During the 19th and half of the 20th Century, most physicians saw pain as a sign of physical vitality and a vital component of the healing process. Since the second half of the 20th Century, a few changes have come about concerning the treatment and perception of pain.

• In 1973 a landmark study was published that showed 73% of all hospitalized medical patients had moderate to severe pain.
• By 1985, patient satisfaction surveys, done by discharged patients from acute care hospitals, evaluating both subjective and objective care, had begun in earnest.
• In 1992. Acute Pain Clinical Practice Guideline  laid the foundation of current pain treatment.
• In 2001, the Medical Board of California passed a law requiring all California-licensed physicians (except pathologists and radiologists) to take a full-day course on “pain management.”
• In May 2005, the National Quality Forum (NQF), an organization established to standardize health care quality measurement and reporting, formally endorsed the CAHPS® Hospital Survey, which was developed in 2002 in joint collaboration with CMS to rate hospitals.
• As part of the Affordable Care Act of 2010, the Hospital VBP (value based purchasing) Program was mandated by Section 3001(a) of the ACA and became Section 1886(o) of the Social Security Act.3.  This states hospitals receiving Medicare reimbursement will have specific percentages of reimbursement with held based upon subjective and objective patient outcome reports.

Basically, what this means is that over the past 50 years, there has been a movement in the direction of listening to patients when it comes to pain control. Patients can now evaluate, through patient satisfaction surveys, how their doctors are treating them. These evaluations may potentially influence how well the hospital will be reimbursed for the services provided by the particular physician, which may influence how the physician alters their practice at a given institution. It is possible that physicians that deny requests for opiate pain medications may not receive positive ratings.

Similarly, over the past 30 years approximately:

• New painkillers have come on the market with approval from the Food and Drug Administration: Percocet in 1974, Vicodin in 1984, OxyContin in 1995 plus many more during the past 14 years.
• From 1991 to 2009, prescriptions for opiate pain medications increased almost threefold, to over 200 million per year.
• Prescriptions for opiate pain medications nearly doubled, from 11% of all prescriptions in 2000 to 19% of all prescriptions prescribed in 2010.
• The United States makes up only 4.6 percent of the world's population; however,  consumes 80 percent of its opiates.
• Prescription opiate medications were involved in 14,800 overdose deaths in 2008, more than cocaine and heroin combined.
• Deaths from unintentional drug overdoses have risen fivefold since 1990.

As we can see, although opioid management for severe acute pain is often beneficial, the effectiveness of long-term opioids for chronic non-cancer-related pain is controversial and may have significant negative effects on individuals and society.   

Perhaps a better understanding of opiate related tolerance, as well as an understanding of strategies to help decrease tolerance, may lend itself to a more practical approach to pain therapy.

As of today, opiate analgesics continue to be the “go-to” treatment for moderate to severe pain, particularly for those with chronic, painful conditions.

As we know, opiate medications work quite well for short-term acute situations such as postoperative pain control; however, when needed for long term therapy, patients may sometimes have difficulty maintaining clinical efficacy due to the development of tolerance. Tolerance is defined as a state in which exposure to a specific medication induces changes that result in a decrease of the drug’s effects over time. Tolerances is exhibited by the need to increase the dosage of opiate medication over time in order to maintain a comparable level of pain relief. 

It is important to recognize that the tolerance (i.e., increase in pain medication) is not in conjunction with a corresponding progression of the disease state.

The exact mechanism of the development of tolerance is not completely understood; however, research has begun to unveil some reasonable ideas. Basically, opioid tolerance is described as the need to take an increasing dose over time to maintain the same level of pain control. Other reasons for an increasing dose may include.

• Progression of the diseases state.
• Increase in metabolic processes whereby the medication is metabolized quicker.
• Induction of specific enzyme systems that decrease the plasma concentration of the medication.

Currently, two separate theories have evolved as to the possible development of opioid tolerance.

Opioid Receptor Desensitization:  

This, my friends, involves a series of complex intracellular mechanisms and upon review; it is found that much is still left to be learned about this process. Activation of the opiate receptors leads to further activation of specific proteins which then decrease excitability of the membranes in the pain pathways. After a variable amount of time, the receptors become desensitized to activation and therefore are unable to activate the proteins which decrease the excitability of the pain pathways.

Down-Regulation of the opiate receptor:  

Each cell membrane has a certain number of opiate receptors. When a receptor is down-regulated, it is drawn into the cell with a membrane closing around the receptor. Once inside the cell, it can no longer function and is effectively down-regulated. Down-regulation is an example of a cell’s negative feedback mechanism. This is survival technique that cells deploy in order to cope with an escalating level of molecular bombardment. As the opiate dose increases, there will be fewer and fewer receptors to stimulate and therefore the medication becomes less effective. 

Conversely, when this molecular bombardment is removed, the cells will slowly again increase the number of receptors available for stimulation. As the opiates are decreased, the receptors available for stimulation are increased and this may lead to cravings or withdrawal symptoms. It is possible that this receptor up-regulation and down-regulation may vary in time from minutes to weeks and possibly even months. Again, this is new research and there is much to be studied and learned.

Here, it is important to mention different strategies which may help decrease the potential for opiate tolerance development such as:

• Non narcotic alternatives, used in conjunction with opiate medications may help to provide reasonable pain control while sparing an increased dose of the opiate therapy. Many pain specialists agree that providing an opioid-sparing treatment plan is the corner stone in proactively minimizing the potential for opioid tolerance.
• Heat
• Cold
• Physical Therapy
• Acupuncture
• Massage Therapy
• Meditation
• What Else?

Clinically, it is critical to monitor all chronic opiate patients for potential tolerance related issues. Tolerance should be suspected whenever the opiate dose is escalated to maintain the same level of pain control, without any concurrent progression of the defined disease. Take the time to understand that increasing the dose of opiate therapy is not always the answer, and quite often may lead to significant negative effects on the patient and their family.  

Whenever possible, explore the option of implementing non-narcotic medication and non-medication alternatives. Remember, providing an opioid-sparing treatment plan for a patient’s pain control is currently the most reliable alternative to decreasing the potential for development of opiate tolerance.

About the Author

Steve Leuck, Pharm.D., is President/Owner of AudibleRx. AudibleRx provides OBRA 90 based Medication Specific Counseling Sessions in digital audio format. Both individual and group memberships are available. Dr. Leuck also works full time as a community pharmacist in a clinic setting where he practices his counseling on a daily basis.