1. Ramesh, Divya PhD
  2. Evans, Heather PhD, RNC-MNN, CLC

Article Content

Learning Objectives/Outcomes:After participating in this CME/CNE activity, the provider should be better able to:


1. Define the ways in which chronic pain can increase impulsivity.


2. Compare various measures and tasks to identify impulsivity.


3. Assess neurobiological changes related to chronic pain and overlap with impulsivity.


4. Identify the ways in which increased impulsivity can be a risk factor for prescription misuse.


Chronic pain is the leading cause of disability, lost productivity, and increasing health care costs in the United States. Over 100 million Americans suffer from chronic pain, leading to an increase in prescription of opioids for pain management in recent years.1,2 Nearly 30% of patients with chronic pain report opioid misuse, which is defined as taking the medication for a purpose other than for what it is prescribed.3 Although not all patients maintained on opioids develop opioid misuse, the risk for addiction and overdose is a concern for health care providers. Despite changes in national guidelines and regulations for prescribing opioids,4 misuse of prescription opioids increased by nearly 250% between 2004 and 2011.5


Patients who are typically at a lower risk for misusing opioids include those who are older, generally compliant, have a record of rarely misusing any medication, and do not have a history of comorbid psychological disorders. Risk factors for opioid misuse include personal history of substance abuse including cigarette smoking, young age, history of criminal activity or legal problem, history of social problems with family or employers, risk-taking impulsive behavior, severe depression or anxiety, and/or multiple psychosocial stressors.6


The presence of chronic pain affects outcomes related to impulsivity and decision-making. Therefore, it is possible that, among patients with chronic pain, those with higher impulsivity have an increased risk for opioid misuse and opioid use disorder (OUD). This illuminates the need for increased screening for behavioral risk factors that can aid clinicians in identifying patients with chronic pain at a higher risk for prescription-opioid misuse.


In this review, we examine the overlapping interactions between pain and executive function, specifically the components of impulsivity and decision-making. Increased impulsivity and poor decision-making are likely to impact day-to-day activities and increase risk of opioid misuse. A detailed look at all cognitive aspects of pain7-and interactions with other factors such as mood, stress, anxiety, coping, disability, and quality of life-is beyond the scope of this review. We have introduced the concept of impulsivity and its different constructs, and questionnaires and tasks to measure impulsivity. We also describe how impulsive traits are related to both chronic pain and risk for opioid misuse and briefly compare the overlap of pain, impulsivity, and OUD, and the interconnectivity between these pathways in the neurocircuitry. Finally, we discuss interventions targeting impulsivity in chronic pain populations and considerations for health care providers.


Impulsivity, Chronic Pain, and Risk for Opioid Misuse

Chronic Pain and Executive Functioning

Pain is a dynamic, complex process8 that is composed of sensory, affective, and cognitive dimensions. The International Association for the Study of Pain describes pain as "an unpleasant sensory and emotional experience with real or potential tissue damage or described in terms of such damage."9 Acute nociceptive pain is typically a symptom of an underlying medical condition that follows the severity of the cause and ends with the resolution of the primary cause.10


The transition of pain from an acute to chronic state is not fully understood.11 It involves adaptations and changes at the level of the spinal cord and the brain, which have been recently defined as the dynamic pain connectome.12 Chronic pain may manifest with sensory changes such as hyperalgesia or allodynia, and changes with emotional regulation and executive functioning. Stress is also implicated across all types of chronic pain disorders. Chronic pain may be viewed as a self-amplifying stressor that contributes to the cumulative load of allostasis (the process by which the body responds to stressors in order to regain homeostasis).


What Is Impulsivity?

