectal, sublingual, topical, neuraxial, and even intraventricular. Opioids can be useful to manage both rest pain and dynamic (incident) pain. Typically, the patient will develop, rather rapidly, tolerance to most adverse effects (eg. sedation, repiratory depression, constipation, and urinary retention).

Opioid analgesic effects are due primarily to agonistic activity at mu receptors with lesser effects at kappa and delta receptors depending on the individual opioids. Mu receptor activity produces a change at presynaptic K channels and indirectly affects voltage gated Na channels, which contribute to the production of excitatory amino acids and release of substance P.

With regards to opiate receptors, mu receptors produce most of the common effects, including analgesia in the brain and periphery, but also adverse effects such as miosis, gastric motility slowing, respiratory depression. Activation of kappa receptors produces spinal analgesia but also miosis and respiratory depression. Sigma receptors activity includes respiratory depression and “sedation.” Delta receptor activation may produce “delusional” symptoms of hallucinations, confusion, and stimulation of respiratory and vasomotor centers.

Clinical Effects of Opioids

Clinical effects of opioids are classified as follows:

  • desirable: analgesia, relief of anxiety
  • undesirable: sedation, urinary retention, respiratory depression, tolerance /dependence
  • circumstantial: euphoria, decreased bowel motility, cough suppression.

Explanation of these effects to patients can be highly beneficial, including the medical provider’s goal of providing analgesia but not necessarily anxiolysis by opioid management alone.

Most of the adverse effects are attenuated by physical tolerance, or have simple treatments to reduce their severity. For example, constipation can be reduced by increasing fiber intake or taking laxative, such as peri-colace, senna compounds, or even lactulose. Nausea can be reduced with antiemetics, including metoclopromide, ondansetron, and the antidopaminergic agent phenergan. Even sedation and mental clouding can be decreased with amphetamin derivatives or modafanil.

Nevertheless, cognitive impairment, particularly for chronic non-cancer pain patients, has been a major concern for medical providers. Multiple studies have been published regarding patients taking opioids for cancer and non-cancer pain. Neuropsychological measures, including logical reasoning, arithmetic skill, reading comprehension, and memory were not affected on stable doses of long-acting opioids. Indeed, one study concluded that adequate pain control may enhance cognitive function.

Opioid Potency

Naturally occurring opioids derived from opium include morphine and codeine. Most opioids in use currently are either partially synthetic derivatives, such as hydrocodone, hydromorphone, oxycodone or purely synthetic compounds, such as methadone, levorphanol, propoxyphene, meperidine, fentanyl, and sufentanil. Mixed agonist/antagonist compounds target primarily kappa receptors for analgesia and have weak mu activation. These drugs include pentazocine, nalbuphine, and butorphanol. The original impetus behind these medications was that an adverse effect — namely respiratory depression — would be avoided. Unfortunately, most of these mixed compounds also have a lower analgesic ceiling than other pure opioid agonists. Potency and duration of action are based on chemical structure of the various opioids and their lipid solubility. In general, more lipid soluble agents have a shorter onset time, shorter half-life, and higher potency. An overview listing individual opioid compounds is presented in Table 1.

Opioid Conversions

No one table or method seems to be the ideal way to convert patients from one opioid or combination compound to another. Clinical experience, coupled with understanding different mechanisms of action of each opioid, suggest the utility of changing opioids or even rotation, particularly when patients are developing side-effects or lack of analgesia due to tolerance to a specific opioid. In general, conversions should be slightly underestimated and breakthrough medications can make up the difference in analgesia. Note that conversion to Fentanyl patches and Methadone are often more complex due to patient pharmacokinetic variability.

Tolerance, Physical Dependence vs. Addiction

A Time article on Oxycontin® in 2001 (“The Perils of Prescribing Opioids!”), along with other negative press reports, have cast a pall over the proper and legitimate use of opioids in the arsenal against intractable pain. Physicians are acutely aware of being required to treat pain but do not want to cause or even be perceived as contributing to addiction. With the negative press of Oxycontin and Vicodin, many patients are requesting to be placed on a nonaddictive drug. Clearly, education for both patients and medical providers that teach the distinction between tolerance, physical dependence, and addiction are sorely needed.

