Opioids as a Solution for Chronic Pain
Opioids have been well-known drugs for the treatment of pain for nearly a millennium, though their clinical use has markedly increased in popularity within the past decades in the United States; however, just as quickly, opioids are being reevaluated for chronic pain treatment due to compounding consequences to patients and the nation as a whole. Emerging literature and clinical evidence have shown early trials to be misleading in opioids’ efficacy in long-term treatment . The opioid problem has become so widespread that on October 26, 2017, the acting Health and Human Services (HHS) declared a nationwide public emergency regarding the opioid crisis in a statement issued by President Trump . The Centers for Disease Control and Prevention (CDC) reported approximately 89 deaths per day and a total 32,445 deaths in 2016 due to prescription opioid overdoses.
This was significantly higher than the 22,598 deaths due to prescription opioid overdoses the CDC reported in 2015. Furthermore, the CDC’s analysis for measuring deaths related to prescription opioids combines the natural, semi-synthetic, and synthetic opioid categories . However, a significant portion of the increase in deaths is caused by illicit opioid overdoses from fentanyl, prescription opioids, and heroin, representing 63% of the approximate 52,000 deaths in 2015 [3, 4]. As a result, in 2017, HHS unveiled a new five-point opioid strategy that prioritizes: (1) Improve access to support services providing prevention, treatment, and recovery; (2) Increase the availability and circulation of life-saving overdose-reversing drugs; (3) Implement better data gathering practices; (4) Support new research on addiction and pain; (5) Enhancing current pain management practices .
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The Role of Chronic Pain
Unlike temporary acute pain, chronic pain is typically described as persistent or repetitive pain beyond the normal recovery period . Due to the complex and subjective nature of pain, operational definitions differ depending on pain duration, frequency, and/or recurrence . Pain can be considered chronic when it persists for at least one month after recovery from an acute injury, is associated with a nonhealing lesion, or extends over several months . Other specifiers of chronic pain can include intensity or severity, pain behaviours (physiological or psychological), and/or primary location .
The prevalence of chronic pain within the general population is quite astounding. A recent national survey estimates the amount of people suffering from chronic pain ranges from about 11% to close to 31% of the American adult population, representing anywhere from 25 to 90 million individuals [8,9]. The devastating consequences of chronic pain are not contained just to the patient themselves but have compounding consequences to society and the economy. Rising with the ageing demographic, chronic pain affects social relations with family and friends, escalates the strain on the health care system, and deepens economic loss the due to lower productivity, increased work disability, and higher rates of unemployment [10, 11].
Chronic pain is more than a physical condition. Patients with chronic pain are at risk of developing further complications or comorbid conditions, such as other physical symptoms, chronic impairments, and psychiatric disorders. Commonly, patients with chronic low-back pain are likely to be diagnosed with major depression, anxiety disorders, and substance abuse. As many as 59% of low-back pain suffers currently exhibit symptoms of psychiatric diagnosis, and many had exhibited psychiatric symptoms prior to the onset of the chronic pain, further underlying psychiatric comorbidity and even predisposition to the development of chronic pain .
This likely arises from the powerful emotional component of chronic pain, stemming from a motivational drive to escape pain (perhaps most notably the physical sensitization of chronic pain, and the long-term stress associated with prolonged pain). It is during these periods that chronic pain patients tend to develop pain-reducing behaviours and habits. Self-administration of opioids may lead to a schedule of reinforcement, which in turn affects the brain’s dopamine release from the nucleus accumbens shell, and creates physical and psychological dependence on the substance. Though the opioid use began as a prescribed treatment for chronic pain, regular use for an extended period of time inherently develops into such dependence, regardless of the patient’s intention or even awareness. Most importantly, it should be stressed that opioid dependence is a chronic problem that should be handled as a psychiatric disease with a high likelihood for relapse . Due to these biopsychosocial components, the opioid epidemic is not simplistic in its origins, consequences, or solutions.
Research has demonstrated evidence of pain’s impact on psychosocial and physical health. A study by Hulla and colleagues (2016) found that suffers of chronic low-back pain (CLBP) in the older adult population experienced greater fatigue, pain interference, and self-reported physical function impairment than their age, gender, and socioeconomic status matched counterparts with no CLBP. The researchers also greater reported sleep disturbance in CLBP suffers, and lower scores in balance tests when compared to the matched non-CLBP individuals . Depression rates are positively correlated with the prevalence of chronic pain, most likely due to the physiological and psychological stress of pain. This relationship can be attributed to common pain-related symptoms – such as sleep dysfunction, cognitive impairments, motor retardation, and psychosocial problems – all of which contribute to, and exacerbate the individual’s diminished quality of life and reduced functionality [11, 14]
Opioids and Mechanisms of Action
The term opioid refers to any substance which binds to opiate receptors. Furthermore, opiate can be used to describe those opioids which are alkaloids, derived from the opiate poppy . Some opioids include semi-synthetic opiates, i.e. substances synthesized from opiates that occur in nature (such as heroin from morphine), as well as synthetic opioids such as fentanyl and methadone. The body has an endogenous opioid system (EOS) in which its three specific receptors are the proteins which opioids bind to and are widely distributed throughout the body, known as mu, delta, and kappa receptors . Receptors for pain are found in both the central nervous system (CNS), peripheral nervous system, and autonomic nervous system. These receptors also bind endorphins, which modulate pain and various other functions in the body. Some of these functions include modulation of reinforcement and reward mechanisms, mood, and stress within deep structures of the brain .
