Additional Positron Emission Tomography (PET) Scan of Brain in Patients Undergoing PET Scan for Diseases Unrelated to Brain
Condition: Pain
Study type: Observational

Summary: 
      Specific Aims:

      • The primary objective is to delineate the brain structures that are involved in pain using
      Positron Emission Tomography (PET) imaging.

      Hypothesis:

      Pain will result in increases in metabolism and neuronal activity in specific delineated
      areas of the brain.
    

Detailed description: 
      Background and Significance:

      Despite advancement in pain management, pain relief and patient satisfaction are still
      inadequate in many patients. Functional imaging techniques have recently made it possible to
      identify the main cerebral components of the human nociceptive system. These comprise at
      least two main human nociceptive components working in parallel called the medial and lateral
      pain systems. This has provided a physical construct for the concept of the human pain
      matrix. Careful study of these areas of the human brain has the potential to drive
      development of new classes of analgesic compounds. PET is an imaging technique that can
      quantify increases in nerve cell activity in selective regions of the brain (1-5). PET
      provides the means to measure tissue concentrations of labeled drugs in brain and other
      tissues and also to measure changes in receptor occupancy.

      Earlier studies have examined the pattern of increased brain activity that follows
      experimentally-induced acute pain (2) and chronic pain syndromes (1,3,5). Distal pain
      pathways (e.g. spinothalamic tract) project to the thalamus and then discrete regions of the
      cortex via thalamocortical projections. Among cortical areas involved in sensation,
      perception, and attention in both humans and monkeys are anterior cingulate gyrus, insular
      cortex, primary somatosensory cortex, and secondary somatosensory cortex. PET studies with
      experimental human pain also demonstrate activation in brain areas related to sensory-motor
      integration. However, depending on the type of noxious stimulation, different areas of brain
      are activated (2). Components of the lateral system such as the primary somatosensory (SI)
      cortex do appear to be frequently activated with tonic (non-phasic experimental pain) and
      phasic pain (67% and 69% of studies show activations, respectively). But only 23% of studies
      of chronic clinical pain studies demonstrate activation of SI.

      We have performed the first clinical study (IRB study #05121504) to investigate the change in
      brain activity associated with significant postoperative pain (6). This was an IRB-approved
      study with just one patient to establish that the methods we have developed will be sensitive
      enough for a more complete randomized clinical trial. We determined that postsurgical pain is
      associated with increased activity in the contralateral primary somatosensory cortex. Other
      brain regions showing increased postsurgical activity were the contralateral parietal cortex,
      bilateral pulvinar and ipsilateral medial dorsal nucleus of the thalamus, contralateral
      putamen, contralateral superior temporal gyrus, ipsilateral fusiform gyrus, ipsilateral
      posterior lobe and contralateral anterior cerebellar lobe. We have received permission from
      the IRB to perform a larger study with 21 patients (IRB study #07050273).

      Although fMRI has also been used for functional brain imaging, the advantages of PET over
      fMRI are (7):

      PET is detected in neural tissue, while fMRI is detected in the venous compartment

        1. PET with 18F-fluoro-2-deoxyglucose (FDG) gives a direct measure of glucose metabolism,
           while fMRI measures blood flow by measuring changes in deoxyhemoglobin concentration

        2. PET has a larger signal-to-noise ratio than fMRI

        3. PET is less susceptible to movement artifacts than fMRI

        4. With PET for brain only the head is in the scanner, less claustrophobic than fMRI

        5. PET does not have the inhomogeneity artifacts of fMRI

        6. PET has the capacity for future ligand-binding studies (e.g. opioid receptor)

      Comparable brain imaging studies have not been performed in primates due to the difficulty of
      having an animal not move for the duration of the scan, without the use of anesthetics.

      To better interpret our PET brain images in the above clinical trials, we need more baseline
      data on the variability in brain activation from person-to person, especially in people with
      no or minimal pain. Clinical oncology utilizes PET imaging for the diagnosis and monitoring
      of many types of cancer, e.g. Hodgkin's disease, non-Hodgkin's lymphoma, and lung cancer. The
      brain of these individuals can be considered within normal range and could be a control for
      our other studies involving postoperative pain and its alleviation. To obtain these 'control'
      brain scans, a patient being scanned for diseases outside the brain would not have to have an
      additional radionuclide injection. Instead, after the primary body scan is completed, the
      patient platform would be moved slightly so the head is now centered in the scanner, and the
      scanning process resumed, for approximately 20 minutes. Since the half-life of the FDG
      radionuclide is about 110 min, there will still be adequate signal available to be picked up
      by the detector during this secondary scan.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Between 18-80 years of age
      
Keywords: PET SCAN; PAIN LEVELS