# Presentation: 045149

## Epidemiology of Chronic Non-Cancer Pain and its Treatment with Opioids

- Mark Sullivan, MD, PhD
- University of Washington

**Notes:**
Frida Kahlo; A Few Small Nips 1935. She had chronic pain after a 1925 bus accident that nearly killed her. Fracturing her right leg and pelvis.
'I suffered two grave accidents in my life. One in which a streetcar knocked me down... The other accident is Diego.' 
A Few Small Nips
1935 
Broken-hearted over her husband's affair with her younger sister Cristina, Frida recreated her sorrow and anger in this painting. Her own pain being too great to depict, she projected it onto another woman's misfortune. A newspaper report about a woman murdered in an act of jealousy provided the artist with the subject matter for this work. The murderer defended his actions before the judge by saying: "But it was just a few small nips!" The violent deed makes symbolic reference to Frida's own mental state and her own emotional injuries. The banner held by love doves, of all things, bears the painting's title. One dove is black, the other white, alluding perhaps to the light and dark sides of love

## “We are threatened with suffering from three directions: from our own body, which is doomed to decay and  dissolution and which cannot do without pain and anxiety as warning signals; from the external world, which may rage at us with overwhelming and merciless forces of destruction; and finally from our relations to other men. The suffering which comes from this last source is perhaps more painful than any other.”--Sigmund Freud, Civilization and its Discontents

**Notes:**
1] death and dying- focus of most work in pain ethics
2] injury and disease- where most success at pain control and pain QI has come
3] The most difficult clinically and ethically

## Slide 3

**Notes:**

NB lower rates of pain, but greater rates of chronicity in the group >65. Perhaps related to countervailing physical health (more degenerative disease) and mental health (fewer severe mental disorders) trends.
Data from the 1999–2002 National Health and Nutrition Examination Survey show that more than one-quarter of Americans (26%) age 20 years and over reported that they
had a problem with pain—of any sort—that persisted for more than 24 hours in duration in the month prior to interview (Figure 28). Adults age 45–64 years were the most likely to
report pain lasting more than 24 hours (30%). Twenty-five percent of young adults age 20–44 reported pain, and adults age 65 years and over were the least likely to report pain
(21%). Women reported pain more often than men, and non-Hispanic white adults reported pain more often than adults of other races and ethnicities. Adults living in families
with income less than twice the poverty level reported pain more often than higher income adults.
Adults 20 years of age and over who reported pain in the month prior to interview (Figure 28) were asked a follow-up question about the duration of that pain. Nearly one-third of
adults 20 years of age and over who reported pain said that it lasted less than 1 month, 12% reported pain that lasted 1–3 months, 14% reported pain that lasted 3 months to 1
year, and 42% reported pain that lasted more than 1 year(data table for Figure 29). Although persons age 65 years and over are less likely to report pain lasting 24 hours or more,
57% of older adults who reported pain indicated that the pain lasted for more than 1 year compared with 37% of adults 20–44 years of age who reported pain (Figure 29).
Conversely, adults 20–44 years were considerably more likely to report relatively short-lived pain. Therefore the duration of pain (long- or short-lived) reported by different age groups
may explain, in part, differences in pain reporting and pain prevalence by age. 
‘‘DURING THE PAST MONTH, (have you/has sampled adult) had a problem with pain that lasted more than 24 hours?’’ For people who responded ‘‘yes’’ to this question, a follow-up question was asked: ‘‘For how long (have you/has sample adult) experienced this pain? Would you say . . .
1 = Less than a month,
2 = At least 1 month but less than 3 months,
3 = At least 3 months but less than 1 year, or
4 = Greater than 1 year?
7 = Refused
9 = Don’t know’’

