Addressing the under-treatment of clinical pain has become a national priority, with a central goal being to identify effective interventions for those subgroups of patients most at risk for suffering unrelieved pain (NIH Program Announcement PA-01 -115). In fact, the under-treatment of pain was recently ruled a form of patient abuse with a California court awarding one million dollars in damages to the family of such a patient. Novel data accumulated by our investigative group has shown that patients maintained on the mu-opioid agonist, methadone, for the treatment of addiction, are significantly hyperalgesic to cold-pressor experimental pain as compared to normal controls. This diminished pain tolerance, in addition to the contextual prohibitions associated with providing known opioid addicts with opioid analgesics, makes them a population uniquely vulnerable to the under treatment of pain. Unfortunately, little is known about how to best manage the pain suffered by the over 120,000 methadone-maintained (MM) patients in this country, in part because the hyperalgesia they suffer appears to be akin to neuropathic pain and opioid-induced. In the proposed series of studies, the Principal Investigator (a first-time RO1 applicant) will build upon her previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspective. Utilizing slightly different double-blind, placebo-controlled designs, the proposed work will evaluate the ability of three classes of medication (N-methyl-D-aspartate (NMDA)-antagonists, adjuvant anticonvulsant analgesics, and novel opioid analgesics) to diminish or reverse the opioid-induced hyperalgesia complicating the pain states suffered by MM patients. Specifically, in a sample of MM patients, (1) dextromethorphan, which interferes with the development of opioid-induced hyperalgesia, (2) gabapentin, which has proven efficacy in treating neuropathic pain, and (3) oxycodone, which has novel opioid activity, will each be evaluated for its ability to ameliorate or diminish the opioid-induced hyperalgesia in these patients as reflected by changes on pain threshold and tolerance to both cold-pressor and electrical pain, at peak and through methadone blood levels. The results of this work will not only provide pharmacologic insight into the mechanisms underlying poor pain tolerance in this at-risk population, but also direction for the medical management of pain complicated by opioid-induced hyperalgesia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA015463-04
Application #
6911536
Study Section
Special Emphasis Panel (ZDA1-MXG-S (17))
Program Officer
Montoya, Ivan
Project Start
2002-09-01
Project End
2008-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
4
Fiscal Year
2006
Total Cost
$522,872
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Nursing
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Compton, Peggy; Kehoe, Priscilla; Sinha, Karabi et al. (2010) Gabapentin improves cold-pressor pain responses in methadone-maintained patients. Drug Alcohol Depend 109:213-9
Compton, Peggy A; Wu, Stephen M; Schieffer, Beatrix et al. (2008) Introduction of a self-report version of the Prescription Drug Use Questionnaire and relationship to medication agreement noncompliance. J Pain Symptom Manage 36:383-95
Zacny, James; Bigelow, George; Compton, Peggy et al. (2003) College on Problems of Drug Dependence taskforce on prescription opioid non-medical use and abuse: position statement. Drug Alcohol Depend 69:215-32