Investigation into the experience of pain has captivated medical research for decades. Despite intense focus and several significant advances, many aspects of the etiologies, assessment, and treatments of pain remain shrouded in mystery. This is partially because the perception of pain is diverse and transcends mere sensation, also involving complex emotional, psychological, and social elements.¹,²,³ The general approach to addressing pain involves first classifying it as either acute or chronic. Relative to chronic pain, acute pain is short lasting and occurs in close temporal proximity to an identifiable cause such as an injury or surgery. This pain usually resolves as the injured tissue heals. When pain lingers longer than the expected time for healing, it is regarded as chronic pain. Chronic pain is typically defined as pain that persists longer than 3-6 months.⁴,⁵ Chronic pain can be the result of a discrete injury, in other words a progression of acute pain, or it can be of insidious onset with difficulty associating it to a distinct event.³ All pain, but especially chronic pain, can be extremely distressing with debilitating impacts on individuals, families, and society.

Chronic pain inflicts a considerable burden both on a personal and a societal level. It is estimated that chronic pain affects 11%-40% of U.S. adults and ˜20% of people worldwide.⁶,⁷ Furthermore, 15%-20% of physician visits are related to chronic pain complaints amounting to a cost of roughly &U20AC;200 billion yearly in Europe and $150 billion yearly in the United States. Even as staggering as these statistics are, many believe that these estimates are too low and that chronic pain is much more pervasive. Given the enormous diversity of chronic pain syndromes, the exact prevalence of chronic pain is difficult to measure. Moreover, many chronic pain patients suffer in solitude and do not seek medical attention. Chronic pain is also often a comorbidity of other illnesses, which may cause the chronic pain component to be overlooked. For example, according to the World Health Organization, unipolar depression, coronary heart disease, cerebrovascular disease, and traffic accidents will be the leading contributors to the global burden of disease by 2030. Chronic pain is often a component of all of these.⁷,⁸

In most of the developed world, opioid medications have become a mainstay in the treatment of chronic pain. This is especially pronounced in the United States, where sales of prescription opioids have quadrupled over the last 15-20 years. As a result, 20% of patients with chronic nonmalignant pain are under treatment with opioids.⁹ This extensive use has brought with it a multitude of issues, including tolerance, physical dependence, and abuse among users. While these issues are challenges, they also present obstacles to treating acute pain in patients with chronic pain who are managed on opioid medications. In addition to the significant percentage of patients who are opioid-tolerant because of treatment of chronic pain, there are other populations of patients whose tolerance to opioids may present challenges in
treating acute pain. These include patients who abuse opioid drugs recreationally (ie, heroin) and former addicts who are enrolled in opioid replacement programs. This chapter, therefore, presents an overview of the management of acute pain in patients with baseline chronic pain and opioid tolerance.

Regular use of opioids can lead to the pharmacologic phenomena of tolerance and dependence. Following continued exposure, a rightward shift in the dose-response curve can occur, leading to increased medication requirements to achieve the same effect. This is known as tolerance and develops to a variety of the drugs’ effects, including analgesia, euphoria, sedation, respiratory depression, and nausea. Interestingly, tolerance to miosis and inhibition of bowel motility does not occur. Dependence refers to a state of neuroadaptation such that removal of an agonist, in this case, opioids, results in the onset of withdrawal symptoms. Endogenous opioids are made constantly within the body, for example, enkephalins, dynorphins, and endorphins, and with the delivery of exogenous opioids, there will be a shutdown of endogenous opioid production, resulting in central nervous system hyperarousal. Symptoms of opioid withdrawal include restlessness, anxiety, tachycardia, diaphoresis, abdominal pain, nausea, vomiting, and diarrhea.¹⁰ While unpleasant, opioid withdrawal is not life-threatening. The molecular mechanisms underlying these phenomena are not fully understood but are thought to involve complex neurobiological elements leading to receptor alteration, desensitization, and internalization.¹¹ Oftentimes, these physiological changes are accompanied by a psychological compulsion to obtain and consume opioid medication. This phenomenon is known as addiction. Addiction is primarily psychological and is characterized by repeated use despite harmful consequences. While it is like and frequently occurs with physical dependence, it is its own distinct entity. Similar to tolerance and dependence, addiction is thought to be multifactorial with complex underlying mechanisms.⁹

Opioid-induced hyperalgesia (OIH) is another adaptation to opioid use that can have detrimental effects. OIH is characterized by a paradoxical increase in pain observed with opioid administration. Before the description of OIH, increasing dosage requirements in patients being treated for pain were attributed to increasing tolerance to the medication and/or progression or exacerbation of the condition responsible for the pain. While these phenomena likely contribute, there is some evidence that OIH also plays a role. Though limited, studies have shown that patients on long-term opioid replacement therapy have a lower tolerance for painful stimuli. Furthermore, some evidence suggests that the onset of OIH may be very rapid as patients who received higher doses of intraoperative opioids reported higher pain scores and consumed more opioids postoperatively. OIH is thought to be the result of a cascade of pronociceptive mediators caused by the docking of opioids onto glial cells in the brain and spinal cord via toll-like receptor-4 (TLR4). Further elucidation of this mechanism may present new targets for treatment.¹¹

A thorough history and physical is an essential component of the evaluation of any acute pain complaint (Fig. 29.1). The aim should be to collect details regarding the patient’s symptoms to help guide treatment decisions. When assessing acute pain in patients with baseline chronic pain and/or opioid tolerance, it is necessary to be aware of some special considerations. First, it is important to review the patient’s maintenance chronic pain medications, including usual drugs, doses, and prescribers. Setting aside prejudices and employing a nonjudgmental approach is essential to make the patient comfortable being forthcoming with information regarding both prescribed and illicit substances used for pain control. It is helpful to explain to
the patient that this knowledge is necessary to provide the best possible treatment. Even when dealing with the most trustworthy patients, verification of this information should be sought by checking the labels on the prescription bottles, contacting the prescribing physician or dispensing pharmacy, and/or checking with the appropriate regulatory program(s) (ie, prescription monitoring database). In emergency settings, dose verification may not be possible. In these instances, patients who report opioid use for the management of chronic pain should be assumed to have some level of tolerance and physiologic dependence. As such, the reported daily opioid amount can be given in two to four divided doses to avoid the risk of opioid withdrawal. Patients’ response, level of sedation, and respiratory status should be monitored closely until verification can be obtained.¹¹

Discussing patient preferences, past experiences, and long-term pain management plans can aid in developing a plan for treatment. Reassurance that treatment of their new acute pain complaints will be prioritized is often helpful. Patients should be made aware that past bad experiences with pain management or opioid addiction will not preclude them from receiving any available treatment options.¹¹ Notwithstanding, acute pain management in patients who have chronic pain and/or opioid tolerance is uniquely challenging as typical initial treatment measures may be less effective, and as such, it is important to manage patient expectations. Making the patient aware that it may be impossible to safely relieve all of their pain will help them to set realistic expectations for the outcome of treatment.