## Slide 4

**Notes:**
In the National Health Interview Survey, adults 18 years of age and over were asked a series of questions about whether they have had four types of pain during the 3 months prior to interview (low back, migraine/severe headache, neck, and facial ache in the jaw or joint in front of the ear). Respondents were instructed to report pain that lasted a whole day or more and not to include minor aches or pains. Respondents could report more than one type of pain and were included in each reported category. Trends in the percentage of Americans reporting each of these types of pain have been stable in recent years (Table 56).
NHANES (1988-94) LBP of at least a month 18%; UK 22% vs 45% Germany

## Slide 5

**Notes:**
Significant effect of even a day of LBP on health status. 2/3 of American suffer from LBP at some time. point prevalence as high as 33% and a one-year prevalence as high as 73% Acute low back pain usually resolves in several weeks, although recurrences are common and low-grade symptoms are often present years after an initial episode. Serious or persistent disability is uncommon even among those with low back pain lasting more than three months. But it is still the most common cause of work-related disability in people under 45 years of age and the most expensive cause of work-related disability, in terms of workers’ compensation and medical expenses. Causes not revealed on imaging for 80% of LBP cases. There is no cure for these.

In the National Health Interview Survey, adult respondents were asked about low back pain in the 3 months prior to interview. Respondents were instructed to report low back pain that lasted a whole day or more and not to include minor aches or pains. Additional questions included respondent-assessed health status, activity limitation due to chronic health conditions, and a series of questions designed to assess serious psychological distress (See Appendix II, Health status, respondent-assessed; Limitation of activity; Serious psychological distress The K6 is designed to identify persons with serious psychological distress using as few questions as possible.
The six items included in the K6 are as follows:
During the past 30 days, how often did you feel . . .
so sad that nothing could cheer you up?
nervous?
restless or fidgety?
hopeless?
that everything was an effort?
worthless?
Possible answers are all of the time (4 points), most of the
time (3 points), some of the time (2 points), a little of the time
(1 point), and none of the time (0 points).
To score the K6, the points are added together yielding a
possible total of 0 to 24 points. A threshold of 13 or more is
used to define serious psychological distress. Persons
answering some of the time to all six questions would not
reach the threshold for serious psychological distress,
because to achieve a score of 13 they would need to answer
most of the time to at least one item.
For more information, see Kessler RC, Barker PR, Colpe LJ, et al. Screening for serious mental illness in the general population. Arch Gen Psychiatry 2003; 60:184–189.).
In 2004, adults who reported low back pain lasting more than 24 hours during the past 3 months reported worse health status, using a number of different measures, than people
who did not report recent low back pain, regardless of age (Figure 37). Overall, 28% of adults with low back pain said they had a limitation of activity caused by a chronic condition,
compared with 10% of adults who did not report low back pain. Adults with recent low back pain were about three times as likely to report fair or poor health status and more than
four times as likely to experience serious psychological distress as people without low back pain. Within each age group, adults with low back pain reported
worse health status than those without low back pain. For example, among adults 65 years and over more than one-half who reported recent low back pain had a limitation in their
usual activity compared with 27% without recent low back pain, and 40% with recent low back pain rated their health as fair or poor, compared with 19% of older people who did not
report recent low back pain.

## Slide 6

**Notes:**
Osteoarthritis is the most common joint disorder and is characterized by joint pain, stiffness, and swelling. Joint pain can also be caused by injury, prolonged abnormal posture, or
repetitious movements (1,2). In 2003, almost one-third of adults age 18 years and over and one-half of adults age 65 years and over reported joint pain, aching, or stiffness
(excluding the back or neck) during the 30 days prior to interview (Table 57). The knee was the site of joint pain most commonly reported, followed by the shoulder, fingers, and
hips. Trends in the prevalence of joint pain have remained stable in recent years. 
In the 2003 National Health Interview Survey only, respondents who reported any joint pain, aching, or stiffness in or around a joint during the past 30 days were asked a follow-up question ‘‘During the past 30 days, how bad was your joint pain on average? Please answer on a scale of 0 to 10 where 0 is no pain or aching and 10 is pain or aching as bad as it can be.’’ In this analysis, a reported score of 7–10 was classified as severe pain and 0–6 as lesser pain.
Severe joint pain increased with age (Figure 32). Women were more likely to report severe joint pain than men (10% compared with 7%). Although non-Hispanic black adults
reported overall joint pain less often than non-Hispanic white adults, they were more likely to report severe joint pain. Asian adults had a lower percentage of severe joint pain than adults in other racial and ethnic groups. Persons with family income below 200% of the poverty line were nearly twice as likely to report severe joint pain as adults with family income of 200% or more of poverty (12%–13% compared with 7%).