Executive function encompasses neurologic processes such as planning, organization, impulsivity, and goal-directed behaviors. Impulsivity has been defined as a predisposition toward rapid, unplanned reactions to internal or external stimuli, with diminished regard to the negative consequences of these reactions.13,14 Most often, impulsivity is measured by self-report measures of trait impulsivity, which assess impulsivity as a long-lasting personality characteristic. Impulsivity is also indexed by laboratory neurocognitive measures that most commonly assess 2 main processes:


1. Impulsive action (ie, compromised ability to inhibit inappropriate behaviors);15 and


2. Impulsive choice or decision-making, reflecting suboptimal choices in the face of delay contingencies or potential reward/risk.16


It is important to note here that these various dimensions of impulsivity often do not correlate to each other, suggesting that self-report and neurocognitive tasks of impulsivity reflect different processes.17,18


Impulsivity Measures: Trait Impulsivity

Barratt Impulsiveness Scale

The Barratt Impulsiveness Scale (BIS-11)19 is one of the most commonly used measures of trait impulsivity. The BIS-11 is a 30-item self-report scale with 3 oblique factors:


1. Attentional/cognitive impulsivity, measuring tolerance for cognitive complexity and persistence;


2. Motor impulsivity, measuring the tendency to act on the spur of the moment; and


3. Nonplanning impulsivity, measuring the lack of sense of the future.



Total scores range from 30 to 120, with nonpsychiatric controls generally scoring 50 to 60.20 The reliability of the BIS-11 is high (r = 0.92), with reliability of subscales ranging between 0.85 and 0.88.21



The UPPS-P22 scale is a 45-item measure designed to measure 4 facets of impulsivity. These facets include urgency (12 items), lack of premeditation (11 items), lack of perseverance (10 items), and sensation seeking (12 items). Items are rated from 1 (agree strongly) to 4 (disagree strongly). All subscales have been demonstrated to have high levels of internal reliability, ranging between 0.81 and 0.93.21


Impulsive Action

Impulsive action or rapid-response impulsivity is characterized by the inability to withhold response to a stimulus until it is adequately appraised.


Continuous Performance Test

Rapid-response impulsivity can be measured using the Continuous Performance Test (CPT).23 In the CPT, participants are instructed to respond to target stimuli and to inhibit responses to incorrect stimuli that are similar to the target. Responses to incorrect stimuli, or commission errors, are indicative of higher impulsivity. Although there are many versions of the CPT, all involve the maintenance of focus throughout the duration of a repetitive task to respond to targets or inhibit responses. The content validity of the CPT is strong, as the task measures ability and willingness to inhibit responses13 and high test-retest reliability (r = 0.73).21


The immediate and delayed memory tasks (IMT/DMT) are a variation of the CPT developed to study sustained attention, working memory, and impulsivity. The IMT/DMT response parameters are more sensitive to impulsive error responding while controlling for attention. The IMT/DMT has 2 task components that each feature a series of 5-digit numbers (eg, 38391) and require the patient to respond to the sequence based on whether it is a match or different from the previous sequence. Subject groups that clinically have high impulsivity, such as personality disorders and substance abuse, have higher commission errors on this task (as opposed to correct detections) than do control groups.24,25


Stop-Signal Task

The Stop-Signal Task (SST) measures motor impulsivity or impulsive action.26 In this task, subjects are required to make quick key responses to visually presented go signals and to inhibit any response when a visual stop signal is suddenly presented. Longer stop-signal reaction times are associated with poor inhibitory control and higher impulsivity. The SST has moderately high reliability, with test-retest reliability coefficients that range from r = 0.6127 to r = 0.65.21 Both stress and substance use can lead to longer reaction times in this task.28 Chronic pain and stress may amplify a deficit in inhibitory control to salient drug cues, which may result in compulsive drug-taking behavior.



The Go/No-Go (GNG)15 task is designed to assess ability to inhibit inappropriate responses. The GNG instructions ask participants to make motor responses as rapidly as possible to visual presentations of stimuli designated as "go," and to withhold motor responses to stimuli with a "no-go" designation. "Go" events are typically more frequent than "no-go" events, in order to establish the "go" response as dominant. Errors of omission (withholding a response when a "go" stimulus is presented) and errors of commission/false alarms (responding to a "no-go" stimulus) are recorded during the task, with the latter measuring impulsive action. The GNG has strong construct validity and test-retest reliability (r = 0.65).21


Impulsive Choice

Impulsive choice encompasses 2 aspects included in the definition of impulsivity: lack of planning and lack of regard for future consequences.16 Additional terms, which have been used to describe this component, include delay discounting, temporal discounting, and decision-making. Impulsive choice is associated with a variety of problematic behaviors, such as opioid abuse.


