Opioid-induced Hyperalgesia in Prescription Opioid Abusers: Effects of Pregabalin

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DESCRIPTION (provided by applicant): The clinical management of pain in prescription opioid abusers presents a challenge to the health care professional. Epidemiological data indicate that a substantial number (40-50%) of the 5.1 million prescription opioid abusers in this country suffer pain on an ongoing basis, yet treatment with opioid analgesics is complicated not only by concerns about drug-seeking and addiction, but also by the neurophysiologic consequences of opioid abuse on pain systems. With direct relevance to pain, an increasingly appreciated neural response to opioid abuse is opioid-induced hyperalgesia (OIH), or a state of heightened sensitivity to noxious stimuli associated with ongoing exposure to opioids, and resulting in a paradoxical increase in pain and decrease in opioid analgesic effects. Opioid-induced hyperalgesia has been well-demonstrated in patients on substitution medication (e.g., methadone, buprenorphine) for the treatment of opioid dependence; notably the investigators have novel pilot data showing that the GABA-agonist gabapentin (GPN) significantly decreases OIH in methadone patients (Compton et al., 2010), providing the first empirical evidence of a pharmacotherapy for OIH in opioid abusers. In an effort to guide its use in the clinical setting, the proposed research will comprehensively evaluate the efficacy of chronic GPN therapy to treat OIH in a well-described population of prescription opioid abusers on buprenorphine therapy, and examine how these effects are mediated by the presence of chronic pain. Directly building upon the data and formalized research activities of the investigative group, the planned project is designed and staffed to be completed in three years, and is anticipated to provide important, valid, and timely detail on the efficacy of GPN for the treatment of OIH in opioid abusers. Importantly, this work will expand the clinical population of interest to focus on prescription opioid abusers, a group of patients for whom chronic pain and addiction complicate outcome, and leaves them uniquely vulnerable to under-treatment or poor pain management. Testing the GPN, the first-known pharmacotherapy to treat OIH in this population, is an important step toward providing adequate pain relief for patients who abuse prescription opioids.