## Epidemiology of chronic pain in the community (UK)

- Postal survey of random sample of 5035, 3605 returned
- 1817 (50%) of patients reported chronic pain (>3 mo), 576 back pain and 570 arthritis
- 49% had low intensity/ low disability pain,       16% had high intensity/ high disability pain
- 17% reported no treatment need
- 	28% reported highest treatment need

- Elliott AM et al. *Lancet* 1999;354:1248-1252

- Elliott AM et al, Lancet, 1999; 354:1248-52

**Notes:**
The results of the questionnaire enable patients to be classified into five hierarchical grades: grade 0 (pain free), grade I (low disability, low intensity), grade II (low disability, high intensity), grade III (high disability, moderately limiting), and grade IV (high disability, severely limiting).
For the purposes of this study, this questionnaire consisted of four questions: Have you sought treatment for your pain or discomfort recently? Have you sought treatment for your pain or discomfort often? Have you taken painkillers for your pain or discomfort recently? Have you taken painkillers for your pain or discomfort often? From the number of positive responses we were able to identify five levels of expressed need for patients with chronic pain from level 0 (no expressed need; answered no to all four questions) to level 4 (high expressed need; answered yes to all four questions).

## Persistent pain in primary care:World Health Organization (WHO) Study

- 5438 patients from 15 sites in 14 countries were assessed by interview and questionnaires
- 22% of primary care patients had persistent pain (>6 months + care or disability)
- More likely to have anxiety or depressive disorder (OR*=4.14)
- Pain-distress relationships were more consistent across cultures than pain-disability

- Gureje et al, *JAMA* 1998;280:147-151

- Gureje, Simon, VonKorff, JAMA, 1998; 280:147-151

## Persistent pain in primary care: WHO Study

- 3197 patients from 15 sites in 14 countries were assessed at baseline and 12 months
- 50% with persistent pain at baseline still had pain at 12 months
- Predicted by number of pain sites at baseline
- 8.8% had new-onset persistent pain
- Predicted by psychiatric disorder, perceived poor health, and occupational role disability

- Gureje et al, *JAMA* 1998;280:147-151

## Cancer vs. non-cancer pain:intensity, distress, interference

-         Zaza C et al. *Pain *2000;87:75-82

**Notes:**
112 patients with chronic cancer-related pain, defined as the presence of pain for at least 3 months, that resulted either from the tumour itself, or from treatment or palliative
measures related to cancer. Compared to means from chronic non-cancer pain studies. 
Pain severity AC= 2.9; DYS= 4.57; ID= 3.78; ANOM= 1.72; P= 0.001 Compared to CNCP= 4.6 (Turk 1998 study)
Interference AC= 3.16; DYS= 4.97; ID= 4.43;  ANOM= 1.87; Compared to CNCP= 4.3 (Turk 1998 study)