The main concerns most clinicians have about prescribing opioids include addiction, diversion, legal liability, and the general “hassle factor” of documentation. The following helps address these concerns. The key concepts of tolerance, physical dependence, and addiction are important to address with patients when starting any opioid, but especially when the patient will be continuing the opioid over an extended period (greater than 1-2 months). When starting opioids, certain core ideas of those topics should be addressed.

Tolerance. Tolerance is a neuroadaptive process to the effects of chronic opioids, as well as other medications, such as beta-blockers. It is indicated by a need for increasing the dose or decreasing dosing interval to maintain drug effect. Tolerance occurs to both analgesia as well as side effects, such as respiratory depression, sedation, and constipation. The occurrence of tolerance is variable and does not in itself imply addiction.

Physical Dependence. Physical dependence is often indicated by withdrawal symptoms upon abrupt cessation or decrease in opioid dosage. These abstinence symptoms may include lacrimation, diaphoresis, tachycardia, abdominal cramping, nausea, and vomiting. The symptoms usually do not persist beyond 72 hours, however, other symptoms such as sleep disturbance or depression can persist for extended periods (2-3 weeks). Physical dependence is expected in those patients taking chronic opioids and does not in itself imply addiction.

Clinical Addiction. Addiction is clearly a psycho-physiologic and behavioral disorder. According to the American Society of Addiction Medicine (AMA), addiction implies the use of a substance resulting in physical, psychologic, and/or social harm to the user with continued use despite harm. Addiction includes at least 2 of the following: a loss of control over use of the drug; the presence of adverse consequences or harm; preoccupation for acquisition of the drug. Table 2 lists some of the typical addictive behaviors contrasted with the intractable pain (IP) patient’s physiologic response to properly-prescribed pain medications.

Typical addictive behaviors IP patient physiologic drug responses
1. Pre-occupation with acquiring specific pain drugs. 1. Develops physical tolerance to opioid’s effects and side effects.
2. Doctor-shopping or has multiple drug sources. 2. Develops physical dependence to opioids (as opposed to addiction).
3. Unwillingness to try other modalities other than drugs of choice. 3. Improved cognitive function when taking pain medication.
4. Deteriorated cognitive and behavioral function when taking drugs. 4. Improved physical functioning, often allowing return to productive life.
  5. Willing to try any other modalities or drugs to maintain pain control.

Table 2. Typical addictive behaviors vs. IP patient benign physiologic drug responses.

Opioid Prescribing: Minimal Requirements

Prescribing opioids does not have to be more difficult than prescribing other drugs. A history and physical should be performed. A diagnosis and plan should be discussed with the patient. Monitoring and follow-up should be maintained. If a patient is starting a new opioid or dosage, one month intervals should be sufficient. Patients on stable doses of opioids can usually be re-evaluated every 3 months. Documentation of all of the above is the most important issue, particularly if any administrative review is required for a particular patient or practice pattern.

Functional Improvement is Key

Beyond the usual “documentation is key” mantra, opioid providers should document — on a clinical reevaluation form — that the patient has displayed some physical, mental, or social functional improvement, as well as improved pain control.

The simplest way of interpreting function is to document that the patient is currently able to do some physical, mental, or social activities that he/she was unable to do before starting the medication (particularly opioids). With that focus, the usage of opioids becomes a tool for pain management and improvement in daily activities rather than a cure. This functional improvement should be documented periodically, usually every 3-6 months depending on the interval of reevaluation and stabilization on a given dosage of opioids.

Opioid “Contracts”

A written agreement, or “contract,” between patient and physician should be a necessary part of opioid therapy. The main components include: the terms of treatment, prohibited behavior, and points of termination. Secondary components include patient responsibilities, education, and additional treatment, as well as pharmacy usage, emergency department visits, and patronage of other physicians. An outcome that is included in the agreement is that the medical provider needs to follow through with oversight duties, including urine screening when appropriate, tapering opioids, or referring to an addictionologist, if indicated.

