Chronic administration of opioid-based analgesics has been associated with the development of increased sensitivity to pain. Research in both animals and humans suggest that this opioid induced hyperalgesia is mediated via central, neuroplastic changes. Experimental designs have been limited to animal subjects because of their invasive nature, and there is a need to characterize opioid-induced hyperalgesia in humans. New techniques such as real-time functional magnetic resonance imaging (rtfMRI) allow for the experimental, non-invasive modulation of central nervous activity in human participants and therefore presents a powerful method for exploring central mechanisms of pain. We propose a comprehensive training plan and subsequent research program into the mechanisms of opioid-induced hyperalgesia, including the use of rtfMRI experimental designs. In the K99 training phase of this grant, Dr. Younger will train at the Stanford University School of Medicine, under the direction of Sean Mackey, MD, PhD, an established pain researcher, as well as a team of collaborating mentors, including Gary Glover, PhD (radiology), David Clark, MD, PhD (opioid-induced hyperalgesia) and Ravi Prasad, PhD (clinical psychology). Training will be conducted via formal coursework, hands-on lab training, mentored research, progress review by the steering committee, regular attendance of colloquia and workshops, and teaching opportunities. The subsequent ROD independent research phase involves a series of studies designed to systematically identify and test the role of central neural structures in opioid-induced hyperalgesia.
Our first aim i s to characterize the central neural correlates of opioid-induced hyperalgesia in humans. Second, we propose to describe the long-term neural effects of prolonged opioid exposure. Last, we will use rtfMRI to experimentally test the role of specific brain structures in the development and maintenance of opioid-induced hyperalgesia. Relevance: Chronic pain affects millions of individuals in the United States, and a large proportion of these individuals are prescribed opioid analgesics. The long-term use of opioids may increase patients' sensitivity to pain, adding to the original complaints of pain and confusing the picture of disease progression. It is important that we understand how the brain is involved in this increased pain sensitivity and what long-term impact these changes may have. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Career Transition Award (K99)
Project #
1K99DA023609-01
Application #
7302152
Study Section
Special Emphasis Panel (ZDA1-GXM-A (19))
Program Officer
Lin, Yu
Project Start
2007-09-30
Project End
2009-08-31
Budget Start
2007-09-30
Budget End
2008-08-31
Support Year
1
Fiscal Year
2007
Total Cost
$86,454
Indirect Cost
Name
Stanford University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Mueller, Christina; Chu, Larry F; Lin, Joanne C et al. (2018) Daily opioid analgesic use reduces blood insulin levels. J Opioid Manag 14:165-170
Ung, Hoameng; Brown, Justin E; Johnson, Kevin A et al. (2014) Multivariate classification of structural MRI data detects chronic low back pain. Cereb Cortex 24:1037-44
Younger, Jarred W; Chu, Larry F; D'Arcy, Nicole T et al. (2011) Prescription opioid analgesics rapidly change the human brain. Pain 152:1803-10
Younger, Jarred W; Shen, Yoshi F; Goddard, Greg et al. (2010) Chronic myofascial temporomandibular pain is associated with neural abnormalities in the trigeminal and limbic systems. Pain 149:222-8
Younger, Jarred; Mackey, Sean (2009) Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med 10:663-72
Shen, Yoshi F; Younger, Jarred; Goddard, Greg et al. (2009) Randomized clinical trial of acupuncture for myofascial pain of the jaw muscles. J Orofac Pain 23:353-9