## Opioid users for cancer pain and non-cancer pain (in Denmark)

- Jarlbaek L et al. *J Pain Sympt Mgmt *1994;27:36-43

## Slide 12

**Notes:**
The National Health and Nutrition Examination Survey (NHANES) collects data on the prescription drug use of survey participants living in the community through in-person
household interviews. Prescription drug use is determined by examining the prescription labels of the participant’s medications.
Between 1988–1994 and 1999–2002, the age-adjusted percentage of women reporting narcotic drug use in the month prior to interview increased by almost one-half from
3.6% to 5.3%. This increase was driven largely by an increase in narcotic drug use among women age 45 years and over (Figure 34). During this period, use of narcotic drugs
rose by almost 75% among women 45–64 years of age to 5.7% and by more than 50% among women 65 years and over to 6.8%. This increased use has been primarily among
non-Hispanic white women (data table for Figure 34). In contrast, reported narcotic drug use among adult men remained stable from 1988–1994 to 1999–2002 and there
were no significant differences in use for men by race or ethnicity.
NHANES prescription drug data: The questionnaire
administered to all participants also included a question on
whether they had taken a prescription drug in the past
month. Those who answered ‘‘yes’’ were asked to show
the interviewer the medication containers for all the
prescriptions. For each drug reported, the interviewer
entered the product’s complete name from the container. If
no container was available, the interviewer asked the
participant to verbally report the name of the drug.
Additionally, participants were asked how long they had
been taking the drug and the main reason for use. All
reported medication names were converted to their
standard generic ingredient name. For multi-ingredient
products, the ingredients were listed in alphabetical order
(i.e., Tylenol #3 would be listed as Acetaminophen;
Codeine). No trade or proprietary names were provided on
the data file. More information on prescription drug data
collection and coding in the NHANES is available from:
www.cdc.gov/nchs/data/nhanes/frequency/rxq_rxdoc.pdf.
More information on NHANES III prescription drug data
collection and coding is available from: www.cdc.gov/nchs/
data/nhanes/nhanes3/PUPREMED-acc.pdf. Also see
Appendix I, National Health and Nutrition Examination
Survey.

## Geographic variation in opioid  prescription claims in 2000 

- Curtis LH et al. *Health Serv Res *2006;41:837-55

- Curtis LH et al, Health Serv Res, 41:837-855; 2006

**Notes:**
Negatively assoc: prescription monitoring program, population proportion 15-24, >65yo
Positively assoc: surgeons per 1000, illicit drug use prevalence, proportion female

## Profile of Opioid Use Episodes in 

- <date/time>

*Provisional Results *
- Profile of Opioid Use Episodes in
- Group Health Cooperative
*Years: 1997-2005, 457,095 episodes of opioid use in adults *

- Supported by NIDA grant DA-022557 (PIs: Michael Von Korff and Connie Weisner)

| 
Episode Type
 | Mean 
Days
Duration | Mean Days Supply | Average Daily Dose 
(mg morphine equiv) |
| --- | --- | --- | --- |
| Acute (<90 days duration)
N=369,649 episodes | 
14 | 
9.4 | 
24.4 mg |
| Episodic(<10 fills & 120 days supply)
N=63,392 episodes | 
103 | 
29.4 | 
4.5 mg |
| Chronic-Lower Dose (10+ fills OR 120+ days supply AND <20 mg)
N=17,777 episodes | 
800 | 
338.4 | 
8.1 mg |
| Chronic-Higher Dose (10+ fills OR 120+ days supply AND >20 mg)
N=6,277 episodes | 
906 | 
834.8 | 
53.7 mg |

**Notes:**
Episode occurs between 6 mo periods of non-use of opioids

## Provisional Results 

- <date/time>

*Supported by NIDR grant DA-022557,  Michael  Von Korff & Connie Weisner  PI’s     *

*Provisional Results *
- Prevalence of opioid use episodes per 1,000 adults:
- chronic non-cancer pain at Group Health Cooperative* **population of approximately 300,000 adults*

- Supported by NIDA grant DA-022557 (PIs: Michael Von Korff and Connie Weisner)

**Notes:**
Chronic low dose prevalence increase from 1% to 2.5% (150% incr)
Chronic higher dose prevalence increase from 0.3% to 1% (300% incr)