Delay discounting involves choices between smaller-sooner rewards and larger-later rewards. A series of choices are presented in order to determine the extent to which individual preferences for smaller-sooner versus larger-later rewards exist. Steeper discounting of the large rewards is indicative of more impulsive behavior, although differences in temporal judgment and reward sensitivity can confound outcomes.


The Delay Discounting Task

This task is designed to measure participants' discounting rate when they are presented with the possibility of receiving a hypothetical reward determined using a choice algorithm. The Delay Discounting Task (DDT)29 is a computerized real-time assessment of temporal discounting processes. Participants make choices between a delayed probabilistic (35% chance of occurrence) option and an adjusting immediate option that is certain.


Participants are exposed to a series of choices in which the delay reward magnitudes are $10, $25, $100, $250, $1000, or $2500, and at delay periods of 1 day, 1 week, 1 month, 6 months, 1 year, 5 years, or 25 years. Several studies have shown that clinically impulsive individuals, when compared to matched healthy controls, show high rates of delay discounting: They are willing to forgo greater rewards available only after some length of time and show a preference for smaller rewards that are available immediately. The DDT demonstrates good test-retest reliability in healthy adults, with correlations ranging from r = 0.64 to r = 0.91.21,30


The Monetary Choice Delay Discounting Questionnaire

The Monetary Choice Delay Discounting Questionnaire (MCQ)31 is a 27-item paper-and-pencil discounting assessment. Participants are presented with a fixed set of choices between smaller, immediate rewards and larger, delayed rewards. For example, on the first trial participants are asked, "Would you prefer $54 today, or $55 in 117 days?"


The participant indicates which alternative she or he would prefer by circling it on the questionnaire. An estimate of a participant's log(k) is made from the participant's pattern of choices across the 27 questions on the monetary-choice questionnaire and by fitting a hyperbolic function with logistic regression.32 The MCQ has a test-retest reliability of 0.71 across 1 year and is associated with impulsivity-related outcomes such as initiation of drug use.33 Higher K values are associated with increased choice of immediate reward and thus of increased impulsive choice.


The Iowa Gambling Task

Decision-making is one of the neurocognitive domains on which both chronic pain and those with OUD are commonly impaired. It is typically indexed in the laboratory with tasks that simulate real-life decision-making such as the Iowa Gambling Task (IGT),34 on which those with decision-making impairments often select choices that yield high immediate gains but have higher future losses.


The IGT is a complex task and poor behavioral performance could be the result of deficits in various distinct neurocognitive processes, such as hypersensitivity to reward, hyposensitivity to losses, failure to learn from past experiences, or impulsive response style.


In the computerized version of the task, participants are asked to choose between 4 decks of cards that result in hypothetical monetary rewards, with the goal to maximize gains. Each deck contains 60 cards and participants must make 100 choices over the testing session. Two of the decks are disadvantageous in that they are associated with high immediate rewards but even higher subsequent losses, whereas the other 2 decks are considered advantageous because they result in an overall long-term gain. The index of decision-making performance on the IGT is a "net score" based on the total number of cards selected from the advantageous minus the disadvantageous decks across all the trials.


Assessment of Misuse Risk Among Patients With Chronic Pain

The Screener and Opioid Assessment for Patients With Pain-Revised

The Screener and Opioid Assessment for Patients With Pain-Revised (SOAPP-R) is a conceptually derived self-report questionnaire designed to predict aberrant medication-related behaviors among patients with chronic pain considered for long-term opioid therapy.35 It consists of 24 questions, and a cutoff score of 18 on the scale shows adequate sensitivity (0.81) and specificity (0.68) in patients with chronic pain.


