Purpose Statement
Opioids can be a very useful tool when treating short term chronic pain; however, using this type of treatment long term is not without some complications to a patient developing a physical dependency, developing a tolerance, or developing hyperalgesia.

Outline
Background Information
“Opiates have been used for centuries and remain to this day the most potent and reliable analgesic agents” (Pasternak, 2011).
They are generally used in scenarios with acute pain, such as trauma and surgeries.
They have also been shown to have efficacy in patients with terminal diseases, particularly cancer, where the risks of addiction are fairly minimal (Wachholtz and Gonzalez, 2014).
Opiate use for long-term conditions that are not terminal is still controversial, part of which is due to the fact that addiction is a significant risk and has been shown to be relatively common (Ballantyne and LaForge, 2007).
Opiates can also cause hyperalgesia and tolerance, which can be difficult to distinguish from each other and cause dosing issues for the prescribing physicians (Häuser et al., 2014)
Other issues arise when there is a history of opioid use or opioid use, which can alter pathways in the brain and make it difficult to judge prescription levels and potential issues that may arise from prescription in both the short- and long-term (Häuser et al., 2014)
There is also very little evidence showing the efficacy of opioids in the long-term as the majority of research has been on terminal or short-term patients who necessarily have an end date to their treatment (Furlan et al., 2014)

Developing a Physical Dependency
One of the most common worries from both short-term and long-term opioid use is the development of a physical dependency or an addiction. Opioids are one of the most addictive classes of drugs and therefore dependence can occur within a very short time frame (Häuser et al., 2014).
Diagnosis of opioid dependence is also very difficult to diagnose, particularly when there is legitimate use for pain.
When the pain returns from stopping use of the drug, the symptoms can be very similar to those of withdrawal (Wachholtz and Gonzalez, 2014).
Physicians have also voiced concerns about the fact that many that have previously been prescribed opioids on the long-term, or had physical dependency problems in the past, may become drug seekers and use their pain problems to get prescribed drugs that they do not necessarily need (Weiss et al., 2015)

Developing Hyperalgesia
Hyperalgesia is an increased sensitivity to pain, which can be caused by damage to nociceptors or peripheral nerves (Wachholtz and Gonzalez, 2014).
Temporary increased sensitivity to pain can be caused by opioid use, which is known as opioid-induced hyperalgesia (OIH).
Through repeated administration of opioids, the baseline nociceptive thresholds diminish and cause higher levels of increased pain intensity. This can mimic the signs of tolerance and it can be difficult to distinguish from tolerance (Ballantyne & Mao, 2013)
Mao stated, “apparent opioid tolerance is not synonymous with pharmacological tolerance, which calls for opioid dose escalation, but may be the first sign of opioid-induced pain sensitivity suggesting a need for opioid dose reduction” (Mao, 2002)
Patients who experience OIH have demonstrated a significant reduction in pain after opioid use is discontinued (Baron & McDonald, 2006; Savage, 1996; Brodner & Taub, 1978).

Developing Tolerance
Tolerance is a term used to describe the reduced capacity to respond to opioids, meaning that the individual requires higher doses to get the same pain-limiting effect (Häuser et al., 2014)
Chou et al. (2015) suggest that tolerance is inevitable for those on opioids long-term because of the nature of the changes in neural pathways that occur as a response to the drugs
Tolerance and hyperalgesia can often be mistaken for each other, which complicates dosing strategies for physicians (Häuser et al., 2014)
Tolerance can also lead to overdoses in some cases where the patient is unaware of the maximal level of opioid that can be present in their system as they attempt to make up for their increased tolerance

Other Potential Risks
There are a number of other risks associated with long-term opioid use that have been suggested
There are increased risks for sexual dysfunction, which can have a limiting quality on a patient’s quality of life (Wachholtz and Gonzalez, 2014)
There are also increased risks of myocardial infarction with long-term use, which means that patients on this treatment regime need constant monitoring to ensure long-term health (Wachholtz and Gonzalez, 2014)
Chou et al. (2015) also suggest that there may also be a higher risk of fracture in some patients, which can also be problematic in that opiate users may not be aware of the fracture due to the pain limiting qualities of the drugs
Higher doses of opiates, often associated with hyperalgesia and tolerance, are associated with greater risks in all of the above areas, which again adds a level of complexity to long-term use cases

Implications for Patients with an Existing Opioid-Use Disorder
Patients that are comorbid for pain and opioid-use disorder are particularly problematic because the mechanisms of pain and addiction are not well understood (Wachholtz, Foster & Cheatle, 2014)
There may be an existing level of hyperalgesia in patients that have already had an opioid-use disorder, which makes dosing particularly difficult and may make opioids difficult to prescribe (Wachholtz et al., 2014)
The changes in psychophysiological pathways can mean that patients do not respond to opioids at all, which again makes dosage and use in these patients extremely problematic (Häuser et al., 2014)
Patients with existing opioid-use disorders can be used to evaluate the potential long-term risks in those without the history as many of the brain changes may mimic each other, elucidating the risks that could potentially occur in those with long-term non-addictive usage for pain

Evidence against Long-Term Opioid Therapy
The majority of studies done on opioid therapies last less than 12 weeks, with many lasting less than six weeks.
There has been no placebo-controlled randomized design that has lasted more than six months (Furlan et al., 2014).
This suggests that opioid use in the long-term may not be useful or even safe, as there is very little evidence backing up its use, and it has been approved for long-term use on the basis of short-term trials (Furlan et al., 2014).
The evidence that does exist in the medium- and long-term suggests that there may be no net positive outcomes for opioid use in anything other than the acute pain setting
Those who use opioids in the long-term without an end date (such as those with chronic disorders) are more likely to develop problems in other areas of their health, including myocardial infarction, fracture, and psychosomatic symptoms linked to physical dependencies (Häuser et al., 2014)

Preliminary Recommendations
Pain management physicians have an ethical responsibility to properly assess, monitor, and follow up with each patient who has chronic pain (Pohl, M. & Smith, L. 2012) Function of the patient is key to proper treatment of pain with opioid medications.
When prescribing opioids, physicians should have an entry, maintenance, and exit strategy. And have a conversation with the patient about the goals of maintenance therapy.
Give the patient all the information about long-term use side effects and let them decide a course of action, also known as about informed consent. A patient themselves often understand their own mechanisms of addiction and can make a decision based on their own past history of usage as well as their feelings about potential addiction
If benefits of the medication trial do not outweigh the harm, then consideration to discontinuing opioids should be given and alternatives to chronic pain medication are in order
More research needs to be done on opioid usage in long-term cases, as there are very few studies that have studied usage in the medium- and long-term, making it difficult to objectively judge the facts
Physicians should also continually monitor the patient for symptoms of hyperalgesia, addiction and tolerance, which may increase case load and complexity but have positive results in the long term (Chou et al., 2015)

Implications
Physicians need to be aware of the risks of long-term opioid usage in those without cancer pain or long-term chronic conditions
More research needs to be done to ensure that the risks can be actively quantified and used to make further recommendations
It is evident that there are complex risks involved with long-term usage, and studies with placebo-controlled trials would help to elucidate the differences between psychological and physical dependence on opioids (Baron & McDonald, 2006)
There are currently no indication that long-term use is effective for many patients, which means that other therapies need to be sought in these cases that are as effective as opioids but without the risks (Chou et al., 2015)
Terminal cancer patients still have the best track record with long-term opioid usage, which means that these drugs can still be safely prescribed in these cases when extreme pain is present. It may be useful to compare and monitor the effects in long-term users with cancer to assess the risks on users with other types of pain to assess how they are likely to react to the drugs