## Provisional Results 

- <date/time>

*Provisional Results *
- Incidence of Opioid Use Episodes per 1,000 Adults:
- Chronic Non-Cancer Pain at Group Health  Cooperative*
- **population of approximately 300,000 adults*

- Supported by NIDA grant DA-022557 (PIs: Michael Von Korff and Connie Weisner)

**Notes:**
Chronic lower dose increase incidence from 0.55 to 0.8% (48% incr)
Chronic higher dose increase incidence from 0.17 to 0.26% (53% incr)

## Trends in opioid use (>60d supply)  Arkansas Medicaid population 2002-05

**40% increase in chronic opioid use 2002-05**

- Supported by NIDA grant DA022560 (PI: Mark Sullivan)

## Who regularly uses prescribedopioids for chronic non-cancer pain?

- Health Care for Communities (HCC)
- Nationally representative household phone survey, 2 waves: 1997-1998, 2000-2001
- DV: _>_ 1 mo regular use of prescribed opioids in 2000-2001
- Asked about all prescribed medications they had taken “at least several times a week for a month or more” in the past 12 months

- Sullivan MD et al. *Arch Intern Med  *2006

## Independent Variables

- WHO-CIDI mental health and substance use disorders in 1997-1998
- Sociodemographics
- Physical Health (PCS from SF-12)
- Pain Interference (from SF-12)
- Self-Report General Health
- Chronic Conditions
- (4 painful conditions: arthritis, back pain, headaches, other pain)
- (13 non-painful conditions: hypertension, diabetes, heart disease...)

- Sullivan MD et al. *Arch Intern Med  *2006

## Characteristics of Users and Non-Users of Opioids for CNCP (continued)

- Sullivan MD et al. *Arch Intern Med  *2006

- Sullivan MD et al, Arch Int Med, 2006

## Characteristics of Users and Non-Users of Opioids for CNCP (continued)

- Sullivan MD et al. *Arch Intern Med  *2006

## Characteristics of Users and Non-Users of Opioids for CNCP (continued)

- Sullivan MD et al. *Arch Intern Med  *2006

## Characteristics of Users and Non-Users of Opioids for CNCP (continued)

- Sullivan MD et al. *Arch Intern Med  *2006

## Characteristics of Users and Non-Users of Opioids for CNCP (continued)

- Sullivan MD et al. *Arch Intern Med  *2006

## Predicting 2001 opioid use from 1998 demographic and clinical variables

- Sullivan MD et al. *Arch Intern Med  *2006

## Predicting 2001 opioid use from 1998 demographic and clinical variables

- Sullivan MD et al. *Arch Intern Med  *2006

## Predicting 2001 opioid use from 1998 demographic and clinical variables

- Sullivan MD et al. *Arch Intern Med  *2006

## Predicting 2001 opioid use from 1998 demographic and clinical variables

- Sullivan MD et al. *Arch Intern Med  *2006

## Predicting 2001 opioid use from 1998 demographic and clinical variables

- Sullivan MD et al. *Arch Intern Med  *2006

## Predicting 2001 opioid use from 1998 demographic and clinical variables

- Sullivan MD et al. *Arch Intern Med  *2006

## Predicting 2001 opioid use from 1998 demographic and clinical variables

- Sullivan MD et al. *Arch Intern Med  *2006

## Who develops opioid abuse/dependence among those receiving opioid therapy for chronic non-cancer pain?

- Using pharmacy and diagnostic codes from VA VISN-16 data warehouse for 2000-2005 to identify individuals with at least 91+ days of opioid use in 2002.  [N= 15,162; ~5% of all pts]
- Excluded individuals with opioid abuse diagnosis in 2000-2002, to ensure that predictors preceded the outcome.
- Dependent Variable:
- 	Diagnosis of Opioid Abuse or Dependence in Years 2003-2005. [N=298; ~2% chronic users]

- Edlund ME et al. *Pain *In Press

- Edlund ME et al, Pain, in press

## Independent variables from 2002

- Mental Health and Substance Use Disorders
- Common Painful conditions (back pain, arthritis, migraines, headaches)
- Sociodemographic factors
- Number of days of opioid supply
- Health care utilization (proxy for medical comorbidity)

- Used multiple logistic regression to investigate diagnosis of opioid abuse/dependence in 2003 to 2005, using covariates from 2002.

