Bennet Davis, MD

Many Americans who are treated with prescription opioid analgesics would be better off with less opioid or none at all. To that end, published opioid prescribing guidelines do provide guidance on the mechanics of tapering patients off opioids^1-4—but they have a major flaw: They do not adequately account for the fact that people who have a diagnosis of chronic pain are a heterogeneous group and require diagnosis-specific treatment planning. A patient-centered approach to opioid tapers must account for the reality that many people who are given a prescription for an opioid to treat pain have significant mental health conditions—for which opioids act as a psychotropic agent. An opioid taper must therefore address psychological trauma, in particular.⁵ (See “Tapering and harm-reduction strategies have failed.”^6-14)

In this article, we present an evidence-based consensus approach to opioid tapering for your practice that is informed by a broader understanding of why patients take prescription opioids and why they, occasionally, switch to illicit drugs when their prescription is tapered. This consensus approach is based on the experience of the authors, members of the pain faculty of Project ECHO (Extension for Community Healthcare Outcomes) of the ECHO Institute, a worldwide initiative that uses adult learning techniques and interactive video technology to connect community providers with specialists at centers of excellence in regular real-time collaborative sessions. We are variously experts in pain medicine, primary care, psychology, addiction medicine, pharmacy, behavioral health therapy, occupational medicine, and Chinese medicine.

Why Americans obtain prescription opioids

There are 4 principal reasons why patients obtain prescription opioids, beyond indicated analgesic uses:

1. Patients seek the antianxiety and antidepressant effects of opioids. Multiple converging lines of evidence suggest that antianxiety and antidepressant effects of opioids are a significant reason that patients in the United States persist in requesting prescriptions for opioids:

• In our experience with more than 500 primary care telemedicine case presentations, at least 50% of patients say that the main effect of opioids prescribed for them is “it makes me feel calm” or “more relaxed.”
• In a 2007 survey of 91,823 US residents older than 18 years, nonmedical use of opioids was statistically associated with panic, social anxiety, and depressive symptoms.¹⁵
• Ten years later, Von Korff and colleagues found that more than half of opioid prescriptions written in the United States were for the small percentage of patients who have a diagnosis of serious anxiety or depression.¹³
• In 2016, Yovell and colleagues reported that ultra-low-dosage buprenorphine markedly reduced suicidal ideation over 4 weeks in 62 patients with varied levels of depression.¹⁶

There is also mechanistic evidence that the antianxiety and antidepressant effects of opioids are significant reasons Americans persist in requesting prescription opioids. The literature suggests that opioid receptors play a role in mood regulation, including alleviation of depression and anxiety; recent research suggests that oxycodone might be a unique mood-altering drug compared to other common prescription opioids because of its ability to affect mood through the δ opioid receptor.^17-20

It should not be a surprise that Americans often turn to opioids to address posttraumatic stress disorder (PTSD), anxiety, and depression. A recent study of the state of the US mental health system concluded that mental health services in the United States are inadequate—despite evidence that > 50% of Americans seek, or consider seeking, treatment for mental health problems for themselves or others.²¹

2. Patients experience pain unrelated to tissue damage. Rather, they are in pain “for psychological reasons.”²² In 2016, Davis and Vanderah wrote: “We theorize that a functional change in the [central nervous system] can occur in response to certain emotional states or traumatic experiences (eg, child abuse, assault, accidents).” They connect this change to central sensitization and a reduced pain-perception threshold,²³ and strongly suspect that many patients with chronic pain have undiagnosed and untreated psychological trauma that has changed the way their central nervous system processes sensory stimuli. The authors call this “trauma-induced hyperalgesia.”

Continue to: Psychological trauma...

 

Psychological trauma is uniquely capable of producing hyperalgesia, compared to anxiety or depression. In a study of veterans, Defrin and colleagues demonstrated hyperalgesia in patients who had a diagnosis of PTSD but not in controls group who had an anxiety disorder only.²⁴

High-dosage prescribing of opioids has fallen by 48% since 2011, yet the decline has not reduced overdose events of any kind.

To support successful opioid tapering, trauma-induced hyperalgesia, when present, must be addressed. Treatment of what the International Association for the Study of Pain calls “pain due to psychological factors”²² requires specific trauma therapy. However, our experience validates what researchers have to say about access to treatment of psychological trauma in the United States: “…[C]linical research has identified certain psychological interventions that effectively ameliorate the symptoms of PTSD. But most people struggling with PTSD don’t receive those treatments.”²⁵

We have no doubt that this is due, in part, to underdiagnosis of psychological trauma, even in mental health clinics. According to Miele and colleagues, “PTSD remains largely undiagnosed and undertreated in mental health outpatients, even in teaching hospitals, with diagnosis rates as low as 4% while published prevalence is between 7% and 50% in this population.”²⁶

3. Patients suffer from opioid use disorder (OUD) and complain of pain to obtain opioids by prescription. For patients with OUD, their use is out of control; they devote increasing mental and physical resources to obtaining, using, and recovering from substances; and they continue to use despite adverse consequences.²⁷ The prevalence of OUD in primary care clinics varies strikingly by the location of clinics. In Washington state, the prevalence of moderate and severe OUD in a large population of patients who had been prescribed opioids through primary care clinics was recently determined to be between 21.5% and 23.9%.¹³

4. Patients are obtaining opioid prescriptions for people other than themselves. While this is a reason that patients obtain opioid prescriptions, it is not necessarily common. Statistics show that the likelihood of a prescription being diverted intentionally is low: Dart and colleagues found that diversion has become uncommon in the general population.²⁸

Continue to: Why we taper opioid analgesics

 

 

Why we taper opioid analgesics

Reasons for an opioid taper include concern that the patient has, or will develop, an OUD; will experience accidental or intentional overdose; might be diverting opioids; is not benefiting from opioid therapy for pain; or is experiencing severe adverse effects. A patient who has nociceptive pain and might have ­opioid-induced hyperalgesia will require a much different opioid taper plan than a patient with untreated PTSD or a patient with severe OUD.

Misunderstanding can lead to inappropriate tapering

We often encounter primary care providers who believe that a large percentage of patients on chronic opioid therapy inevitably develop OUD. This is a common reason for initiating opioid taper. Most patients on a chronic opioid do become physically dependent, but only a small percentage of patients develop psychological dependence (ie, ­addiction or OUD).²⁹

Physical dependence is “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 blood level of the drug, and/or administration of an antagonist.”³⁰ Symptoms of opioid withdrawal include muscle aches; abdominal cramping; increased lacrimation, rhinorrhea, and perspiration; diarrhea; agitation and anxiety; insomnia; and piloerection. Opioid withdrawal symptoms are caused by physical dependence, not by addiction. They can be mitigated by tapering slowly and instituting adjuvant medications, such as clonidine, to attenuate symptoms.

Psychological dependence, or addiction (that is, OUD, as described in the Diagnostic and Statistical Manual of Mental Disorders 5th edition²⁷), comprises primarily 3 behavioral criteria:

• Loss of control of the medication, with compulsive use
• Continued use despite adverse consequences of using opioids, such as arrest for driving under the influence and deterioration of social, family, or work performance
• Obsession or preoccupation with obtaining and using the substance. In properly selected chronic opioid therapy patients, there is evidence that new-onset OUD is not as common as has been thought. A recent study of the risk for opioid addiction after use of an opioid for ≥ 90 days for chronic noncancer pain found that the absolute rate of de novo OUD among patients treated for 90 days was 0.72%.²⁹ A systematic review by Fishbain and colleagues of 24 studies of opioid-exposed patients found a risk of 3.27% overall—0.19% for patients who did not have a history of abuse or addiction.³¹ As Director of the National Institute on Drug Abuse Norma Volkow, MD, wrote in 2016: “Addiction occurs in only a small percentage of people who are exposed to opioids—even among those with preexisting vulnerabilities.”³²

Assessment should focus on why the patient is taking an opioid

A strong case can be made that less opioid is better for many of the people for whom these medications are prescribed for chronic noncancer pain. However, a one-size-fits-all dosage reduction and addiction-focused ­approach to opioid tapering has not worked: The assessment and treatment paradigm must change, in our view.