Current Opioid Misuse Measure

The Current Opioid Misuse Measure (COMM)36 is a 17-item brief patient self-assessment to monitor patients with chronic pain on opioid therapy. It identifies key issues to determine whether patients already on long-term opioid treatment are exhibiting aberrant medication-related behaviors. Reliability (coefficient [alpha]) of the COMM ranges between 0.83 and 0.86, and it is a valid tool to detect current misuse of opioids among patients with chronic pain.


Other measures have also been developed to screen patients with pain for addiction risk potential. The 5-item Opioid Risk Tool is a validated questionnaire that predicts which patients will display aberrant drug-related behaviors. Scores of 8 or higher suggest high risk for opioid misuse.37


A similar rating tool, DIRE (diagnosis, intractability, risk, and efficacy) is a clinician-rating scale used to determine suitability for long-term opioid treatment for chronic pain.38 Scores higher than 14 on the DIRE suggest a greater feasibility of opioid therapy for patients with pain.


The Pain Assessment and Documentation Tool is another clinician-completed scale, which provides a detailed documentation of the patient's progress and care.39


The Screening Instrument for Substance Abuse Potential is a self-report screening questionnaire for substance-abuse potential based mostly on the alcohol literature.40


Unfortunately, these measures, other than the SOAPP-R and the COMM, lack cross-validation studies.


Chronic Pain and Impulsivity

Chronic pain is a complex process that is not inherently impulsive. However, chronic pain can cause negative affective states or stress, which can lead to rapid, unplanned reactions in certain individuals. As proposed by our model, chronic pain, stress, and negative emotionality contribute to impulsivity (Figure 1).42 Clinically, impulsivity in chronic pain has been studied by using self-report questionnaires and decision-making tasks. Patients with chronic pain show moderate impulsivity traits on self-report measures such as the BIS-11.43 On the IGT, patients with chronic pain make poor choices in the task, as they are unable to develop an advantageous strategy and are less persistent in their choices, switching more often between competing responses.44,45 These findings suggest that chronic pain might impose a high cost on executive control, undermining functions such as impulsivity and decision-making.

Figure 1 - Click to enlarge in new windowFigure 1. A schematic model shows the interplay between chronic pain, stress, negative emotionality, and impulsivity that can lead to drug use. Chronic pain can dramatically alter an individual's response to stressors, predisposing them to opioid misuse. (Adapted from Hassamal et al.

Impulsivity and Risk for Opioid Misuse

Impulsivity is one factor that may predispose some individuals with chronic pain to a higher risk of misusing prescription opioids. Stress from chronic pain can lead to negative emotional states, overwhelming an individual's ability to resist using drugs (Figure 1). It is likely that drug seeking is much more likely to occur during emotionally charged states (ie, chronic pain and related stress), as deficits in inhibitory control become more pronounced during heightened motivational states.46 Thus, in response to chronic pain, impulsive individuals may use opioids in an unplanned fashion without regard to the long-term consequences.


Several laboratory studies have examined risk to opioid misuse among those with chronic pain. Studies examining different facets of impulsivity measures using instruments such as the UPPS-P and the BIS-11 demonstrated that impulsiveness and urgency are associated with current and future risk of opioid misuse.47,48 Studies by Tompkins and colleagues classified patients with chronic pain as high or low risk for opioid misuse based on the SOAPP-R. Of note, high-risk participants exhibited greater delay discounting and higher trait impulsivity.49,50 Higher trait impulsivity score on the BIS-11 is also associated with increased likelihood of trying more analgesics, suggesting that they are more likely to discount the probability of becoming addicted (ie, short-term pain relief is a preferable goal than the long-term goal of stable pain management without addiction). Thus, impulsivity in chronic pain populations is predictive of opioid misuse and should be an important consideration while developing treatment outcomes and building resilience to OUD in this population.


