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Pain is recognized as a sensory and emotional experience in humans. Unfortunately, there is no objective test for measuring pain. This has hampered both the clinical management and the scientific understanding of pain. In the clinical setting, physicians daily encounter difficulties in diagnosing chronic pain conditions. The findings of commonly used testing modalities (magnetic resonance imaging [MRI], computed tomography, electromyography) are frequently normal. History and physical examination are highly subjective tests and prone to examiner bias. Complaints of chronic pain patients are frequently labeled “psychogenic” in origin. The majority of chronic pain patients suffer from depression; however, it is difficult to determine if depression is a consequence of chronic pain or vice versa. Indeed, emotional and pain brain networks share similar anatomic structures.


Most of the limited knowledge of central nervous system (CNS) pain processing is derived from animal research using electrophysiologic recordings. The animal data do not provide adequate insight into human aspects of pain processing, such as the affective component of pain. There is need for a better understanding of the following aspects of human pain networks: (1) chronic pain states in which altered CNS processing is taking place; (2) effects of various drugs on brain activation in acute and chronic pain; and (3) perception of pain in altered states of conciousness.


The initial findings that provided an insight into human CNS pain networks were accomplished by functional brain imaging using positron emission tomography (PET) technology, followed by studies using functional magnetic resonance imaging (fMRI). Although still in their infancy, these tools are extremely valuable in bridging the gap between clinical practice and animal research in understanding pain.


Functional brain imaging techniques are based on similar methods of measuring brain neuronal activity. Glucose is the main energy source for human brain metabolism. The coupling between regional cerebral blood flow and local cerebral glucose use has been established and supported by experimental data. Glucose metabolism reflects the brain neuronal synaptic and presynaptic activity needed for maintenance of membrane potentials and restoration of ion gradients. Functional brain imaging, by measuring the regional blood flow, provides indirect data on regional brain neuronal activity, be it local activation or inhibition.


PET is an instrument that allows accurate measurements of small concentrations of radioactivity in living tissue. Positron-emitting isotopes have been incorporated as tracers into a wide range of molecules to provide information about various biologic processes after inhalation or intravenous administration. By using this technique, the whole brain metabolic activity in pain states can be measured. The ability to overlap brain metabolic activity data acquired by PET with structural magnetic images of brain (MRI) enhanced the effective spatial resolution of PET. There are numerous studies using this technology in medicine.


The first brain mapping study focusing on pain used PET. This study demonstrated that painful heat produced activation in multiple brain areas, including cortical and subcortical structures.1 Since then, PET with various experimental ...

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