## Predictors of opioid abuse/dependence diagnoses (2003-05) among individuals with >90d use of opioids in 2002

## Predictors of opioid abuse/dependence diagnoses (2003-05) among individuals with >90d use of opioids in 2002 (continued)

## Collaborators

- Mark Edlund, MD, PhDDiane Steffick, PhD Teresa Hudson, PharmD
- University of Arkansas for Medical Sciences
- Kenneth Wells, MD, MPH
- 	Lily Zhang, MS
- University of California, Los Angeles
- Jurgen Unutzer, MD, MPH
- University of Washington

## Summary of results

- Individuals who regularly use of opioids for CNCP have high rates of medical (painful and non-painful) and psychiatric comorbidity.
- Psychiatric disorders (MH and SA) are associated with use of opioids for CNCP.
- Among individuals with opioid use for CNCP, psychiatric disorders are risk factors for development of opioid abuse/dependence.

## Discussion of results

- Though individuals with psychiatric disorders are more likely to receive  opioids for CNCP _and_ to abuse opioids, they have been excluded as ‘high risk’ from almost all opioid clinical trials.
- Thus there is a serious mismatch between the evidence base for opioid use and current clinical practice

## Discussion of results

- Substance abuse has received the most attention as a risk factor for misuse of prescribed opioids.
- But the population attributable risk for opioid abuse from mental health disorders (OR=1.46, prevalence=45%) is likely greater than the population attributable risk from non-opioid substance disorders       (OR=2.43, prevalence=7.6%).

**Notes:**
Population attributable risk is the proportion of disease in a study population that us attributable to the exposure and thus could be eliminated if the exposure were eliminated. Need prospective incidence data for valid calculation but estimate based on this data is PAR=17% for MH disorders and PAR=10% for SA disorders.

## Does rejection hurt? An fMRI study of social exclusion

- Participants underwent fMRI:
- 	excluded from virtual ball tossing game, mimicking social rejection.
- Increased activity in anterior cingulate cortex  correlated positively with distress.    Increased activity in right ventral prefrontal cortex correlated negatively with distress.
- Parallel to findings of physical pain studies.

- Eisenberger et al, Science, 2003

**Notes:**
It has been suggested that, in mammalian species, the social-attachment system borrowed the computations of the pain system to prevent the potentially harmful consequences of social separation. Mounting evidence from the animal lesion and human neuroimaging literatures suggests that physical and social pain overlap in their underlying neural circuitry and computational processes. We review evidence suggesting that the anterior cingulate cortex plays a key role in the physical-social pain overlap. 

## The brain in pain:physical or social?

- In mammals, the social-attachment system borrowed computations of the pain system to prevent the harmful consequences of social separation.

## Clinical implications

- Diagnosis and treatment of psychiatric disorders (MH and SA) are important  when considering patients for chronic opioid therapy.
- However, which psychiatric services would actually help these individuals is not well defined.

## May I never see in the patient anything but a fellow creature in pain. --Oath of Maimonides

**Notes:**
Maimonides (March 30, 1135 or 1138–December 13, 1204) was a Jewish rabbi, physician, and philosopher in Spain and Egypt during the Middle Ages. He was one of the various medieval Jewish philosophers who also influenced the non-Jewish world. Although his copious works on Jewish law and ethics were initially met with opposition during his lifetime, he was posthumously acknowledged to be one of the foremost rabbinical arbiters and philosophers in Jewish history. Today, his works and his views are considered a cornerstone of Orthodox Jewish thought and study.