The concept of an opioid “contract” or, more appropriately termed, “consent” seems comforting for clinicians as it appears to allow some protection from litigation in the future. It is critical, however, that after the patient signs the contract, the medical provider maintains vigilance for potential signs of addiction as well as consistency of documentation. The periodic reevaluations must be done thoroughly and professionally and documented accordingly.

Some Key Points of Opioid Therapy

The following lists the authors’ recommendations of what physicians should do to treat patients with opioids appropriately while making sure that their practices are in line with current thoughts on opioid therapy.

  1. A trial of opioid therapy is appropriate for chronic non-cancer pain, especially in conjunction with other therapies such as physical therapy, psychotherapy, muscle relaxants, and anti-neuropathic pain agents such as gabapentin.
  2. Documentation is crucial to supporting continued opioid therapy beyond a perioperative or acute period. An initial history and physical and follow-up note for each adjustment is appropriate. Issues regarding usage pattern and functional improvement should be included in each notation.
  3. An opioid consent form can help decrease misunderstandings between patient and medical provider about maintenance on chronic opioids and how important following usage patterns will be tracked. Patients must understand the importance of calling their provider prior to changing dosages. Furthermore, the medical provider must be willing and able to follow through with the guidelines, including periodic urine testing and checking with pharmacies.
  4. Opioid therapy should be periodically evaluated by functional improvement of the patient. If a patient is escalating close to 180 mg of morphine equivalents, other opioids may be considered for opioid rotation, as well as non-opioid analgesics. Patients who require over 180 mg equivalent morphine a day may be best referred to a physician who specializes in high dose opioid therapy. Non-pharmacologic strategies, such as physical therapy and pain psychological therapy, can be great adjuncts. Other interventional therapies, such as corticoid injections and spinal cord stimulation may be appropriate.
  5. Continued opioid therapy should be monitored for addiction patterns or behaviors. A psychologist who specializes in chronic pain should ideally assess most patients on chronic opioids therapy to make sure their expectations are in line with all therapies and to adjust to what may be lifetime therapy.
  6. Patients who are not improving pain relief or function — but escalating in opioid dosage — may need to be tapered or even detoxified. Methadone and currently buprenorphine may be transition agents to accomplish that goal. Only addictionologists and other providers skilled with the use and dosing of methadone and buprenophine should perform the tapering to minimize withdrawal symptoms and possible return to, and reescalation of, opioids.
  7. Patients preparing for surgery who are on chronic opioids at atypical dosages for primary care providers or surgeons may need to have a pain management consult prior to surgery and have a pain specialist assist in perioperative management. One way to assure better pain control is to work with the patient and surgical specialists a few weeks prior to surgery so perioperative pain control may be more effective.


This article is a brief running guideline derived from the authors’ clinical experience and information currently available. Clearly all pain specialists and medical providers who treat pain issues wish to improve opioid therapy since the use of opioids for chronic and intractable pain is now well-established and remains the “gold standard.”

Opioid dosages above 180mg equivalent of morphine have not been well-validated, but a growing number of anecdotal reports suggest that a small percentage of intractable pain patients may not only benefit but thrive on much higher daily dosages of opioids. Some physicians are beginning to specialize in high dose opioid therapy, including intrathecal opioids, since there may be little or no options in some patients. While some authorities fear irreversible tolerance, or even opioid-induced pain sensitivities, the prevalence of these potential problems is unknown. Known cases are not enough to prohibit opioid trials.

A trial, using extended release morphine (Kadian®), has been tracking some of the clinical experiences of primary care practitioners treating chronic non-malignant pain. The study includes indices of physical function, sleep hygiene, and satisfaction scores. Hopefully, positive data will soon be presented since the effectiveness of opioids in the hands of community-based physicians is essential to bringing effective relief to the many under-treated pain patients who suffer needlessly.

Last updated on: December 20, 2011
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