Continue to: During assessment...

 

During assessment, we must adopt the means to identify the reason that a patient is using a prescription opioid. It is of particular importance that we identify patients using opioids for their psychotropic properties, particularly when the goal is to cope with the effects of psychological trauma. The subsequent treatment protocol will then need to include time for effective, evidence-based behavioral health treatment of anxiety, PTSD, or depression. If opioids are serving primarily as psychotropic medication, an attempt to taper before establishing effective behavioral health treatment might lead the patient to pursue illegal means of procuring opioid medication.

Antianxiety and antidepressant effects of opioids are a significant reason that patients persist in requesting prescriptions.

We acknowledge that primary care physicians are not reimbursed for trauma screening and that evidence-based intensive trauma treatment is generally unavailable in the United States. Both of these shortcomings must be corrected if we want to stem the opioid crisis.

If diversion is suspected and there is evidence that the patient is not currently taking prescribed opioids (eg, a negative urine drug screen), discontinuing the opioid prescription is the immediate next step for the sake of public safety.

Considering a taper? Take this 5-step approach

Once it appears that tapering an opioid is indicated, we propose that you take the following steps:

• Establish whether it is safe to continue prescribing (follow the route provided in “2 decisions to make before continuing to prescribe an opioid for chronic noncancer pain”); if continuing it is not safe, take steps to protect the patient and the community
• Determine whether assessment by a trauma-informed behavioral health expert is needed, assuming that, in your judgment, it is safe to continue the opioid (TABLE³³). When behavioral health assessment is needed, you need 3 questions answered by that assessment: (1) Are psychological factors present that might put the patient at risk during an opioid taper? (2) What are those factors? (3) What needs to done about them before the taper is started? Recalling that psychological trauma often is not assessed by behavioral health colleagues, it is necessary to provide the behavioral health provider with a specific request to assess trauma burden, and state the physical diagnoses that are causing pain or provide a clear statement that no such diagnoses can be made. (See the FIGURE, which we developed in conjunction with behavioral health colleagues to help the consultant understand what the primary care physician needs from a behavioral health assessment.)
• Obtain consultation from a physical therapist, pain medicine specialist, and, if possible, an alternative or complementary medicine provider to determine what nonpharmacotherapeutic modalities can be instituted to treat pain before tapering the opioid.
• Initiate the Screening, Brief Intervention and Referral to Treatment (SBIRT) approach if OUD is suspected (www.samhsa.gov/sbirt).³⁴ This motivational interviewing tool identifies patients with a substance use disorder, severity of use, and appropriate level of treatment. (If OUD is suspected during assessment, next steps are to stop prescribing and implement harm-reduction strategies, such as primary care level medically assisted treatment [MAT] with buprenorphine, followed by expert behavioral health-centered addiction treatment.)
• Experiment with dosage reduction according to published guidance, if (1) psychological factors are absent or have been adequately addressed, according to the behavioral health consultant, and (2) nonpharmacotherapeutic strategies are in place.^8-11

Shifting to a patient-centered approach

The timing and choice of opioid tapers, in relation to harm reduction and intervention targeting the root cause of a patient’s complaint of pain, have not been adequately explored. In our practice, we’ve shifted from an addiction-centered, dosage-centered approach to opioid taper to a patient-centered approach³⁵ that emphasizes behavioral-medical integration—an approach that we broadly endorse. Such an approach (1) is based on a clear understanding of why the patient is taking opioid pain medication, (2) engages medical and complementary or alternative medicine specialists, (3) addresses underdiagnosis of psychological trauma, and (4) requires a quantum leap in access to trauma-specific behavioral health treatment resources. ³⁶

Continue to: To underscore the case...

 

To underscore the case for shifting to a patient-centered approach³⁵ we present sample cases in “How a patient-centered approach to tapering opioids looks in practice.”

An eye toward the future. To inform future approaches to opioid tapering, more resources need to be deployed to

• support screening and risk stratification for PTSD, anxiety, and related disorders at the primary care level,
• continue the effort to identify and treat OUD,
• develop best-practice responses to screening, and
• make harm-reduction strategies that are now reserved for patients with OUD available to those who don't have OUD.

We urge that research be pursued into best practices for chronic pain interventions that target psychological trauma, anxiety, and depression.

CORRESPONDENCE
Bennet Davis MD, 2092 East Calle de Dulcinea, Tucson, AZ 85718; [email protected].

Many Americans who are treated with prescription opioid analgesics would be better off with less opioid or none at all. To that end, published opioid prescribing guidelines do provide guidance on the mechanics of tapering patients off opioids^1-4—but they have a major flaw: They do not adequately account for the fact that people who have a diagnosis of chronic pain are a heterogeneous group and require diagnosis-specific treatment planning. A patient-centered approach to opioid tapers must account for the reality that many people who are given a prescription for an opioid to treat pain have significant mental health conditions—for which opioids act as a psychotropic agent. An opioid taper must therefore address psychological trauma, in particular.⁵ (See “Tapering and harm-reduction strategies have failed.”^6-14)

In this article, we present an evidence-based consensus approach to opioid tapering for your practice that is informed by a broader understanding of why patients take prescription opioids and why they, occasionally, switch to illicit drugs when their prescription is tapered. This consensus approach is based on the experience of the authors, members of the pain faculty of Project ECHO (Extension for Community Healthcare Outcomes) of the ECHO Institute, a worldwide initiative that uses adult learning techniques and interactive video technology to connect community providers with specialists at centers of excellence in regular real-time collaborative sessions. We are variously experts in pain medicine, primary care, psychology, addiction medicine, pharmacy, behavioral health therapy, occupational medicine, and Chinese medicine.

Why Americans obtain prescription opioids

There are 4 principal reasons why patients obtain prescription opioids, beyond indicated analgesic uses:

1. Patients seek the antianxiety and antidepressant effects of opioids. Multiple converging lines of evidence suggest that antianxiety and antidepressant effects of opioids are a significant reason that patients in the United States persist in requesting prescriptions for opioids:

• In our experience with more than 500 primary care telemedicine case presentations, at least 50% of patients say that the main effect of opioids prescribed for them is “it makes me feel calm” or “more relaxed.”
• In a 2007 survey of 91,823 US residents older than 18 years, nonmedical use of opioids was statistically associated with panic, social anxiety, and depressive symptoms.¹⁵
• Ten years later, Von Korff and colleagues found that more than half of opioid prescriptions written in the United States were for the small percentage of patients who have a diagnosis of serious anxiety or depression.¹³
• In 2016, Yovell and colleagues reported that ultra-low-dosage buprenorphine markedly reduced suicidal ideation over 4 weeks in 62 patients with varied levels of depression.¹⁶

There is also mechanistic evidence that the antianxiety and antidepressant effects of opioids are significant reasons Americans persist in requesting prescription opioids. The literature suggests that opioid receptors play a role in mood regulation, including alleviation of depression and anxiety; recent research suggests that oxycodone might be a unique mood-altering drug compared to other common prescription opioids because of its ability to affect mood through the δ opioid receptor.^17-20

It should not be a surprise that Americans often turn to opioids to address posttraumatic stress disorder (PTSD), anxiety, and depression. A recent study of the state of the US mental health system concluded that mental health services in the United States are inadequate—despite evidence that > 50% of Americans seek, or consider seeking, treatment for mental health problems for themselves or others.²¹

2. Patients experience pain unrelated to tissue damage. Rather, they are in pain “for psychological reasons.”²² In 2016, Davis and Vanderah wrote: “We theorize that a functional change in the [central nervous system] can occur in response to certain emotional states or traumatic experiences (eg, child abuse, assault, accidents).” They connect this change to central sensitization and a reduced pain-perception threshold,²³ and strongly suspect that many patients with chronic pain have undiagnosed and untreated psychological trauma that has changed the way their central nervous system processes sensory stimuli. The authors call this “trauma-induced hyperalgesia.”

