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Center for Substance Abuse Treatment. Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2012. (Treatment Improvement Protocol (TIP) Series, No. 54.)

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Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders.

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Chronic Pain Impact

Chronic noncancer pain (CNCP) is common in the general population as well as in people who have a substance use disorder (SUD) (Exhibit 1-1). Chronic pain is not harmless; it has physiological, social, and psychological dimensions that can seriously harm health, functioning, and well-being. As a multidimensional condition with both objective and subjective aspects, CNCP is difficult to assess and treat. Although CNCP can be managed, it usually cannot be completely eliminated. When patients with CNCP have comorbid SUD or are recovering from SUD, a complex condition becomes even more difficult to manage.

Exhibit 1-1. Statistics on Substance Use and Chronic Pain in the United States.

Exhibit 1-1

Statistics on Substance Use and Chronic Pain in the United States.


This Treatment Improvement Protocol (TIP) is for primary care providers who treat or are likely to treat adult patients with or in recovery from SUDs who present with CNCP. Given the prevalence of CNCP in the population, this audience includes virtually all primary care providers. Addiction specialists, psychiatrists, nurses, and other clinicians may find information here that will help them ensure that their patients with CNCP receive adequate pain treatment. By providing a shared basic understanding of and a common language for these two chronic conditions, this TIP facilitates cooperation and communication between healthcare professionals treating pain and those treating addiction.


This TIP equips clinicians with practical guidance and tools for treating CNCP in adults with histories of SUDs. It does not describe how to treat SUDs or other behavioral health disorders in patients with CNCP; however, it provides readers with information about SUD assessments and referrals for further evaluation. For patients with histories of SUDs, the most controversial and possibly hazardous pain treatment in widespread use is opioid treatment. For this reason, this topic receives significant attention in Chapters 3 and 4.


Many terms important to the treatment of CNCP in people with SUDs are used inconsistently. Clinicians should not assume that their definitions of addiction, CNCP, physical dependence, recovery, tolerance, or other terms are shared by others, especially by patients and their families.

It is especially important that clinicians clarify with their patients terms related to substance use. For example, patients with histories of SUDs who are no longer using substances may or may not consider themselves to be in recovery. Likewise, some mutual-help groups may not regard patients as abstinent if they are treated for SUDs with medications such as naltrexone, buprenorphine, or methadone. Many people equate physical dependence or tolerance with addiction. However, if clinicians prescribing opioids for CNCP equate these terms, they may misdiagnose their patients on opioids as having an addiction, when in fact they do not.

In 2001, the American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine formed a Liaison Committee on Pain and Addiction to standardize the use of the terms addiction, physical dependence, and tolerance among pain professionals. Shared understandings of these and other terms facilitate research, advance dialog among professionals in the fields of addiction and pain, and help patients make informed decisions about their treatment.

Definitions used in this TIP are presented below.