Once an opioid is ingested, it will bind to receptors that signal pain. Opioids are classified as agonist drugs, exacerbating neural inhibition effects through binding to the body’s receptors designed for the endogenous opioids [16, 17, 18]. This action is accompanied with a powerful analgesic effect, and a variety of side effects related to activation of related receptors. Some side effects may include constipation, an itch, pupillary constriction, mental clouding, and respiratory depression [19, 20]. Less commonly, mechanisms in the central nervous system may result in opioid-induced hyperalgesia, a paradoxical response which may lead to increased pain. With long term use, opioid users often experience a decreased responsiveness to the analgesic effects of opioids over time, known as tolerance . In the EOS, chronic use of opiates alters the receptors due to increased binding and activation. When the drug treatment is decreased or discontinued, the dysfunctional opioid receptors create the physical symptoms of withdrawal .
The signals from the opioid receptors converge onto the CNS during use. By activation or inhibition, the CNS affects other outputs from different brain systems, such as those from motor systems, which can induce behavioral changes in a chronic pain patient. Because those suffering from chronic pain often experience chronic and seemingly inescapable stress due to their constant state of discomfort, opiates act as a positive reinforcer as a result of their analgesic effects, including euphoria and sedation . This pain-reduction reinforcement may compel a patient to increase the frequency of opiate use. As a result of repeated use, patients commonly develop physical and psychological dependence on the opiate, characterized by potent withdrawal symptoms .
These outcomes present serious addictive patterns of use, which may occur with or without the presence of pain. Furthermore, iatrogenic opioid addiction appears to be rare in patients who do not already present existing predispositions, such as biological substrates that induce cravings for opioids.
Opioid Treatment for Chronic Pain
The contemporary use of opioids for chronic pain treatment is a complex issue, as patients can recognize both the benefits and harm of opioid use. Opioids have become one of the most common treatments for chronic pain in the United States; an opioid prescription is given in 15% to 20% of office visits, equating to nearly 4 million Americans per year receiving a prescription for a long-acting opioid [24, 25]. However, while opioids seem to be an acceptable treatment for short-term acute pain, their efficacy for chronic pain has come under more scrutiny within recent years. An increasing amount of clinical evidence has discouraged the use of opioids in chronic pain patients due to the inherent problems related to use.
As many as 19% of those who were prescribed long-term opiate treatment abused the drugs or became addicted. Furthermore, medical use of all opioids except codeine has risen dramatically over the 21st century, with an overall increase of 1,448% from 1996 to 2011. Subsequently, misuse of opioids, which can be described as non-medical prescription opioid use (NMPOU), has dangerously increased by 4,680% within the same timeframe [28,29]. This increase in NMPOU has paralleled the prescription of opioids by physicians, specifically for chronic pain. Contrary to the scientific evidence suggesting that opioids are ineffective for chronic pain, 92% of physicians and patients believe they reduce pain, and 57% report better quality of life. It is this disconnect between the scientific authorities and practitioners that have caused these rates of misuse to soar.
Chronic Pain and Opioid Dependence
Chronic pain patients with long-term prescriptions to opioids are at higher risks of developing a tolerance and/or physical dependence to opioids, though some individuals are more at risk than others . Drug tolerance is defined as the repeated use of a substance, which reduces both physical and/or psychological effects of the drug so that higher doses are required to achieve similar effects of a former smaller dose . Physical dependence is typically characterized by the development of both tolerance and withdrawal symptoms if administration of the drug ceases, the dose is reduced, or a drug antagonist is administered .
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) indicates opioid withdrawal symptoms may occur within minutes to several days after discontinuation or reduction of the last dose and can include anxiety, fever, nausea or vomiting, muscle aches, and insomnia. Once a patient begins to suffer significant distress and/or impairment in their ability to function in social, occupational, or other important areas that are not related to another mental disorder or medical condition, they may be clinically diagnosed with opioid withdrawal syndrome . Dependence is not to be confused with addiction, which describes the behaviour of compulsive substance use that is commonly characterized by the inability to stop its use, failure to meet prior obligations, and sometimes tolerance and physical dependence .
Oftentimes, the psychological distress and physical discomfort associated with opioid withdrawal syndrome may mimic some of the symptoms of chronic pain, which may make it difficult to distinguish between the two . It has also been demonstrated that withdrawal may also increase baseline pain levels. Anecdotal evidence from chronic pain patients showed opioid withdrawal increased pain within the original pain site. However, there is also evidence to suggest that experienced addicts are capable of distinguishing withdrawal symptoms from chronic pain . Although subjective experiences of withdrawal (e.g. muscle aches) may be related to chronic pain, qualitative studies of addicts going through withdrawal described their experience as flu-like. This is most likely due to some of the withdrawal symptoms that often occur with the flu, such as fever, sweating, and hot and cold flashes.