Continue to: Psychological trauma...

 

Psychological trauma is uniquely capable of producing hyperalgesia, compared to anxiety or depression. In a study of veterans, Defrin and colleagues demonstrated hyperalgesia in patients who had a diagnosis of PTSD but not in controls group who had an anxiety disorder only.²⁴

High-dosage prescribing of opioids has fallen by 48% since 2011, yet the decline has not reduced overdose events of any kind.

To support successful opioid tapering, trauma-induced hyperalgesia, when present, must be addressed. Treatment of what the International Association for the Study of Pain calls “pain due to psychological factors”²² requires specific trauma therapy. However, our experience validates what researchers have to say about access to treatment of psychological trauma in the United States: “…[C]linical research has identified certain psychological interventions that effectively ameliorate the symptoms of PTSD. But most people struggling with PTSD don’t receive those treatments.”²⁵

We have no doubt that this is due, in part, to underdiagnosis of psychological trauma, even in mental health clinics. According to Miele and colleagues, “PTSD remains largely undiagnosed and undertreated in mental health outpatients, even in teaching hospitals, with diagnosis rates as low as 4% while published prevalence is between 7% and 50% in this population.”²⁶

3. Patients suffer from opioid use disorder (OUD) and complain of pain to obtain opioids by prescription. For patients with OUD, their use is out of control; they devote increasing mental and physical resources to obtaining, using, and recovering from substances; and they continue to use despite adverse consequences.²⁷ The prevalence of OUD in primary care clinics varies strikingly by the location of clinics. In Washington state, the prevalence of moderate and severe OUD in a large population of patients who had been prescribed opioids through primary care clinics was recently determined to be between 21.5% and 23.9%.¹³

4. Patients are obtaining opioid prescriptions for people other than themselves. While this is a reason that patients obtain opioid prescriptions, it is not necessarily common. Statistics show that the likelihood of a prescription being diverted intentionally is low: Dart and colleagues found that diversion has become uncommon in the general population.²⁸

Continue to: Why we taper opioid analgesics

 

 

Why we taper opioid analgesics

Reasons for an opioid taper include concern that the patient has, or will develop, an OUD; will experience accidental or intentional overdose; might be diverting opioids; is not benefiting from opioid therapy for pain; or is experiencing severe adverse effects. A patient who has nociceptive pain and might have ­opioid-induced hyperalgesia will require a much different opioid taper plan than a patient with untreated PTSD or a patient with severe OUD.

Misunderstanding can lead to inappropriate tapering

We often encounter primary care providers who believe that a large percentage of patients on chronic opioid therapy inevitably develop OUD. This is a common reason for initiating opioid taper. Most patients on a chronic opioid do become physically dependent, but only a small percentage of patients develop psychological dependence (ie, ­addiction or OUD).²⁹

Physical dependence is “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 blood level of the drug, and/or administration of an antagonist.”³⁰ Symptoms of opioid withdrawal include muscle aches; abdominal cramping; increased lacrimation, rhinorrhea, and perspiration; diarrhea; agitation and anxiety; insomnia; and piloerection. Opioid withdrawal symptoms are caused by physical dependence, not by addiction. They can be mitigated by tapering slowly and instituting adjuvant medications, such as clonidine, to attenuate symptoms.

Psychological dependence, or addiction (that is, OUD, as described in the Diagnostic and Statistical Manual of Mental Disorders 5th edition²⁷), comprises primarily 3 behavioral criteria:

• Loss of control of the medication, with compulsive use
• Continued use despite adverse consequences of using opioids, such as arrest for driving under the influence and deterioration of social, family, or work performance
• Obsession or preoccupation with obtaining and using the substance. In properly selected chronic opioid therapy patients, there is evidence that new-onset OUD is not as common as has been thought. A recent study of the risk for opioid addiction after use of an opioid for ≥ 90 days for chronic noncancer pain found that the absolute rate of de novo OUD among patients treated for 90 days was 0.72%.²⁹ A systematic review by Fishbain and colleagues of 24 studies of opioid-exposed patients found a risk of 3.27% overall—0.19% for patients who did not have a history of abuse or addiction.³¹ As Director of the National Institute on Drug Abuse Norma Volkow, MD, wrote in 2016: “Addiction occurs in only a small percentage of people who are exposed to opioids—even among those with preexisting vulnerabilities.”³²

Assessment should focus on why the patient is taking an opioid

A strong case can be made that less opioid is better for many of the people for whom these medications are prescribed for chronic noncancer pain. However, a one-size-fits-all dosage reduction and addiction-focused ­approach to opioid tapering has not worked: The assessment and treatment paradigm must change, in our view.

Continue to: During assessment...

 

During assessment, we must adopt the means to identify the reason that a patient is using a prescription opioid. It is of particular importance that we identify patients using opioids for their psychotropic properties, particularly when the goal is to cope with the effects of psychological trauma. The subsequent treatment protocol will then need to include time for effective, evidence-based behavioral health treatment of anxiety, PTSD, or depression. If opioids are serving primarily as psychotropic medication, an attempt to taper before establishing effective behavioral health treatment might lead the patient to pursue illegal means of procuring opioid medication.

Antianxiety and antidepressant effects of opioids are a significant reason that patients persist in requesting prescriptions.

We acknowledge that primary care physicians are not reimbursed for trauma screening and that evidence-based intensive trauma treatment is generally unavailable in the United States. Both of these shortcomings must be corrected if we want to stem the opioid crisis.

If diversion is suspected and there is evidence that the patient is not currently taking prescribed opioids (eg, a negative urine drug screen), discontinuing the opioid prescription is the immediate next step for the sake of public safety.

Considering a taper? Take this 5-step approach

Once it appears that tapering an opioid is indicated, we propose that you take the following steps:

• Establish whether it is safe to continue prescribing (follow the route provided in “2 decisions to make before continuing to prescribe an opioid for chronic noncancer pain”); if continuing it is not safe, take steps to protect the patient and the community
• Determine whether assessment by a trauma-informed behavioral health expert is needed, assuming that, in your judgment, it is safe to continue the opioid (TABLE³³). When behavioral health assessment is needed, you need 3 questions answered by that assessment: (1) Are psychological factors present that might put the patient at risk during an opioid taper? (2) What are those factors? (3) What needs to done about them before the taper is started? Recalling that psychological trauma often is not assessed by behavioral health colleagues, it is necessary to provide the behavioral health provider with a specific request to assess trauma burden, and state the physical diagnoses that are causing pain or provide a clear statement that no such diagnoses can be made. (See the FIGURE, which we developed in conjunction with behavioral health colleagues to help the consultant understand what the primary care physician needs from a behavioral health assessment.)
• Obtain consultation from a physical therapist, pain medicine specialist, and, if possible, an alternative or complementary medicine provider to determine what nonpharmacotherapeutic modalities can be instituted to treat pain before tapering the opioid.
• Initiate the Screening, Brief Intervention and Referral to Treatment (SBIRT) approach if OUD is suspected (www.samhsa.gov/sbirt).³⁴ This motivational interviewing tool identifies patients with a substance use disorder, severity of use, and appropriate level of treatment. (If OUD is suspected during assessment, next steps are to stop prescribing and implement harm-reduction strategies, such as primary care level medically assisted treatment [MAT] with buprenorphine, followed by expert behavioral health-centered addiction treatment.)
• Experiment with dosage reduction according to published guidance, if (1) psychological factors are absent or have been adequately addressed, according to the behavioral health consultant, and (2) nonpharmacotherapeutic strategies are in place.^8-11