  • addiction. A primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use or compulsive use, continued use despite harm, and craving (Savage et al., 2003); clinicians commonly refer to these behaviors as the “3Cs.”
  • addictive substance. The phrase addictive substance is controversial. The phrase draws attention to the properties of the substance; however, some experts prefer to emphasize the importance of individual variability, environment, and situational factors in addiction. Evidence suggests that animals will self-administer all drugs commonly sought by humans (with the exception of hallucinogens). Evidence also suggests that, if animals are exposed to a sufficient dose for a sufficient time, a substantial percentage will develop behaviors remarkably similar to those that suggest addiction in humans (e.g., “drug seeking” despite electrical shocks). Nonrewarding drugs (see Neurobiology of Addiction, below) do not elicit these behaviors in animals or humans. In this TIP, drugs or medications that elicit “drug seeking” behaviors are referred to as addictive.
  • behavioral health. The term comprises substance use issues, mental health issues, and the prevention of both.
  • chronic noncancer pain (CNCP). Pain that is (1) unassociated with an imminently terminal condition, and (2) unlikely to abate as a result of tissue healing, thus requiring long-term management. The term often refers to pain not caused by ongoing tissue pathology (e.g., backache, fibromyalgia). The term is problematic because it includes pain associated with sickle cell disease or recurrent pancreatitis, in which both neurological sensitization and tissue damage, at least in part, are likely. Inflammatory arthritis, connective tissue diseases, ischemia, and other conditions cause pain that persists for years yet are not, at least initially, life threatening.
  • chronic pain syndrome. Intractable pain of 6 months or longer, with marked alteration of behavior; depression or anxiety; marked restriction in daily activities; frequent use of medication and medical services; no clear relationship to organic disorder; and a history of multiple, non-productive tests, treatment, and surgeries (U.S. Commission on the Evaluation of Pain, 1987). This term is used casually and imprecisely to refer to pain, distress, and dysfunction that are not fully attributable to an identifiable medical condition.
  • hyperalgesia. An abnormally intense response to a normally noxious stimulus.
  • narcotic. Substance used to induce narcosis or stupor. Narcotic is not a synonym for the opioid class of medications.
  • opioid-induced hyperalgesia. Hyperalgesia that results from the effects of opioids on the central nervous system (CNS).
  • pain. An unpleasant sensory or emotional experience associated with actual or potential tissue damage or described in terms of such damage (International Association for the Study of Pain, 1986). Pain is subjective and may not always be corroborated by objective data.
  • physical dependence. A state of adaptation that is manifested by a drug-class-specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing the level of the drug in the blood, or administration of an antagonist (a substance that opposes the action of the drug) (Savage et al., 2003).
  • pseudoaddiction. A controversial term coined to describe aberrant drug-related behaviors (e.g., clock watching, drug seeking), that resemble those of patients with addiction but that actually result from inadequate treatment of pain (Weissman & Haddox, 1989).
  • recovery. A process of change through which an individual with an SUD achieves abstinence, wellness, and improved health and quality of life (Center for Substance Abuse Treatment [CSAT], 2007).
  • relapse. A return to substance abuse after a period of abstinence.
  • substance use disorder (SUD). A condition that includes alcohol and drug problems. SAMHSA recognizes that several terminologies (e.g., substance abuse and addiction) can be applied and respects that some individuals and communities may choose to use different terminologies (CSAT, 2007).
  • tolerance. A state of adaptation in which exposure to a substance induces changes that result in a diminution of one or more of the substance’s effects over time (Savage et al., 2003).

Pain and Addiction Basics

Studies indicate that CNCP and addiction frequently co-occur (Chelminski et al., 2005; Rosenblum et al., 2003; Savage, Kirsh, & Passik, 2008). Chronic pain and addiction have many shared neurophysiological patterns. Most chronic pain involves abnormal neural processing, which can occur at various levels of the peripheral and CNS. Similarly, the disease of addiction results when normal neural processes, primarily in the brain’s memory, reward, and stress systems, are altered into dysfunctional patterns. A full understanding of each condition is still emerging, and there is much to be learned regarding neurobiologic interactions between the conditions when they co-exist.

Chronic pain and addiction are not static conditions. Both fluctuate in intensity over time and under different circumstances and require ongoing management. Treatment for one condition can support or conflict with treatment for the other; a medication that may be appropriately prescribed for a particular chronic pain condition may be inappropriate given the patient’s substance use history. Other commonalities include the following:

  • Both are neurobiological conditions with evidence of disordered CNS function.
  • Both are mediated by genetics and environment.
  • Both may have significant behavioral components.
  • Both may have serious harmful consequences if untreated.
  • Both often require multifaceted treatment.

Chronic pain and SUDs have similar physical, social, emotional, and economic effects on health and well-being (Green, Baker, Smith, & Sato, 2003). Patients with one or both of these conditions may report insomnia, depression, impaired functioning, and other symptoms. Effective CNCP management in patients with or in recovery from SUDs must address both conditions simultaneously (Trafton, Oliva, Horst, Minkel, & Humphreys, 2004).

Neurobiology of Pain

Both pain and responses to pain are shaped by culture, temperament, psychological state, memory, cognition, beliefs and expectations, co-occurring health conditions, gender, age, and other biopsychosocial factors. Because pain is both a sensory and an emotional experience, it is by nature subjective.

When nociceptors are excited, the stimulus is converted through transduction into action potentials that travel to the dorsal horn of the spinal cord. Signals then continue from the dorsal horn to the brain along multiple pathways in the cord: to the somatosensory cortex, where pain is evaluated; to the limbic system, where emotional reactions are mediated; to the autonomic centers that control such automatic functions as breathing, perspiration, and heart rate; and to other parts of the brain, where a behavioral response to the stimuli is determined. Nociceptive impulses are also transmitted to nearby terminals of the same nerve, where they may lead to diffuse pain and release of inflammatory substances that produce the flare and swelling that is a protective response to tissue injury (Exhibit 1-2).

image of the pain pathways

Exhibit 1-2

The Pain Pathways.

Nociceptive input triggers a pain-inhibiting response. Signals traveling the ascending pathways are met by descending signals that emerge at various points along the spinal cord and brain. This antinociceptive response involves a panoply of chemicals, including endorphins, enkephalins, gamma-aminobutyric acid, norepinephrine, serotonin, oxytocin, and relaxin. Inhibitory signaling serves to attenuate nociceptive input, dampening the formation of pain sensation and providing pain relief (Brookoff, 2005).

