Clinicians managing patients with chronic non-cancer pain (CNCP) are typically faced with the dilemma of providing the appropriate standard of care to alleviate suffering including the use of opioids, while not complicating recovery by exposing the vulnerable patient to the potential of opioid abuse and addiction. It has been considered the standard of care to provide patients suffering from CNCP with opioids, even on a long- term basis. However, there is ongoing debate regarding this policy of responsible opioid prescribing in chronic pain patients given the rising prevalence of prescription opioid abuse and addiction in the country (Johnston, 2008). Numerous studies have identified high prevalence rates of substance use disorder in chronic pain patients (Polantin, Kinney et al, 1993~ Compton et al, 1998~ Martell et all, 2006). Reported prevalence of opioid abuse in chronic pain patients ranges from 3-40% (Fishbain et al, 1992, 2008~ Martell et al, 2007~ Ives et al, 2006). Diagnosing abuse and addiction in patients with chronic pain on opioids is very complex. It is difficult to ascertain who will become problematic users of prescription opioids when initiating therapy. There have been attempts at mitigating this problem of predicting which patients are at risk for opioid addiction (OA), with the utilization of questionnaires and interview protocols which have been promising, but not well validated (Turk et al, 2008). This project is the first in a series of studies to assess the behavioral and genotypic characteristics of patients who develop OA. There is a growing body of evidence indicating that risk for OA has substantial genetic origins (Kreek et al, 2005). There has been considerable evidence from clinical and animal studies regarding the mu opioid receptor (MOR) gene (OPRM1) as critical to the rewarding and analgesic properties of opioid analgesics. It is the specific aim of this project to perform genome-wide analysis in approximately 2,000 patients with CNCP having been treated for OA. To date it has been difficult to identify a control group of patients who are chronically exposed to opioids but do not develop addiction. In our study, 2000 patients with chronic pain who are receiving long-term opioid therapy and who have not displayed evidence of addiction will serve as our controls. In addition, we will assess psychiatric co-morbidities, aberrant behaviors, substance use, addiction and socioeconomic factors in both groups. This will allow us to substantiate in the control group the absence of addiction and also to elucidate specific psychosocial factors and specific behaviors in the experimental group suggestive of addiction. This data will form the basis of subsequent studies in developing behavioral and genetic risk profiling for prospective testing in patients with chronic pain initiating opioid therapy.

Public Health Relevance

This project is the first in a series of studies to assess the behavioral and genotypic characteristics of patients who develop opioid addiction. It is the specific aim of this project to perform genome-wide analysis in approximately 2000 patients with chronic non cancer pain having been treated for opioid addiction and a control group of 2000 pain patients maintained on chronic opioid therapy not displaying signs of addiction. This data will form the basis of subsequent studies in developing behavioral and genetic risk profiling for prospective testing in patients with chronic pain initiating opioid therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA032776-03
Application #
8666728
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Duffy, Sarah Q
Project Start
2012-07-15
Project End
2017-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
3
Fiscal Year
2014
Total Cost
$576,509
Indirect Cost
$129,400
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Cheatle, Martin D (2016) Biopsychosocial Approach to Assessing and Managing Patients with Chronic Pain. Med Clin North Am 100:43-53
Wachholtz, Amy; Foster, Simmie; Cheatle, Martin (2015) Psychophysiology of pain and opioid use: implications for managing pain in patients with an opioid use disorder. Drug Alcohol Depend 146:1-6
Cheatle, Martin D; Shmuts, Rachel (2015) The risk and benefit of benzodiazepine use in patients with chronic pain. Pain Med 16:219-21
Cheatle, Martin D (2015) Prescription Opioid Misuse, Abuse, Morbidity, and Mortality: Balancing Effective Pain Management and Safety. Pain Med 16 Suppl 1:S3-8
Peppin, John F; Cheatle, Martin D; Kirsh, Kenneth L et al. (2015) The complexity model: a novel approach to improve chronic pain care. Pain Med 16:653-66
Dhingra, Lara; Perlman, David C; Masson, Carmen et al. (2015) Longitudinal analysis of pain and illicit drug use behaviors in outpatients on methadone maintenance. Drug Alcohol Depend 149:285-9
Cheatle, Martin D; Webster, Lynn R (2015) Opioid Therapy and Sleep Disorders: Risks and Mitigation Strategies. Pain Med 16 Suppl 1:S22-6
Cheatle, Martin; Comer, Dominique; Wunsch, Martha et al. (2014) Treating pain in addicted patients: recommendations from an expert panel. Popul Health Manag 17:79-89
Cheatle, Martin D; Wasser, Thomas; Foster, Carolyn et al. (2014) Prevalence of suicidal ideation in patients with chronic non-cancer pain referred to a behaviorally based pain program. Pain Physician 17:E359-67
Cheatle, Martin D (2014) Suicidal ideation in patients with chronic pain: The risk-benefit of pharmacotherapy. Pain 155:2446-7

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