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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.
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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.

Last updated on: December 20, 2011
First published on: September 1, 2004