Fuqiang Zhao1, Denise Welsh1, Mangay Williams1, Alexandre Coimbra1, Mark O. Urban2, Richard Hargreaves2, Jeffrey Evelhoch1, Donald S. Williams1
1Imaging Department, Merck Research Laboratories, West Point, PA, United States; 2Neuroscience Department, Merck Research Laboratories, West Point, PA, United States
To validate the fMRI signals in the spinal cord and the brain of rats induced by noxious stimulation as a pain biomarker, and to determine its utility in elucidation of mechanisms of action of analgesics, the effect of buprenorphine (BPN), a partial -opioid agonist, on pain fMRI signals was investigated. The pain fMRI signals in the caudate putamen and thalamus region were totally suppressed, while those in spinal cord, cerebellum, thalamic relay of somatosensory pathway, and primary somatosensory cortex were only partially (if at all) suppressed. Such a suppression pattern is consistent with the density of opioid receptor distribution in brain, supporting the idea that fMRI can provide anatomical action sites of the analgesics, which should help to understand their mechanisms of action.