Shifting to a patient-centered approach

The timing and choice of opioid tapers, in relation to harm reduction and intervention targeting the root cause of a patient’s complaint of pain, have not been adequately explored. In our practice, we’ve shifted from an addiction-centered, dosage-centered approach to opioid taper to a patient-centered approach³⁵ that emphasizes behavioral-medical integration—an approach that we broadly endorse. Such an approach (1) is based on a clear understanding of why the patient is taking opioid pain medication, (2) engages medical and complementary or alternative medicine specialists, (3) addresses underdiagnosis of psychological trauma, and (4) requires a quantum leap in access to trauma-specific behavioral health treatment resources. ³⁶

Continue to: To underscore the case...

 

To underscore the case for shifting to a patient-centered approach³⁵ we present sample cases in “How a patient-centered approach to tapering opioids looks in practice.”

An eye toward the future. To inform future approaches to opioid tapering, more resources need to be deployed to

• support screening and risk stratification for PTSD, anxiety, and related disorders at the primary care level,
• continue the effort to identify and treat OUD,
• develop best-practice responses to screening, and
• make harm-reduction strategies that are now reserved for patients with OUD available to those who don't have OUD.

We urge that research be pursued into best practices for chronic pain interventions that target psychological trauma, anxiety, and depression.

CORRESPONDENCE
Bennet Davis MD, 2092 East Calle de Dulcinea, Tucson, AZ 85718; [email protected].

Many Americans who are treated with prescription opioid analgesics would be better off with less opioid or none at all. To that end, published opioid prescribing guidelines do provide guidance on the mechanics of tapering patients off opioids^1-4—but they have a major flaw: They do not adequately account for the fact that people who have a diagnosis of chronic pain are a heterogeneous group and require diagnosis-specific treatment planning. A patient-centered approach to opioid tapers must account for the reality that many people who are given a prescription for an opioid to treat pain have significant mental health conditions—for which opioids act as a psychotropic agent. An opioid taper must therefore address psychological trauma, in particular.⁵ (See “Tapering and harm-reduction strategies have failed.”^6-14)

In this article, we present an evidence-based consensus approach to opioid tapering for your practice that is informed by a broader understanding of why patients take prescription opioids and why they, occasionally, switch to illicit drugs when their prescription is tapered. This consensus approach is based on the experience of the authors, members of the pain faculty of Project ECHO (Extension for Community Healthcare Outcomes) of the ECHO Institute, a worldwide initiative that uses adult learning techniques and interactive video technology to connect community providers with specialists at centers of excellence in regular real-time collaborative sessions. We are variously experts in pain medicine, primary care, psychology, addiction medicine, pharmacy, behavioral health therapy, occupational medicine, and Chinese medicine.

Why Americans obtain prescription opioids

There are 4 principal reasons why patients obtain prescription opioids, beyond indicated analgesic uses:

1. Patients seek the antianxiety and antidepressant effects of opioids. Multiple converging lines of evidence suggest that antianxiety and antidepressant effects of opioids are a significant reason that patients in the United States persist in requesting prescriptions for opioids:

• In our experience with more than 500 primary care telemedicine case presentations, at least 50% of patients say that the main effect of opioids prescribed for them is “it makes me feel calm” or “more relaxed.”
• In a 2007 survey of 91,823 US residents older than 18 years, nonmedical use of opioids was statistically associated with panic, social anxiety, and depressive symptoms.¹⁵
• Ten years later, Von Korff and colleagues found that more than half of opioid prescriptions written in the United States were for the small percentage of patients who have a diagnosis of serious anxiety or depression.¹³
• In 2016, Yovell and colleagues reported that ultra-low-dosage buprenorphine markedly reduced suicidal ideation over 4 weeks in 62 patients with varied levels of depression.¹⁶

There is also mechanistic evidence that the antianxiety and antidepressant effects of opioids are significant reasons Americans persist in requesting prescription opioids. The literature suggests that opioid receptors play a role in mood regulation, including alleviation of depression and anxiety; recent research suggests that oxycodone might be a unique mood-altering drug compared to other common prescription opioids because of its ability to affect mood through the δ opioid receptor.^17-20

It should not be a surprise that Americans often turn to opioids to address posttraumatic stress disorder (PTSD), anxiety, and depression. A recent study of the state of the US mental health system concluded that mental health services in the United States are inadequate—despite evidence that > 50% of Americans seek, or consider seeking, treatment for mental health problems for themselves or others.²¹

2. Patients experience pain unrelated to tissue damage. Rather, they are in pain “for psychological reasons.”²² In 2016, Davis and Vanderah wrote: “We theorize that a functional change in the [central nervous system] can occur in response to certain emotional states or traumatic experiences (eg, child abuse, assault, accidents).” They connect this change to central sensitization and a reduced pain-perception threshold,²³ and strongly suspect that many patients with chronic pain have undiagnosed and untreated psychological trauma that has changed the way their central nervous system processes sensory stimuli. The authors call this “trauma-induced hyperalgesia.”

Continue to: Psychological trauma...

 

Psychological trauma is uniquely capable of producing hyperalgesia, compared to anxiety or depression. In a study of veterans, Defrin and colleagues demonstrated hyperalgesia in patients who had a diagnosis of PTSD but not in controls group who had an anxiety disorder only.²⁴

High-dosage prescribing of opioids has fallen by 48% since 2011, yet the decline has not reduced overdose events of any kind.

To support successful opioid tapering, trauma-induced hyperalgesia, when present, must be addressed. Treatment of what the International Association for the Study of Pain calls “pain due to psychological factors”²² requires specific trauma therapy. However, our experience validates what researchers have to say about access to treatment of psychological trauma in the United States: “…[C]linical research has identified certain psychological interventions that effectively ameliorate the symptoms of PTSD. But most people struggling with PTSD don’t receive those treatments.”²⁵

We have no doubt that this is due, in part, to underdiagnosis of psychological trauma, even in mental health clinics. According to Miele and colleagues, “PTSD remains largely undiagnosed and undertreated in mental health outpatients, even in teaching hospitals, with diagnosis rates as low as 4% while published prevalence is between 7% and 50% in this population.”²⁶

3. Patients suffer from opioid use disorder (OUD) and complain of pain to obtain opioids by prescription. For patients with OUD, their use is out of control; they devote increasing mental and physical resources to obtaining, using, and recovering from substances; and they continue to use despite adverse consequences.²⁷ The prevalence of OUD in primary care clinics varies strikingly by the location of clinics. In Washington state, the prevalence of moderate and severe OUD in a large population of patients who had been prescribed opioids through primary care clinics was recently determined to be between 21.5% and 23.9%.¹³

4. Patients are obtaining opioid prescriptions for people other than themselves. While this is a reason that patients obtain opioid prescriptions, it is not necessarily common. Statistics show that the likelihood of a prescription being diverted intentionally is low: Dart and colleagues found that diversion has become uncommon in the general population.²⁸

Continue to: Why we taper opioid analgesics

 

 

Why we taper opioid analgesics

Reasons for an opioid taper include concern that the patient has, or will develop, an OUD; will experience accidental or intentional overdose; might be diverting opioids; is not benefiting from opioid therapy for pain; or is experiencing severe adverse effects. A patient who has nociceptive pain and might have ­opioid-induced hyperalgesia will require a much different opioid taper plan than a patient with untreated PTSD or a patient with severe OUD.