Impact of Chronic Pain on Neurocircuitry: Shift From Sensory to Mesolimbic Pathways

Chronic pain is not a singular pathway mediated by a single neurotransmitter or a specific mechanism. Along with sensory pathways, it involves reorganization of higher-order brain functions including emotional regulation and cognitive functions and behavioral and social manifestations. Chronic pain is thought to be a sensory phenomenon that requires significant cognitive attention,51 involving processes such as emotion regulation, learning, recall of past experiences, and decision-making.44,52-55


Patients with chronic pain display impairments in tasks assessing decision-making, such as the IGT and discounting tasks. Thus, it is reasonable to hypothesize that there is neurobiological overlap of the brain regions modulating pain and executive functions such as impulsivity and decision-making.53


On the other hand, overlap of pain pathways with the reward circuitry may give insight into understanding the impact of pain on executive functioning and the risk of opioid misuse in this population. This is reasonable because both pain and OUD are characterized by impaired self-regulation and decision-making, and higher impulsivity, stress, and drug seeking.56


The aversive nature of pain, and the reward from relief of pain, is mediated by brain reward mesocorticolimbic circuitry. Neurobiological processes underlying OUD also overlap with affective aspects of chronic pain.10,57,58 Overlapping adaptations of the neural network in the amygdala (eg, amplifying noradrenaline signaling, and corticotrophin-releasing factor [CRF], and dynorphin-mediated signaling) related to chronic pain or OUD may drive common maladaptive negative emotional responses to stress.58 Structures within the amygdala contain some of the highest levels of stress neurotransmitters and hormones, such as catecholamines and stress hormones.


Chronic pain-related stress triggers release of catecholamines and stress hormones in the brain, preparing the individual to cope with the stressful situation. This process is mediated by a stress circuit in which increased levels of CRF result in increased cortisol, norepinephrine, and dopamine, affecting the reward pathways involved in addiction, decision-making, and impulsivity, such as the ventral tegmental area (VTA), nucleus accumbens (NAc), and the medial prefrontal cortex (mPFC).41,42,59-63


Interindividual variability in risk to opioid misuse results from differences in the coordinated stress response. The response consists of the function and interplay of numerous hormones, neurotransmitters, and neuropeptides in the brain.64 Chronic pain may result in a prolonged state of stress, resulting in an exaggerated response in the amygdala network, which may drive certain patients with chronic pain to actively seek opioids to alleviate not only their pain but also the dysphoria and psychological perceptions of pain.


The amygdala is connected to the parts of the brain critically involved in emotional regulation and reward, including the lateral hypothalamus and the VTA. It is important to note that the neurobiological adaptations may impact pain's cross-sensitization with stress and reward circuitry maintaining aberrant drug use, after chronic opioid treatment.57


The hyperactivity of stress and reward circuits due to such cross-sensitization also leads to an accompanying decreased mesolimbic dopaminergic activity.10,65-67 The mesolimbic dopamine neurons projecting from the VTA to NAc are associated with reward, impulsivity, decision-making, and addiction risk.42,68 This pathway is highly susceptible to stress-related signaling and adaptations to chronic pain. These findings are corroborated by functional MRI studies showing changes in the reward circuitry, specifically in connections to and from the NAc of individuals with chronic pain.69-71


Additional regions show functional abnormality including connections between the NAc and the PFC. The medial PFC shows increased activity in patients with chronic pain, which is thought to be associated with transition from acute to chronic pain.72 In addition, comparison of brain function between chronic pain and highly impulsive individuals shows similar altered connectivity in the NAc between both populations. Changes in the NAc circuitry are have been demonstrated to be associated with riskier choices on a gambling task.69


Chronic opioid administration also triggers CRF release from the hypothalamic-pituitary-adrenal axis and enhances dopaminergic activity in the mesolimbic pathway.59 Opioid-dependent individuals perform poorly on gambling tasks, which is associated with morphological changes in the reward circuitry.73-75 Thus, both chronic pain and opioid misuse activate mesolimbic pathways in a similar fashion and each leads to synaptic adaptations in dopamine receptors and dopamine levels in the VTA, which confers a risk to increased impulsivity or relapse to drug use.76