Pain may be acute (e.g., postoperative pain), acute intermittent (e.g., migraine headache, pain caused by sickle cell disease), or chronic (persistent pain that may or may not have a known etiology). These categories are not mutually exclusive; for example, acute pain may be superimposed on chronic pain. Acute nociceptive or neuropathic pain can transform into chronic neuropathic pain in which the original sensations are extended and amplified.

Chronic Pain

Chronic pain can be nociceptive, neuropathic, or a mixture of both (Exhibit 1-3). Pains such as migraine and fibromyalgia, in which there is no noxious stimulus and no apparent neurological lesion, are attributed to dysfunction of a structurally intact CNS.

Exhibit 1-3. Pain Types.

Exhibit 1-3

Pain Types.

Chronic pain often results from a process of neural sensitization following injury or illness in which thresholds are lowered, responses are amplified (hyperalgesia), normally non-noxious stimulation becomes painful (allodynia), and spontaneous neural discharges occur. Increased signaling disconnected from nociceptive input can become autonomous, self-sustaining, and progressive, leading to the continuous perception of pain even in the absence of ongoing tissue damage. Thus, chronic pain is not equivalent to prolonged acute pain and for clinical purposes is best considered a distinct disorder (Brookoff, 2005).

The etiology of the abnormal processing in chronic pain is not fully understood. However, there are two main, nonexclusive causes. First, tissue damage can trigger the release of chemicals that sensitize the nerve fibers and alter gene expression, causing changes in signaling through many different mechanisms. Some of these changes enable non-pain-conducting fibers to trigger pain in the CNS. Second, pain can result from injured nerve fibers that regenerate in a neuroma, which generates pain signals with little or no stimulation.

When injury occurs to key pain-processing sectors of the CNS (e.g., the dorsal horn, thalamus), neural signals that pass through them may be interpreted as pain. Injury may also lead to degeneration of pain inhibitory cells. Modulation of nociceptive stimuli and inhibitory responses can occur at one or more locations in the CNS: the peripheral nerves, spinal cord neurons and tracts, thalamus, and cortex (Compton & Gebhart, 2003). Accurate identification of the source of the chronic pain, and of the neurological processes that modulate it, can lead to rational therapeutic approaches that target the source of aberrant signaling on the CNS pathway.

Pain’s Effect on Health

Persistent pain can have significant adverse effects on health. When pain stimuli continuously trigger the stress response, the acute signs of sympathetic activation (e.g., rapid heart rate, sweating) may cease or appear intermittently, yet the body continues to be stressed. This situation contributes to a sense of exhaustion.

Continued pain can trigger emotional responses, including sleeplessness, anxiety, and depressive symptoms, which in turn produce more pain. Such feedback cycles may continue to cause pain after the physiological causes have been addressed. Several studies show that the outcome of pain treatment is worse in the presence of depression, or when depression does not respond to treatment, and that the future course of pain syndromes can be, in part, predicted by emotional status. The physiological and psychological sequelae of CNCP can be exacerbated by such factors as inactivity and overuse of sedating drugs. Physical inactivity and a lack of engagement with life may also lead to increased levels of anxiety, depression, and an increased risk for suicidal ideation; these increases may lead a person to use substances in an attempt to treat these sequelae of CNCP and the losses that occur due to its presence.

Neurobiology of Addiction

A person may use substances initially for several reasons, such as to experience the euphoric effects, to relieve stress, to overcome anxiety or depression (or both), or to blunt the pain (National Institute on Drug Abuse [NIDA], 2007). With repeated exposure, however, substance use in some people can become uncontrollable. The defining characteristics of the disease of addiction have been summarized as the “3Cs” (see the definition of addiction). Changes to the brain occur in a process that is mediated by both genetic and environmental factors, which result in an overvaluation of the substance, a devaluation of other things, and impaired control of substance-related behavior. Evidence indicates that addiction is a chronic disease.

The primary rewarding effects of addictive substances occur in the cortico-mesolimbic dopamine systems, where several structures link to control the basic emotions and connect them to memories, which drive behavior. These systems produce sensations of pleasure in response to actions that support survival (e.g., eating, sex) and sensations of fear in response to potential dangers. In a cascading effect, these sensations trigger the endocrine and autonomic nervous systems, stimulating bodily responses. The prefrontal cortex also plays a role in the formation of addictions, modifying pleasure and pain signals based on other considerations. Thus, the brain’s reward and stress systems reinforce life-sustaining behaviors.