Misunderstanding can lead to inappropriate tapering

We often encounter primary care providers who believe that a large percentage of patients on chronic opioid therapy inevitably develop OUD. This is a common reason for initiating opioid taper. Most patients on a chronic opioid do become physically dependent, but only a small percentage of patients develop psychological dependence (ie, ­addiction or OUD).²⁹

Physical dependence is “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 blood level of the drug, and/or administration of an antagonist.”³⁰ Symptoms of opioid withdrawal include muscle aches; abdominal cramping; increased lacrimation, rhinorrhea, and perspiration; diarrhea; agitation and anxiety; insomnia; and piloerection. Opioid withdrawal symptoms are caused by physical dependence, not by addiction. They can be mitigated by tapering slowly and instituting adjuvant medications, such as clonidine, to attenuate symptoms.

Psychological dependence, or addiction (that is, OUD, as described in the Diagnostic and Statistical Manual of Mental Disorders 5th edition²⁷), comprises primarily 3 behavioral criteria:

• Loss of control of the medication, with compulsive use
• Continued use despite adverse consequences of using opioids, such as arrest for driving under the influence and deterioration of social, family, or work performance
• Obsession or preoccupation with obtaining and using the substance. In properly selected chronic opioid therapy patients, there is evidence that new-onset OUD is not as common as has been thought. A recent study of the risk for opioid addiction after use of an opioid for ≥ 90 days for chronic noncancer pain found that the absolute rate of de novo OUD among patients treated for 90 days was 0.72%.²⁹ A systematic review by Fishbain and colleagues of 24 studies of opioid-exposed patients found a risk of 3.27% overall—0.19% for patients who did not have a history of abuse or addiction.³¹ As Director of the National Institute on Drug Abuse Norma Volkow, MD, wrote in 2016: “Addiction occurs in only a small percentage of people who are exposed to opioids—even among those with preexisting vulnerabilities.”³²

Assessment should focus on why the patient is taking an opioid

A strong case can be made that less opioid is better for many of the people for whom these medications are prescribed for chronic noncancer pain. However, a one-size-fits-all dosage reduction and addiction-focused ­approach to opioid tapering has not worked: The assessment and treatment paradigm must change, in our view.

Continue to: During assessment...

 

During assessment, we must adopt the means to identify the reason that a patient is using a prescription opioid. It is of particular importance that we identify patients using opioids for their psychotropic properties, particularly when the goal is to cope with the effects of psychological trauma. The subsequent treatment protocol will then need to include time for effective, evidence-based behavioral health treatment of anxiety, PTSD, or depression. If opioids are serving primarily as psychotropic medication, an attempt to taper before establishing effective behavioral health treatment might lead the patient to pursue illegal means of procuring opioid medication.

Antianxiety and antidepressant effects of opioids are a significant reason that patients persist in requesting prescriptions.

We acknowledge that primary care physicians are not reimbursed for trauma screening and that evidence-based intensive trauma treatment is generally unavailable in the United States. Both of these shortcomings must be corrected if we want to stem the opioid crisis.

If diversion is suspected and there is evidence that the patient is not currently taking prescribed opioids (eg, a negative urine drug screen), discontinuing the opioid prescription is the immediate next step for the sake of public safety.

Considering a taper? Take this 5-step approach

Once it appears that tapering an opioid is indicated, we propose that you take the following steps:

• Establish whether it is safe to continue prescribing (follow the route provided in “2 decisions to make before continuing to prescribe an opioid for chronic noncancer pain”); if continuing it is not safe, take steps to protect the patient and the community
• Determine whether assessment by a trauma-informed behavioral health expert is needed, assuming that, in your judgment, it is safe to continue the opioid (TABLE³³). When behavioral health assessment is needed, you need 3 questions answered by that assessment: (1) Are psychological factors present that might put the patient at risk during an opioid taper? (2) What are those factors? (3) What needs to done about them before the taper is started? Recalling that psychological trauma often is not assessed by behavioral health colleagues, it is necessary to provide the behavioral health provider with a specific request to assess trauma burden, and state the physical diagnoses that are causing pain or provide a clear statement that no such diagnoses can be made. (See the FIGURE, which we developed in conjunction with behavioral health colleagues to help the consultant understand what the primary care physician needs from a behavioral health assessment.)
• Obtain consultation from a physical therapist, pain medicine specialist, and, if possible, an alternative or complementary medicine provider to determine what nonpharmacotherapeutic modalities can be instituted to treat pain before tapering the opioid.
• Initiate the Screening, Brief Intervention and Referral to Treatment (SBIRT) approach if OUD is suspected (www.samhsa.gov/sbirt).³⁴ This motivational interviewing tool identifies patients with a substance use disorder, severity of use, and appropriate level of treatment. (If OUD is suspected during assessment, next steps are to stop prescribing and implement harm-reduction strategies, such as primary care level medically assisted treatment [MAT] with buprenorphine, followed by expert behavioral health-centered addiction treatment.)
• Experiment with dosage reduction according to published guidance, if (1) psychological factors are absent or have been adequately addressed, according to the behavioral health consultant, and (2) nonpharmacotherapeutic strategies are in place.^8-11

Shifting to a patient-centered approach

The timing and choice of opioid tapers, in relation to harm reduction and intervention targeting the root cause of a patient’s complaint of pain, have not been adequately explored. In our practice, we’ve shifted from an addiction-centered, dosage-centered approach to opioid taper to a patient-centered approach³⁵ that emphasizes behavioral-medical integration—an approach that we broadly endorse. Such an approach (1) is based on a clear understanding of why the patient is taking opioid pain medication, (2) engages medical and complementary or alternative medicine specialists, (3) addresses underdiagnosis of psychological trauma, and (4) requires a quantum leap in access to trauma-specific behavioral health treatment resources. ³⁶

Continue to: To underscore the case...

 

To underscore the case for shifting to a patient-centered approach³⁵ we present sample cases in “How a patient-centered approach to tapering opioids looks in practice.”

An eye toward the future. To inform future approaches to opioid tapering, more resources need to be deployed to

• support screening and risk stratification for PTSD, anxiety, and related disorders at the primary care level,
• continue the effort to identify and treat OUD,
• develop best-practice responses to screening, and
• make harm-reduction strategies that are now reserved for patients with OUD available to those who don't have OUD.

We urge that research be pursued into best practices for chronic pain interventions that target psychological trauma, anxiety, and depression.

CORRESPONDENCE
Bennet Davis MD, 2092 East Calle de Dulcinea, Tucson, AZ 85718; [email protected].

The care of people with pain has been wrought with ineffective and unnecessary treatment, including the misuse of opioids, largely because we do not have an accurate conceptualization of pain. The absence of animal and human models of central nervous system (CNS) pain processing ensures that our understanding of pain will remain incomplete for the foreseeable future, but enough evidence exists to help family physicians develop an understanding of pain that goes beyond what we learned in medical school and that can help us more effectively treat patients with pain.

In this review, we will briefly discuss the established concepts of nociceptive and neuropathic pain. And then, with those concepts in mind, we will explore a third type of pain that for lack of a better term, we will call “pain for psychological reasons.” We hypothesize that this pain may be the consequence of changes in nervous system function that arise from developmental trauma, other traumatic experiences in a patient’s life, or mental health disorders. It is this third type of pain that may offer us insights into conditions such as fibromyalgia.

While we do not yet have validated diagnostic criteria for this third type of pain, we believe that there is enough information to present initial criteria so that one may distinguish it from nociceptive and neuropathic pain.

