1. Brain PET Scans in Patients with Minimal Pain Departments of Anesthesiology, Radiology, and Neurology Rush University Medical Center Rush Medical College Chicago, IL Asokumar Buvanendran, MD, Amjad Ali, MD, Travis R. Stoub, PhD, Jeffrey S. Kroin, Ph.D., Kenneth J. Tuman, M.D.

2. Introduction Positron emission tomography (PET) is an imaging technique that can quantify increases in nerve cell activity in selective regions of the brain. Positron emission tomography (PET) is an imaging technique that can quantify increases in nerve cell activity in selective regions of the brain. Earlier studies have examined the pattern of increased brain activity that follows experimentally-induced acute pain. 1,2,3 Earlier studies have examined the pattern of increased brain activity that follows experimentally-induced acute pain. 1,2,3 1 Brain 1998;121:931. 2 J Neurophysiol 1999; 82:1934. 3 Anesth Analg 2007; 105:1784.

3. Can Pain Be Measured? Is Seeing Believing?

4. Increased Activity in the Brain with Pain 6 different areas are being studied:6 different areas are being studied: Anterior Cingulate Cortex (ACC)Anterior Cingulate Cortex (ACC)  Primary Somatosenory Cortex (S1)  Secondary Somatosensory Cortex (S2)  Insular Cortex (IC)  Pre-frontal Cortex (PF)  Thalamus

5. Moderate Postoperative Pain and Brain Activation After TKA Baseline MRI of the brain and PET scanBaseline MRI of the brain and PET scan Epidural Anesthesia and Analgesia for postoperative painEpidural Anesthesia and Analgesia for postoperative pain Stopped epidural:Moderate pain → PETStopped epidural:Moderate pain → PET Epidural infusing: No Pain → PETEpidural infusing: No Pain → PET

6. Postoperative Moderate Pain after Left TKA Thalamus Contralateral Somatosensory Cortex Right side Precuneus

7. Current Study However, baseline PET activity (pre-stimulation or pre-surgery) in the brain has not been examined in detail. However, baseline PET activity (pre-stimulation or pre-surgery) in the brain has not been examined in detail. Knowledge of baseline activity in patients with no pain or mild pain prior to surgical or anesthetic intervention is important for future research involving PET assessment of modulation of postoperative pain. Knowledge of baseline activity in patients with no pain or mild pain prior to surgical or anesthetic intervention is important for future research involving PET assessment of modulation of postoperative pain. In this study we examine PET brain activation at rest in six patients with minimal pain. In this study we examine PET brain activation at rest in six patients with minimal pain.

8. Methods  In a quiet room with low ambient light, fasted patients were injected intravenously with the PET radionuclide 18F-fluoro-2-deoxyglucose.  After waiting at least 30 min, a brain PET scan was performed.  Prior to each PET scan, pain scores were measured using the verbal rating scale, with 0=no pain, 10=worst imaginable pain.

9. Analysis  For the patients, digital files of PET scans were co- localized with a standard stereotaxic MRI.  To compare PET scans among different patients, a linear normalization was applied by dividing regional activity by whole brain activity for each scan. 1  A relevant increase in glucose metabolism was assumed if more than 50 adjacent voxels showed a Z score > 2.  A relevant increase in glucose metabolism was assumed if more than 50 adjacent voxels showed a Z score > 2. 2 1 Eur Neuropsychopharm 2002;12:527-44. 2 JNNP 2003; 74:922

10. The mean baseline pain score in the six patients was 1.17 (range 0-2). Results PET activation in these subjects was primarily in the occipital lobe, and putamen bilaterally Putamen Occipital lobe

11. There was no significant activation in pain- related regions Somatosensory cortex (SI or SII) SI SII

12. Anterior cingulate gyrus (ACC) ACC There was no significant activation in pain-related regions

13. Insula Also, no activation in thalamus There was no significant activation in pain-related regions

14. Discussion To fully comprehend acute, chronic, and postoperative pain PET studies, baseline brain activation must be characterized.To fully comprehend acute, chronic, and postoperative pain PET studies, baseline brain activation must be characterized. In patients reporting minimal pain, we have established that there was no brain activation in pain-related regions.In patients reporting minimal pain, we have established that there was no brain activation in pain-related regions. This suggests that changes in brain activation after intervention (e.g. joint replacement surgery) will not be obscured by the patient’s baseline brain activity as long as the baseline pain score is 2 or less.This suggests that changes in brain activation after intervention (e.g. joint replacement surgery) will not be obscured by the patient’s baseline brain activity as long as the baseline pain score is 2 or less.

15. Some activity in superior temporal gyrus and frontal cortex: Not Pain Activated site Sup Temporal Gyrus Frontal cortex