Reward Response

Feelings of reward emerge from the core of the limbic system after neurons in the ventral tegmental area (VTA) release the neurotransmitter dopamine into the nucleus accumbens (NAc). Neural activity within this VTA–NAc circuit is necessary to experience reward, but other areas within the broader brain reward circuit also exert a strong influence. For example, the hippocampus contributes information from the past that may be relevant to the current experience. The amygdala adds critical information about the emotional valence of the stimulus that activated the reward circuit, thus contributing to the overall motivational power of the experience. In addition, parts of the prefrontal cortex (i.e., anterior cingulate and orbitofrontal cortices) help integrate all the information, a vital function that allows the individual to decide whether to initiate or suppress a particular behavior in response to the stimulus.

Most addictive substances increase the levels of dopamine in limbic targets well beyond what occurs in naturally rewarding situations (e.g., sex, food). Some drugs (e.g., marijuana, heroin) produce dopaminergic effects indirectly. Amphetamines cause the release of dopamine, and cocaine prevents its reuptake; both effects result in amplified messaging that eventually disrupts normal neuronal signaling.

It appears that the brain adjusts to excess dopamine levels by producing less dopamine and by reducing the number of receptors that respond to it in the receiving (postsynaptic) neuron. As a result, the pleasurable effects of a drug become diminished with continued use. The pleasurable effects of normal activities also are blunted, creating a state called anhedonia (an inability to experience pleasure).

It is commonly believed that continued substance use is driven by the need to prevent symptoms of withdrawal; however, this idea is misleading. Withdrawal, as commonly conceptualized, involves rebound symptoms resulting from the drug’s absence. In the case of opioids, these symptoms include, but are not limited to, anxiety, sweating, tachycardia, diarrhea, piloerection, and chills. Although unpleasant, these symptoms are typically absent after a relatively brief period of detoxification or weaning and do not explain phenomena such as addiction relapse and prolonged craving. Even though detoxification is quick and technically easy, the prevention of relapse is extremely difficult and, in fact, the majority of those who attain abstinence experience at least one relapse (Dennis, Foss, & Scott, 2007). These more difficult problems are thought to result from the prolonged impairment of hedonic tone and conditioned responses that lead to intense craving.

Stress Response

The dysregulation of the brain’s reward system that occurs through substance use is paralleled by similar dysregulating effects in the stress system. Use of an addictive substance increases the flow of neurochemicals (e.g., corticotropin-releasing factor, norepinephrine, dynorphin). These chemicals can produce a negative emotional state that manifests as chronic irritability, emotional pain, lethargy, disinterest in natural rewards, and other dysphoric conditions. The stress response becomes more sensitive with repeated withdrawal and can persist into abstinence (Koob, 2009).

An individual may seek to avert the stress response by again using the substance. This negative reinforcement combines with the positive reinforcement of the substance’s euphoric effects in an operant process that creates a compulsion for substance use. Thus, addiction is reflected in compulsive use combined with loss of control mediated by memory (cue-induced triggers for reuse), substance-induced reductions in executive functioning that hamper rational decisionmaking, and habit formation (Koob, 2009).

Risk Factors for Addiction

People who use substances with addictive potential may develop tolerance to some of their effects and develop some degree of physical dependence. However, only a minority develops the disease of addiction. Important risk factors for addiction include genetics, psychological factors, and environmental factors.

Genetics plays a substantial role in risk factors for addiction: NIDA (2007) estimates that between 40 and 60 percent of a person’s vulnerability to addiction may be genetic. The disease of addiction may be more heritable than type 2 diabetes, hypertension, and breast cancer (Nestler, 2005). Genes also underlie human variability in drug metabolism, susceptibility to psychiatric disorders that commonly co-occur with addiction, and response to environmental risk factors (e.g., drug availability, peer group pressure [Vaillant, 2003]).

Mental illness is another major risk factor for addiction (Volkow & Li, 2009), and the two conditions have high comorbidity (NIDA, 2009). One condition can follow the other (NIDA, 2007). For example, a person may attempt to relieve depression or anxiety with substances, and this behavior may lead to addiction. Conversely, chronic substance use may lead to mental disorders, such as psychosis, or make existing mental illness worse (NIDA, 2007). Environmental influences on addiction include, but are not limited to, poverty, poor parental support, living in a community with high drug availability, and using substances at an early age (NIDA, 2007, 2009; Volkow & Li, 2009).