Nociceptive and neuropathic pain: The current paradigm

Nociceptive pain. The sensory pain experience, or nociceptive pain, is produced by noxious stimuli that either damage, or are capable of damaging, tissues (eg, burns, cuts, fractures, inflammation, and increased pressure in a hollow viscus). Noxious stimuli are detected at the molecular level by specific pain sensory receptors embedded in our tissues called nociceptors.

The process by which noxious stimuli lead to the experience of sensory pain consists of 4 steps—transduction, transmission, modulation, and perception—which are described in “From periphery to brain: The process of nociceptive pain.”^1-4

Neuropathic pain. While nociceptive pain can be easily traced from a peripheral nociceptive fiber to the brain and typically resolves when the nociceptive stimulus stops, neuropathic pain (NPP) results from changes to the function of the nervous system and is typically caused by injury to the nerves. Such changes, referred to as neuronal sensitization, may not quickly resolve, as is the case with postherpetic neuralgia. In fact, the changes can become permanent. NPP fundamentally differs from nociceptive pain because it results from changes in the central processing of pain that can lead a person to perceive pain sensations even in the absence of tissue pathology.

This third type of pain may be the consequence of changes in nervous system function that arise from developmental trauma, other traumatic experiences in a patient's life, or mental health disorders.

Common causes of NPP that persists even after tissue damage has healed include trauma (eg, amputation of a limb), ischemia (eg, pressure palsy), disease (eg, the metabolic injury of diabetes or the injury caused by a shingles infection), and drug treatment (eg, chemotherapy). The underlying mechanisms of NPP and the neuronal plasticity (the ability of the nervous system to rewire itself) that initiate and then maintain NPP are important areas of active research that may eventually lead to the development of more effective treatments.

Timing is critical. Neuroplastic changes in the nervous system following nerve injury are time-dependent. Synaptic plasticity can occur within seconds to minutes, while cellular plasticity occurs within hours to days. Synaptic and cellular plasticity happen relatively fast and may be reversible.

 

In contrast, systems plasticity (when new CNS neuronal connections are formed in response to nerve injury) takes place over the months and years following nerve injury and is often irreversible. When we recognize NPP and intervene before system neuroplastic changes occur, it may be possible to prevent pain from becoming chronic (TABLE 1⁵). In cases of nerve injury, researchers have long suspected that early and aggressive pain treatment within the first few months that may include sympathetic and peripheral neural blockade reduces the likelihood that the patient will have chronic pain.^6,7

From this discussion, one can understand why pharmacotherapeutic agents such as antiepileptic drugs and some antidepressants are effective for treating the changes in nervous system pain processing that cause NPP, and why nerve blocks and neural stimulation—treatments that alter peripheral and central pain processing—might be effective for neuropathic but not acute or chronic nociceptive pain.

It’s time to update our understanding of pain

The International Association for the Study of Pain (IASP)—a group of health care providers, scientists, and policymakers seeking to improve pain relief worldwide—notes in its definition of pain that the complaint, “I hurt” does not necessarily imply that there is a painful stimulus in the form of tissue injury.⁸ Yet most of us have been taught to think of pain solely as the result of tissue pathology, and we assume that emotional factors merely modify how the physical damage is perceived. This traditional concept of pain is incomplete. It leads clinicians to misdiagnose the cause of pain, initiate expensive and unnecessary treatment, engage in well-meaning but misguided prescribing behavior, and miss opportunities to help patients.

 

Pain in the absence of any pathophysiologic cause or injury

The clinician’s search for a pain diagnosis is typically predicated on the notion that there must be an underlying tissue injury of severity equal to the severity of the patient’s pain complaints. This approach to a pain evaluation rests on 2 assumptions that are not true for all patients:

1. Pain is simply a sensory experience that is always caused by tissue damage of some type.
2. The severity of the pain experienced by a patient should be tightly bound to the severity of the pain stimulus (ie, tissue damage).

These assumptions are true of acute nociceptive pain, they may or may not be true for NPP, but they do not apply to the third type of pain—pain for psychological reasons. While tissue pathology in humans and animals with nociceptive pain is usually visible, measurable, and correlates with observed pain behaviors, the damage to nerve tissue and the ensuing changes in nervous system function with NPP are not always visible or able to be imaged. These changes produce pain that can appear more severe than expected based on a brief exam. Some of the time, however, characteristic symptoms and physical signs of NPP will be present, and perhaps electrodiagnostic or other tests will be abnormal, thus providing some objective sense of changes in nervous system function.

In contrast, pain behavior due to the third type of pain usually appears very much out of proportion, and unbound to, tissue pathology. Furthermore, the patient’s pain behaviors often reflect heightened emotional pain processing (TABLE 2⁹). The resulting emotionally charged presentation can be alarming and suggestive of extreme tissue injury, but there may be absolutely no evidence of tissue injury or pathology.

Functional change in the CNS

There is evidence from experimental studies that psychologic factors change nervous system function. In one review, the authors concluded, “Pain…can vary widely between people and even within an individual depending on…the psychological state of the person.”¹⁰ In a second review, the authors concluded that our emotional state has an enormous influence on pain; a negative emotional state increases pain, whereas a positive state lowers pain.¹¹

But can psychological factors induce long-term changes in nervous system function analogous to the systems neuroplasticity responsible for irreversible changes in NPP? And can psychologically induced changes in nervous system sensory processing lead to pain without any tissue or nerve damage?

We theorize that a functional change in the CNS can occur in response to certain emotional states or traumatic experiences (eg, child abuse, assault, accidents). (More on this in a bit.) When such changes occur, mildly painful stimuli are amplified and processed through overly sensitized, dysregulated, ramped-up emotional and somatosensory pain circuits in the brain. This is analogous to the functional changes in the nervous system that occur with NPP; however, when the nervous system changes are due to psychological factors, there may be no tissue or nerve injury.

 

Childhood trauma influences adult pain. One of the more compelling narratives emerging in health care has to do with the influence that childhood developmental trauma can have on health, including pain. In his chapter on the impact of early life trauma on health and disease, Lanius states:¹²

“Women were 50% more likely than men to have experienced 5 or more categories of adverse childhood experiences. We believe that here is a key to what in mainstream epidemiology appears as women’s natural proneness to ill-defined health problems like fibromyalgia, chronic fatigue syndrome, obesity, irritable bowel syndrome, and chronic non-malignant pain syndromes. In light of our findings, we now see these as medical constructs, artifacts resulting from medical blindness to social realities and ignorance of the impact of gender.”

Brain activity in response to emotional insult mimics physical pain, and it is difficult to tell from images of brain activity whether a person is experiencing one or the other.

Lanius¹² suggests that adverse childhood experiences¹³ (trauma such as abuse and sexual assault) can lead to long-term changes within the nervous system, including areas of pain processing. My coauthor and I describe these changes here in terms of nervous system sensitization or dysregulation, and we believe that these changes lead to a bias toward hyperactivation of emotional pain circuits, which leads to the emotionally laden pain behaviors that often seem out of proportion to tissue pathology.

The care of people with pain has been wrought with ineffective and unnecessary treatment, including the misuse of opioids, largely because we do not have an accurate conceptualization of pain. The absence of animal and human models of central nervous system (CNS) pain processing ensures that our understanding of pain will remain incomplete for the foreseeable future, but enough evidence exists to help family physicians develop an understanding of pain that goes beyond what we learned in medical school and that can help us more effectively treat patients with pain.

In this review, we will briefly discuss the established concepts of nociceptive and neuropathic pain. And then, with those concepts in mind, we will explore a third type of pain that for lack of a better term, we will call “pain for psychological reasons.” We hypothesize that this pain may be the consequence of changes in nervous system function that arise from developmental trauma, other traumatic experiences in a patient’s life, or mental health disorders. It is this third type of pain that may offer us insights into conditions such as fibromyalgia.