The exact mechanism underlying the hypofunction of dopaminergic circuitry is unknown. One commonality that may link these disorders is an increase in brain-derived neurotrophic factor (BDNF). Neurotrophins such as BDNF play a key role in neural plasticity related to stress.77,78 However, chronic pain and stress through mediators such as cortisol and excitatory amino acids can decrease BDNF expression in the brain.77,79,80 BDNF is also a critical modulator of VTA dopamine function in opioid dependence. Intra-VTA administration of BDNF is shown to be a negative modulator of opioid reward and blunted morphine-evoked dopamine release.81 In the spinal cord, microglial-derived BDNF is responsible for the pain sensitization associated with chronic opioid exposure.82 Therefore, it is hypothesized that variability in BDNF signaling can be a contributing risk factor among patients with chronic pain in developing OUD.76,83


Conclusion-Considerations for Health Care Providers

From a clinical perspective, high-risk, impulsive individuals may be more likely to seek opioids, as they discount the risk of addiction while getting effective pain treatment. High-risk individuals are more likely to misuse opioids, whereas low-risk individuals are more likely to avoid opioid therapy to limit the risk for addiction. There may be a link between the neurobiological reorganization of brain reward circuits and opioid misuse. However, targeting these reward/impulsivity circuits may provide new therapies for pain symptom management and could alter the trajectory of outcomes related to chronic pain.


Pain-induced maladaptation of reward/impulsivity circuits may be reversible with therapy, allowing for amelioration of pain and restoration of normal executive functioning. Thus, identifying the risk level and impulsivity traits in individuals may determine the appropriate treatment strategy and aid in identifying those individuals who might benefit most from opioid therapy with lower risk of addiction.


There is a need for well-designed prospective, randomized, controlled trial research, addressing appropriate pain management strategies. One possibility is to develop effective analgesics that have lower abuse potential and are protective against impulsivity induced by chronic pain. Cognitive-based interventions have been widely used for chronic pain management and treating substance abuse. However, only a handful of studies have examined whether cognitive-based interventions among patients with chronic pain who show risk potential of opioid misuse could increase overall compliance with opioids.


In a small pilot study with 42 patients meeting criteria for high risk for opioid misuse, patients were randomized to either standard control (high-risk control; n = 21) or experimental compliance treatment consisting of monthly urine screens, compliance checklists, and individual and group motivational counseling (high-risk experimental; n = 21) based on SOAPP-R scores.84 The study recruited 20 patients who met criteria, indicating low potential for misuse (low-risk control; n = 20). Patients were followed up for 6 months and completed pre- and post-study questionnaires and monthly electronic diaries. Significant differences were demonstrated among groups, with 73.7% of the high-risk control patients demonstrating positive scores on the drug misuse index, compared with 26.3% from the high-risk experimental group and 25% from the low-risk controls (P < 0.05).


Physical activity interventions may also be helpful for improving executive functions in this population.85 Thus, the structured nature of cognitive-based interventions and the neurologic benefits of physical exercise may facilitate resilience and self-management behaviors leading to improved opioid compliance.


Comprehensive assessment and careful monitoring are necessary for all patients with chronic pain who are considered for long-term opioid therapy. Pain management protocols with opioids should follow a process of initial evaluation, risk assessment, intervention, monitoring, and, if needed, corrective action. Managing patients with chronic pain in a primary care setting, however, is extremely challenging. Time and resources are limited, and often there is scant access to specialty pain clinics, addiction services, or behavioral health specialists. Clinicians may also find it necessary to include office-based and technology-assisted interventions and employ community assets. Several factors may influence selecting an assessment tool to best meet the needs of the practice (eg, daily volume and support staff). These factors include cost, time needed to complete the assessment, whether it is self-administered or requires administration by a staff member, and the ease of scoring the instrument.


Inclusion of the SOAPP-R, COMM, and self-report impulsivity scales is reasonable within pain management practices to identify these behaviors over the course of pain management. Identifying the misuse risk level and incorporating a comprehensive treatment protocol that includes screening measures, compliance checklists, pill counts, and complementary interventions will hopefully decrease the abuse potential of prescribed opioids among patients with chronic pain.




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Chronic pain; Impulsivity; Opioids