Addiction to one substance can be linked with addiction to other substances in a pattern termed cross-addiction. An individual who voluntarily or involuntarily decreases use of one substance may increase use of another substance with similar effects on the brain (e.g., the person with an alcohol use disorder may use barbiturates for the sedative effects). The term cross-addiction is also used to describe simultaneous addiction (e.g., co-occurring addictions to nicotine, alcohol, and marijuana).

Cross-addiction is not official diagnostic nomenclature; rather, it refers to the observation that a person with an addiction to one substance may develop addiction to a subsequent substance, especially if the original drug of choice becomes inaccessible or is relinquished for other reasons. For example, a study of patients hospitalized for controlled-release oxycodone addiction found that the majority (77 percent) had previously had a non-opioid SUD (Potter, Hennessey, Borrow, Greenfield, & Weiss, 2004).

Individuals with chronic pain and histories of SUDs may be at increased risk of cross-addiction to any medication that acts on the brain as a reinforcing agent (Edlund, Sullivan, Steffick, Harris, & Wells, 2007). Because of cross-addiction, persons who abuse marijuana may be at increased risk for opioid addiction. People with alcohol use disorders have been found to be more than 18 times as likely to report nonmedical use of prescription medications as people who do not drink (McCabe, Cranford, & Boyd, 2006).

The Cycle of Chronic Pain and Addiction

Although multiple factors influence the course of addiction, CNCP provides both positive and negative reinforcement of substance use. Positive reinforcement occurs when a behavior is followed by a consequence that is desirable—a donkey’s walking may be rewarded by a carrot. Negative reinforcement occurs when a behavior is followed by the elimination of a negative consequence—a donkey’s walking may eliminate the blows from a stick. For example, euphoria is a positive reinforcer for taking heroin, and pain reduction is a negative reinforcer for taking heroin. Prescribed opioids, benzodiazepines, or other medications may dramatically relieve pain or distress (e.g., depression, anxiety). Unprescribed substances may be used for similar reasons; for example, alcohol may promote relaxation or sleep. Such relief is a strong reinforcement for repeated consumption of the substance.

Unfortunately, analgesic and anxiolytic efficacy may diminish over the course of weeks, months, or years as tolerance develops. This loss of efficacy often elicits dose escalation to recapture efficacy. This escalation is rewarded, as the increased dose is initially more effective than the lower dose.

If the drug produces physical dependence, the person may have not only increased pain when the substance is absent, but also withdrawal symptoms (e.g., anxiety, nausea, cramps, insomnia). Withdrawal symptoms may lead to an increase in symptoms of depression and an increase in the potential risk for suicide. All these symptoms are relieved by ingesting more of the drug that caused the dependence. A similar situation may occur if the drug is one that elicits rebound symptoms. For example, ergot relieves migraine, but excessive use leads to rebound headaches that are more persistent and treatment resistant than were the original headaches.

An illusion of benefit produced by reinforcing drugs can create a paradoxical situation in which long-term use of the substance creates the very symptoms the person hopes to alleviate. People commonly drink to relax or “cheer up,” yet chronic alcohol abuse leads to depression and anxiety.

In some people, a cycle develops in which pain or distress elicits severe preoccupation with the substance that previously provided relief. This cycle—seeking pain relief, experiencing relief, and then having pain recur—can be very difficult to break, even in the person without an addiction, and the development of addiction markedly exacerbates the difficulty. The propensity to develop this cycle is influenced by genetic and environmental factors; some people will experience greater degrees of analgesia than others, and some will have more severe or prolonged abstinence symptoms. Genetic variability in susceptibility to these experiences may explain some cases of iatrogenic addiction.

Summary of TIP

The management of CNCP in patients with a comorbid SUD is challenging for both patients and clinicians; however, it can be done successfully. This TIP advises clinicians to conduct a careful assessment; develop a treatment plan that addresses pain, functional impairment, and psychological symptoms; and closely monitor patients for relapse. Even the best treatment is unlikely to completely eliminate chronic pain, and efforts to achieve total pain relief can be self-defeating. Patients may benefit when clinicians team with other professionals ( e.g., psychologists, addiction counselors, pharmacists, holistic care providers). Patients must also assume a significant amount of responsibility for optimal management of their pain. Educating patients, family members, and caregivers in this process, and helping patients improve their quality of life, can be gratifying for everyone involved.

Key Points

  • CNCP and the disease of addiction involve neurophysiological processes.
  • Both genetic and environmental factors contribute to and influence the development and course of CNCP and addiction.
  • Clinicians must understand CNCP, addiction, and other behavioral health issues to best serve the chronic pain patient with or in recovery from an SUD.
  • Despite the complexities of CNCP and SUDs, patients with these co-occurring, chronic conditions can be treated effectively.


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