While we do not yet have validated diagnostic criteria for this third type of pain, we believe that there is enough information to present initial criteria so that one may distinguish it from nociceptive and neuropathic pain.

Nociceptive and neuropathic pain: The current paradigm

Nociceptive pain. The sensory pain experience, or nociceptive pain, is produced by noxious stimuli that either damage, or are capable of damaging, tissues (eg, burns, cuts, fractures, inflammation, and increased pressure in a hollow viscus). Noxious stimuli are detected at the molecular level by specific pain sensory receptors embedded in our tissues called nociceptors.

The process by which noxious stimuli lead to the experience of sensory pain consists of 4 steps—transduction, transmission, modulation, and perception—which are described in “From periphery to brain: The process of nociceptive pain.”^1-4

Neuropathic pain. While nociceptive pain can be easily traced from a peripheral nociceptive fiber to the brain and typically resolves when the nociceptive stimulus stops, neuropathic pain (NPP) results from changes to the function of the nervous system and is typically caused by injury to the nerves. Such changes, referred to as neuronal sensitization, may not quickly resolve, as is the case with postherpetic neuralgia. In fact, the changes can become permanent. NPP fundamentally differs from nociceptive pain because it results from changes in the central processing of pain that can lead a person to perceive pain sensations even in the absence of tissue pathology.

This third type of pain may be the consequence of changes in nervous system function that arise from developmental trauma, other traumatic experiences in a patient's life, or mental health disorders.

Common causes of NPP that persists even after tissue damage has healed include trauma (eg, amputation of a limb), ischemia (eg, pressure palsy), disease (eg, the metabolic injury of diabetes or the injury caused by a shingles infection), and drug treatment (eg, chemotherapy). The underlying mechanisms of NPP and the neuronal plasticity (the ability of the nervous system to rewire itself) that initiate and then maintain NPP are important areas of active research that may eventually lead to the development of more effective treatments.

Timing is critical. Neuroplastic changes in the nervous system following nerve injury are time-dependent. Synaptic plasticity can occur within seconds to minutes, while cellular plasticity occurs within hours to days. Synaptic and cellular plasticity happen relatively fast and may be reversible.

 

In contrast, systems plasticity (when new CNS neuronal connections are formed in response to nerve injury) takes place over the months and years following nerve injury and is often irreversible. When we recognize NPP and intervene before system neuroplastic changes occur, it may be possible to prevent pain from becoming chronic (TABLE 1⁵). In cases of nerve injury, researchers have long suspected that early and aggressive pain treatment within the first few months that may include sympathetic and peripheral neural blockade reduces the likelihood that the patient will have chronic pain.^6,7

From this discussion, one can understand why pharmacotherapeutic agents such as antiepileptic drugs and some antidepressants are effective for treating the changes in nervous system pain processing that cause NPP, and why nerve blocks and neural stimulation—treatments that alter peripheral and central pain processing—might be effective for neuropathic but not acute or chronic nociceptive pain.

It’s time to update our understanding of pain

The International Association for the Study of Pain (IASP)—a group of health care providers, scientists, and policymakers seeking to improve pain relief worldwide—notes in its definition of pain that the complaint, “I hurt” does not necessarily imply that there is a painful stimulus in the form of tissue injury.⁸ Yet most of us have been taught to think of pain solely as the result of tissue pathology, and we assume that emotional factors merely modify how the physical damage is perceived. This traditional concept of pain is incomplete. It leads clinicians to misdiagnose the cause of pain, initiate expensive and unnecessary treatment, engage in well-meaning but misguided prescribing behavior, and miss opportunities to help patients.

 

Pain in the absence of any pathophysiologic cause or injury

The clinician’s search for a pain diagnosis is typically predicated on the notion that there must be an underlying tissue injury of severity equal to the severity of the patient’s pain complaints. This approach to a pain evaluation rests on 2 assumptions that are not true for all patients:

1. Pain is simply a sensory experience that is always caused by tissue damage of some type.
2. The severity of the pain experienced by a patient should be tightly bound to the severity of the pain stimulus (ie, tissue damage).

These assumptions are true of acute nociceptive pain, they may or may not be true for NPP, but they do not apply to the third type of pain—pain for psychological reasons. While tissue pathology in humans and animals with nociceptive pain is usually visible, measurable, and correlates with observed pain behaviors, the damage to nerve tissue and the ensuing changes in nervous system function with NPP are not always visible or able to be imaged. These changes produce pain that can appear more severe than expected based on a brief exam. Some of the time, however, characteristic symptoms and physical signs of NPP will be present, and perhaps electrodiagnostic or other tests will be abnormal, thus providing some objective sense of changes in nervous system function.

In contrast, pain behavior due to the third type of pain usually appears very much out of proportion, and unbound to, tissue pathology. Furthermore, the patient’s pain behaviors often reflect heightened emotional pain processing (TABLE 2⁹). The resulting emotionally charged presentation can be alarming and suggestive of extreme tissue injury, but there may be absolutely no evidence of tissue injury or pathology.

Functional change in the CNS

There is evidence from experimental studies that psychologic factors change nervous system function. In one review, the authors concluded, “Pain…can vary widely between people and even within an individual depending on…the psychological state of the person.”¹⁰ In a second review, the authors concluded that our emotional state has an enormous influence on pain; a negative emotional state increases pain, whereas a positive state lowers pain.¹¹

But can psychological factors induce long-term changes in nervous system function analogous to the systems neuroplasticity responsible for irreversible changes in NPP? And can psychologically induced changes in nervous system sensory processing lead to pain without any tissue or nerve damage?

We theorize that a functional change in the CNS can occur in response to certain emotional states or traumatic experiences (eg, child abuse, assault, accidents). (More on this in a bit.) When such changes occur, mildly painful stimuli are amplified and processed through overly sensitized, dysregulated, ramped-up emotional and somatosensory pain circuits in the brain. This is analogous to the functional changes in the nervous system that occur with NPP; however, when the nervous system changes are due to psychological factors, there may be no tissue or nerve injury.

 

Childhood trauma influences adult pain. One of the more compelling narratives emerging in health care has to do with the influence that childhood developmental trauma can have on health, including pain. In his chapter on the impact of early life trauma on health and disease, Lanius states:¹²

“Women were 50% more likely than men to have experienced 5 or more categories of adverse childhood experiences. We believe that here is a key to what in mainstream epidemiology appears as women’s natural proneness to ill-defined health problems like fibromyalgia, chronic fatigue syndrome, obesity, irritable bowel syndrome, and chronic non-malignant pain syndromes. In light of our findings, we now see these as medical constructs, artifacts resulting from medical blindness to social realities and ignorance of the impact of gender.”

Brain activity in response to emotional insult mimics physical pain, and it is difficult to tell from images of brain activity whether a person is experiencing one or the other.

Lanius¹² suggests that adverse childhood experiences¹³ (trauma such as abuse and sexual assault) can lead to long-term changes within the nervous system, including areas of pain processing. My coauthor and I describe these changes here in terms of nervous system sensitization or dysregulation, and we believe that these changes lead to a bias toward hyperactivation of emotional pain circuits, which leads to the emotionally laden pain behaviors that often seem out of proportion to tissue pathology.

The care of people with pain has been wrought with ineffective and unnecessary treatment, including the misuse of opioids, largely because we do not have an accurate conceptualization of pain. The absence of animal and human models of central nervous system (CNS) pain processing ensures that our understanding of pain will remain incomplete for the foreseeable future, but enough evidence exists to help family physicians develop an understanding of pain that goes beyond what we learned in medical school and that can help us more effectively treat patients with pain.