Notwithstanding, of the chronic pain patients, prescribed opioids, about 8%-12% were found to develop an addiction, but nearly one in four developed opioid dependence [36, 37]. However, there are certain factors (such as emotional trauma, prolonged distress, and premorbid disorders) that may increase the rate of addiction in chronic pain patients. Those with chronic low-back pain commonly displayed lifetime histories of psychiatric symptoms before chronic pain onset. In fact, 94% of the chronic low-back pain sufferers had a prior history of substance abuse. Even if premorbid psychiatric diagnoses are absent, the prolonged emotional distress and trauma associated with chronic pain may predispose a patient to misuse and/or addiction.
Some current screening tools involve the use of identifying possible psychological comorbidities and assessing the personal or family history of drug abuse, which present as strong indicators for addiction . For example, in a meta-analysis of psychiatric disorder and symptomology among NMPOU in substance abuse treatment, 43% of patients presented mental health problems (both diagnosis and symptoms) . Another tool developed by Belgrade, Schamber, and Lindgren (2006), takes a nuanced approach that implements a measure to predict the likelihood of success (i.e. improving pain) and risk . Regardless, in order to safely and effectively treat chronic pain patients, it is essential for health care providers to use screening measures that can help identify possible behaviours that may be indicative of current or possible development of an addictive disorder, and exhaust more non-invasive treatment options to treat the patient and maximize treatment outcomes
Traditional Treatments for Opioid Dependence
The treatment and prevention of opioid misuse have created a large economic burden for the U.S., with the costs estimating around $78.5 billion dollars as of 2013. The initial step for long-term treatment of opioid dependence is to put patients through a detoxification process. Detoxification is the removal of opioids from the system, which puts individuals in a state of withdrawal and results in extreme discomfort. In order to maximize treatment retention and avoid a possible relapse into opioid misuse, the goal of detoxification is to remove opioids from the system using a controlled and humane manner. Pharmacological treatments are commonly used to reduce the effects of withdrawal and to help assist the patient in successful detoxification. Two common approaches to detoxification include the sudden discontinuation of opioid use, initiated by an opioid antagonist (e.g. naloxone or naltrexone) along with administration of an alpha2 adrenergic agonist (e.g. clonidine) to reduce withdrawal symptoms; or tapering off opioids using a lower dose opioid, such as buprenorphine or methadone
The theoretical advantage to the first approach is the fact that alpha2 adrenergic agonists are not opioids, but show effectiveness in reducing the intensity of withdrawal syndrome. This helps increase the patient’s duration in treatment and their likelihood to complete treatment when compared to a placebo. However, some alpha2 adrenergic agonists, such as clonidine, have shown to be associated with potentially dangerous side effects, including sedation and hypotension. The tapering off method of detoxification (paired with a slow decrease and replacement of a lower dose opioid agonist) has been shown to have similar levels of reduced withdrawal intensity and treatment completion as opioid discontinuation. The tapering off method of detoxification requires longer treatment duration but results in fewer side effects than the discontinuation with alpha2 adrenergic agonists alone. Overall, the current evidence suggests that pharmacological treatments provide benefits to those undergoing detoxification. The next step is for patients to consult with their healthcare providers to discuss if this option is suitable based on a variety of factors.
Mental health appears to play a significant role in opioid abuse and chronic pain suffering. Psychiatric disorders appear in an alarming amount of cases for both chronic pain and long-term use of opioids, even for prescribed medical use, especially if the two occur together. Furthermore, Wright and Gatchel (2002) described that some chronic pain patients adopt a “sick role”, which results in the relinquishment from their occupational and social responsibilities, thereby causing emotional distress. This emotional distress can result in pain-related cognitions, which give meaning to this emotional experience of pain, that trigger negative emotional and behavioural reaction which intensify the experience of pain.
Based on this evidence showing a link between emotional and social health, an appropriate response would be to improve investigations into psychosocial interventions that work specifically for chronic pain patients with substance dependence. Psychosocial interventions have been shown to be effective for both chronic pain management and opioid dependence independently. These interventions would best be implemented into interdisciplinary programs that utilize various healthcare professionals who share a common goal of rehabilitation, communication, and commitment to the patients they are serving.
Oftentimes, psychosocial treatments are used in conjunction with pharmacological treatments to teach patients how to manage their chronic pain, improve their physical and emotional functioning, and to decrease with the severity of their chronic pain condition. Additionally, in patients with opioid dependence, psychosocial treatments serve to provide education on how to control the urge to use substances and promote abstinence, while also coping with the internal conflict that often coincides with dependence.
Psychosocial interventions exist in many different forms with various techniques for treating a wide range of ailments. Some of the common approaches include behavioural treatments, cognitive-behaviour therapy (CBT), individual, group and couples counselling, and many others. Other types of therapies may differ in their structure and theoretical backgrounds, each utilizes similar therapeutic techniques to educate the patient on effectively managing their pain, modify the processes underlying dependent behaviour, and treat psychiatric comorbidities.