In this review, we will briefly discuss the established concepts of nociceptive and neuropathic pain. And then, with those concepts in mind, we will explore a third type of pain that for lack of a better term, we will call “pain for psychological reasons.” We hypothesize that this pain may be the consequence of changes in nervous system function that arise from developmental trauma, other traumatic experiences in a patient’s life, or mental health disorders. It is this third type of pain that may offer us insights into conditions such as fibromyalgia.

While we do not yet have validated diagnostic criteria for this third type of pain, we believe that there is enough information to present initial criteria so that one may distinguish it from nociceptive and neuropathic pain.

Nociceptive and neuropathic pain: The current paradigm

Nociceptive pain. The sensory pain experience, or nociceptive pain, is produced by noxious stimuli that either damage, or are capable of damaging, tissues (eg, burns, cuts, fractures, inflammation, and increased pressure in a hollow viscus). Noxious stimuli are detected at the molecular level by specific pain sensory receptors embedded in our tissues called nociceptors.

The process by which noxious stimuli lead to the experience of sensory pain consists of 4 steps—transduction, transmission, modulation, and perception—which are described in “From periphery to brain: The process of nociceptive pain.”^1-4

Neuropathic pain. While nociceptive pain can be easily traced from a peripheral nociceptive fiber to the brain and typically resolves when the nociceptive stimulus stops, neuropathic pain (NPP) results from changes to the function of the nervous system and is typically caused by injury to the nerves. Such changes, referred to as neuronal sensitization, may not quickly resolve, as is the case with postherpetic neuralgia. In fact, the changes can become permanent. NPP fundamentally differs from nociceptive pain because it results from changes in the central processing of pain that can lead a person to perceive pain sensations even in the absence of tissue pathology.

This third type of pain may be the consequence of changes in nervous system function that arise from developmental trauma, other traumatic experiences in a patient's life, or mental health disorders.

Common causes of NPP that persists even after tissue damage has healed include trauma (eg, amputation of a limb), ischemia (eg, pressure palsy), disease (eg, the metabolic injury of diabetes or the injury caused by a shingles infection), and drug treatment (eg, chemotherapy). The underlying mechanisms of NPP and the neuronal plasticity (the ability of the nervous system to rewire itself) that initiate and then maintain NPP are important areas of active research that may eventually lead to the development of more effective treatments.

Timing is critical. Neuroplastic changes in the nervous system following nerve injury are time-dependent. Synaptic plasticity can occur within seconds to minutes, while cellular plasticity occurs within hours to days. Synaptic and cellular plasticity happen relatively fast and may be reversible.

 

In contrast, systems plasticity (when new CNS neuronal connections are formed in response to nerve injury) takes place over the months and years following nerve injury and is often irreversible. When we recognize NPP and intervene before system neuroplastic changes occur, it may be possible to prevent pain from becoming chronic (TABLE 1⁵). In cases of nerve injury, researchers have long suspected that early and aggressive pain treatment within the first few months that may include sympathetic and peripheral neural blockade reduces the likelihood that the patient will have chronic pain.^6,7

From this discussion, one can understand why pharmacotherapeutic agents such as antiepileptic drugs and some antidepressants are effective for treating the changes in nervous system pain processing that cause NPP, and why nerve blocks and neural stimulation—treatments that alter peripheral and central pain processing—might be effective for neuropathic but not acute or chronic nociceptive pain.

It’s time to update our understanding of pain

The International Association for the Study of Pain (IASP)—a group of health care providers, scientists, and policymakers seeking to improve pain relief worldwide—notes in its definition of pain that the complaint, “I hurt” does not necessarily imply that there is a painful stimulus in the form of tissue injury.⁸ Yet most of us have been taught to think of pain solely as the result of tissue pathology, and we assume that emotional factors merely modify how the physical damage is perceived. This traditional concept of pain is incomplete. It leads clinicians to misdiagnose the cause of pain, initiate expensive and unnecessary treatment, engage in well-meaning but misguided prescribing behavior, and miss opportunities to help patients.

 

Pain in the absence of any pathophysiologic cause or injury

The clinician’s search for a pain diagnosis is typically predicated on the notion that there must be an underlying tissue injury of severity equal to the severity of the patient’s pain complaints. This approach to a pain evaluation rests on 2 assumptions that are not true for all patients:

1. Pain is simply a sensory experience that is always caused by tissue damage of some type.
2. The severity of the pain experienced by a patient should be tightly bound to the severity of the pain stimulus (ie, tissue damage).

These assumptions are true of acute nociceptive pain, they may or may not be true for NPP, but they do not apply to the third type of pain—pain for psychological reasons. While tissue pathology in humans and animals with nociceptive pain is usually visible, measurable, and correlates with observed pain behaviors, the damage to nerve tissue and the ensuing changes in nervous system function with NPP are not always visible or able to be imaged. These changes produce pain that can appear more severe than expected based on a brief exam. Some of the time, however, characteristic symptoms and physical signs of NPP will be present, and perhaps electrodiagnostic or other tests will be abnormal, thus providing some objective sense of changes in nervous system function.

In contrast, pain behavior due to the third type of pain usually appears very much out of proportion, and unbound to, tissue pathology. Furthermore, the patient’s pain behaviors often reflect heightened emotional pain processing (TABLE 2⁹). The resulting emotionally charged presentation can be alarming and suggestive of extreme tissue injury, but there may be absolutely no evidence of tissue injury or pathology.

Functional change in the CNS

There is evidence from experimental studies that psychologic factors change nervous system function. In one review, the authors concluded, “Pain…can vary widely between people and even within an individual depending on…the psychological state of the person.”¹⁰ In a second review, the authors concluded that our emotional state has an enormous influence on pain; a negative emotional state increases pain, whereas a positive state lowers pain.¹¹

But can psychological factors induce long-term changes in nervous system function analogous to the systems neuroplasticity responsible for irreversible changes in NPP? And can psychologically induced changes in nervous system sensory processing lead to pain without any tissue or nerve damage?

We theorize that a functional change in the CNS can occur in response to certain emotional states or traumatic experiences (eg, child abuse, assault, accidents). (More on this in a bit.) When such changes occur, mildly painful stimuli are amplified and processed through overly sensitized, dysregulated, ramped-up emotional and somatosensory pain circuits in the brain. This is analogous to the functional changes in the nervous system that occur with NPP; however, when the nervous system changes are due to psychological factors, there may be no tissue or nerve injury.

 

Childhood trauma influences adult pain. One of the more compelling narratives emerging in health care has to do with the influence that childhood developmental trauma can have on health, including pain. In his chapter on the impact of early life trauma on health and disease, Lanius states:¹²

“Women were 50% more likely than men to have experienced 5 or more categories of adverse childhood experiences. We believe that here is a key to what in mainstream epidemiology appears as women’s natural proneness to ill-defined health problems like fibromyalgia, chronic fatigue syndrome, obesity, irritable bowel syndrome, and chronic non-malignant pain syndromes. In light of our findings, we now see these as medical constructs, artifacts resulting from medical blindness to social realities and ignorance of the impact of gender.”

Brain activity in response to emotional insult mimics physical pain, and it is difficult to tell from images of brain activity whether a person is experiencing one or the other.

Lanius¹² suggests that adverse childhood experiences¹³ (trauma such as abuse and sexual assault) can lead to long-term changes within the nervous system, including areas of pain processing. My coauthor and I describe these changes here in terms of nervous system sensitization or dysregulation, and we believe that these changes lead to a bias toward hyperactivation of emotional pain circuits, which leads to the emotionally laden pain behaviors that often seem out of proportion to tissue pathology.